Elytra Absorb Ultraviolet Radiation but Transmit Infrared Radiation in Neotropical Canthon Species (Coleoptera, Scarabaeinae)

Abstract

Strategies to deal with global radiation may be related to important aspects of species biology and ecology by reflecting, transmitting or absorbing the radiation of varying wavelengths differently. The elytra capacity to manage infrared, visible and ultraviolet radiations (from 185 to 1400 nm) was assessed with a spectrophotometric analysis in five Canthon species of dung beetles; we calculated the reflectance, transmittance, and absorbance capacity of the elytra of these species. These species have different ecologies: two species preferentially inhabit forest areas (Canthon angularis and Canthon lividus lividus), two species preferentially inhabit open areas (Canthon chalybaeus and Canthon tetraodon) including agricultural crops, and one species does not present a clear habitat preference and can be found in both habitats (Canthon quinquemaculatus). All the species show a similar pattern in which the light from shorter wavelengths and higher frequencies is almost entirely absorbed by the elytra, while radiation from longer wavelengths and lower frequencies can mostly pass through the elytra. However, C. quinquemaculatus seems to have significantly higher rates of reflectance and transmittance in the visible and near-infrared spectrum. This different pattern found in C. quinquemaculatus may be associated with its capacity to establish populations both in agricultural and forest areas.

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Visualization of viscoelastic behavior in skin equivalent using optical coherence tomography-based straingraphy

Abstract

Background/Purpose

The relationships between the skin components and these mechanical roles are still unclear. To clarify these relationships, we investigated spatial mapping of the mechanical behavior of cultured skin equivalents (SEs) using optical coherence tomography (OCT)-based straingraphy.

Methods

We built a strain relaxation test system combined with OCT and developed an algorithm that could visualize a time-dependent strain distribution, named dynamic-optical coherence straingraphy (D-OCSA). Using this system, we analyzed how the spatial mechanical changes in the SEs depended on the culture duration. For quantitative analysis of viscoelastic behavior, we defined a relaxation attenuation coefficient of strain rate, which indicates the ratio of viscosity and elasticity in the Klevin-Voight model.

Results

By culturing for 4 days in comparison to culturing for 1 day, the strain relaxation attenuation coefficient of the whole skin, especially at the region of the dermal-epidermal junction (DEJ), significantly increased in the negative direction. In tissue slices taken for microscopy, several cracks were observed in the SEs cultured for 4 days.

Conclusion

This study is the first to provide quantified evidence that the DEJ is a dynamically specialized region. An OCT-based straingraphy system (D-OCSA) would be beneficial for evaluating the quality of SEs, as well as functional analysis of their mechanics.

Wrinkle and roughness measurement by the Antera 3D and its application for evaluation of cosmetic products

Abstract

Background

Skin topographic measurements are of paramount importance in the field of dermo-cosmetic evaluation. The aim of this study was to investigate how the Antera 3D, a multi-purpose handheld camera, correlates with other topographic techniques and changes in skin topography following the use of a cosmetic product.

Methods

Skin topographic measurements were collected on 26 female volunteers aged 45-70 years with the Antera 3D, the DermaTOP and image analysis on parallel-polarized pictures. Different filters for analysis from the Antera 3D were investigated for repeatability, correlations with other imaging techniques and ability to detect improvements of skin topography following application of a serum.

Results

Most of Antera 3D parameters were found to be strongly correlated with the DermaTOP parameters. No association was found between the Antera 3D parameters and measurements on parallel-polarized photographs. The measurements repeatability was comparable among the different filters for analysis, with the exception of wrinkle max depth and roughness Rt. Following a single application of a tightening serum, both Antera 3D wrinkles and texture parameters were able to record significant improvements, with the best improvements observed with the large filter.

Conclusion

The Antera 3D demonstrated its relevance for cosmetic product evaluation. We also provide recommendations for the analysis based on our findings.

