bluuebunny/crossref_metadata_2025 huggingface dataset:
Incentivizing Narrow-Spectrum Antibiotics Development with Refunding
Authors: Böttcher Lucas , Gersbach Hans
Published: July 2020

The rapid rise of antibiotic resistance is a serious threat to global public health. Without further incentives, pharmaceutical companies have little interest in developing antibiotics, since the success probability is low and development costs are huge. The situation is exacerbated by the “antibiotics dilemma”: Developing narrow-spectrum antibiotics against resistant bacteria is most beneficial for society, but least attractive for companies since their usage is more limited than for broad-spectrum drugs and thus sales are low. Starting from a general mathematical framework for the study of antibiotic-resistance dynamics with an arbitrary number of antibiotics, we identify efficient treatment protocols and introduce a market-based refunding scheme that incentivizes pharmaceutical companies to develop narrow-spectrum antibiotics: Successful companies can claim a refund from a newly established antibiotics fund that partially covers their development costs. The proposed refund involves a fixed and variable part. The latter (i) increases with the use of the new antibiotic for currently resistant strains in comparison with other newly developed antibiotics for this purpose— the resistance premium—and (ii) decreases with the use of this antibiotic for non-resistant bacteria. We outline how such a refunding scheme can solve the antibiotics dilemma and cope with various sources of uncertainty inherent in antibiotic R&D. Finally, connecting our refunding approach to the recently established antimicrobial resistance (AMR) action fund, we discuss how the antibiotics fund can be financed.
Development and large-scale validation of a highly accurate SARS-COV-2 serological test using regular test strips for autonomous and affordable finger-prick sample collection, transportation, and storage
Authors: Alvim Renata G. F. , Lima Tulio M. , Rodrigues Danielle A. S. , Marsili Federico F. , Bozza Vicente B. T. , Higa Luiza M. , Monteiro Fabio L. , Abreu Daniel P. B. , Leitão Isabela C. , Carvalho Renato S. , Galliez Rafael M. , Castineiras Terezinha M. P. P. , Travassos Leonardo H. , Nobrega Alberto , Tanuri Amilcar , Ferreira Orlando C. , Castilho Leda R. , Vale André M.
Published: July 2020

Accurate serological tests are essential tools to allow adequate monitoring and control of COVID-19 spread. Production of a low-cost and high-quality recombinant viral antigen can enable the development of reliable and affordable serological assays, which are urgently needed to facilitate epidemiological surveillance studies in low-income economies. Trimeric SARS-COV-2 spike (S) protein was produced in serum-free, suspension-adapted HEK293 cells. Highly purified S protein was used to develop an ELISA, named S-UFRJ test. It was standardized to work with different types of samples: (i) plasma or serum from venous blood samples; (ii) eluates from dried blood spots (DBS) obtained by collecting blood drops from a finger prick. We developed a cost-effective, scalable technology to produce S protein based on its stable expression in HEK293 cells. Using this recombinant antigen, we presented a workflow for test development in the setting of a pandemic, starting from limited amounts of samples up to reaching final validation with hundreds of samples. Test specificity was determined to be 98.6%, whereas sensitivity was 95% for samples collected 11 or more days after symptoms onset. A ROC analysis allowed optimizing the cut-off and confirming the high accuracy of the test. Endpoint titers were shown to correlate with virus neutralization assessed as PRNT90. There was excellent agreement between plasma and DBS samples, significantly simplifying sample collection, storing, and shipping. An overall cost estimate revealed that the final retail price could be in the range of one US dollar. The S-UFRJ assay developed herein meets the quality requirements of high sensitivity and specificity. The low cost and the use of mailable DBS samples allow for serological surveillance and follow-up of SARS-CoV-2 vaccination of populations regardless of geographical and socio-economic aspects. We hope the detailed guidelines for the development of an affordable and accurate anti-spike SARS-COV-2 ELISA, such as S-UFRJ described here, will stimulate governmental and non-governmental health agencies in other countries to engage in much-needed large-scale studies monitoring the spread and immunity to SARS-COV-2 infection.
Inequalities in air pollution exposure are increasing in the United States
Authors: Jbaily Abdulrahman , Zhou Xiaodan , Liu Jie , Lee Ting-Hwan , Verguet Stéphane , Dominici Francesca
Published: July 2020

Exposure to ambient air pollution contributes substantially to the global burden of disease, and in 2015, ambient exposure to PM2.5 (fine particles with a mass median aerodynamic diameter of less than 2.5 μm) was the fifth-ranking risk factor of mortality globally. We analyzed data from the US zip code tabulation areas (N=32047) for 2000-2016 and found strong evidence of inequalities in exposure to PM2.5 among both racial/ethnic and income groups. Most alarming, we found that these inequalities have been increasing over time. From 2010 to 2016 inequalities in the exposure to PM2.5 levels above 8 μg/m3 across racial/ethnic, and income groups increased by factors of 1.6 and 4.0 respectively. As shown in our powerful map visualizations, these results indicate that air pollution regulations must not only decrease PM2.5 concentration levels nationwide but also prioritize reducing environmental injustice across the US.
Replication assessment of NUS1 variants in Parkinson’s Disease
Authors: Bustos Bernabe I. , Bandres-Ciga Sara , Gibbs J. Raphael , Krainc Dimitri , Mencacci Niccolo E. , Gan-Or Ziv , Lubbe Steven J. ,   for the International Parkinson’s Disease Genomics Consortium (IPDGC).
Published: July 2020

