Abstract
Cell-free protein synthesis has emerged in recent years as a powerful tool that can potentially transform the production of recombinant proteins. Cell-free protein synthesis harnesses the synthetic power of living cells while eliminating many of the constraints of traditional cell-based gene expression methods. Due to the lack of physical barriers separating the protein synthesis machinery from the surrounding environment, a cell-free protein synthesis reaction mixture can be directly programmed using diverse genetic material for the instant production of recombinant proteins without complicated cloning procedures. However, a number of issues must be addressed for this technology to be widely accepted as an alternative platform for protein production, including quality-control of translation machinery preparations, and high reagent cost. This review describes recent efforts to make cell-free protein synthesis more affordable and more easily accessible for generic applications.Τετάρτη 8 Αυγούστου 2018
Role of tyrosine residue (Y213) in nuclear retention of PCNA1 in human malaria parasite Plasmodium falciparum
Abstract
Proliferating Cell Nuclear Antigen (PCNA) undergoes several post-translational modifications including phosphorylation leading to its regulation in mammalian and yeast systems. Plasmodium falciparum possesses two PCNAs (PCNA1 & PCNA2) with an edge of PfPCNA1 over PfPCNA2 for DNA replication. Recent phospho-proteome data report phosphorylation of S191 residue without its functional implication. In mammalian cells, phosphorylation of HsPCNA at Y211 stabilizes chromatin bound PCNA. We find tyrosine (but not S191) to be conserved in PfPCNAs and it is important for its nuclear localization and foci formation of PfPCNA1. Further, a Y213F mutation in PfPCNA1 leads to its functional loss both in yeast and parasite. We highlight the importance of evolutionarily conserved tyrosine in PCNA from parasite to mammal linked with DNA replication and cell proliferation.Translational Insights into Gastrointestinal Stromal Tumor and Current Clinical Advances
Abstract
Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma of the gastrointestinal tract and, in the vast majority of cases, is characterized by activating mutations in KIT or, less commonly, PDGFRA. Mutations in these type III receptor tyrosine kinases (RTKs) account for over 85% of GIST cases, and the majority of KIT primary mutations respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib. However, drug resistance develops over time, most commonly due to secondary kinase mutations. Sunitinib and regorafenib are approved for the treatment of imatinib-resistant GIST in the second and third lines, respectively. However, resistance to these agents also develops and new therapeutic options are needed. In addition, a small number of GISTs harbor primary activating mutations that are resistant to currently available TKIs, highlighting an additional unmet medical need. Several novel and selective TKIs that overcome known mechanisms of resistance in GIST have been developed and show promise in early clinical trials. Additional emerging targeted therapies in GIST include modulation of cellular signaling pathways downstream of KIT, antibodies targeting KIT and PDGFRA and immune checkpoint inhibitors. These advancements highlight the rapid evolution in the understanding of this malignancy and provide perspective on the encouraging horizon of current and forthcoming therapeutic strategies for GIST.First evaluation of floating microplastics in the Northwestern Adriatic Sea
Abstract
Plastic pollution in the marine environment is becoming a problem of global concern, and the Mediterranean is believed to be one of the worst affected regional seas. The present study presents data on floating microplastics in the Northwestern Adriatic Sea in order to evaluate the possible contribution of two significant potential sources: the lagoon of Venice and the Po River. Samples were collected in March and April 2014 along two transects located off Pellestrina Island (Venice) and the Po Delta, each consisting of four sampling stations at 0.5, 3, 10, and 20 km from the shoreline. Microplastics were quantified and classified according to their colors and shapes and analyzed by micro-attenuated total reflection-FT-IR. Microplastics were found in all samples, albeit with high spatial and temporal variability. The highest concentrations were observed in March at the offshore station of the Pellestrina transect (10.4 particles m−2) and the two landward stations off the Po Delta (2.1 and 4.3 particles m−2), highlighting the influence of various factors, such as surface circulation and river discharges, in determining specific accumulation patterns. The most common polymers were polyethylene and polypropylene, and most of the particles were secondary microplastics (83.5%). The patchy distribution of microplastics observed in the study area is driven by hydrodynamic and meteorological factors acting on short time scales.
