Publication date: Available online 22 February 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Pascale Dewachter, Sylvie Chollet-Martin, Claudie Mouton-Faivre, Luc de Chaisemartin, Pascale Nicaise-Roland
BackgroundNeuromuscular blocking agents (NMBAs) are the main agents involved during perioperative immediate hypersensitivity. The etiological diagnosis (IgE-mediated allergy vs nonallergy) is linked to the clinical presentation together with tryptase and histamine levels and skin test results. The role of basophil activation test (BAT) needs to be better defined in this setting.ObjectivesTo assess the role of BAT compared with the results of skin testing in 31 patients experiencing immediate NMBA hypersensitivity and compare skin test results and BAT performances in the identification of alternative NMBAs.MethodsHistamine and tryptase levels were quantified. Anesthetic drugs, including NMBAs, were skin-tested. Basophil CD63 and CD203c expressions were measured in response to serial dilutions of the different NMBAs.ResultsAllergy and Nonallergy groups involved 19 and 12 patients, respectively. Circulating histamine and tryptase levels were significantly increased in allergic patients. In the Allergy group, while skin test results were positive in 100% (19 of 19) of the cases, BAT positivity to the culprit NMBA reached 78.9% (15 of 19) when combining CD63 and CD203c. NMBAs cross-reactivity was identified through skin testing and BAT in 36.8% (7 of 19) and 26.3% (5 of 19) of the cases, respectively. The concordance (culprit and cross-reactive NMBAs) between skin tests and BATs was between 73.6% (14 of 19) and 100% (19 of 19) for each NMBA. Negative skin-tested NMBAs were uneventfully used in 7 NMBA-allergic patients. In the Nonallergy group, skin test results were negative in 100% of the cases while BAT result was positive once (CD63 upregulation).ConclusionIn our technical conditions, BAT does not replace skin testing in the assessment of NMBA allergy.
Τετάρτη 21 Φεβρουαρίου 2018
Comparison of Basophil Activation Test and Skin Testing Performances in NMBA Allergy
Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer
Computational prediction of neoantigens: do we need more data or new approaches?
Polyphosphate Metabolic Gene Expression Analyses Reveal Mechanisms of Phosphorus Accumulation and Release in Microlunatus phosphovorus Strain JN459
Fatty acid addition and thermotolerance of Kluyveromyces marxianus
Annals of Work Exposures and Health Performance, 2017
Age-dependent skin texture analysis and evaluation using mobile camera image
Abstract
Background/Purpose
The aim of this study was to evaluate skin condition, expensive equipment is required, continuous skin care is difficult. Therefore, we obtain the skin image using mobile camera, and propose a new algorithm that easily and simply extracts skin features.
Methods
We analyze skin features, extracting the wrinkle length, cell area, and the number of cells. To get accurate skin features, we obtain a new skin binary image, and apply Watershed segmentation to it. So, we improve the accuracy of skin analysis. Therefore, we compare and analyze the degree of matching distribution of wrinkles, the shape of the cell, etc., using similarity between the ground truth and the proposed algorithm result image.
Results
We extract skin surface features using a mobile camera image, and verify the change in skin features with age. Also, we demonstrate the superiority of the proposed algorithm through the similarity between the ground truth and proposed result image.
Conclusion
The proposed method in this study shows that the skin surface can be quantitatively evaluated by the similarity with ground truth. We also propose a method to diagnose and manage individual skin condition using a mobile camera in real life.
Neuroprotective effect of Annona glabra extract against ethanol-induced apoptotic neurodegeneration in neonatal rats
Publication date: Available online 21 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Hongru Ma, Jianfeng Han, Qinchuan Dong
The present study aimed to investigate the neuroprotective effect of Annona glabra extract (AGE) against ethanol-induced neurodegeneration in neonatal rats. AGE is known to contain various pharmacological and therapeutic properties. Phytochemical analysis of AGE was performed to understand the presence of vital therapeutic components. Neonatal rats were assigned to the following groups: group I (normal control rats receiving normal saline), group II (control rats receiving ethanol), and group III (treated rats receiving ethanol-AGE). The lipid peroxidation, reduced glutathione (GSH), glutathione peroxidase (Gpx), superoxide dismutase (SOD), catalase, and acetylcholine esterase (AChE) levels were determined. Behavioral parameters, histological features, neuronal cell viability, and apoptosis were also investigated. The presence of flavonoids, terpenoid, glycosides, steroids, saponins, tannins, anthraquinones, and acidic compounds was noted in the AGE. Ethanol supplementation drastically increased the malondialdehyde (MDA) content to 52.17 nmol/g in the control rats (group II). However, the MDA content was reduced to 27.34 nmol/g in ethanol-AGE-treated neonatal rats (group III) compared with control rats. The GSH content was substantially reduced, to 33.68 mg/g, in control rats compared with in normal control rats. However, the GSH content was significantly increased, to 59.32 mg/g, following ethanol-AGE supplementation. Gpx, SOD, catalase, and AChE enzyme activities were increased in treated neonatal rats compared with their respective controls. Locomotor activities, such as crossing, grooming, rearing, and sniffing, were increased in ethanol-AGE-treated neonatal rats compared with controls. Reduced levels of intact pyramidal cells and cells with degenerative alterations appeared in the control rats. However, ethanol-AGE supplementation reduced degenerative alterations and hippocampal damage. Reduced cultured hippocampal neuron cell viability and increased apoptosis were noted in the control rats, whereas these impacts were significantly recovered following ethanol-AGE supplementation. Based on all these data, we concluded that the supplementation of AGE was very effective against ethanol-induced neurodegeneration in neonatal rats.
Reduced graphene oxide coated Cu2−xSe nanoparticles for targeted chemo-photothermal therapy
Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Shu Jun Zhen, Ting Ting Wang, Yu Xin Liu, Zhu Lian Wu, Hong Yan Zou, Cheng Zhi Huang
Recently, copper chalcogenide semiconductors have been reported as new near-infrared (NIR) photothermal agents. However, it is difficult to modify them with recognition molecules, and their photothermal conversion efficiencies are relatively low, making it difficult to achieve the targeted photothermal ablation of cancer cells with a high efficiency. In this study, reduced graphene oxide (rGO) was first coated on the surface of Cu2-xSe nanoparticles (NPs) to provide abundant functional groups for the next modification and to increase the photothermal conversion efficiency. Then, doxorubicin (DOX) was loaded and folic acid (FA) molecules were covalently linked onto the surface of Cu2−xSe/rGO nanocomposites. The formed DOX@Cu2−xSe@rGO-FA nanocomposites were successfully used as chemo-photothermal agents for the targeted killing of cancer cells by utilizing the recognition ability of FA, chemotherapy effect of DOX and photothermal effects of rGO and Cu2−xSe NPs. Under the 980-nm NIR laser irradiation, the nanocomposites showed significantly enhanced chemo-photothermal therapy effect, which can be potentially applied in the nanomedicine field.
Platelet-rich plasma-induced feedback inhibition of activin A/follistatin signaling: A mechanism for tumor-low risk skin rejuvenation in irradiated rats
Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Nesreen Nabil Omar, Rasha R. Rashed, Rania M. El-Hazek, Walaa A. El-Sabbagh, Engy R. Rashed, Mona A. El-Ghazaly
BackgroundPlatelet-rich plasma (PRP) is a source of natural growth factors and is emerging as a treatment modality to mitigate radiotherapy- induced adverse effects. Activin A (ACTA) is a member of the transforming growth factor-β (TGF-β) superfamily, which has been shown to modulate the inflammatory response and macrophages polarization between different phenotypes. The aim of this study is to determine the value of PRP in preventing radiation-induced malignancies in light of the cross-talk between PRP and activin A type II receptors (ActR-IIA)/follistatin (FST) signaling pathways where the inflammatory responses at 2 different time points were evaluated.Material and MethodsMale albino rats were exposed to radiation and given PRP over the course of 6 days. Rats were sacrificed on day 7 or day 28 post radiation.ResultsQuantitative real-time reverse transcriptase polymerase chain reaction (QRT-PCR) and western-blot showed that after 7 days of administrating of PRP, ActR-IIA/FST signaling was markedly induced and was associated with the expressions of inflammatory, natural killer and M1 macrophages markers, TNF-α, IL-1β, IFN-γ and IL-12. By contrast, on day 28 of PRP administration, ActR-IIA/FST signaling and the expressions of proinflammatory cytokines were downregulated in parallel with inducing M2 macrophages phenotype as indicated by arginase-1, IL-10 and dectin-1.ConclusionThe suppression of inflammation and induction of M2 macrophages phenotype in response to PRP administration were found significantly linked to ActR-IIA/FST signaling downregulation. Furthermore, the specific M2 macrophage subtype was found to express dectin-1 receptors which have high affinity for tumor cells thereby is expected to reduce the potential for developing tumors after radiotherapy.