A profile of Propionibacterium acnes resistance and sensitivity at a tertiary dermatological centre in Singapore

Propionibacterium acnes (P. acnes) is a key component in the pathogenesis of acne. Both topical and oral antibiotics are key therapeutic options. Unfortunately, antibiotic resistance is rapidly increasing globally. Many countries have reported greater than 50% of P.acnes strains acquiring resistance to topical macrolides^1-3. In Singapore, antibiotic resistance rates of 8% in 1999⁴ rising to 14.9%⁵ in 2007 were reported. We aimed to update the local prevalence of antibiotic resistance and identify features which may distinguish patients demonstrating antibiotic resistance from those who are pan-sensitive.

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Pulsed-dye laser therapy for carcinoma in situ of the penis

Carcinoma in situ (CIS) of the penis is a precancerous condition with a 5 to 10% risk for progression into an invasive penile squamous cell carcinoma (SCC)¹. Clinical variants of genital CIS encompass bowenoid papulosis, erythroplasia of Queyrat and Bowen's disease. Treatment options of penile CIS include topical application of 5-fluorouracil (5-FU) or imiquimod, photodynamic therapy (PDT), ablative laser therapy, cryotherapy and surgery² .

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Omalizumab updosing allows disease activity control in refractory patients with chronic spontaneous urticaria

Omalizumab has been shown to be a very effective drug in chronic spontaneous urticaria (CSU) improving patients' quality of life.¹ Phase III clinical trials ASTERIA I/II and GLACIAL showed respectively 58.8-52.4% of patients achieving a twice daily average Urticaria Activity Score 7 (UAS7td)≤6 at week 12.² Outside of clinical trials, the response varies between 77-83%.³ However, some patients do not achieve well-controlled activity of the disease with the licensed dose of omalizumab (300mg/4 weeks).

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Dermoscopic features of pilar leiomyomas

Cutaneous pilar leiomyomas are benign smooth muscle neoplasms that usually present as painful firm erythematous to brown coloured papules and nodules.¹ Dermoscopy has been used as an auxiliary tool in the diagnosis of various cutaneous tumors. Herein we report the various dermoscopic features of 48 cutaneous pilar leiomyomas in five patients.

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A synergetic biomineralization strategy for immobilizing strontium during calcification of the coccolithophore Emiliania huxleyi

Abstract

The coccolithophore species Emiliania huxleyi has one of the most global distributions in the modern oceans. They are characteristically covered with calcite scales called coccoliths. In this study, stable strontium immobilization during the calcification process was investigated to indirectly assess a proposed bioremediation approach for removing Sr²⁺ contamination from marine environments. Results indicate that E. huxleyi has high Sr²⁺ tolerance and removal efficiency in response to Sr²⁺ stress ranging from 5.6 to 105.6 ppm. Sr²⁺ immobilization during E. huxleyi calcification indicates a concentration-dependent synergistic mechanism. At lower concentrations of Sr²⁺ (25.6 ppm), Sr²⁺ is incorporated into coccoliths through competitive supply between Sr²⁺ and Ca²⁺. In addition, calcite productivity decreases with increased Sr²⁺ removal efficiency due to crystallographic transformation of coccoliths from hydrated calcite into aragonite at 55.6 ppm Sr²⁺. Further formation of strontianite at 105.6 ppm Sr²⁺ is due to precipitation of Sr²⁺ on the edge of the rims and radial arrays of the coccoliths. Our study implies that coccolithophores are capable of significant removal of Sr²⁺ from the marine environment.

Effects of Personal Protective Equipment Use and Good Workplace Hygiene on Symptoms of Neurotoxicity in Solvent-Exposed Vehicle Spray Painters

Abstract

Objectives

To assess the association between the use of personal protective equipment (PPE) and good workplace hygiene and symptoms of neurotoxicity in solvent-exposed vehicle spray painters.

Methods

Exposure control measures including PPE-use and workplace hygiene practices and symptoms of neurotoxicity were assessed in 267 vehicle repair spray painters. Symptoms were assessed using an adapted version of the EUROQUEST Questionnaire.