The NUS1 gene was recently associated with Parkinson’s disease (PD) in the Chinese population. Here, as part of the International Parkinson’s Disease Genomics Consortium (IPDGC), we have leveraged large-scale PD case-control cohorts to comprehensively assess the NUS1 association in individuals of European descent. Burden analysis of rare nonsynonymous damaging variants across case-control individuals from whole-exome and -genome datasets did not find evidence of NUS1 association with PD. Overall, single variant tests for rare (MAF<0.01) and common (MAF>0.01) variants, including 15 PD-GWAS cohorts and summary statistics from the largest PD GWAS meta-analysis to date, also did not uncover any associations. Our results indicate a lack of evidence for a role of rare damaging nonsynonymous NUS1 variants in PD in unrelated case-control cohorts of European descent, suggesting that the previously observed association could be driven by extremely rare population-specific variants.
Long Term Safety and Efficacy of Sub-Lingual Ketamine Troches / Lozenges in Chronic Non-Malignant Pain Management
Authors: Maudlin Ben , Gibson Stephen B. , Aggarwal Arun
Published: July 2020

Introduction

Chronic non-malignant pain is a disabling condition that results in a reduction in function and quality of life when inadequately managed. Sub-lingual ketamine has been shown to be efficacious for use in chronic pain. Despite its use for decades in chronic non-malignant pain, there is no published long-term data on safety, side effects or adverse drug reactions. The aim of this case-series is to provide the initial evidence for safety and efficacy in this patient group.

Methods

We present a retrospective review of twenty-nine patients (n=29) from a metropolitan tertiary pain service who have been receiving sub-lingual ketamine troches / lozenges between the period of 2012-2019. Patients were identified from the outpatient pain clinic, who had been admitted for inpatient subcutaneous ketamine infusions as part of opiate detoxification or management of central sensitisation due to a chronic neuropathic pain syndrome. An initial review was performed to check the patient started taking the ketamine troches. Each of these medical records was reviewed manually to extract information to a datasheet.

Results

There was a wide range of dosages used from 25-600mg in divided doses. The duration of treatment ranged from 2-89 months. There was no association with either the dosage or duration of treatment and frequency of side effects. There was an overall reduction in the use of opioids, gabapentinoids or benzodiazepines in 59% of patients with 39% having a complete cessation of an analgesic agent. Side effects were reported in 24%, but only 7% discontinued the treatment due to the side effect (drowsiness). There were no reports of renal impairment, cystitis, or hepatotoxicity.

Discussion

This retrospective case-series has demonstrated that sub-lingual ketamine is a safe and effective analgesic agent to use in chronic non-malignant pain management. It is indicated in a variety of chronic pain conditions and has an excellent safety profile, with no association between the frequency in side effects and duration of therapy or total daily dosages. The study has also shown that the “safe” dose may be higher than the previous consensus.

Contribution Statement

A.A and S.G. recruited the patients. A.A. & B.M. created the parameters for the data collection sheet. B.M Collected most of the data from the medical records, entered it into a datasheet, wrote the manuscript, ran the statistics, performed the data analysis, and generated the figures and tables. A.A. Edited the manuscript. S.G. and A.A were the research supervisors.
Low genetic diversity in a population of Tricolored Blackbird (Agelaius tricolor), a species pending Endangered status
Authors: Liu Irene A. , Meese Robert J.
Published: July 2020

The Tricolored Blackbird (Agelaius tricolor) is a colonial songbird, found almost exclusively in California, whose total population size has sharply declined over the past century. It is currently under review to be listed as Endangered under both the California and U.S. Endangered Species Acts. Here we assess the genetic diversity of a breeding population in California’s Central Valley, comparing our findings with previously sampled conspecific and congeneric populations. First, we genotyped 50 adults at 9 microsatellite loci in our focal population and estimated allelic and Shannon diversity, observed and expected heterozygosity, and the inbreeding coefficient (FIS). Second, we compared our results to those of the one existing study on Tricolored Blackbird conservation genetics and found that levels of allelic diversity and heterozygosity in our focal population were similar to those of 11 previously studied populations. Unlike the earlier study, which found moderately high mean inbreeding coefficients, we detected no evidence of inbreeding in our focal population. Third, we used 7 of the 9 loci to compare the genetic diversity of our focal population with populations of 2 previously sampledAgelaiuscongeners. We found that allelic diversity, Shannon diversity, and expected heterozygosity in our Tricolored Blackbird population were most similar to those of an isolated Red-winged Blackbird (A. phoeniceus) population in the Bahamas. We discuss possible reasons for the different results from the conspecific study, outline why the collective findings from both studies support the need for protective measures, and urge conservation action to maintain existing genetic diversity and gene flow before ongoing population losses lead to adverse fitness consequences.
Genetic architecture of 11 abdominal organ traits derived from abdominal MRI using deep learning
Authors: Liu Yi , Basty Nicolas , Whitcher Brandon , Bell Jimmy D , Sorokin Elena , van Bruggen Nick , Thomas E. Louise , Cule Madeleine
Published: July 2020