Characterization and adsorption capacity of potassium permanganate used to modify activated carbon filter media for indoor formaldehyde removal
Abstract
This study examined the effect of potassium permanganate (KMnO4)-modified activated carbon for formaldehyde removal under different face velocities and different initial formaldehyde concentrations in building environment. We chose the coconut shell activated carbon due to their high density and purity. Moreover, they have a clear environmental advantage over coal-based carbons, particularly in terms of acidification potential. The chemical properties were characterized by FTIR to show the functional groups, EDS to calculate each component of their energy bands to know how the ratio is. Also, the morphology of the surface was examined with scanning electron microscopy (SEM). The BET determines specific surface area, pore size, and pore volume. It was found that where the initial formaldehyde concentration and the face velocity are low, adsorption capacity is high. The adsorption isotherms of formaldehyde on modified activated carbon are well fitted by both Langmuir and Freundlich equations. The rate parameter for the pseudo-first-order model, pseudo-second-order model, and intraparticle diffusion model was compared. The correlation coefficient of pseudo-second-order kinetic model (0.999 > R2 > 0.9548) is higher than the coefficient of pseudo-first-order kinetic model (0.5785 < R2 < 0.8755) and intraparticle diffusion model (0.9752 < R2 < 0.9898). Thus, pseudo-second-order kinetic model is more apposite to discuss the adsorption kinetic in this test, and the overall rate of the modified activated carbon adsorption process appears to be influenced by more than one step that is both the intraparticle diffusion model and membrane diffusion.
Three‐step algorithm for biological therapy targeted IgE and IL‐5 in severe asthma
Immunity, Inflammation and Disease, EarlyView.
Histiocytofibrome avec induction sébacée
Publication date: Available online 7 August 2018
Source: Annales de Dermatologie et de Vénéréologie
Author(s): E. Lorier Roy, M.-H. Jégou, A. Osio
Résumé
Introduction
L'histiocytofibrome, ou dermatofibrome (DF), est une lésion bénigne commune revêtant de multiples aspects cliniques et histologiques. Le phénomène d'induction sébacée en regard d'un dermatofibrome est rare et peu décrit. L'observation détaillée d'un cas de DF avec induction sébacée permet de préciser et d'illustrer ici la sémiologie clinique et dermatoscopique de cette lésion, ainsi que celle de ses diagnostics différentiels.
Observation
Un homme de 52 ans consultait pour un examen de surveillance, qui révélait une lésion papuleuse ferme du milieu du dos. La surface de la lésion apparaissait comme une zone un peu pigmentée dans sa partie supérieure, faite de plusieurs petits lobules blanchâtres. L'examen histologique concluait à un histiocytofibrome avec induction sébacée.
Discussion
Le phénomène d'induction sébacée en regard d'un dermatofibrome est peu fréquent ; dans la très grande majorité des cas, il est observé sur la région des épaules. L'aspect dermatoscopique de surface, avec de multiples globules ou structures compactes arrondies blanchâtres (clods) regroupés en amas, est caractéristique. L'origine du phénomène d'induction sébacée est inconnue ; on peut évoquer un micro-environnement favorable de la peau des épaules, associé à des facteurs de croissance sécrétés par le DF.
Summary
Background
Histiocytoma or dermatofibroma (DF) is a common benign skin tumour with several clinical and histopathological variants. Sebaceous induction overlying a dermatofibroma is rare and infrequently reported. Using a detailed clinical case, herein the semiological and dermoscopic features of this lesion are described and illustrated, and the differential diagnoses presented.
Patients and methods
A 52-year-old man consulted for a physical examination, which revealed a firm papular lesion of the upper middle back. The upper part of the nodule was covered by a slightly hyperpigmented surface, with numerous small whitish lobules. Microscopic examination revealed a dermatofibroma with sebaceous induction.
Discussion
Sebaceous induction overlying a dermatofibroma is not frequent, and it occurs in most cases on or near the shoulder. The typical dermoscopic pattern involves many whitish globules or clumps grouped into clusters. The aetiology is unknown but could stem from a conducive microenvironment in shoulder skin, associated with growth factors secreted by the DF.
Pemphigoïde bulleuse localisée sur lambeau cutané
Publication date: Available online 7 August 2018
Source: Annales de Dermatologie et de Vénéréologie
Author(s): C. Ivan, H. Kassem Youssef, E. Backobi, F. Chouta Ngaha, H. Nojavan, C. Michel
Τρίτη 7 Αυγούστου 2018
Mechanistic and pharmacological assessment of murine IL-23 mediated psoriasiform dermatitis; implications for drug discovery
Animal models of Psoriasis (PsO) are important for our understanding of the pathophysiology of human disease but rarely manifest all features of the disease. In order to facilitate greater understanding of the underlying biology of PsO it is key that we understand the strengths and limitations of models used.