Exploring the non-covalent binding behaviours of 7-hydroxyflavone and 3-hydroxyflavone with hen egg white lysozyme: Multi-spectroscopic and molecular docking perspectives
Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Sourav Das, Mostofa Ataur Rohman, Atanu Singha Roy
The interactions of bio-active flavonoids, 7-hydroxyflavone (7HF) and 3-hydroxyflavone (3HF) with hen egg white lysozyme (HEWL) have been established using differential spectroscopic techniques along with the help of molecular docking method. The characteristic dual fluorescence of 3HF due to the excited intramolecular state proton transfer (ESIPT) process is altered markedly upon binding with HEWL. Both the flavonoids quenched the intrinsic fluorescence of HEWL through static quenching mechanism while the binding affinity of 7HF was found to be greater than 3HF under experimental conditions. The binding constant (Kb) values were estimated to be in the order of 104 M−1 and decreased with the rise in temperature. The contributions of the thermodynamic parameters (ΔH° and ΔS°) revealed that hydrophobic forces along with hydrogen bonding played a crucial role in the interaction of HEWL with 7HF and 3HF respectively and this finding was aptly supported by the molecular docking studies. The donor (HEWL) to acceptors (7HF and 3HF) binding distances were calculated using the Föster's theory. The phenomena of blue shifting of the emission maxima of the residues indicated the increase in hydrophobicity around the Trp micro-environment upon addition of the flavonoids was observed from synchronous and 3D fluorescence measurements whereas REES study indicated the decrease in mobility of the Trp residues upon addition of the ligands. The CD, FTIR and thermal melting studies indicated the alteration in the structural stability of HEWL on ligand binding and it was found that the % α-helical content decreased on complexation with 7HF and 3HF respectively as compared to native state. The flavonoids were found to inhibit the enzymatic activity of HEWL. The molecular docking results and accessible surface area (ASA) calculations revealed that the flavonoids bind within the active site of HEWL. The negative ΔG° values obtained from experimental and molecular docking studies indicate the spontaneity of the interaction processes.
Graphical abstract
Synthesis and characterization of Tamoxifen citrate modified reduced graphene oxide nano sheets for breast cancer therapy
Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Yu-jin Zhang, Bao-an Li, Zhao-yuan Li, Ning xia, Hai-ying Yu, Ya-zhi Zhang
Theranostic agents are of immense consideration in the current generation nanomedicine. In this study, we have developed a facile approach for the fabrication of Tamoxifen citrate modified nanosized reduced graphene oxide (nano-rGO) with more stability and low cytotoxicity. The prepared nano-rGO sheets were characterized using HR-TEM and AFM imaging techniques. Further, the cytotoxicity was assessed using MTT assay on female BALB/c nude mice MCF-7 cell lines. In addition, by means of continuous-wave near-infrared laser, cancer cells in vivo were significantly ablated because of the photothermal effect stimulated by tamoxifen modified nano-rGO. These results indicated that the prepared tamoxifen modified nano-rGO has the ability to apply in the photothermal therapy of breast cancers. Consequently, further exploration of photothermal therapeutics is desirable for the synthesis of novel nano materials with additional functionalities.
Graphical abstract
Effect of carbon limitation on photosynthetic electron transport in Nannochloropsis oculata
Publication date: Available online 21 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Tomáš Zavřel, Milán Szabó, Bojan Tamburic, Christian Evenhuis, Unnikrishnan Kuzhiumparambil, Petra Literáková, Anthony W.D. Larkum, John A. Raven, Jan Červený, Peter J. Ralph
This study describes the impacts of inorganic carbon limitation on the photosynthetic efficiency and operation of photosynthetic electron transport pathways in the biofuel-candidate microalga Nannochloropsis oculata. Using a combination of highly-controlled cultivation setup (photobioreactor), variable chlorophyll a fluorescence and transient spectroscopy methods (electrochromic shift (ECS) and P700 redox kinetics), we showed that net photosynthesis and effective quantum yield of Photosystem II (PSII) decreased in N. oculata under carbon limitation. This was accompanied by a transient increase in total proton motive force and energy-dependent non-photochemical quenching as well as slightly elevated respiration. On the other hand, under carbon limitation the rapid increase in proton motive force (PMF, estimated from the total ECS signal) was also accompanied by reduced conductivity of ATP synthase to protons (estimated from the rate of ECS decay in dark after actinic illumination). This indicates that the slow operation of ATP synthase results in the transient build-up of PMF, which leads to the activation of fast energy dissipation mechanisms such as energy-dependent non-photochemical quenching. N. oculata also increased content of lipids under carbon limitation, which compensated for reduced NAPDH consumption during decreased CO2 fixation. The integrated knowledge of the underlying energetic regulation of photosynthetic processes attained with a combination of biophysical methods may be used to identify photo-physiological signatures of the onset of carbon limitation in microalgal cultivation systems, as well as to potentially identify microalgal strains that can better acclimate to carbon limitation.
Photodynamic effect and mechanism study of selenium-enriched phycocyanin from Spirulina platensis against liver tumours
Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Zijian Liu, Xiang Fu, Wei Huang, Chunxia Li, Xinyan Wang, Bei Huang
Selenium-containing phycocyanin (Se-PC) has been proved to have many biological effects, including anti-inflammatory and antioxidant. In this study, we investigated the photodynamic therapy (PDT) effects of Se-PC against liver tumour in vitro and in vivo experiment. Our results demonstrated that the half lethal dose of Se-PC PDT on HepG2 cells was 100μg/ml PC containing 20% selenium. Se-PC location migration from lysosomes to mitochondria was time dependent. In in vivo experiments, the tumour inhibition rate was 75.4% in the Se-PC PDT group, compared to 52.6% in PC PDT group. Histological observations revealed that the tumour cells outside the tissue showed cellular necrosis, and those inside the tissue exhibited apoptotic nuclei and digested vacuoles in the cytoplasm after Se-PC PDT treatment. Antioxidant enzyme analysis indicated that GSH-Px activity was linked to the selenium content of Se-PC, and SOD activity was affected by PC PDT. Therefore, Se-PC PDT could induce cell death through free radical production of PDT in tumours and enhance the activity of antioxidant enzymes with selenium in vivo. The mechanism of Se-PC PDT against liver tumour involves hematocyte damage and mitochondria-mediated apoptosis accompanied with autophagy inhibition during early stage of tumour development, which displayed new prospect and offered relatively safe way for cancer therapy.
The effect of combined photobiomodulation and curcumin on skin wound healing in type I diabetes in rats
Publication date: Available online 21 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Hasan Soleimani, Abdollah Amini, Soudabeh Taheri, Ensieh Sajadi, Sasha Shafikhani, Lucia A. Schuger, Vijaya B. Reddy, Seyed Kamran Ghoreishi, Ramin Pouriran, Sufan Chien, Mohammad Bayat
The purpose of the present scientific study was to analyze the effects of combined pulsed wave Photobiomodulation (PW PBM) and Curcumin on the microbial flora; in addition, the tensiometrical wounds properties for type one diabetes mellitus (TIDM) in an experimental animal model.TIDM induction was performed in thirty rats. In the entire animals, one full-thickness excision was implemented on their backs. Randomly, the divisions of rats into 5 groups took place. The primary group was considered as the control group and did not receive any treatment. The secondary group (placebo) received sesame oil by gastric gavage. The third group received PWPBM (890 nm, 80 Hz, 0.2 J/cm2). The fourth group received curcumin (40 mg/kg, which was dissolved in sesame oil) by gastric gavage. Eventually, the fifth group received PW PBM + curcumin. Precisely, on day 7, microbiological examinations, and on the 15th day microbiological and tensiometrical examinations were conducted. The data were analyzed by statistical tests.PW PBM, significantly exacerbated tensiometrical properties of the TIDM repairing wound. PW PBM, curcumin, and PWPBM + curcumin significantly decreased colony forming units compared to the control and the placebo groups indeed.It was remarkably attained that PW PBM significantly accelerated the process of wound healing in the STZ-induced TIDM. The PW PBM was statistically more compelling compared to the curcumin and PWPBM + curcumin. PW PBM, curcumin, and PWPBM + curcumin significantly decreased colony forming units compared to the control and placebo groups.
Catalytic potential of bio-synthesized silver nanoparticles using Convolvulus arvensis extract for the degradation of environmental pollutants
Publication date: Available online 21 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Tahir Rasheed, Muhammad Bilal, Chuanlong Li, Faran Nabeel, Muhammad Khalid, Hafiz M.N. Iqbal
Herein, we reported a facile, green and environmental friendlier biosynthesis of silver nanoparticles using the Convolvulus arvensis extract. The influences of various physicochemical factors such as the concentration of the plant extract, reaction time, and different pH levels were investigated by UV–Vis spectroscopy. The UV–Visible absorption spectrum of biogenic silver nanoparticles at λmax around ~400 nm suggested the biosynthesis of silver nanoparticles. Fourier transform infrared spectroscopy was employed to confirm the chemical transformation and role of various phyto-reductants in the conversion of Ag+ to Ag0. The surface morphology, topography, and elemental composition were analyzed by scanning electron microscopy, transmission electron microscopy, and energy dispersive X-ray spectroscopy, respectively. X-ray diffraction corroborated the face-centered cubic crystalline structure. The dynamic light scattering and zeta potential demonstrate the size distribution (90.9 nm) and surface charge (−18.5). Finally, the newly developed C. arvensis based silver nanoparticles were exploited as a catalyst for the catalytic reduction of azo dyes in the presence of NaBH4 as a reducing agent, and reducing the activity of C. arvensis based silver nanoparticles was evaluated by a decrease in optical density using UV–Vis spectrophotometer. The nanoparticles developed herein displayed potential efficiency for the degradation of all the tested dye pollutants. Conclusively, plant-based synthesis of nanoparticles provides an environmentally-responsive option for the reduction of highly environmental-polluted organic compounds including toxic azo dyes as compared to chemical and physical methods.