Cardiometabolic diseases are an increasing global health burden. While well established socioeconomic, environmental, behavioural, and genetic risk factors have been identified, our understanding of the drivers and mechanisms underlying these complex diseases remains incomplete. A better understanding is required to develop more effective therapeutic interventions. Magnetic resonance imaging (MRI) has been used to assess organ health in a number of studies, but large-scale population-based studies are still in their infancy. Using 38,683 abdominal MRI scans in the UK Biobank, we used deep learning to systematically quantify parameters from individual organs (liver, pancreas, spleen, kidneys, lungs and adipose depots), and demonstrate that image derived phenotypes (volume, fat and iron content) reflect organ health and disease. We show that these traits have a substantial heritable component (8%-44%), and identify 93 independent genome-wide significant associations, including 3 associations with liver fat and one with liver iron that have not previously been reported, and 73 in traits that have not previously been studied. Overall our work demonstrates the utility of deep learning to systematically quantify health parameters from high-throughput MRI across a range of organs and tissues of the abdomen, and to generate new insights into the genetic architecture of complex traits.
Phospho-IWS1-dependent U2AF2 splicing is cell-cycle-regulated, promotes proliferation and predicts poor prognosis of EGFR- mutant lung adenocarcinoma
Authors: Laliotis Georgios I. , Chavdoula Evangelia , Paraskevopoulou Maria D. , Kaba Abdul D. , La Ferlita Alessandro , Singh Satishkumar , Anastas Vollter , Alaimo Salvatore , Orlacchio Arturo , Nair Keith A. , Taraslia Vasiliki , Vlachos Ioannis , Capece Marina , Hatzigeorgiou Artemis , Palmieri Dario , Tsatsanis Christos , Sehgal Lalit , Carbone David P. , Coppola Vincenzo , Tsichlis Philip N.
Published: July 2020

The authors have withdrawn their manuscript. While attempting to reproduce the data on the alternative splicing of exon 2 of U2AF2, they observed that the proposed splicing mechanism could not give rise to a functional U2AF2 protein. In addition, they observed evidence of manipulation in the electropherogram of the splicing junction between exons 1 and 3 and in the primary data on which this electropherogram was based, which were deposited in Mendeley by the first author. These observations raise questions on the integrity of the reported results. In light of this information, the authors have no confidence in the key findings of the paper, and therefore, do not wish it to be cited. If you have any questions, please contact the corresponding author.
Species packing and the latitudinal gradient in beta-diversity
Authors: Cao Ke , Condit Richard , Mi Xiangcheng , Chen Lei , Ren Haibao , Xu Wubing , Burslem David F. R. P. , Cai Chunrong , Cao Min , Chang Li-Wan , Chu Chengjin , Cui Fuxin , Du Hu , Ediriweera Sisira , Gunatilleke C.S.V. , Gunatilleke I.U.A.N. , Hao Zhanqing , Jin Guangze , Li Jinbo , Li Buhang , Li Yide , Liu Yankun , Ni Hongwei , O’Brien Michael J. , Qiao Xiujuan , Shen Guochun , Tian Songyan , Wang Xihua , Xu Han , Xu Yaozhan , Yang Libing , Yap Sandra L. , Lian Juyu , Ye Wanhui , Yu Mingjian , Su Sheng-Hsin , Chang-Yang Chia-Hao , Guo Yili , Li Xiankun , Zeng Fuping , Zhu Daoguang , Zhu Li , Sun I-Fang , Ma Keping , Svenning Jens-Christian
Published: July 2020

The decline in species richness at higher latitudes is among the most fundamental patterns in ecology. Whether changes in species composition across space (beta-diversity) contribute to this gradient of overall species richness (gamma-diversity) remains hotly debated. Previous studies that failed to resolve the issue suffered from a well-known tendency for small samples in areas with high gamma-diversity to have inflated measures of beta-diversity. Here, we provide here a novel analytical test, using beta-diversity metrics that correct the gamma-diversity and sampling biases, to compare beta-diversity and species packing across a latitudinal gradient in tree species richness of 21 large forest plots along a large environmental gradient in East Asia. We demonstrate that after accounting for topography and correcting the gamma-diversity bias, tropical forests still have higher beta-diversity than temperate analogs. This suggests that beta-diversity contributes to the latitudinal species richness gradient as a component of gamma-diversity. Moreover, both niche specialization and niche marginality (a measure of niche spacing along an environmental gradient) also increase towards the equator, after controlling for the effect of topographic heterogeneity. This supports the joint importance of tighter species packing and larger niche space in tropical forests while also demonstrating the importance of local processes in controlling beta-diversity.
Gone in 40 years, the curious case of the Himalayan Quail: an attempt at rediscovery and implications for conservation
Authors: Pop Paul , Pandey Puneet , Singh Randeep
Published: July 2020

