bluuebunny/crossref_metadata_2025 huggingface dataset:
How rare and common risk variation jointly affect liability for autism spectrum disorder
Authors: Klei Lambertus , McClain Lora Lee , Mahjani Behrang , Panayidou Klea , De Rubeis Silvia , Säll Grahnat Anna-Carin , Karlsson Gun , Lu Yangyi , Melhem Nadine , Xu Xinyi , Reichenberg Abraham , Sandin Sven , Hultman Christina M. , Buxbaum Joseph D. , Roeder Kathryn , Devlin Bernie
Published: November 2020

Background

Genetic studies have implicated rare and common variation in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability. How these rare and common risk variants jointly affect liability for individuals requires further study.

Methods

To explore how common and rare variants jointly affect liability, we assessed two cohorts of ASD families characterized for rare and common genetic variation (Simons Simplex Collection and Population-Based Autism Genetics & Environment Study). We analyzed data from 3,011 affected subjects, as well as two cohorts of unaffected individuals characterized for common genetic variation: 3,011 subjects matched for ancestry to ASD subjects; and 11,950 subjects for estimating allele frequencies. We used genetic scores, which assessed the relative burden of common genetic variation affecting risk for ASD (henceforth burden), and determined how this burden was distributed among three subpopulations: ASD subjects who carry a rare damaging variant implicated in risk for ASD (mutation carriers); ASD subjects who do not (non-carriers); and unaffected subjects, who are assumed to be non-carriers.

Results

Burden harbored by ASD subjects is stochastically greater than that harbored by control subjects. For mutation carriers, their average burden is intermediate between non-carrier ASD and control subjects. Both carrier and non-carrier ASD subjects have greater burden, on average, than control subjects. The effects of common and rare variants likely combine additively to determine individual-level liability.

Limitations

Only 258 ASD subjects were known mutation carriers. This relatively small subpopulation limits this study to characterizing general patterns of burden, as opposed to effects of specific mutations or genes. Also, a small fraction of subjects that are categorized as non-carriers could be mutation carriers.

Conclusions

Liability arising from common and rare risk variation likely combine additively to determine risk for any individual diagnosed with ASD. On average, ASD subjects carry a substantial burden of common risk variation, even if they also carry a rare mutation affecting risk.
Retrospectivein silicoHLA predictions from COVID-19 patients reveal alleles associated with disease prognosis
Authors: Warren René L. , Birol Inanç
Published: November 2020

Background

The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants.

Methods

By combining the predictive power of multiplein silicoHLA predictors, we have previously identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small cohorts at the COVID-19 pandemic onset. Since then, newer and larger patient cohorts with controls and associated demographic and clinical data have been deposited in public repositories. Here, we report on HLA-I and HLA-II alleles, along with their associated risk significance in one such cohort of 126 patients, including COVID-19 positive (n=100) and negative patients (n=26).

Results

We recapitulate an enrichment of DPA1*02:02 in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p=0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes reveal nominally significant risk associations with A*11:01 (FET p=0.0078), C*04:01 (FET p=0.0087) and DQA1*01:02 (FET p=0.0121).

Conclusions

While enrichment of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with the latter three alleles tend to fare worse overall. This is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0023), and may hold potential clinical value.
Estimating the Financial Impact of Gene Therapy*
Authors: Wong Chi Heem , Li Dexin , Wang Nina , Gruber Jonathan , Conti Rena , Lo Andrew W.
Published: November 2020

We assess the potential financial impact of future gene therapies by identifying the 109 late-stage gene therapy clinical trials currently underway, estimating the prevalence and incidence of their corresponding diseases, developing novel mathematical models of the increase in quality-adjusted life years for each approved gene therapy, and simulating the launch prices and the expected spending of these therapies over a 15-year time horizon. The results of our simulation suggest that an expected total of 1.09 million patients will be treated by gene therapy from January 2020 to December 2034. The expected peak annual spending on these therapies is $25.3 billion, and the total spending from January 2020 to December 2034 is $306 billion. We decompose their annual estimated spending by treated age group as a proxy for U.S. insurance type, and consider the tradeoffs of various methods of payment for these therapies to ensure patient access to their expected benefits.
The effect of eviction moratoria on the transmission of SARS-CoV-2
Authors: Nande Anjalika , Sheen Justin , Walters Emma L , Klein Brennan , Chinazzi Matteo , Gheorghe Andrei , Adlam Ben , Shinnick Julianna , Tejeda Maria Florencia , Scarpino Samuel V , Vespignani Alessandro , Greenlee Andrew J , Schneider Daniel , Levy Michael Z , Hill Alison L
Published: November 2020