The chitosan – Porphyrazine hybrid materials and their photochemical properties
Publication date: Available online 21 February 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Dorota Chełminiak-Dudkiewicz, Marta Ziegler-Borowska, Magdalena Stolarska, Lukasz Sobotta, Michal Falkowski, Jadwiga Mielcarek, Tomasz Goslinski, Jolanta Kowalonek, Katarzyna Węgrzynowska-Drzymalska, Halina Kaczmarek
Three magnesium sulfanyl porphyrazines differing in the size of peripheral substituents (3,5-dimethoxybenzylsulfanyl, (3,5-dimethoxybenzyloxy)benzylsulfanyl, 3,5-bis[(3,5-bis[(3,5-dimethoxybenzyloxy)benzyloxy]benzylsulfanyl) were exposed to visible and ultraviolet radiation (UV A + B + C) in order to determine their photochemical properties. The course of photochemical reactions in dimethylformamide solutions and the ability of the systems to generate singlet oxygen were studied by UV–Vis spectroscopy, which additionally gave information on aggregation processes. The porphyrazines were found to be stable upon visible light irradiation conditions, but when exposed to high energy UV radiation, the efficient photodegradation of these macrocycles was observed. Therefore, these three magnesium sulfanyl porphyrazines were incorporated into chitosan matrix. The obtained thin films of chitosan doped with porphyrazines were subjected to polychromatic UV-radiation and studied by spectroscopic methods (UV–Vis, FTIR), scanning electron microscopy (SEM) and atomic force microscopy (AFM). Application of chitosan as a polymer matrix for porphyrazines was found to be successful method that effectively stopped the unwelcome degradation of macrocycles, thus worth considering for their photoprotection. In addition, the surface properties of the hybrid material were determined by contact angle measurements and calculation of surface free energy. Intermolecular interactions between these novel porphyrazines and chitosan were detected. The mechanism of photochemical reactions occurring in studied systems has been discussed.
Graphical abstract
Experimental and computational assessment of mycosynthesized CdO nanoparticles towards biomedical applications
Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Gowri S., Gopinath K., Arumugam A.
The present study reports the biogenic synthesis of Cadmium Oxide Nanoparticles (CdO NPs) using plant pathogenic fungus Nigrospora oryzae culture filtrate. Further, the effect of the NPs on the cancer cell line (HeLa) is explored. The sample was characterized using Thermogravimetric/Differential Thermal (TG/DTA), Powder X-ray Diffraction (XRD), X-ray Photoelectron spectroscopy (XPS), UV–Visible Diffuse Reflectance Spectroscopy (UV-DRS), Field Emission Transmission Electron Microscopy (FE-SEM) with Energy Dispersive X-ray Spectroscopy (EDX), High Resolution Transmission Electron Microscopy (HR-TEM) and Selected Area Electron Diffraction (SAED) analysis. Antibacterial activity was evaluated against both Gram positive and Gram negative bacterial strains and it showed maximum activity against Proteus vulgaris. The larvicidal activity was performed to evaluate the maximum ability of synthesized CdO NPs against Anopheles stephensi. Subsequently, MTT assay also depicted the dose-dependent anticancer activity of CdO NPs against cancer cell line (HeLa). Additionally, the inhibitory effect of CdO NPs was analyzed through extensive docking with cancerous protein agent. Results enlighten that Transketolase protein exhibited high docking score of −4.8 k/mol with H-bond interactions found with Lys75 and Asn185 amino acid residues. DFT study was performed on CdO to understand the charge transfer reaction for the inhibitory mechanism. Convincingly, this study explores the understanding of CdO NPs against HeLa cells.
Graphical abstract
Efficient visible light induced synthesis of silver nanoparticles by Penicillium polonicum ARA 10 isolated from Chetomorpha antennina and its antibacterial efficacy against Salmonella enterica serovar Typhimurium
Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180
Author(s): Sahadevan Neethu, Sebastian Jose Midhun, M.A. Sunil, Soman Soumya, E.K. Radhakrishnan, Mathew Jyothis
The green synthesis of silver nanoparticles (AgNPs) using biological systems such as fungi has evolved to become an important area of nanobiotechnology. Herein, we report for the first time the light-induced extracellular synthesis of silver nanoparticles using algicolous endophytic fungus Penicillium polonicum ARA 10, isolated from the marine green alga Chetomorpha antennina. Parametric optimization, including the concentration of AgNO3, fungal biomass, ratio of cell filtrate and AgNO3, pH, reaction time and presence of light, was done for rapid AgNPs production. The obtained silver nanoparticles (AgNPs) were characterized by UV–Visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy and Transmission electron microscopy (HRTEM-EDAX). The AgNPs showed a characteristic UV–visible peak at 430 nm with an average size of 10-15 nm. The NH stretches in FTIR indicate the presence of protein molecules. The Raman vibrational bands suggest that the molecules responsible for the reduction and stability of AgNPs were extracellular proteins produced by P.polonicum. Antibacterial evaluation of AgNPs against the major foodborne bacterial pathogen Salmonella enterica serovar Typhimurium MTCC 1251, was assessed by well diffusion, Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assay. Killing kinetic studies revealed complete killing of the bacterial cells within 4 h and the bactericidal nature of synthesized nanoparticles was confirmed by fluorescent microscopy and scanning electron microscopy. Furthermore, the bactericidal studies with Transmission electron microscopy (TEM) at different time intervals explored the presence of AgNPs in the cell wall of S.Typhimurium at about 30 min and the complete bacterial lysis was found at 24 h. The current research opens an insight into the green synthesis of AgNPs and the mechanism of bacterial lysis by direct damage to the cell wall.
Graphical abstract
Protective role of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand for arylhydrocarbon receptor, in chronic mite-induced dermatitis
The skin is a sensory organ that recognizes physiologic and pathologic chemical stimuli to ensure self-defense and homeostasis. Aryl hydrocarbon receptor (AHR) is a chemical receptor that can bind and be activated by structurally diverse external and internal chemicals including dioxins as well as various phytochemicals and photo-induced chemicals with a wide range of affinities [1–4]. Upon ligand binding, the ligand-AHR complex translocates from the cytoplasm to the nucleus, binds to its specific DNA recognition site, and then upregulates the transcription of various responsive genes such as CYP1A1, which is a member of a multigene family of xenobiotic-metabolizing enzymes [1,2].
Introduction of the TERT and BMI1 Genes into Murine Dermal Papilla Cells Ameliorates Hair Inductive Activity
Dermal papilla cells (DPCs) play important roles in the regeneration and development of hair follicles. Once DPCs are cultured, however, both hair inductive activity and proliferation capability of DPCs are rapidly lost. The possible reasons are cellular senescence induced by various biological stresses [1] and limitation of the number of cell division in culture [2]. To extend the life span of DPCs, we focused on two genes, telomere reverse transcriptase (TERT) and B-cell-specific Moloney murine leukemia virus insertion region 1 (BMI1).
A critical review of melanoma self-screening tools on YouTube – a missed opportunity?
The estimated number of new cases of skin melanoma in the UK is around 15,400 per year and the incidence is rising.1 Commonly, lay individuals are the first to detect their own lesions, either incidentally or during a deliberate self-examination. To reduce patient mortality, early recognition and detection through patient self-examination is key.2 Given this, reliable and accurate information to assist individuals in early detection is essential.
Pedotransfer functions of potentially toxic elements in tropical soils cultivated with vegetable crops
Abstract
The anthropogenic input of potentially toxic elements (PTEs) from industry, agrochemicals, etc., into the environment are of great concern. Models derived from pedotransfer functions can provide estimates of the levels of PTEs based on soil attributes. Based on the importance of these models in studies in contaminated areas, we assessed the concentrations of the reactive contents of Ba, Cu, Cr, Ni, Pb, and Zn in soils cultivated with vegetable crops in the state of São Paulo, Brazil. We also evaluated the influence of chemical and physical soil attributes on their reactivity and availability. The reactive contents of PTEs represent the fraction of PTEs easily sorbed at the adsorptions sites of organic matter, iron hydroxides, or clay. This fraction can supply information about the PTE content that is more or less readily released into the soil solution. The reactive and available fraction was extracted with 0.43 M HNO3 and 0.01 M CaCl2, respectively. The proportion of reactivity of metal pools decreased in the order of Ba>Zn > Cu > Pb > Ni > Cr. The empirical models were able to predict the relationship between the reactive fractions, the pseudototal content, and the soil attributes. The available concentrations of Cr, Cu, Ni, and Pb in the soils were lower than the limit of quantification, while 3% of the Ba content and 1% of the Zn content were available in the soil solution in relation to their pseudototal content, suggesting low mobility of these elements in the soil.
Assessment of groundwater vulnerability by applying the modified DRASTIC model in Beihai City, China
Abstract
This study assesses vulnerability of groundwater to pollution in Beihai City, China, as a support of groundwater resource protection. The assessment result not only objectively reflects potential possibility of groundwater to contamination but also provides scientific basis for the planning and utilization of groundwater resources. This study optimizes the parameters consisting of natural factors and human factors upon the DRASTIC model and modifies the ratings of these parameters, based on the local environmental conditions for the study area. And a weight of each parameter is assigned by the analytic hierarchy process (AHP) to reduce the subjectivity of humans to vulnerability assessment. The resulting scientific ratings and weights of modified DRASTIC model (AHP-DRASTLE model) contribute to obtain the more realistic assessment of vulnerability of groundwater to contaminant. The comparison analysis validates the accuracy and rationality of the AHP-DRASTLE model and shows it suits the particularity of the study area. The new assessment method (AHP-DRASTLE model) can provide a guide for other scholars to assess the vulnerability of groundwater to contamination. The final vulnerability map for the AHP-DRASTLE model shows four classes: highest (2%), high (29%), low (55%), and lowest (14%). The vulnerability map serves as a guide for decision makers on groundwater resource protection and land use planning at the regional scale and that it is adapted to a specific area.