Himalayan Quail (Ophrysia superciliosa) is a Galliforme species currently classified as Critically Endangered by the IUCN. Given the fact that the species has only been recorded over a period of 40 years in the 19thcentury, this classification needs more scrutiny. The aim of this study was to explore the possibility of detecting the species in their known historical distribution in the lower Himalayas, and understand if possible, the factors which led to their decline or extinction. The potential habitats in districts of Nainital and Dehradun of Uttrakhand (India), where the species which has been recorded between 1836 to 1876, have been scoured thoroughly insofar as logistics and other factors permitted using trail and point transects. We did not detect any sign of the species in any of the areas, thereby corroborating the results of past surveys/expeditions in search of this species. Domesticated/feral species (grazing pressure and hunting by dogs), natural predation by species such as Yellow-throated Marten (Martes flavigula), hunting by humans, population growth and resulting land-use change, biogeochemical events, and tourism may all have contributed in varying degrees to their decline or extinction. It was found that most, if not all, proposals of strategies to find the species have been thus far unemployed or futile. We suggest improving the chances of re-discovering this species using tools such as molecular/genetic analysis and Unmanned Aerial Vehicles. Management recommendations include stress on grazing laws, sterilization of dogs, awareness about unchecked human population growth and measures for limiting the effects of unsustainable tourism.
What executive function network is that? An image-based meta-analysis of network labels
Authors: Witt Suzanne T. , van Ettinger-Veenstra Helene , Salo Taylor , Riedel Michael C. , Laird Angela R.
Published: July 2020

The current state of label conventions used to describe brain networks related to executive functions is highly inconsistent, leading to confusion among researchers regarding network labels. Visually similar networks are referred to by different labels, yet these same labels are used to distinguish networks within studies. We performed a literature review of fMRI studies and identified nine frequently-used labels that are used to describe topographically or functionally similar neural networks: central executive network (CEN), cognitive control network (CCN), dorsal attention network (DAN), executive control network (ECN), executive network (EN), frontoparietal network (FPN), working memory network (WMN), task positive network (TPN), and ventral attention network (VAN). Our aim was to meta-analytically determine consistency of network topography within and across these labels. We hypothesized finding considerable overlap in the spatial topography among the neural networks associated with these labels. An image-based meta-analysis was performed on 158 group-level statistical maps (SPMs) received from authors of 69 papers listed on PubMed. Our results indicated that there was very little consistency in the SPMs labeled with a given network name. We identified four clusters of SPMs representing four spatially distinct executive function networks. We provide recommendations regarding label nomenclature and propose that authors looking to assign labels to executive function networks adopt this template set for labeling networks.
MAVE-NN: learning genotype-phenotype maps from multiplex assays of variant effect
Authors: Tareen Ammar , Kooshkbaghi Mahdi , Posfai Anna , Ireland William T. , McCandlish David M. , Kinney Justin B.
Published: July 2020

Multiplex assays of variant effect (MAVEs) are a family of methods that includes deep mutational scanning (DMS) experiments on proteins and massively parallel reporter assays (MPRAs) on gene regulatory sequences. However, a general strategy for inferring quantitative models of genotype-phenotype (G-P) maps from MAVE data is lacking. Here we introduce MAVE-NN, a neural-network-based Python package that implements a broadly applicable information-theoretic framework for learning G-P maps—including biophysically interpretable models—from MAVE datasets. We demonstrate MAVE-NN in multiple biological contexts, and highlight the ability of our approach to deconvolve mutational effects from otherwise confounding experimental nonlinearities and noise.
Fast scanning high optical invariant two-photon microscopy for monitoring a large neural network activity with cellular resolution
Authors: Ota Keisuke , Oisi Yasuhiro , Suzuki Takayuki , Ikeda Muneki , Ito Yoshiki , Ito Tsubasa , Kobayashi Kenta , Kobayashi Midori , Odagawa Maya , Matsubara Chie , Kuroiwa Yoshinori , Horikoshi Masaru , Matsushita Junya , Hioki Hiroyuki , Ohkura Masamichi , Nakai Junichi , Oizumi Masafumi , Miyawaki Atsushi , Aonishi Toru , Ode Takahiro , Murayama Masanori
Published: July 2020