Results

Frequent respirator and glove use was inversely and significantly associated with symptoms of neurotoxicity in a dose-dependent manner (P < 0.05 for trend) with the strongest protective effect found for consistent glove use (odds ratios [OR] 0.1–0.2, P < 0.01, for reporting ≥10 and ≥5 symptoms). A clear dose–response trend was also observed when combining frequency of respirator and glove use (P < 0.05 for reporting ≥5 and ≥10 symptoms), with an overall reduction in risk of 90% (OR, 0.1, P < 0.01) for those who consistently used both types of PPE. Protective effects were most pronounced for the symptom domains of psychosomatic (P < 0.05 for trend, for combined PPE use), mood (P < 0.05), and memory and concentration symptoms combined (P < 0.05), with reductions in risk of >80%. Poor hygiene workplace practices, such as solvent exposure to multiple body parts (OR 3.4, P = 0.11 for reporting ≥10 symptoms), were associated with an increased risk of symptoms. When using a general workplace hygiene score derived from a combination of PPE-use and (good) workplace practice factors an inverse and significant dose–response trend was observed for reporting ≥5 (P < 0.01) and ≥10 symptoms (P < 0.01).

Conclusions

This study has shown that PPE-use and good workplace hygiene are associated with a strongly reduced risk of symptoms of neurotoxicity in solvent-exposed vehicle spray painters.

Autologous Fat Graft for the Treatment of Sighted Posttraumatic Enophthalmos and Sunken Upper Eyelid

Purpose: The treatment of enophthalmos and sunken upper eyelid is challenging. Although autologous fat graft has been widely used in breast augmentation, buttock contouring, and facial rejuvenation, its application in enophthalmos and sunken upper eyelid is not yet widely utilized. The clinical safety and value of autologous fat graft in sighted patients with enophthalmos and sunken upper eyelid are unclear. This study retrospectively analyzed the cosmetic results and safety of autologous fat graft in the correction of sighted traumatic enophthalmos and sunken upper eyelid. Methods: Autologous fat graft was performed in 9 patients with posttraumatic enophthalmos and sunken upper eyelid. The visual acuity, orbital swelling, eye movement, enophthalmos, and sunken upper eyelid were observed. Results: Eight to 24 months after autologous fat graft, enophthalmos and sunken upper eyelid in 9 patients improved significantly. Although orbital swelling occurred in the early postoperative period, no vision loss, eye movement limitation, or fat embolism had occurred. Conclusion: Autologous fat graft is an effective, predictable, scarless, and minimally invasive surgery for the correction of the sighted posttraumatic enophthalmos and sunken upper eyelid. The possible risk of fat embolization and blindness from the compression of the optic nerve should not be neglected. Further studies and more cases must be performed. Accepted for publication October 14, 2017. Supported by the National Basic Research Program of China (973 Program, No. 2015CB554100), National Natural Science Foundation of China (No. 81271035/H1205), and Foundation for Returned Personals Studying Abroad from Human Resources Department of Sichuan Province in 2015, People's Republic of China. HC, QZ, and QQ are co-first authors. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Hui Chen, M.D., Ophthalmology Department, Sichuan Provincial People's Hospital, No. 32, 1st Ring Road, 2nd West Section, Chengdu City, Sichuan 610072, People's Republic of China. E-mail: 540685790@qq.com; Zhenglin Yang, Ph.D., Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, No. 32, 1st Ring Road, 2nd West Section, Chengdu City, Sichuan 610072, People's Republic of China. E-mail: zliny@yahoo.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Paracanthal “One-Snip” Decompression in a Cadaver Model of Retrobulbar Hemorrhage

Purpose: The authors assess the effectiveness of a modified paracanthal or "one-snip" procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage. Methods: This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or "one-snip" procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques. Results: Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11–18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups. Conclusions: Compared with traditional lateral canthotomy and inferior cantholysis, the modified paracanthal or "one-snip" procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression. Accepted for publication September 28, 2017. Supported in part by the NIH-NEI P30 Core Grant (IP30EY025585-01A1) and Unrestricted Grant from The Research to Prevent Blindness, Inc., awarded to the Cole Eye Institute. The authors have no conflicts of interest to disclose. Correspondence address and reprint requests to Alexander D. Blandford, M.D., Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk i-13, Cleveland, OH 44195. E-mail: blandfa@ccf.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Deep Orbital Sub-Q Hyaluronic Acid Filler Injection for Enophthalmic Sighted Eyes in Parry–Romberg Syndrome