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess municipal eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.
Remote fingerstick blood collection for SARS-CoV-2 antibody testing
Authors: Garcia-Beltran Wilfredo F. , Miller Tyler E. , Kirkpatrick Grace , Nixon Andrea , Astudillo Michael G. , Yang Diane , Mahanta Lisa M. , Murali Mandakolathur , Dighe Anand , Lennerz Jochen , Thierauf Julia , Naranbhai Vivek , Iafrate A. John
Published: November 2020

The rapid worldwide spread of SARS-CoV-2 infection has propelled the accelerated development of serological tests that can detect anti-SARS-CoV-2 antibodies. These have been used for studying the prevalence and spread of infection in different populations, helping establish a recent diagnosis of COVID-19, and will likely be used to confirm humoral immunity after infection or vaccination. However, nearly all lab-based high-throughput SARS-CoV-2 serological assays require a serum sample from venous blood draw, limiting their applications and scalability. Here, we present a method that enables large scale SARS-CoV-2 serological studies by combining self or office collection of fingerprick blood with a volumetric absorptive microsampling device (Mitra, Neoteryx, LLC) with a high-throughput electrochemiluminescence-based SARS-CoV-2 total antibody assay (Roche Elecsys, Roche Diagnostics, Inc.) that is EUA approved for use on serum samples and widely used by clinical laboratories around the world. We found that the Roche Elecsys assay has a high dynamic range that allows for accurate detection of SARS-CoV-2 antibodies in serum samples diluted 1:20 as well as contrived dried blood extracts. Extracts of dried blood from Mitra devices acquired in a community seroprevalence study showed near identical sensitivity and specificity in detection of SARS-CoV-2 antibodies as compared to neat sera using predefined thresholds for each specimen type. Overall, this study affirms the use of Mitra dried blood collection device with the Roche Elecsys SARS-CoV-2 total antibody assay for remote or at-home testing as well as large-scale community seroprevalence studies.
Performance evaluation of the Simtomax®CoronaCheck rapid diagnostic test
Authors: Ducrest P. J. , Freymond A. , Segura J.-M.
Published: November 2020

The aim of this study was to evaluate the diagnostic performance of Simtomax®CoronaCheck, a serology rapid diagnostic test (RDT) for the detection of IgG and IgM against SARS-CoV-2. 48 plasma samples positive for SARS-CoV-2 based on RT-PCR and 98 negative control samples were studied. Diagnostic performance of the IgG/IgM RDT was assessed against RT-PCR and the electro-chemiluminescence immunoassay (ECLIA) Elecsys®Anti-SARS-CoV-2 total Ig. Overall, the RDT sensitivity was 92% (95% confidence interval [95%CI]: 79-97), specificity 97% (95% CI: 91-99%), PPV 94% (95% CI: 81-98) and the NPV 96% (95% CI: 89-99). When considering only samples collected ≥ 15 days post-symptoms (DPS), the sensitivity increased to 98% (95%CI: 86-100) and the specificity was 97% (95% CI: 91-99%). Two samples with 180 DPS were still positive for IgG. Globally, this IgG/IgM RDT displayed a high diagnostic accuracy for SARS-CoV-2 IgG/IgM detection in plasma samples in high COVID-19 prevalence settings. It could be effectively used, in absence of facilities for routine diagnostic serology, for samples with a DPS between 15 and 180 days.

Highlights

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The rapid diagnostic test Simtomax CoronaCheck displays a high sensitivity of 98% and a high specificity of 97% for SARS-CoV-2 IgG/IgM detection in plasma samples after 15 days post-symptoms.

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The rapid diagnostic test Simtomax CoronaCheck can detect SARS-CoV-2 antibodies in plasma up to 180 days after symptom onset.