Fast and wide imaging with single-cell resolution, high signal-to-noise ratio and no optical aberration has the potential to open up new avenues of investigation in biology. However, this imaging is challenging because of the inevitable tradeoffs among those parameters. Here, we overcome the tradeoffs by combining a resonant scanning system, a large objective with low magnification and high numerical aperture, and highly sensitive large-aperture photodetectors. The result is a practically aberration-free, fast scanning high optical invariant two-photon microscopy (FASHIO-2PM) that enables calcium imaging from a large network composed of ∼16k neurons at 7.5 Hz in a 9 mm2contiguous image plane including more than 10 sensory-motor and higher-order regions of the cerebral cortex in awake mice. Through a network analysis based on single-cell activities, we discover that the brain exhibits small-world-ness rather than scale-freeness. FASHIO-2PM will enable revealing biological dynamics by simultaneous monitoring of macroscopic activity and its composing elements.
Dynamic tracking of variant frequencies depicts the evolution of mutation sites amongst SARS-CoV-2 genomes from India
Authors: Hudson B. Shenu , Kolte Vaishnavi , Khan Azra , Sharma Gaurav
Published: July 2020

With the exponential spread of the COVID-19 pandemic across the world within the twelve months, SARS-CoV-2 strains are continuously trying to adapt themselves in the host environment by random mutations. While doing so, some variants with evolutionary advantages such as better human to human transmissibility potential might get naturally selected. This short communication demonstrates how the mutation frequency patterns are evolving in 2,457 SAR-CoV-2 strains isolated from COVID-19 patients across diverse Indian states. We have identified 19 such variants showing contrasting mutational probabilities in the span of seven months. Out of these, 14 variants are showing increasing mutational probabilities suggesting their propagation with time due to their unexplored evolutionary advantages. Whereas mutational probabilities of five variants have significantly decreased in June onwards as compared to March/April, suggesting their termination with time. Further in-depth investigation of these identified variants will provide valuable knowledge about the evolution, infection strategies, transmission rates, and epidemiology of SARS-CoV-2.
The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms
Authors: Urra José Miguel , Ferreras-Colino Elisa , Contreras Marinela , Cabrera Carmen M. , Fernández de Mera Isabel G. , Villar Margarita , Cabezas-Cruz Alejandro , Gortázar Christian , de la Fuente José
Published: July 2020

The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. The characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to advance in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti-α-Gal IgM/IgG antibodies produced in response to bacterial microbiota. In addition to anti-α-Gal antibody-mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to α-Gal may contribute to the control of COVID-19. To address this hypothesis, we characterized the antibody response to α-Gal in patients at different stages of COVID-19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti-SARS-CoV-2 (Spike) IgG antibody titers increased, reduction in anti-α-Gal IgE, IgM and IgG antibody titers and alteration of anti-α-Gal antibody isotype composition correlated with COVID-19 severity. The results suggested that the inhibition of the α-Gal-induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with α-Gal epitopes to modify the microbiota and increase the α-Gal-induced protective immune response and reduce the severity of COVID-19.
Syncytia formation by SARS-CoV-2 infected cells
Authors: Buchrieser Julian , Dufloo Jeremy , Hubert Mathieu , Monel Blandine , Planas Delphine , Rajah Maaran Michael , Planchais Cyril , Porrot Françoise , Guivel-Benhassine Florence , Van der Werf Sylvie , Casartelli Nicoletta , Mouquet Hugo , Bruel Timothée , Schwartz Olivier
Published: July 2020

Severe cases of COVID-19 are associated with extensive lung damage and the presence of infected multinucleated syncytial pneumocytes. The viral and cellular mechanisms regulating the formation of these syncytia are not well understood. Here, we show that SARS-CoV-2 infected cells express the viral Spike protein (S) at their surface and fuse with ACE2-positive neighbouring cells. Expression of S without any other viral proteins triggers syncytia formation. Type-I interferon (IFN)-induced transmembrane proteins (IFITMs), a family of restriction factors that block the entry of many viruses, inhibit S-mediated fusion, with IFITM1 being more active than IFITM2 and IFITM3. On the contrary, the TMPRSS2 serine protease, which is known to enhance infectivity of cell-free virions, processes both S and ACE2 and increases syncytia formation by accelerating the fusion process. TMPRSS2 thwarts the antiviral effect of IFITMs. Our results show that the pathological effects of SARS-CoV-2 are modulated by cellular proteins that either inhibit or facilitate syncytia formation.

One Sentence Summary

Syncytia produced by SARS-CoV-2 infected cells and regulation of their formation by IFITMs and TMPRSS2.
10 years of EPOC: A scoping review of Emotiv’s portable EEG device
Authors: Williams Nikolas S , McArthur Genevieve M , Badcock Nicholas A
Published: July 2020

BACKGROUND

Commercially-made low-cost electroencephalography (EEG) devices have become increasingly available over the last decade. One of these devices, Emotiv EPOC, is currently used in a wide variety of settings, including brain-computer interface (BCI) and cognitive neuroscience research.

PURPOSE

The aim of this study was to chart peer-reviewed reports of Emotiv EPOC projects to provide an informed summary on the use of this device for scientific purposes.