Purpose: The authors present a consecutive series of deep orbital Sub-Q injections to treat enophthalmic sighted eyes in Parry–Romberg syndrome patients. Methods: Retrospective, interventional case series in 2 centers. Data were collected on patient demographics, Parry–Romberg syndrome onset age, previous orbital and eyelid surgeries, diplopia, ocular movement restriction before and after the injection, number of injections, interval between injections, indication for any top-up or dissolution of filler, and any other complications. In all cases, the hyaluronic acid gel used was Restylane Sub-Q + Lidocaine. Results: A total of 8 injections on 3 patients with Parry–Romberg syndrome, and significant enophthalmos is reported. All injections were with deep orbital Sub-Q filler. All patients were females, aged 32, 24, and 52 years old while their symptoms started at 15, 16, and 30 years old, respectively. None had orbital surgery prior to the injection. Follow up period was 2, 7, and 5 years respectively. All presented a significant enophthalmos of 4 mm which reduced to 1 mm after the injection, and duration effect was 18, 24, and 20 months, respectively. We observed a significant improvement in enophthalmos, lagophthalmos, exposure keratopathy, and even ocular motility. Lagophthalmos improved from 1, 4, and 7 mm to 0, 1, and 2 mm post injection. Ocular motility improved with no onset of new limitation or diplopia. Lower eyelid retraction increased in 1 patient after orbital injection. No other complications occurred. Conclusions: Deep orbital Sub-Q hyaluronic injection for treatment of enophthalmos in Parry–Romberg syndrome is an useful option in sighted eyes. Accepted for publication November 16, 2017. Case 1 was presented at DOG (German Ophthalmological Society), Berlin, 2015. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Raman Malhotra, Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, West Sussex, RH19 3DZ, United Kingdom. E-mail: raman.malhotra@qvh.nhs.uk © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Improving Outcomes of Posterior Approach Levatorpexy for Congenital Ptosis With Reduced Levator Function

Purpose: The authors present a new series of our experience using posterior approach levatorpexy for congenital ptosis with poorer levator function (LF) in comparison with our first published report. This technique avoids a skin incision or any resection in addition to no excision of tissue. Methods: A consecutive series of 16 patients. Retrospective review of levatorpexy for congenital ptosis. Data included eyelid margin reflex distance 1, pretarsal show, contour, and complications, including nocturnal lagophthalmos, eyelid lag on downgaze, and dry eye. Surgery was considered successful if the following 4 criteria were simultaneously met: a postoperative margin reflex distance 1 of ≥2 mm and ≤4.5 mm, intereyelid height asymmetry of ≤1 mm, no overcorrection compare to opposite eye, and satisfactory eyelid contour. Results: Mean age was 10.3 years (range 1–26 years). Mean LF was 7.3 mm (2–14 mm), while 66% (12) had LF ≤7 mm. Preoperative phenylephrine test was positive in 87.5% of patients. Mean preoperative and postoperative margin reflex distance 1 was 1.34 mm and 3.2 mm, respectively. Fourteen patients (87%) achieved the desired eyelid height and fulfilled our criteria set of success. Among 10 patients with LF ≤7 mm, 9 (90%) achieved the desired eyelid height and fulfilled our criteria set of success. Ninety-four percent did not report nocturnal lagophthalmos. Three patients needed a further levatorpexy procedure due to undercorrection. Mean postoperative follow up was up 11.2 (range 6–36) months. Conclusions: Posterior approach levatorpexy is an useful first-line choice for congenital ptosis for all ranges of LF. It is popular among parents due to its avoidance of a skin incision or any resection or excision of tissue. Accepted for publication November 18, 2017. Presented at European Society of Ophthalmic Plastic and Reconstructive Surgery in Athens, Greece, September 15, 2016. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Raman Malhotra, Corneoplastic Unit, Queen Victoria Hospital, East Grinstead, West Sussex, RH19 3DZ, United Kingdom. E-mail: raman.malhotra@qvh.nhs.uk © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Experimental study of sector and linear array ultrasound accuracy and the influence of navigated 3D-reconstruction as compared to MRI in a brain tumor model

Abstract

Purpose

Currently, intraoperative ultrasound in brain tumor surgery is a rapidly propagating option in imaging technology. We examined the accuracy and resolution limits of different ultrasound probes and the influence of 3D-reconstruction in a phantom and compared these results to MRI in an intraoperative setting (iMRI).