Dermoscopy and Overdiagnosis of Melanoma In Situ
Mepolizumab Treatment of Pediatric Eosinophilic Granulomatosis With Polyangiitis
Trenchlike Ulcer on a Newborn’s Scalp
Association of Patient Satisfaction With Medical Scribe Use in Dermatology
Accuracy of Dermoscopic Criteria for the Diagnosis of Melanoma In Situ
Association of Hidradenitis Suppurativa With Body Image
Pemphigus and Solid Cancers
Association Between Pemphigus and Neurologic Diseases
Incidence of Melanoma in the Cardiothoracic Transplant Population
Comorbidities in Autoimmune Skin Diseases
Characterization, evaluation, and mechanistic insights on the adsorption of antimonite using functionalized carbon nanotubes
Abstract
Floating catalytic chemical vapor deposition technique was used for synthesizing carbon nanotubes (CNTs) using ferrocene in benzene as the hydrocarbon source. The functionalization of CNTs was carried out by oxidation followed by grafting of potassium iodide (KI) and mercaptoethanol (HS(CH2)2OH) ligands to produce iodide-grafted CNTs (CNT-I) and thiol-functionalized CNTs (CNT-SH), respectively. The resulting adsorbents have been thoroughly characterized by various techniques. Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) studies revealed the efficient grafting of the ligands. Further, their adsorption capacities towards antimonite have been assessed. The adsorption kinetics fitted the pseudo-second-order model for both the adsorbents. Moreover, the adsorption of Sb(III) followed Langmuir and Freundlich's model. The maximum adsorption capacity of CNT-I and CNT-SH for Sb(III) at pH 7 was found to be 200 and 140.85 mg/g, respectively. The interference effect of various ions on the adsorption of antimonite was studied. A suitable mechanism for Sb(III) adsorption has been postulated using TEM, XRD, XPS, and FTIR. The adaptability of the adsorbents was demonstrated by the removal capacity of Sb(III) at parts per billion levels from nuclear decontamination formulation (NAC) and tap water matrix as well.
Replies to critics
Abstract
I respond to the critical comments by Randolph Clarke, Alfred Mele, and Derk Pereboom on my book Causation and Free Will. I discuss some features of the view that our freedom is exclusively based on actual causes, including the role played in it by absences of reasons, absence causation, modal facts, and finally some additional thoughts on how a compatibilist can respond to the manipulation argument for incompatibilism.
Single-Cell Stimulation in Barrel Cortex Influences Psychophysical Detection Performance
A single whisker stimulus elicits action potentials in a sparse subset of neurons in somatosensory cortex. The precise contribution of these neurons to the animal's perception of a whisker stimulus is unknown. Here we show that single-cell stimulation in rat barrel cortex of both sexes influences the psychophysical detection of a near-threshold whisker stimulus in a cell type–dependent manner, without affecting false alarm rate. Counterintuitively, stimulation of single fast-spiking putative inhibitory neurons increased detection performance. Single-cell stimulation of putative excitatory neurons failed to change detection performance, except for a small subset of deep-layer neurons that were highly sensitive to whisker stimulation and that had an unexpectedly strong impact on detection performance. These findings indicate that the perceptual impact of excitatory barrel cortical neurons relates to their firing response to whisker stimulation and that strong activity in a single highly sensitive neuron in barrel cortex can already enhance sensory detection. Our data suggest that sensory detection is based on a decoding mechanism that lends a disproportionally large weight to interneurons and to deep-layer neurons showing a strong response to sensory stimulation.
SIGNIFICANCE STATEMENT Rat whisker somatosensory cortex contains a variety of neuronal cell types with distinct anatomical and physiological characteristics. How each of these different cell types contribute to the animal's perception of whisker stimuli is unknown. We explored this question by using a powerful electrophysiological stimulation technique that allowed us to target and stimulate single neurons with different sensory response types in whisker cortex. In awake, behaving animals, trained to detect whisker stimulation, only costimulation of single fast-spiking inhibitory neurons or single deep-layer excitatory neurons with strong responses to whisker stimulation enhanced detection performance. Our data demonstrate that single cortical neurons can have measurable impact on the detection of sensory stimuli and suggest a decoding mechanism based on select cell types.
The Development of Neuronal Polarity: A Retrospective View
In 1988, Carlos Dotti, Chris Sullivan, and I published a paper on the establishment of polarity by hippocampal neurons in culture, which continues to be frequently cited 30 years later (Dotti et al., 1988). By following individual neurons from the time of plating until they had formed well developed axonal and dendritic arbors, we identified the five stages of development that lead to the mature expression of neuronal polarity. We were surprised to find that, before axon formation, the cells pass through a multipolar phase, in which several, apparently identical short neurites undergo periods of extension and retraction. Then one of these neurites begins a period of prolonged growth, becoming the definitive axon; the remaining neurites subsequently become dendrites. This observation suggested that any of the initial neurites were capable of becoming axons, a hypothesis confirmed by later work. In this Progressions article, I will try to recall the circumstances that led to this work, recapture some of the challenges we faced in conducting these experiments, and consider why some of today's neuroscientists still find this paper relevant.
Visual Experience Facilitates BDNF-Dependent Adaptive Recruitment of New Neurons in the Postembryonic Optic Tectum
Postembryonic brain development is sensitive to environmental input and sensory experience, but the mechanisms underlying healthy adaptive brain growth are poorly understood. Here, we tested the importance of visual experience on larval zebrafish (Danio rerio) postembryonic development of the optic tectum (OT), a midbrain structure involved in visually guided behavior. We first characterized postembryonic neurogenic growth in OT, in which new neurons are generated along the caudal tectal surface and contribute appositionally to anatomical growth. Restricting visual experience during development by rearing larvae in dim light impaired OT anatomical and neurogenic growth, specifically by reducing the survival of new neurons in the medial periventricular gray zone. Neuronal survival in the OT was reduced only when visual experience was restricted for the first 5 d following new neuron generation, suggesting that tectal neurons exhibit an early sensitive period in which visual experience protects these cells from subsequent neuronal loss. The effect of dim rearing on neuronal survival was mimicked by treatment with an NMDA receptor antagonist early, but not later, in a new neuron's life. Both dim rearing and antagonist treatment reduced BDNF production in the OT, and supplementing larvae with exogenous BDNF during dim rearing prevented neuronal loss, suggesting that visual experience protects new tectal neurons through neural activity-dependent BDNF expression. Collectively, we present evidence for a sensitive period of neurogenic adaptive growth in the larval zebrafish OT that relies on visual experience-dependent mechanisms.
SIGNIFICANCE STATEMENT Early brain development is shaped by environmental factors via sensory input; however, this form of experience-dependent neuroplasticity is traditionally studied as structural and functional changes within preexisting neurons. Here, we found that restricting visual experience affects development of the larval zebrafish optic tectum, a midbrain structure involved in visually guided behavior, by limiting the survival of newly generated neurons. We found that new tectal neurons exhibit a sensitive period soon after cell birth in which adequate visual experience, likely mediated by neuronal activity driving BDNF production within the tectum, would protect them from subsequent neuronal loss over the following week. Collectively, we present evidence for neurogenic adaptive tectal growth under different environmental lighting conditions.
Local Corticotropin-Releasing Factor Signaling in the Hypothalamic Paraventricular Nucleus
Corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular nucleus (PVN) initiate hypothalamic–pituitary–adrenal axis activity through the release of CRF into the portal system as part of a coordinated neuroendocrine, autonomic, and behavioral response to stress. The recent discovery of neurons expressing CRF receptor type 1 (CRFR1), the primary receptor for CRF, adjacent to CRF neurons within the PVN, suggests that CRF also signals within the hypothalamus to coordinate aspects of the stress response. Here, we characterize the electrophysiological and molecular properties of PVN-CRFR1 neurons and interrogate their monosynaptic connectivity using rabies virus-based tracing and optogenetic circuit mapping in male and female mice. We provide evidence that CRF neurons in the PVN form synapses on neighboring CRFR1 neurons and activate them by releasing CRF. CRFR1 neurons receive the majority of monosynaptic input from within the hypothalamus, mainly from the PVN itself. Locally, CRFR1 neurons make GABAergic synapses on parvocellular and magnocellular cells within the PVN. CRFR1 neurons resident in the PVN also make long-range glutamatergic synapses in autonomic nuclei such as the nucleus of the solitary tract. Selective ablation of PVN-CRFR1 neurons in male mice elevates corticosterone release during a stress response and slows the decrease in circulating corticosterone levels after the cessation of stress. Our experiments provide evidence for a novel intra-PVN neural circuit that is activated by local CRF release and coordinates autonomic and endocrine function during stress responses.
SIGNIFICANCE STATEMENT The hypothalamic paraventricular nucleus (PVN) coordinates concomitant changes in autonomic and neuroendocrine function to organize the response to stress. This manuscript maps intra-PVN circuitry that signals via CRF, delineates CRF receptor type 1 neuron synaptic targets both within the PVN and at distal targets, and establishes the role of this microcircuit in regulating hypothalamic–pituitary–adrenal axis activity.
Functional Segmentation of the Anterior Limb of the Internal Capsule: Linking White Matter Abnormalities to Specific Connections
The anterior limb of the internal capsule (ALIC) carries thalamic and brainstem fibers from prefrontal cortical regions that are associated with different aspects of emotion, motivation, cognition processing, and decision-making. This large fiber bundle is abnormal in several psychiatric illnesses and a major target for deep brain stimulation. Yet, we have very little information about where specific prefrontal fibers travel within the bundle. Using a combination of tracing studies and diffusion MRI in male nonhuman primates, as well as diffusion MRI in male and female human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions within the capsule. Fractional anisotropy (FA) abnormalities in patients with bipolar disorder were detected when FA was averaged in the ALIC segment that carries ventrolateral prefrontal cortical connections. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and demonstrate the utility of applying connectivity profiles of large white matter bundles based on animal anatomic studies to human connections and associating disease abnormalities in those pathways with specific connections. The ability to functionally segment large white matter bundles into their components begins a new era of refining how we think about white matter organization and use that information in understanding abnormalities.