METHODS

We followed a five-stage methodological framework for a scoping review that included a systematic search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. We searched the following electronic databases: PsychINFO, MEDLINE, Embase, Web of Science, and IEEE Xplore. We charted study data according to application (BCI, clinical, signal processing, experimental research, and validation) and location of use (as indexed by the first author’s address).

RESULTS

We identified 382 relevant studies. The top five publishing countries were the United States (n = 35), India (n = 25), China (n = 20), Poland (n = 17), and Pakistan (n = 17). The top five publishing cities were Islamabad (n = 11), Singapore (n = 10), Cairo, Sydney, and Bandung (n = 7 each). Most of these studies used Emotiv EPOC for BCI purposes (n = 277), followed by experimental research (n = 51). Thirty-one studies were aimed at validating EPOC as an EEG device and a handful of studies used EPOC for improving EEG signal processing (n = 12) or for clinical purposes (n = 11).

CONCLUSIONS

In its first 10 years, Emotiv EPOC has been used around the world in diverse applications, from control of robotic limbs and wheelchairs to user authentication in security systems to identification of emotional states. Given the widespread use and breadth of applications, it is clear that researchers are embracing this technology.
Characteristics of viable but nonculturableVibrio parahaemolyticusinduced under extended periods of cold-starvation with various NaCl concentrations
Authors: Yoon Jae-Hyun , Hyun Jeong-Eun , Moon Sung-Kwon , Lee Sun-Young
Published: July 2020

This study was undertaken to examine the induction of VBNC states ofVibrio parahaemolyticusunder prolonged cold-starvation with various NaCl concentrations and their responsive characteristics to maintain cell viability.V. parahaemolyticusentered the viable but nonculturable (VBNC) state in artificial sea water at 4°C within 80 day and persisted in the VBNC state for 150 days. During cold-starvation, bacterial cells were used to estimate their cell functions, including cytotoxicity, fatty acid composition, membrane potential, and morphology. Cytotoxic effect ofV. parahaemolyticuscells against animal cell lines was decreased to below 50% after 80 days. VBNCV. parahaemolyticuscells showed decreasing levels of palmitic, vaccenic, and hexadecenoic acid on membrane, concomitantly with the formation of empty gaps between the cytoplasmic and outer membrane, in comparison with those of the pure cultures. Starvation at 4°C for 30 days resulted in a high increase inN-phenyl-1-napthylamine intensity withinV. parahaemolyticuscells. Membrane potential and cellular composition were strongly affected by increasing NaCl contents of the microcosms after its evolution into the VBNC state. VBNCV. parahaemolyticuscells may undergo selected physiological changes such as the modulation of membrane potential and re-arrangement of cellular composition.
MITF reprograms the extracellular matrix and focal adhesion in melanoma
Authors: Dilshat Ramile , Fock Valerie , Kenny Colin , Gerritsen Ilse , Lasseur Romain Maurice Jacques , Travnickova Jana , Eichhoff Ossia , Cerny Philipp , Möller Katrin , Sigurbjörnsdóttir Sara , Kirty Kritika , Einarsdottir Berglind Ósk , Cheng Phil F. , Levesque Mitchell , Cornell Robert , Patton E. Elizabeth , Larue Lionel , de Tayrac Marie , Magnúsdóttir Erna , Ogmundsdottir Margrét H. , Steingrímsson Eiríkur
Published: July 2020

The microphthalmia associated transcription factor (MITF) is a critical regulator of melanocyte development and differentiation. It also plays an important role in melanoma where it has been described as a molecular rheostat that, depending on activity levels, allows reversible switching between different cellular states. Here we show that MITF directly represses the expression of genes associated with the extracellular matrix (ECM) and focal adhesion pathways in human melanoma cells as well as of regulators of epithelial to mesenchymal transition (EMT) such as CDH2, thus affecting cell morphology and cell-matrix interactions. Importantly, we show that these effects of MITF are reversible, as expected from the rheostat model. The number of focal adhesion points increased upon MITF knockdown, a feature observed in drug resistant melanomas. Cells lacking MITF are similar to the cells of minimal residual disease observed in both human and zebrafish melanomas. Our results suggest that MITF plays a critical role as a repressor of gene expression and is actively involved in shaping the microenvironment of melanoma cells in a cell-autonomous manner.
Identification of areas of very high biodiversity value to achieve the EU Biodiversity Strategy for 2030 key commitments
Authors: Miu Iulia V. , Rozylowicz Laurentiu , Popescu Viorel D. , Anastasiu Paulina
Published: July 2020

Background

The European Union strives to increase protected areas of the EU terrestrial surface to 30% by year 2030, of which one third should be strictly protected. Designation of the Natura 2000 network, the backbone of nature protection in the EU, was mostly an expert-opinion process with little systematic conservation planning. The designation of the Natura 2000 network in Romania followed the same non-systematic approach, resulting in a suboptimal representation of invertebrates and plants. To help identify areas with very high biodiversity without repeating past planning missteps, we present a reproducible example of spatial prioritization using Romania’s current terrestrial Natura 2000 network and coarse-scale terrestrial species occurrence.