Potential adverse effects of antimicrobial chemotherapy based on ultraviolet-A irradiation of polyphenols against the oral mucosa in hamsters and wounded skin in rats
Publication date: Available online 7 August 2018
Source: Journal of Photochemistry and Photobiology B: Biology
Author(s): Keisuke Nakamura, Taichi Tenkumo, Takayuki Mokudai, Midori Shirato, Kirika Ishiyama, Taro Kanno, Keiichi Sasaki, Yoshimi Niwano
Abstract
Antimicrobial chemotherapy based on ultraviolet-A (UVA) irradiation of polyphenol solution has been proposed as an adjunctive treatment for dental caries. However, the safety of this treatment has not been thoroughly evaluated. Therefore, the aim of the present study was to assess the influence of this treatment on the oral mucosa in hamsters and wounded skin in rats. An oral mucosal irritation test was performed in hamsters. The cheek pouch was everted and treated with UVA irradiation (wavelength: 365 nm) of pure water, 1 mg/mL of caffeic acid, or 1 mg/mL of grape seed extract using a light-emitting diode at an irradiance of 275 mW/cm2. Each treatment was performed for 2 or 5 min and repeated three times. Macroscopic and histological evaluations were performed 24 h after the last treatment. We also examined the effects of the treatment on the healing process of skin wounds in rats. Full-thickness skin wounds created on the back of the rats were treated for 2 min as described above, but only once. The wound area was then assessed daily for 9 days. The results demonstrated that the treatment induced oral mucosal irritation depending on the irradiation time; however, it did not influence the wound healing process. The oral mucosal irritation potential of three treatment sessions performed for 2 and 5 min was minimal and mild to moderate, respectively, according to histological analysis. These findings suggest that the duration of treatment based on UVA irradiation of polyphenols in the oral cavity should be as short as possible, considering the clinical efficacy of the antimicrobial effects and the irritation potential.
Graphical Abstract
The association between ambient air pollution exposure and mental health status in Chinese female college students: a cross-sectional study
Abstract
The association between exposure to air pollution and mental health has not been adequately studied. Accordingly, this study aimed to explore the association between exposure to ambient air pollution and mental health status among female college students. We performed a cross-sectional study involving female students attending college located in Anshan, a heavy industry city in Northeast China. The investigation was performed using electronic questionnaires including the Symptom Checklist-90 (SCL-90), Pittsburgh Sleep Quality Index (PSQI), Cornell Medical Index (CMI), and general well-being (GWB) scale between March and April 2017. The individual daily average of time spent outdoors in each season was used as an indicator of exposure to ambient air pollution. The association between mental health status and exposure to ambient air pollution was analyzed using general linear regression. Of the 412 female participants, 346 (83.98%) submitted valid questionnaires. Multivariate linear regression indicated that GWB was negatively associated with the SCL-90 score, and annual average daily outdoor time and sleep quality were positively associated with the SCL-90 score. This study demonstrated that exposure to ambient air pollution may be a risk factor for mental health problems among female college students.
The importance of early implementation of laser treatment in facial scars: A single-institution retrospective study
Background: Interest in minimizing scars especially on face has been rising recently.
Mycosis fungoides in Puerto Rico
Mycosis fungoides (MF) and Sezary syndrome compromise about 53% of cutaneous lymphomas. Disease stage depends on involved body surface area, clinical presentation and the presence or absence systemic involvement, which will determine treatment. MF is generally diagnosed at early stages and carries a chronic and indolent disease course. In 2007, 30 MF cases in Puerto Rico were described from 1983 to 2002. We performed a retrospective chart review of MF cases (1999-2016) to compare these populations and identify any changes in disease prognosis and treatment response given different and new treatment modalities are now available.
Real-world use of secukinumab for the treatment of plaque psoriasis and psoriatic arthritis: Experience of four dermatology units in Spain
Introduction: Worldwide, there is an increasing trend to use real-world data to inform decision making in health care. The data regarding appropriate drug use, effectiveness, and cost-effectiveness in real-world clinical practice is intended to complement the findings from clinical trials, and to evaluate a drug's real-world value. Secukinumab is a fully humanized anti–interleukin (IL) 17A antibody that specifically binds to IL-17A receptors. In recent years, IL-17A has been recognized to play an important role in the disease pathology.
Comorbid conditions in lichen planopilaris: A retrospective data analysis of 334 patients
Background: Lichen planopilaris (LPP) is a rare cicatricial, lymphocyte mediated alopecia. It is thought to have an autoimmune pathogenesis, and possibly related to other autoimmune diseases; however, data are limited. In addition, studies examining comorbid conditions are lacking.
Small molecule inhibitor of the Wnt pathway (SM04755) as a potential topical treatment for psoriasis
Background: Psoriasis (PSO) is an autoimmune disease causing patches of thick, inflamed, scaly skin due to excessive proliferation of skin cells. Wnt signaling plays an important role in PSO, regulating inflammation and keratinocyte proliferation. SM04755, a novel, topical small-molecule Wnt pathway inhibitor was previously shown to inhibit inflammation and keratinocyte proliferation in vitro and in an IMQ-induced mouse PSO model. In this study, the effects of SM04755 on inflammation and skin health were evaluated in a model using reconstitution of ICR scid mice with minor histocompatibility mismatched naive CD4+ T lymphocytes, which more closely resembles human PSO pathophysiology.
Time to tumor response and planned subgroup analyses from the BOLT trial for sonidegib in advanced basal cell carcinoma
Background: Sonidegib 200 mg once daily (qd) was approved in the United States for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy based on results of the phase 2 BOLT study (NCT01327053). Here we report time to tumor response and planned subgroup analyses from the 30-month efficacy data from BOLT.
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