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The rapid diagnostic test Simtomax CoronaCheck could be effectively used as an alternative to serological analysis using laboratory facilities.
Psychological and social impact of COVID-19 in Pakistan: Need for Gender Responsive Policies
Authors: Rabbani Fauziah , Khan Hyder Ali , Piryani Suneel , Khan Areeba Raza , Abid Fahad
Published: November 2020

BACKGROUND

COVID-19 has rapidly crossed borders, infecting people throughout the world. Women may be especially vulnerable to depression and anxiety due to the pandemic,

AIMS

This study attempted to assess how gender impacts risk perceptions, anxiety levels behavioral responses to the COVID 19 pandemic in Pakistan in order to recommend gender responsive health policies

METHODS

A cross-sectional online survey was conducted. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale (HADS), and questions on their risk perceptions, preventive behavior and information exposure. Regression analysis was used to assess effects of factors such as age, gender and household income on anxiety levels.

RESULTS

Of the 1390 respondents, 478 were women, and 913 were men. Women considered their chances of survival to be relatively lower than men (59 % women vs 73% men). They were also more anxious (62% women vs 50% men), and more likely to adopt precautionary behavior, such as avoiding going to the hospital (78% women vs. 71% men), not going to work (72% women and 57% men), and using disinfectants (93% women and 86% men). Men were more likely to trust friends, family and social media as reliable sources of COVID-19 information, while women were more likely to trust doctors.

CONCLUSION

Women experience a disproportion burden of the psychological and social impact of the pandemic compared to men. Involving doctors in healthcare communication targeting women, might prove effective. Social media and radio programs may be effective in disseminating information related to COVID among men.
Features of creatine-kinase in COVID-19 patients within various specific periods: A cohort study
Authors: Wan Shanshan , Qu Gaojing , Yu Hui , Zhu Haoming , Huang Guoxin , Chen Lei , Zhang Meiling , Liu Jiangtao , Pei Bin
Published: November 2020

Background

Coronavirus disease 2019 (COVID-19) has been declared as a threat to the global. Due to the lack of efficient treatments, indicators were urgently needed during the evolvement of disease to analyze the illness and prognosis, and prevent the aggravation of COVID-19.

Methods

Patients’ general information, clinical type, all CK values and outcome were collected. CK value of all cases during disease course started from different initial time were analyzed.

Results

All cases underwent 504 tests of CK since symptom onset and the median value was 51.7 (35.0-91.5) U/L. The first median value on the day 8 from exposure onset was 78.1 (69.1-85.8) U/L then showed an upward trend from the day 8 to the day 12 (reaching a peak of 279.3 U/L), finally showed a fluctuation decline after the day 12. The CK median value in critical cases reached the peak (625.5 U/L) on the transforming date, and then decreased rapidly to the normal range. Before death, the CK median value in dead cases firstly increased until the day −14 with a peak as 470.0 U/L, then decreased with fluctuation until day −2, and finally increased again on the day 0.

Conclusions

CK reached its peak on the day when it became critical type, dynamic detection of CK can guide clinical judgment of prognosis. The increase of CK is a high risk factor of death. Severe cell damage 2 weeks before death might determines the outcome of the disease even if CK drops to the normal range afterward.
The characteristics of HIV-positive patients with mild/asymptomatic and moderate/severe course of COVID-19 disease – a report from Central and Eastern Europe
Authors: Kowalska Justyna D. , Kase Kerstin , Vassilenko Anna , Harxhi Arjan , Lakatos Botond , Lukić Gordana Dragović , Verhaz Antonija , Yancheva Nina , Dumitrescu Florentina , Jilich David , Machala Ladislav , Skrzat-Klapaczyńska Agata , Matulionyte Raimonda
Published: November 2020

Background

There is currently no evidence suggesting that COVID-19 takes a different course in HIV-positive patients on antiretroviral treatment compared to the general population. However, little is known about the relation between specific HIV-related factors and the severity of the COVID-19 disease.

Methods

We performed a retrospective analysis of cases collected through an on-line survey distributed by the Euroguidelines in Central and Eastern Europe Network Group. In statistical analyses characteristics of HIV-positive patients asymptomatic/moderate and moderate/severe course were compared.