Methods

We used 371 terrestrial Natura 2000 Sites of Community Importance (Natura 2000 SCI), designated to protect 164 terrestrial species listed under Annex II of Habitats Directive in Romania in our spatial prioritization analyses (marine Natura 2000 sites and species were excluded). Species occurrences in terrestrial Natura 2000 sites were aggregated at a Universal Traverse Mercator spatial resolution of 1 km2. To identify priority terrestrial Natura 2000 sites for species conservation, and to explore if the Romanian Natura 2000 network sufficiently represents species included in Annex II of Habitats Directive, we used Zonation v4, a decision support software tool for spatial conservation planning. We carried out the analyses nationwide (all Natura 2000 sites) as well as separately for each biogeographic region (i.e., Alpine, Continental, Pannonian, Steppic and Black Sea).

Results

The results of spatial prioritization of terrestrial Natura 2000 vary greatly by planning scenario. The performance of national-level planning of top priorities is minimal. On average, when 33% of the landscape of Natura 2000 sites is protected, only 20% of the distribution of species listed in Annex II of Habitats Directive are protected. As a consequence, the representation of species by priority terrestrial Natura 2000 sites is lessened when compared to the initial set of species. When planning by taxonomic group, the top-priority areas include only 10% of invertebrate distribution in Natura 2000. When selecting top-priority areas by biogeographical region, there are significantly fewer gap species than in the national level and by taxa scenarios; thusly, the scenario outperforms the national-level prioritization. The designation of strictly protected areas as required by the EU Biodiversity Strategy for 2030 should be followed by setting clear objectives, including a good representation of species and habitats at the biogeographical region level.
Chimpanzee (Pan troglodytes verus) density and environmental gradients at their biogeographical range edge
Authors: Wessling Erin G. , Dieguez Paula , Llana Manuel , Pacheco Liliana , Pruetz Jill D. , Kühl Hjalmar S.
Published: July 2020

Identifying ecological gradients at the range edge of a species is an essential step in revealing the underlying mechanisms and constraints that limit the species’ geographic range. We aimed to describe the patterns of variation in chimpanzee (Pan troglodytes verus) density and habitat characteristics perpendicular to the northern edge of their range and to investigate potential environmental mechanisms underlying chimpanzee distribution in a savanna-mosaic habitat. We estimated chimpanzee densities at six sites forming a 126 km latitudinal gradient at the biogeographical range edge of the western chimpanzee in the savanna-mosaic habitats of southeastern Senegal. To accompany these data, we used systematically placed vegetation plots to characterize the habitats at each site for habitat heterogeneity, tree density and size, floral assemblages, among other variables. We found that both biotic and abiotic factors are potential determinants of the chimpanzee range limit in this ecoregion. Specifically, chimpanzee-occupied landscapes at the limit had smaller available floral assemblages, less habitat heterogeneity, and contained fewer closed canopy habitats in which chimpanzees could seek refuge from high temperatures than landscapes farther from the range limit. This pattern was accompanied by a decline in chimpanzee density with increasing proximity to the range limit. Our results provide several indications of the potential limits of food species diversity, thermal refuge, and water availability to the chimpanzee niche and the implications of these limits for chimpanzee biogeography, especially in the face of climate change predictions, as well as to species distributional modeling more generally.
Dynamics in Natural and Designed Elastins and Their Relation to Elastic Fiber Structure and Recoil
Authors: Carvajal Ma. Faye Charmagne A. , Preston Jonathan M. , Jamhawi Nour M. , Sabo T. Michael , Bhattacharya Shibani , Aramini James M. , Wittebort Richard J. , Koder Ronald L.
Published: July 2020

Elastin fibers assemble in the extracellular matrix from the precursor protein tropoelastin and provide the flexibility and spontaneous recoil required for arterial function. Unlike many proteins, a structure-function mechanism for elastin has been elusive. We have performed detailed NMR relaxation studies of the dynamics of the minielastins24x′and20x′using solution NMR, and of purified bovine elastin fibers in the presence and absence of mechanical stress using solid state NMR. The low sequence complexity of the minielastins enables us to determine dynamical timescales and degrees of local ordering with residue-specific resolution in the cross-link and hydrophobic modules using NMR relaxation. We find an extremely high degree of disorder, with order parameters for the entirety of the hydrophobic domains near zero, resembling that of simple chemical polymers and less than the order parameters that have been observed in other intrinsically disordered proteins. We find that backbone order parameters in natural, purified elastin fibers are comparable to those found in24x′and20x′in solution. The difference in dynamics, compared to the minielastins, is that backbone correlation times are significantly slowed in purified elastin. Moreover, when elastin is mechanically stretched, the high chain disorder in purified elastin is retained - showing that any change in local ordering is below that detectable in our experiment. Combined with our previous finding of a 10-fold increase in the ordering of water when fully hydrated elastin fibers are stretched by 50%, these results support the hypothesis that stretch induced solvent ordering, i.e., the hydrophobic effect, is a key player in the elastic recoil of elastin as opposed to configurational entropy loss.