SIGNIFICANCE STATEMENT The anterior limb of the internal capsule (ALIC) connects prefrontal cortex with the thalamus and brainstem and is abnormal in psychiatric illnesses. However, we know little about the location of specific prefrontal fibers within the bundle. Using a combination of animal tracing studies and diffusion MRI in animals and human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions. We then demonstrated that differences in FA values between bipolar disorder patients and healthy control subjects were specific to a given segment. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and for refining how we think about white matter organization in general.
Transcranial Magnetic Stimulation over Left Inferior Frontal and Posterior Temporal Cortex Disrupts Gesture-Speech Integration
Language and action naturally occur together in the form of cospeech gestures, and there is now convincing evidence that listeners display a strong tendency to integrate semantic information from both domains during comprehension. A contentious question, however, has been which brain areas are causally involved in this integration process. In previous neuroimaging studies, left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) have emerged as candidate areas; however, it is currently not clear whether these areas are causally or merely epiphenomenally involved in gesture-speech integration. In the present series of experiments, we directly tested for a potential critical role of IFG and pMTG by observing the effect of disrupting activity in these areas using transcranial magnetic stimulation in a mixed gender sample of healthy human volunteers. The outcome measure was performance on a Stroop-like gesture task (Kelly et al., 2010a), which provides a behavioral index of gesture-speech integration. Our results provide clear evidence that disrupting activity in IFG and pMTG selectively impairs gesture-speech integration, suggesting that both areas are causally involved in the process. These findings are consistent with the idea that these areas play a joint role in gesture-speech integration, with IFG regulating strategic semantic access via top-down signals acting upon temporal storage areas.
SIGNIFICANCE STATEMENT Previous neuroimaging studies suggest an involvement of inferior frontal gyrus and posterior middle temporal gyrus in gesture-speech integration, but findings have been mixed and due to methodological constraints did not allow inferences of causality. By adopting a virtual lesion approach involving transcranial magnetic stimulation, the present study provides clear evidence that both areas are causally involved in combining semantic information arising from gesture and speech. These findings support the view that, rather than being separate entities, gesture and speech are part of an integrated multimodal language system, with inferior frontal gyrus and posterior middle temporal gyrus serving as critical nodes of the cortical network underpinning this system.
Neurogenesis during Abstinence Is Necessary for Context-Driven Methamphetamine-Related Memory
Abstinence from methamphetamine addiction enhances proliferation and differentiation of neural progenitors and increases adult neurogenesis in the dentate gyrus (DG). We hypothesized that neurogenesis during abstinence contributes to context-driven drug-seeking behaviors. To test this hypothesis, the pharmacogenetic rat model (GFAP-TK rats) was used to conditionally and specifically ablate neurogenesis in the DG. Male GFAP-TK rats were trained to self-administer methamphetamine or sucrose and were administered the antiviral drug valganciclovir (Valcyte) to produce apoptosis of actively dividing GFAP type 1 stem-like cells to inhibit neurogenesis during abstinence. Hippocampus tissue was stained for Ki-67, NeuroD, and DCX to measure levels of neural progenitors and immature neurons, and was stained for synaptoporin to determine alterations in mossy fiber tracts. DG-enriched tissue punches were probed for CaMKII to measure alterations in plasticity-related proteins. Whole-cell patch-clamp recordings were performed in acute brain slices from methamphetamine naive (controls) and methamphetamine experienced animals (+/–Valcyte). Spontaneous EPSCs and intrinsic excitability were recorded from granule cell neurons (GCNs). Reinstatement of methamphetamine seeking enhanced autophosphorylation of CaMKII, reduced mossy fiber density, and induced hyperexcitability of GCNs. Inhibition of neurogenesis during abstinence prevented context-driven methamphetamine seeking, and these effects correlated with reduced autophosphorylation of CaMKII, increased mossy fiber density, and reduced the excitability of GCNs. Context-driven sucrose seeking was unaffected. Together, the loss-of-neurogenesis data demonstrate that neurogenesis during abstinence assists with methamphetamine context-driven memory in rats, and that neurogenesis during abstinence is essential for the expression of synaptic proteins and plasticity promoting context-driven drug memory.
SIGNIFICANCE STATEMENT Our work uncovers a mechanistic relationship between neurogenesis in the dentate gyrus and drug seeking. We report that the suppression of excessive neurogenesis during abstinence from methamphetamine addiction by a confirmed phamacogenetic approach blocked context-driven methamphetamine reinstatement and prevented maladaptive changes in expression and activation of synaptic proteins and basal synaptic function associated with learning and memory in the dentate gyrus. Our study is the first to demonstrate an interesting and dysfunctional role of adult hippocampal neurogenesis during abstinence to drug-seeking behavior in animals self-administering escalating amounts of methamphetamine. Together, these results support a direct role for the importance of adult neurogenesis during abstinence in compulsive-like drug reinstatement.
Differential Contributions of Nucleus Accumbens Subregions to Cue-Guided Risk/Reward Decision Making and Implementation of Conditional Rules
The nucleus accumbens (NAc) is a key node within corticolimbic circuitry for guiding action selection and cost/benefit decision making in situations involving reward uncertainty. Preclinical studies have typically assessed risk/reward decision making using assays where decisions are guided by internally generated representations of choice-outcome contingencies. Yet, real-life decisions are often influenced by external stimuli that inform about likelihoods of obtaining rewards. How different subregions of the NAc mediate decision making in such situations is unclear. Here, we used a novel assay colloquially termed the "Blackjack" task that models these types of situations. Male Long–Evans rats were trained to choose between one lever that always delivered a one-pellet reward and another that delivered four pellets with different probabilities [either 50% (good-odds) or 12.5% (poor-odds)], which were signaled by one of two auditory cues. Under control conditions, rats selected the large/risky option more often on good-odds versus poor-odds trials. Inactivation of the NAc core caused indiscriminate choice patterns. In contrast, NAc shell inactivation increased risky choice, more prominently on poor-odds trials. Additional experiments revealed that both subregions contribute to auditory conditional discrimination. NAc core or shell inactivation reduced Pavlovian approach elicited by an auditory CS+, yet shell inactivation also increased responding during presentation of a CS–. These data highlight distinct contributions for NAc subregions in decision making and reward seeking guided by discriminative stimuli. The core is crucial for implementation of conditional rules, whereas the shell refines reward seeking by mitigating the allure of larger, unlikely rewards and reducing expression of inappropriate or non-rewarded actions.
SIGNIFICANCE STATEMENT Using external cues to guide decision making is crucial for adaptive behavior. Deficits in cue-guided behavior have been associated with neuropsychiatric disorders, such as attention deficit hyperactivity disorder and schizophrenia, which in turn has been linked to aberrant processing in the nucleus accumbens. However, many preclinical studies have often assessed risk/reward decision making in the absence of explicit cues. The current study fills that gap by using a novel task that allows for the assessment of cue-guided risk/reward decision making in rodents. Our findings identified distinct yet complementary roles for the medial versus lateral portions of this nucleus that provide a broader understanding of the differential contributions it makes to decision making and reward seeking guided by discriminative stimuli.
Diversity of Internal Sensory Neuron Axon Projection Patterns Is Controlled by the POU-Domain Protein Pdm3 in Drosophila Larvae
Internal sensory neurons innervate body organs and provide information about internal state to the CNS to maintain physiological homeostasis. Despite their conservation across species, the anatomy, circuitry, and development of internal sensory systems are still relatively poorly understood. A largely unstudied population of larval Drosophila sensory neurons, termed tracheal dendrite (td) neurons, innervate internal respiratory organs and may serve as a model for understanding the sensing of internal states. Here, we characterize the peripheral anatomy, central axon projection, and diversity of td sensory neurons. We provide evidence for prominent expression of specific gustatory receptor genes in distinct populations of td neurons, suggesting novel chemosensory functions. We identify two anatomically distinct classes of td neurons. The axons of one class project to the subesophageal zone (SEZ) in the brain, whereas the other terminates in the ventral nerve cord (VNC). We identify expression and a developmental role of the POU-homeodomain transcription factor Pdm3 in regulating the axon extension and terminal targeting of SEZ-projecting td neurons. Remarkably, ectopic Pdm3 expression is alone sufficient to switch VNC-targeting axons to SEZ targets, and to induce the formation of putative synapses in these ectopic target zones. Our data thus define distinct classes of td neurons, and identify a molecular factor that contributes to diversification of axon targeting. These results introduce a tractable model to elucidate molecular and circuit mechanisms underlying sensory processing of internal body status and physiological homeostasis.
SIGNIFICANCE STATEMENT How interoceptive sensory circuits develop, including how sensory neurons diversify and target distinct central regions, is still poorly understood, despite the importance of these sensory systems for maintaining physiological homeostasis. Here, we characterize classes of Drosophila internal sensory neurons (td neurons) and uncover diverse axonal projections and expression of chemosensory receptor genes. We categorize td neurons into two classes based on dichotomous axon target regions, and identify the expression and role of the transcription factor Pdm3 in mediating td axon targeting to one of these target regions. Our results provide an entry point into studying internal sensory circuit development and function, and establish Pdm3 as a regulator of interoceptive axon targeting.
Dorsal Raphe Serotonin Neurons Mediate CO2-Induced Arousal from Sleep
Arousal from sleep in response to CO2 is a critical protective phenomenon. Dysregulation of CO2-induced arousal contributes to morbidity and mortality from prevalent diseases, such as obstructive sleep apnea and sudden infant death syndrome. Despite the critical nature of this protective reflex, the precise mechanism for CO2-induced arousal is unknown. Because CO2 is a major regulator of breathing, prevailing theories suggest that activation of respiratory chemo- and mechano-sensors is required for CO2-induced arousal. However, populations of neurons that are not involved in the regulation of breathing are also chemosensitive. Among these are serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) that comprise a component of the ascending arousal system. We hypothesized that direct stimulation of these neurons with CO2 could cause arousal from sleep independently of enhancing breathing. Dialysis of CO2-rich acidified solution into DRN, but not medullary raphe responsible for modulating breathing, caused arousal from sleep. Arousal was lost in mice with a genetic absence of 5-HT neurons, and with acute pharmacological or optogenetic inactivation of DRN 5-HT neurons. Here we demonstrate that CO2 can cause arousal from sleep directly, without requiring enhancement of breathing, and that chemosensitive 5-HT neurons in the DRN critically mediate this arousal. Better understanding mechanisms underlying this protective reflex may lead to interventions to reduce disease-associated morbidity and mortality.