Results

In total 34 HIV-positive patients diagnosed with COVID-19 were reported by 12 countries (Estonia, Czech Republic, Lithuania, Albania, Belarus, Romania, Serbia, Bosnia and Herzegovina, Poland, Russia, Hungary, Bulgaria). Asymptomatic courses of COVID-19 were reported in four (12%) cases, 11 (32%) patients presented with mild disease not requiring hospitalization, moderate disease with respiratory and/or systemic symptoms was observed in 14 (41%) cases, and severe disease with respiratory failure was found in five (15%) patients. The only HIV-related characteristics differentiating a moderate/severe course of the disease from asymptomatic/mild disease course was the use of or PI or NNRTI as part of the cART regimen (40.0% vs. 5.3%, p=0.0129 for PI and 31.6 % vs. 0.0%, p= 0.0239 for NNRTI).

Conclusions

In our analyses HIV viral suppression and immunological status were not playing a role in the course of COVID-19 disease. On the contrary the cART regimen could contribute to severity of SARS-CoV-2 infection. Large and prospective studies are necessary to further investigate this relations.
A possible stimulus to induce SPAWNING in Ezo abaloneHaliotis discus hannaiduring stormy weather: Fenton reaction induces spawning behavior
Authors: Matsumoto Yukio , Yatsuya Kousuke
Published: November 2020

Synchronous spawning is an important behavior to increase fertilization success of invertebrates with external fertilization. Previous work has shown that it is possible to induce spawning behavior using free radicals in tank experiments, but the stimulus for spawning in the wild is not fully understood. Ezo abaloneHaliotis discus hannaimainly spawn during stormy weather. Rainwater contains H2O2and iron (II) ions (Fe2+). We propose that during stormy weather water layers in the ocean are mixed and the surface layer containing H2O2and Fe2+interacts with the ocean bottom; this leads to conditions suitable for the Fenton reaction to occur. Hydroxyl radicals (·OH) are generated during the oxidization of Fe2+by H2O2and we hypothesized these induce spawning behavior of abalone in the wild. This study observed thatH. discus hannaireleased eggs after salinity decreased due to the rainfall during stormy conditions. In addition, our tank experiment demonstrated that ·OH generated by the Fenton reaction induced synchronous spawning behavior between the sexes. This study provides a new hypothesis about control of synchronous spawning inH. discus hannaiand the results could be applicable to other invertebrates.
Genome ARTIST_v2 software – a support for annotation of class II natural transposons in new sequenced genomes
Authors: Ecovoiu Alexandru Al. , Ghita Iulian Cristian , Chifiriuc David Ioan Mihail , Ghionoiu Iulian Constantin , Ciuca Andrei Mihai , Bologa Alexandru Marian , Ratiu Attila Cristian
Published: November 2020

Transposon annotation is a very dynamic field of genomics and various tools assigned to support this bioinformatics endeavor were reported. Genome ARTIST (GA) software was initially developed for mapping artificial transposons mobilized during insertional mutagenesis projects. Now, the new functions of GA_v2 qualify it as an effective companion for mapping and annotation of class II natural transposons in assembled genomes, contigs or sequencing reads.

Tabular export of mapping and annotation data for subsequent high-throughput data analysis, the export of a list of flanking sequences around either the coordinates of insertion or around the target site duplications (TSDs) and generation of a consensus sequence for the respective flanking sequences are all key assets of GA_v2.

Additionally, we developed two accompanying short scripts that enable the user to annotate transposons existent in assembled genomes and to use various annotation offered by FlyBase forDrosophila melanogastergenome.

Herein, we present the applicability of GA_v2 for a preliminary annotation of the class II transposon P-element in the genome ofD. melanogasterstrain Horezu, Romania, which was sequenced with Nanopore technology in our laboratory. Our results point that GA_v2 is a reliable tool to be integrated in pipelines designed to perform transposon annotation in new sequenced genomes.