SIGNIFICANCE

Elastin is responsible for the spontaneous recoil of arterial walls that is necessary for cardiovascular function. Despite this critical role, the mechanism driving entropic recoil has remained unclear. Elastin is unusual in that it is intrinsically disordered in both soluble and fibrous forms. Using NMR, we have determined the timescales and amplitudes of dynamics in two soluble elastin mimetics and in relaxed and stretched states of purified bovine elastin fibers. Although dynamical timescales are different, both the soluble elastin mimetic and fibrillar elastin display an exceptionally high degree of disorder. No detectable increase in protein ordering was observed upon stretching, suggesting that entropic recoil is primarily driven by the hydrophobic effect and not configurational entropy loss.
Heparan sulfate assists SARS-CoV-2 in cell entry and can be targeted by approved drugs in vitro
Authors: Zhang Qi , Chen Catherine Z. , Swaroop Manju , Xu Miao , Wang Lihui , Lee Juhyung , Wang Amy Q. , Pradhan Manisha , Hagen Natalie , Chen Lu , Shen Min , Luo Zhiji , Xu Xin , Xu Yue , Huang Wenwei , Zheng Wei , Ye Yihong
Published: July 2020

The cell entry of SARS-CoV-2 has emerged as an attractive drug repurposing target for COVID-19. Here we combine genetics and chemical perturbation to demonstrate that ACE2-mediated entry of SARS-CoV and CoV-2 requires the cell surface heparan sulfate (HS) as an assisting cofactor: ablation of genes involved in HS biosynthesis or incubating cells with a HS mimetic both inhibit Spike-mediated viral entry. We show that heparin/HS binds to Spike directly, facilitates the attachment of viral particles to the cell surface to promote cell entry. We screened approved drugs and identified two classes of inhibitors that act via distinct mechanisms to target this entry pathway. Among the drugs characterized, Mitoxantrone is a potent HS inhibitor, while Sunitinib and BNTX disrupt the actin network to indirectly abrogate HS-assisted viral entry. We further show that drugs of the two classes can be combined to generate a synergized activity against SARS-CoV-2-induced cytopathic effect. Altogether, our study establishes HS as an attachment factor that assists SARS coronavirus cell entry, and reveals drugs capable of targeting this important step in the viral life cycle.
Genome analyses reveal the hybrid origin of the staple food crop white Guinea yam
Authors: Sugihara Yu , Darkwa Kwabena , Yaegashi Hiroki , Natsume Satoshi , Shimizu Motoki , Abe Akira , Hirabuchi Akiko , Ito Kazue , Oikawa Kaori , Tamiru-Oli Muluneh , Ohta Atsushi , Matsumoto Ryo , Paterne Agre , De Koeyer David , Pachakkil Babil , Yamanaka Shinsuke , Muranaka Satoru , Takagi Hiroko , White Ben , Asiedu Robert , Innan Hideki , Asfaw Asrat , Adebola Patrick , Terauchi Ryohei
Published: July 2020

White Guinea yam (Dioscorea rotundata) is an important staple tuber crop of West Africa. However, its origin remains unclear. In this study, we re-sequenced 336 accessions of white Guinea yam and compared them with the sequences of the wildDioscoreaspecies using an improved reference genome sequence ofD. rotundata. Our results suggest a hybrid origin of white Guinea yam from crosses between the rainforest wild speciesD. praehensilisand the savannah-adaptedD. abyssinica. We identified a higher genomic contribution fromD. abyssinicain the sex chromosome of Guinea yam and an extensive introgression around theSWEETIEgene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improvement of this crop through molecular breeding.
Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins
Authors: Siddiqui Mohammad Quadir , Badmalia Maulik D. , Patel Trushar R.
Published: July 2020

Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.
Development of a genetically-encoded oxytocin sensor
Authors: Mignocchi Neymi , Krüssel Sarah , Jung Kanghoon , Lee Dongmin , Kwon Hyung-Bae
Published: July 2020

Oxytocin (OXT) is a neuropeptide originating in the paraventricular nucleus (PVN) of the hypothalamus, with a role in influencing various social behaviors. However, pinpointing its actions only during the time animals are performing specific behaviors has been difficult to study. Here we developed an optogenetic gene expression system designed to selectively label neuronal populations activated by OXT in the presence of blue-light, named “OXTR-iTango2”. The OXTR-iTango2 was capable of inducing gene expression of a reporter gene in both human embryonic kidney (HEK) cells and neurons in a quantitative manner.In vivoexpression of OXTR-iTango2 selectively labeled OXT-sensitive neurons in a blue-light dependent manner. Furthermore, we were able to detect a subset of dopamine (DA) neurons in the ventral tegmental area (VTA) that receive OXT activation during social interaction. Thus, we provide a genetically-encoded, scalable optogenetic toolset to target neural circuits activated by OXT in behaving animals with a high temporal resolution.