SIGNIFICANCE STATEMENT Although CO2-induced arousal is critical to a number of diseases, the specific mechanism is not well understood. We previously demonstrated that serotonin (5-HT) neurons are important for CO2-induced arousal, as mice without 5-HT neurons do not arouse to CO2. Many have interpreted this to mean that medullary 5-HT neurons that regulate breathing are important in this arousal mechanism. Here we found that direct application of CO2-rich aCSF to the dorsal raphe nucleus, but not the medullary raphe, causes arousal from sleep, and that this arousal was lost with genetic ablation or acute inhibition of 5-HT neurons. We propose that 5-HT neurons in the dorsal raphe nucleus can be activated directly by CO2 to cause arousal independently of respiratory activation.
Commonalities and Differences in the Substrates Underlying Consolidation of First- and Second-Order Conditioned Fear
Consolidation of newly formed fear memories requires a series of molecular events within the basolateral complex of the amygdala (BLA). Once consolidated, new information can be assimilated into these established associative networks to form higher-order associations. Much is known about the molecular events involved in consolidating newly acquired fear memories but little is known about the events that consolidate a secondary fear memory. Here, we show that, within the male rat BLA, DNA methylation and gene transcription are crucial for consolidating both the primary and secondary fear memories. We also show that consolidation of the primary, but not the secondary, fear memory requires de novo protein synthesis in the BLA. These findings show that consolidation of a fear memory and its updating to incorporate new information recruit distinct processes in the BLA, and suggest that DNA methylation in the BLA is fundamental to consolidation of both types of conditioned fear.
SIGNIFICANCE STATEMENT Our data provide clear evidence that a different set of mechanisms mediate consolidation of learning about cues that signal learned sources of danger (i.e., second-order conditioned fear) compared with those involved in consolidation of learning about cues that signal innate sources of danger (i.e., first-order conditioned fear). These findings carry important implications because second-order learning could underlie aberrant fear-related behaviors (e.g., in anxiety disorders) as a consequence of neutral secondary cues being integrated into associative fear networks established through first-order pairings, and thereby becoming potent conditioned reinforcers and predictors of fear. Therefore, our data suggest that targeting such second-order conditioned triggers of fear may require pharmacological intervention different to that typically used for first-order conditioned cues.
Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range and Receptive Field Organization of Mouse Retinal Ganglion Cells
In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial, and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells. This genetic modification allowed us to investigate the impact of horizontal cells on ganglion cell signaling independent of the actual mode of feedback in the outer retina and without pharmacological manipulation of signal transmission. In control and genetically modified mice (both sexes), we recorded the light responses of transient OFF-α retinal ganglion cells in the intact retina. Excitatory postsynaptic currents (EPSCs) were reduced and the cells were tuned to lower temporal frequencies and higher contrasts, presumably because photoreceptor output was attenuated. Moreover, receptive fields of recorded cells showed a significantly altered surround structure. Our data thus suggest that horizontal cells are responsible for adjusting the dynamic range of retinal ganglion cells and, together with amacrine cells, contribute to the center/surround organization of ganglion cell receptive fields in the mouse.
SIGNIFICANCE STATEMENT Horizontal cells represent a major neuronal class in the mammalian retina and provide lateral feedback and feedforward signals to photoreceptors and bipolar cells, respectively. The mode of signal transmission remains controversial and, moreover, the contribution of horizontal cells to visual processing is still elusive. To address the question of how horizontal cells affect retinal output signals, we recorded the light responses of transient OFF-α retinal ganglion cells in a newly generated mouse line. In this mouse line, horizontal cell signals were no longer modulated by light. With light response recordings, we show that horizontal cells increase the dynamic range of retinal ganglion cells for contrast and temporal changes and contribute to the center/surround organization of their receptive fields.
Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus Basalis of Meynert
Associative learning is crucial for daily function, involving a complex network of brain regions. One region, the nucleus basalis of Meynert (NBM), is a highly interconnected, largely cholinergic structure implicated in multiple aspects of learning. We show that single neurons in the NBM of nonhuman primates (NHPs; n = 2 males; Macaca mulatta) encode learning a new association through spike rate modulation. However, the power of low-frequency local field potential (LFP) oscillations decreases in response to novel, not-yet-learned stimuli but then increase as learning progresses. Both NBM and the dorsolateral prefrontal cortex encode confidence in novel associations by increasing low- and high-frequency LFP power in anticipation of expected rewards. Finally, NBM high-frequency power dynamics are anticorrelated with spike rate modulations. Therefore, novelty, learning, and reward anticipation are separately encoded through differentiable NBM signals. By signaling both the need to learn and confidence in newly acquired associations, NBM may play a key role in coordinating cortical activity throughout the learning process.
SIGNIFICANCE STATEMENT Degradation of cells in a key brain region, the nucleus basalis of Meynert (NBM), correlates with Alzheimer's disease and Parkinson's disease progression. To better understand the role of this brain structure in learning and memory, we examined neural activity in the NBM in behaving nonhuman primates while they performed a learning and memory task. We found that single neurons in NBM encoded both salience and an early learning, or cognitive state, whereas populations of neurons in the NBM and prefrontal cortex encode learned state and reward anticipation. The NBM may thus encode multiple stages of learning. These multimodal signals might be leveraged in future studies to develop neural stimulation to facilitate different stages of learning and memory.
Ephexin1 Is Required for Eph-Mediated Limb Trajectory of Spinal Motor Axons
The precise assembly of a functional nervous system relies on the guided migration of axonal growth cones, which is made possible by signals transmitted to the cytoskeleton by cell surface-expressed guidance receptors. We investigated the function of ephexin1, a Rho guanine nucleotide exchange factor, as an essential growth-cone guidance intermediary in the context of spinal lateral motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using in situ mRNA detection, we first show that ephexin1 is expressed in LMC neurons of chick and mouse embryos at the time of spinal motor axon extension into the limb. Ephexin1 loss of function and gain of function using in ovo electroporation in chick LMC neurons, of either sex, perturbed LMC axon trajectory selection, demonstrating an essential role of ephexin1 in motor axon guidance. In addition, ephexin1 loss in mice of either sex led to LMC axon trajectory selection errors. We also show that ephexin1 knockdown attenuates the growth preference of LMC neurites against ephrins in vitro and Eph receptor-mediated retargeting of LMC axons in vivo, suggesting that ephexin1 is required in Eph-mediated LMC motor axon guidance. Finally, both ephexin1 knockdown and ectopic expression of nonphosphorylatable ephexin1 mutant attenuated the retargeting of LMC axons caused by Src overexpression, implicating ephexin1 as an Src target in Eph signal relay in this context. In summary, our findings demonstrate that ephexin1 is essential for motor axon guidance and suggest an important role in relaying ephrin:Eph signals that mediate motor axon trajectory selection.
SIGNIFICANCE STATEMENT The proper development of functioning neural circuits requires precise nerve connections among neurons or between neurons and their muscle targets. The Eph tyrosine kinase receptors expressed in neurons are important in many contexts during neural-circuit formation, such as axon outgrowth, axon guidance, and synaptic formation, and have been suggested to be involved in neurodegenerative disorders, including amyotrophic lateral sclerosis and Alzheimer's disease. To dissect the mechanism of Eph signal relay, we studied ephexin1 gain of function and loss of function and found ephexin1 essential for the development of limb nerves toward their muscle targets, concluding that it functions as an intermediary to relay Eph signaling in this context. Our work could thus shed new light on the molecular mechanisms controlling neuromuscular connectivity during embryonic development.
Pronounced Hyperactivity, Cognitive Dysfunctions, and BDNF Dysregulation in Dopamine Transporter Knock-out Rats
Dopamine (DA) controls many vital physiological functions and is critically involved in several neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder. The major function of the plasma membrane dopamine transporter (DAT) is the rapid uptake of released DA into presynaptic nerve terminals leading to control of both the extracellular levels of DA and the intracellular stores of DA. Here, we present a newly developed strain of rats in which the gene encoding DAT knockout Rats (DAT-KO) has been disrupted by using zinc finger nuclease technology. Male and female DAT-KO rats develop normally but weigh less than heterozygote and wild-type rats and demonstrate pronounced spontaneous locomotor hyperactivity. While striatal extracellular DA lifetime and concentrations are significantly increased, the total tissue content of DA is markedly decreased demonstrating the key role of DAT in the control of DA neurotransmission. Hyperactivity of DAT-KO rats can be counteracted by amphetamine, methylphenidate, the partial Trace Amine-Associated Receptor 1 (TAAR1) agonist RO5203648 ((S)-4-(3,4-Dichloro-phenyl)-4,5-dihydro-oxazol-2-ylamine) and haloperidol. DAT-KO rats also demonstrate a deficit in working memory and sensorimotor gating tests, less propensity to develop obsessive behaviors and show strong dysregulation in frontostriatal BDNF function. DAT-KO rats could provide a novel translational model for human diseases involving aberrant DA function and/or mutations affecting DAT or related regulatory mechanisms.