Methods

An agarose gel phantom with predefined gel targets was examined with iMRI, a sector (SUS) and a linear (LUS) array probe with two-dimensional images. Additionally, 3D-reconstructed sweeps in perpendicular directions were made of every target with both probes, resulting in 392 measurements. Statistical calculations were performed, and comparative boxplots were generated.

Results

Every measurement of iMRI and LUS was more precise than SUS, while there was no apparent difference in height of iMRI and 3D-reconstructed LUS. Measurements with 3D-reconstructed LUS were always more accurate than in 2D-LUS, while 3D-reconstruction of SUS showed nearly no differences to 2D-SUS in some measurements. We found correlations of 3D-reconstructed SUS and LUS length and width measurements with 2D results in the same image orientation.

Conclusions

LUS provides an accuracy and resolution comparable to iMRI, while SUS is less exact than LUS and iMRI. 3D-reconstruction showed the potential to distinctly improve accuracy and resolution of ultrasound images, although there is a strong correlation with the sweep direction during data acquisition.

Isolation and evaluation of cocktail phages for the control of multidrug-resistant Escherichia coli serotype O104: H4 and E. coli O157: H7 isolates causing diarrhea

Abstract

Escherichia coli serotype O157: H7 and E. coli O104: H4 are well known foodborne pathogens causing sever enteric illness. Using bacteriophages as biocontrol agents of some foodborne pathogens and multidrug-resistant (MDR) bacteria has a great attention nowadays. This study aims to test the effect of cocktail phages on the growth of some foodborne pathogens and MDR E. coli. Routine conventional PCR was used to confirm the identification of E. coli isolates. Double-layered culture technique was used to isolate phages from sewage water. Morphology of bacteriophage was described using transmission electron microscopy, and spot test was performed to determine host range of the phage cocktail. Phage cocktail of Siphoviridae and Podoviridae family infecting E. coli O157: H7, E. coli O104: H4 and untypeable E. coli (neither O157 nor O104) has been isolated from sewage water. Phage cocktail showed both lytic and lysogenic activity. Lytic activity was observed against E. coli O157: H7, E. coli O104: H4 isolates, Staphylococcus. aureus ATCC6538 and Pseudomonas aeruginosa ATCC 10145, while the lysogenic activity was observed against the untypeable strain. The tested phage cocktail showed a promising inhibitory action on E. coli O157: H7 and O104: H4, S. aureus ATCC6538 and P. aeruginosa ATCC 10145, suggesting the possibility of its use as a biocontrol tool or as natural food preservatives for many food products.

Glutamate residues at positions 162 and 164 influence the beta-lactamase activity of SHV-14 obtained from Klebsiella pneumoniae

Abstract

Extensive production of SHV-14 beta-lactamase makes Klebsiella pneumoniae resistant to beta-lactams. The presence of omega-loop has been reported to influence the beta-lactamase activity, which is also present in SHV-14. Its omega-loop has three glutamates in nearly alternating positions 162, 164 and 167 but their concise role on the behaviour of SHV-14 is unknown. To uncover the influence of each glutamate on SHV-14, we replaced glutamates with alanine and estimated the effect of each mutation by assessing the change in beta-lactam sensitivities in the surrogate Escherichia coli cells and catalytic efficiencies for hydrolysis with the purified proteins. On expression, the clone of wild-type SHV-14 aggravated the resistance of host by 60–500 folds against penicillin and cephalosporin groups of antibiotics. However, the expression of mutated enzymes (especially E164A) substantially reduced the resistance level as compared to the wild type, and the results were in synchrony with the estimated enzymatic efficiencies of wild-type and mutated proteins. Therefore, with further support from the in silico analysis, we hypothesise that mutation at the glutamate residues in the omega-loop of SHV-14 can considerably modulate the beta-lactam sensitivity and hydrolysis, thus revealing the importance of such glutamates as the target for inhibitor design in future.