SIGNIFICANCE STATEMENT Here, we present a newly developed strain of rats in which the gene encoding the dopamine transporter (DAT) has been disrupted (Dopamine Transporter Knockout rats [DAT-KO rats]). DAT-KO rats display functional hyperdopaminergia accompanied by pronounced spontaneous locomotor hyperactivity. Hyperactivity of DAT-KO rats can be counteracted by amphetamine, methylphenidate, and a few other compounds exerting inhibitory action on dopamine-dependent hyperactivity. DAT-KO rats also demonstrate cognitive deficits in working memory and sensorimotor gating tests, less propensity to develop compulsive behaviors, and strong dysregulation in frontostriatal BDNF function. These observations highlight the key role of DAT in the control of brain dopaminergic transmission. DAT-KO rats could provide a novel translational model for human diseases involving aberrant dopamine functions.
Serotonin Disinhibits a Caenorhabditis elegans Sensory Neuron by Suppressing Ca2+-Dependent Negative Feedback
Neuromodulators, such as serotonin (5-HT), alter neuronal excitability and synaptic strengths, and define different behavioral states. Neuromodulator-dependent changes in neuronal activity patterns are frequently measured using calcium reporters because calcium imaging can easily be performed on intact functioning nervous systems. With only 302 neurons, the nematode Caenorhabditis elegans provides a relatively simple, yet powerful, system to understand neuromodulation at the level of individual neurons. C. elegans hermaphrodites are repelled by 1-octanol, and the initiation of these aversive responses is potentiated by 5-HT. 5-HT acts on the ASH polymodal nociceptors that sense the 1-octanol stimulus. Surprisingly, 5-HT suppresses ASH Ca2+ transients while simultaneously potentiating 1-octanol-dependent ASH depolarization. Here we further explore this seemingly inverse relationship. Our results show the following (1) 5-HT acts downstream of depolarization, through Gαq-mediated signaling and calcineurin, to inhibit L-type voltage-gated Ca2+ channels; (2) the 1-octanol-evoked Ca2+ transients in ASHs inhibit depolarization; and (3) the Ca2+-activated K+ channel, SLO-1, acts downstream of 5-HT and is a critical regulator of ASH response dynamics. These findings define a Ca2+-dependent inhibitory feedback loop that can be modulated by 5-HT to increase neuronal excitability and regulate behavior, and highlight the possibility that neuromodulator-induced changes in the amplitudes of Ca2+ transients do not necessarily predict corresponding changes in depolarization.
SIGNIFICANCE STATEMENT Neuromodulators, such as 5-HT, modify behavior by regulating excitability and synaptic efficiency in neurons. Neuromodulation is often studied using Ca2+ imaging, whereby neuromodulator-dependent changes in neuronal activity levels can be detected in intact, functioning circuits. Here we show that 5-HT reduces the amplitude of depolarization-dependent Ca2+ transients in a C. elegans nociceptive neuron, through Gαq signaling and calcineurin but that Ca2+ itself inhibits depolarization, likely through Ca2+-activated K+ channels. The net effect of 5-HT, therefore, is to increase neuronal excitability through disinhibition. These results establish a novel 5-HT signal transduction pathway, and demonstrate that neuromodulators can change Ca2+ signals and depolarization amplitudes in opposite directions, simultaneously, within a single neuron.
Deficient Surveillance and Phagocytic Activity of Myeloid Cells Within Demyelinated Lesions in Aging Mice Visualized by Ex Vivo Live Multiphoton Imaging
Aging impairs regenerative processes including remyelination, the synthesis of a new myelin sheath. Microglia and other infiltrating myeloid cells such as macrophages are essential for remyelination through mechanisms that include the clearance of inhibitory molecules within the lesion. Prior studies have shown that the quantity of myeloid cells and the clearance of inhibitory myelin debris are deficient in aging, contributing to the decline in remyelination efficiency with senescence. It is unknown, however, whether the impaired clearance of debris is simply the result of the reduced number of phagocytes or if the dynamic activity of myeloid cells within the demyelinating plaque also declines with aging and this question is relevant to the proper design of therapeutics to mobilize myeloid cells for repair. Herein, we describe a high-resolution multiphoton ex vivo live imaging protocol that visualizes individual myelinated/demyelinated axons and lipid-containing myeloid cells to investigate the demyelinated lesion of aging female mice. We found that aging lesions have fewer myeloid cells and that these have reduced phagocytosis of myelin. Although the myeloid cells are actively migratory within the lesion of young mice and have protrusions that seem to survey the environment, this motility and surveillance is significantly reduced in aging mice. Our results emphasize the necessity of not only increasing the number of phagocytes, but also enhancing their activity once they are within demyelinated lesions. The high-resolution live imaging of demyelinated lesions can serve as a platform with which to discover pharmacological agents that rejuvenate intralesional remodeling that promotes the repair of plaques.
SIGNIFICANCE STATEMENT The repair of myelin after injury depends on myeloid cells that clear debris and release growth factors. As organisms age, remyelination becomes less efficient correspondent with fewer myeloid cells that populate the lesions. It is unknown whether the dynamic activity of cells within lesions is also altered with age. Herein, using high-resolution multiphoton ex vivo live imaging with several novel features, we report that myeloid cells within demyelinated lesions of aging mice have reduced motility, surveillance, and phagocytic activity, suggesting an intralesional impairment that may contribute to the age-related decline in remyelination efficiency. Medications to stimulate deficient aging myeloid cells should not only increase their representation, but also enter into lesions to stimulate their activity.
Cortical Neural Activity Predicts Sensory Acuity Under Optogenetic Manipulation
Excitatory and inhibitory neurons in the mammalian sensory cortex form interconnected circuits that control cortical stimulus selectivity and sensory acuity. Theoretical studies have predicted that suppression of inhibition in such excitatory–inhibitory networks can lead to either an increase or, paradoxically, a decrease in excitatory neuronal firing, with consequent effects on stimulus selectivity. We tested whether modulation of inhibition or excitation in the auditory cortex of male mice could evoke such a variety of effects in tone-evoked responses and in behavioral frequency discrimination acuity. We found that, indeed, the effects of optogenetic manipulation on stimulus selectivity and behavior varied in both magnitude and sign across subjects, possibly reflecting differences in circuitry or expression of optogenetic factors. Changes in neural population responses consistently predicted behavioral changes for individuals separately, including improvement and impairment in acuity. This correlation between cortical and behavioral change demonstrates that, despite the complex and varied effects that these manipulations can have on neuronal dynamics, the resulting changes in cortical activity account for accompanying changes in behavioral acuity.
SIGNIFICANCE STATEMENT Excitatory and inhibitory interactions determine stimulus specificity and tuning in sensory cortex, thereby controlling perceptual discrimination acuity. Modeling has predicted that suppressing the activity of inhibitory neurons can lead to increased or, paradoxically, decreased excitatory activity depending on the architecture of the network. Here, we capitalized on differences between subjects to test whether suppressing/activating inhibition and excitation can in fact exhibit such paradoxical effects for both stimulus sensitivity and behavioral discriminability. Indeed, the same optogenetic manipulation in the auditory cortex of different mice could improve or impair frequency discrimination acuity, predictable from the effects on cortical responses to tones. The same manipulations sometimes produced opposite changes in the behavior of different individuals, supporting theoretical predictions for inhibition-stabilized networks.
Aging Affects Adaptation to Sound-Level Statistics in Human Auditory Cortex
Optimal perception requires efficient and adaptive neural processing of sensory input. Neurons in nonhuman mammals adapt to the statistical properties of acoustic feature distributions such that they become sensitive to sounds that are most likely to occur in the environment. However, whether human auditory responses adapt to stimulus statistical distributions and how aging affects adaptation to stimulus statistics is unknown. We used MEG to study how exposure to different distributions of sound levels affects adaptation in auditory cortex of younger (mean: 25 years; n = 19) and older (mean: 64 years; n = 20) adults (male and female). Participants passively listened to two sound-level distributions with different modes (either 15 or 45 dB sensation level). In a control block with long interstimulus intervals, allowing neural populations to recover from adaptation, neural response magnitudes were similar between younger and older adults. Critically, both age groups demonstrated adaptation to sound-level stimulus statistics, but adaptation was altered for older compared with younger people: in the older group, neural responses continued to be sensitive to sound level under conditions in which responses were fully adapted in the younger group. The lack of full adaptation to the statistics of the sensory environment may be a physiological mechanism underlying the known difficulty that older adults have with filtering out irrelevant sensory information.
SIGNIFICANCE STATEMENT Behavior requires efficient processing of acoustic stimulation. Animal work suggests that neurons accomplish efficient processing by adjusting their response sensitivity depending on statistical properties of the acoustic environment. Little is known about the extent to which this adaptation to stimulus statistics generalizes to humans, particularly to older humans. We used MEG to investigate how aging influences adaptation to sound-level statistics. Listeners were presented with sounds drawn from sound-level distributions with different modes (15 vs 45 dB). Auditory cortex neurons adapted to sound-level statistics in younger and older adults, but adaptation was incomplete in older people. The data suggest that the aging auditory system does not fully capitalize on the statistics available in sound environments to tune the perceptual system dynamically.
Indoor radon concentration in Korea residential environments
Abstract
The purpose of this study is to provide basic data for the evaluation and management of health effects with respect to exposure to radon within residential environments in South Korea. It is part of a case-control study to develop a management plan based on indoor radon exposure levels and assess their impact on health. To investigate the long-term cumulative concentration levels of radon, 599 patients who have respiratory diseases were recruited in South Korea, and alpha track detectors were installed in their residences for a period of 3 months from mid-2015 to late 2016. A survey was then conducted to determine the factors affecting the radon concentration. The radon concentration levels were analyzed in conjunction with the survey results. The results show that the arithmetic mean of the radon concentrations in domestic residences was in the range of 70.8 ± 65.2 Bq/m3. An analysis of covariance (ANCOVA) was performed to identify the environmental factors affecting the radon concentration and contributing to variations in the residential radon concentration based on the height of the residence. The results show that the contribution of the local environmental factor to the variation in radon concentration (p < 0.05) was greater than that of other environmental factors. Although no statistically significant difference was found with regard to the construction year of the building before the control (p > 0.05), the same was found with regard to the construction year after the control (p < 0.05).