Electroactive haloalkaliphiles exhibit exceptional tolerance to free ammonia

Abstract

Electrochemical activity in bacteria has been observed in numerous environments and conditions. However, enrichments in circumneutral freshwater media where acetate is the main electron donor seem to invariably lead to the dominance of Geobacter spp. Here we report on an electroactive bacterial consortium which was enriched on acetate as electron donor, but in a medium which reproduces hydrolysed urine (high pH, high salinity and high free ammonia). The consortium was found to be free of Geobacter species, whereas a previously undescribed community dominated by species closely related to Pseudomonas and Desulfuromonas was established. The salient features of this community were as follows: (i) high electroactivity, with anodic current densities up to 47.4 ± 2.0 A m^–2; (ii) haloalkaliphilicity, with top performance at a medium pH of 10 and 19.5 ± 0.5 mS cm⁻¹; and (iii) a remarkably high tolerance to free ammonia toxicity at over 2200 mgNH₃-N L⁻¹. This community is likely to find applications in microbial electrochemical technology for nutrient recovery from source-separated urine.

Social networks as a tool for science communication and public engagement: focus on Twitter

Abstract

Social networks have been used to teach and engage people about the importance of science. The integration of social networks in the daily routines of faculties and scientists is strongly recommended to increase their personal brand, improve their skills, enhance their visibility, share and communicate science to society, promote scientific culture, and even as a tool for teaching and learning. Here we review the use of Twitter in science and comment on our previous experience of using this social network as a platform for a Massive Online Open Course (MOOC) in Spain and Latin America. We propose to extend this strategy to a pan-European Microbiology MOOC in the near future.

Vector-borne diseases and climate change: a European perspective

Abstract

Climate change has already impacted the transmission of a wide range of vector-borne diseases in Europe, and it will continue to do so in the coming decades. Climate change has been implicated in the observed shift of ticks to elevated altitudes and latitudes, notably including the Ixodes ricinus tick species that is a vector for Lyme borreliosis and tick-borne encephalitis. Climate change is also thought to have been a factor in the expansion of other important disease vectors in Europe: Aedes albopictus (the Asian tiger mosquito), which transmits diseases such as Zika, dengue and chikungunya, and Phlebotomus sandfly species, which transmits diseases including Leishmaniasis. In addition, highly elevated temperatures in the summer of 2010 have been associated with an epidemic of West Nile Fever in Southeast Europe and subsequent outbreaks have been linked to summer temperature anomalies. Future climate-sensitive health impacts are challenging to project quantitatively, in part due to the intricate interplay between non-climatic and climatic drivers, weather-sensitive pathogens and climate-change adaptation. Moreover, globalisation and international air travel contribute to pathogen and vector dispersion internationally. Nevertheless, monitoring forecasts of meteorological conditions can help detect epidemic precursors of vector-borne disease outbreaks and serve as early warning systems for risk reduction.

The aberrant splicing of BAF45d links splicing regulation and transcription in glioblastoma

Abstract

Background

Glioblastoma, the most aggressive primary brain tumor, is a genetically heterogeneous tumor. Alternative spicing (AS) plays a key role in numerous pathologies, including cancer. The objective of our study was to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation.

Methods

We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery. Biopsies were taken from the tumor center as well as from adjacent normal-appearing tissue. We used a global splicing array to identify candidate genes aberrantly spliced in these glioblastoma samples. Mechanistic and functional studies were performed to elucidate the role of our top candidate splice variant, BAF45d, in glioblastoma.

Results

BAF45d is part of the switch/sucrose non-fermentable (SWI/SNF) complex and plays a key role in the development of the CNS. The BAF45d/6A-isoform is present in 85% of over 200 glioma samples that have been analyzed, and contributes to the malignant glioma phenotype through the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d splicing is mediated by polypyrimidine-tract-binding protein 1 (PTBP1) and that BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing regulation and transcription.

Conclusions

Our data indicate that AS is a mechanism that contributes to the malignant phenotype of glioblastoma. Understanding the consequences of this biological process will uncover new therapeutic targets for this devastating disease.