Free will, causation, and absence
Abstract
This paper comments on Carolina Sartorio's Causation and Free Will, challenging the non-modal conception of reasons-sensitivity that Sartorio advances.
Commentary on Rosefeldt: Should Metaphysics Care About Ontological Commitment from Casual Utterances?
Abstract
Tobias Rosefeldt argues that in order to reconcile a physics-based fundamental ontology with the ontological implications of our everyday utterances, philosophers should pursue a 'linguistics-based conciliatory' strategy: They should refer to the results of linguistic research in order to avoid ontological commitment to problematic entities. Whereas Rosefeldt is not an advocate of radical forms of naturalized metaphysics, his argument is driven by the motivation behind pleas for a naturalization of the discipline. I claim that although there is a need for reconciliation, Rosefeldt's favored account falls short of this goal. More generally, I argue that so-called 'conciliatory accounts' fail to do justice to the motivation that necessitated them in the first place, as the role they assign to analyses of everyday speech in search of ontological commitments is at odds with said motivation. 'Conciliatory accounts', hence, sit uneasily between radically naturalistic and traditional armchair approaches to metaphysics.
Vermicompost dose and mycorrhization determine the efficiency of copper phytoremediation by Canavalia ensiformis
Abstract
The phytoremediation of copper (Cu)-contaminated sandy soils can be influenced by the addition of vermicompost to the soil and the mycorrhization of plants. The objective of this study was to evaluate the effects of inoculation with the mycorrhizal fungus Rhizophagus clarus and the addition of different doses of bovine manure vermicompost on the phytoremediation of a sandy soil with a high Cu content using Canavalia ensiformis. Soil contaminated with 100 mg kg−1 Cu received five doses of vermicompost and was cultivated with C. ensiformis, with and without inoculation with mycorrhizal fungus, and the Cu and nutrients in the soil and soil solution were evaluated. The concentrations of Cu and other nutrients and the biomass and Cu phytotoxicity in the plants were quantified by gauging the photochemical efficiency, concentration of photosynthetic pigments and activity of oxidative stress enzymes. The vermicompost increased the soil pH and nutrient concentrations and reduced the Cu content of the solution. When the vermicompost was applied at a dose equivalent to 80 mg phosphorus (P) kg−1, the phytoextraction efficiency was higher, but the phytostabilization efficiency was higher for vermicompost doses of 10 and 20 mg P kg−1. The presence of mycorrhizal fungi increased Cu phytostabilization, especially at vermicompost doses of 10 and 20 mg P kg−1. The use of vermicompost at low doses and inoculation with mycorrhizal fungi increase the phytostabilization potential of C. ensiformis in sandy soil contaminated by Cu.
Differences in fluorescence characteristics and bioavailability of water-soluble organic matter (WSOM) in sediments and suspended solids in Lihu Lake, China
Abstract
The spectral characteristics, spatial distribution, and bioavailability of water-soluble organic matter (WSOM) in suspended solids and surface sediments of Lihu Lake, China, were investigated through excitation–emission matrix spectra and parallel factor analysis. The average content of dissolved organic carbon (DOC) in the sediments reached 643.28 ± 58.34 mg C/kg and that in suspended solids was 714.87 ± 69.24 mg C/kg. The fluorescence intensity of WSOM totaled 90.87 ± 5.65 and 115.42 ± 8.02 RU/g for the sediments and suspended solids, respectively. The DOC and fluorescence intensity of the WSOM showed an increasing trend moving from the west to the east of the lake. The WSOM in sediments and suspended solids contained two humic-like (C1 and C2) and one tryptophan-like (C3) components. These components had different fluorescent peaks and relative proportions. In the sediments, the relative proportions of C1, C2, and C3 were 33.71% ± 0.71, 26.83% ± 0.68, and 39.50% ± 0.71%, respectively. Meanwhile, C1 (35.77 ± 0.84%), C2 (34.07 ± 0.61%), and C3 (30.16 ± 0.75%) had similar relative percentages in suspended solids. The sediments had a lower humification index (3.02 ± 0.08) than the suspended solids (4.04 ± 0.15). Exchangeable nitrogen for the sediments and suspended solids was dominated by exchangeable ammonium nitrogen and soluble organic nitrogen, respectively. WSOM plays an important role in migration and transformation of nitrogen in sediments and suspended solids. The sediment-derived WSOM exhibited higher lability and biological activity than did the suspended solid-derived WSOM. The relative ratio of the intensity of protein-like fluorescent component to that of the humic-like one can be used as a reference index to evaluate the lability and biological activity of WSOM in sediments and suspended solids.
How to know one’s experiences transparently
Abstract
I would like to propose a demonstrative transparency model of our immediate, introspective self-knowledge of experiences. It is a model entirely in line with transparency. It rests on three elements: mental demonstration, the capacity to apply (non-mental) concepts to what is given in experience, and ordinary inference. The model avoids inner sense, acquaintance, and any special kind of normativity or rationality. The crucial and new ingredient is mental demonstration. By mental demonstration we can refer indexically to the contents of our own experiences in a unique way. This allows for the application of ordinary, non-mental concepts in order to arrive at a judgment about what it is that one is experiencing. In a transparent way one can then move inferentially to the self-ascription of an experience with such a content. I compare the demonstrative model with other accounts of introspective self-knowledge.
Précis of Causation and free will
Abstract
This is a precis of my book Causation and Free Will. I go over the main features of my compatibilist account of free will, which is based on the actual causes of our behavior.
Emission and performance analysis on the effect of exhaust gas recirculation in alcohol-biodiesel aspirated research diesel engine
Abstract
In this study, the effect of blending pentanol to biodiesel derived from mahua oil on emissions and performance pattern of a diesel engine under exhaust gas recirculation (EGR) mode was examined and compared with diesel. The purpose of this study is to improve the feasibility of employing biofuels as a potential alternative in an unmodified diesel engine. Two pentanol-biodiesel blends denoted as MOBD90P10 and MOBD80P20 which matches to 10 and 20 vol% of pentanol in biodiesel, respectively, were used as fuel in research engine at 10 and 20% EGR rates. Pentanol is chosen as a higher alcohol owing to its improved in-built properties than the other first-generation alcohols such as ethanol or methanol. Experimental results show that the pentanol and biodiesel blends (MOBD90P10 and MOBD80P20) have slightly higher brake thermal efficiency (0.2–0.4%) and lower brake-specific fuel consumption (0.6 to 1.1%) than that of neat biodiesel (MOBD100) at all engine loads. Nitrogen oxide (NOx) emission and smoke emission are reduced by 3.3–3.9 and 5.1–6.4% for pentanol and biodiesel blends compared to neat biodiesel. Introduction of pentanol to biodiesel reduces the unburned hydrocarbon (2.1–3.6%) and carbon monoxide emissions (3.1–4.2%) considerably. In addition, at 20% EGR rate, smoke, NOX emissions, and BTE drop by 7.8, 5.1, and 4.4% respectively. However, CO, HC emissions, and BSFC increased by 2.1, 2.8, and 3.8%, respectively, when compared to 0% EGR rate.
Demyelination during anti-tumour necrosis factor therapy for psoriasis
Summary
Anti-tumour necrosis factor (anti-TNF) therapies have been associated with neurological complications, including in rare cases demyelinating disease. It is currently unknown whether patients who have received more than one immunosuppressive agent or anti-TNF have a greater risk of demyelination. We report the case of a 37-year-old woman with psoriasis who presented with an acute episode of demyelination while on anti-TNF therapy. This case was complicated by the fact that progressive multifocal leukoencephalopathy was considered the likely diagnosis initially and was only definitively excluded by brain biopsy. This case demonstrates the difficulty establishing the correct diagnosis in patients with atypical presentations on immunomodulating therapies. We present this rare case of demyelination in a patient who received multiple immunosuppressive therapies to highlight this challenging clinical situation and discuss management with a literature review.
Intercropping efficiency of four arsenic hyperaccumulator Pteris vittata populations as intercrops with Morus alba
Abstract
Soils that are slightly or moderately contaminated with arsenic (As) can be safely utilized by intercropping As hyperaccumulator Pteris vittata with cash crops. Introducing hyperaccumulators into crop planting systems results in the alleviation of the adverse effects of As and competition effect for resources. The balance between these two effects determines intercropping efficiency. The effect of using different hyperaccumulator populations on such balance is the focus of this study. Through a tank experiment, four P. vittata populations were compared on the basis of their intercropping efficiencies and physiological and morphological characteristics. The evaluation of the intercropping efficiency of P. vittata was mainly based on the capabilities of the species to promote growth and decrease As concentrations in intercropped Morus alba. Two populations of P. vittata were appropriate for intercropping with M. alba, with the alleviation effect of As harm as the main effect on the intercropping system. These populations showed extensive root overlap with M. alba and efficient uptake of bioavailable As, thus depleting As in the rhizosphere and lowering As risk. After different P. vittata populations were used, varied interspecific interactions were observed. Root overlap and aboveground morphological parameters are the key factors determining intercropping efficiency among P. vittata populations.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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https://www.youtube.com/watch?v=DFOhpBjLqN4&t=1s , Η ΘΕΡΑΠΕΙΑ ΓΙΑ ΟΛΕΣ ΤΙΣ ΑΣΘΕΝΕΙΕΣ 1 Περιεχόμενα Σύντομο βιογραφικό Πρόλογος μεταφραστ...