GA_v2 is open source software compatible with Ubuntu, Mac OS and Windows and is available athttps://github.com/genomeartist/genomeartistand atwww.genomeartist.ro.
The unbiased estimation of the fraction of variance explained by a model
Authors: Pospisil Dean A. , Bair Wyeth
Published: November 2020

The correlation coefficient squared,r2, is often used to validate quantitative models on neural data. Yet it is biased by trial-to-trial variability: as trial-to-trial variability increases, measured correlation to a model’s predictions decreases; therefore, models that perfectly explain neural tuning can appear to perform poorly. Many solutions to this problem have been proposed, but some prior methods overestimate model fit, the utility of even the best performing methods is limited by the lack of confidence intervals and asymptotic analysis, and no consensus has been reached on which is the least biased estimator. We provide a new estimator,, that outperforms all prior estimators in our testing, and we provide confidence intervals and asymptotic guarantees. We apply our estimator to a variety of neural data to validate its utility. We find that neural noise is often so great that confidence intervals of the estimator cover the entire possible range of values ([0, 1]), preventing meaningful evaluation of the quality of a model’s predictions. We demonstrate the use of the signal-to-noise ratio (SNR) as a quality metric for making quantitative comparisons across neural recordings. Analyzing a variety of neural data sets, we find ~ 40% or less of some neural recordings do not pass even a liberal SNR criterion.

Author Summary

Quantifying the similarity between a model and noisy data is fundamental to the verification of advances in scientific understanding of biological phenomena, and it is particularly relevant to modeling neuronal responses. A ubiquitous metric of similarity is the correlation coefficient. Here we point out how the correlation coefficient depends on a variety of factors that are irrelevant to the similarity between a model and data. While neuroscientists have recognized this problem and proposed corrected methods, no consensus has been reached as to which are effective. Prior methods have wide variation in their precision, and even the most successful methods lack confidence intervals, leaving uncertainty about the reliability of any particular estimate. We address these issues by developing a new estimator along with an associated confidence interval that outperforms all prior methods.
Occurrence but not intensity of mortality rises towards the climatic trailing edge of tree species ranges in European forests
Authors: Changenet Alexandre , Ruiz-Benito Paloma , Ratcliffe Sophia , Fréjaville Thibaut , Archambeau Juliette , Porte Annabel J. , Zavala Miguel A. , Dahlgren Jonas , Lehtonen Aleksi , Garzón Marta Benito
Published: November 2020

Aim

Tree mortality is increasing worldwide, leading to changes in forest composition and altering global biodiversity. Yet, due to the multi-faceted stochastic nature of tree mortality, large-scale spatial patterns of mortality across species ranges and their underlying drivers remain difficult to understand. Our main goal is to describe the geographical patterns and drivers of the occurrence and intensity of tree mortality in Europe. We hypothesize that the occurrence of mortality represents background mortality and is higher in the margin than the core populations, whereas the intensity of mortality could have a more even distribution according to the spatial and temporal stochasticity of die-off events.

Location

Europe (Spain, France, Germany, Belgium, Sweden and Finland)

Time period

1981 to 2014.

Major taxa studied

More than 1.5 million trees belonging to 20 major forest tree species

Methods

We develop hurdle models to tease apart the occurrence and intensity of tree mortality in National Forest Inventory plots at range-wide scale. The occurrence of mortality indicates that at least one tree has died in the plot and the intensity of mortality refers to the number of trees dead per plot.

Results

The highest mortality occurrence was found in peripheral regions and the climatic trailing edge linked with drought, whereas the intensity of mortality was driven by competition, drought and high temperatures and was uniformly scattered across species ranges.

Main conclusions

Our findings provide a new perspective in our understanding of tree mortality across species ranges. We show that tree background mortality but not die-off is generally higher in the trailing edge populations, but whether other demographic traits such as growth, reproduction and regeneration would also decrease at the trailing edge of European tree populations needs to be explored.
Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer
Authors: Chauhan Lakshya , Ram Uday , Hari Kishore , Jolly Mohit Kumar
Published: November 2020

Phenotypic (non-genetic) heterogeneity has significant implications for development and evolution of organs, organisms, and populations. Recent observations in multiple cancers have unravelled the role of phenotypic heterogeneity in driving metastasis and therapy recalcitrance. However, the origins of such phenotypic heterogeneity are poorly understood in most cancers. Here, we investigate a regulatory network underlying phenotypic heterogeneity in small cell lung cancer, a devastating disease with no molecular targeted therapy. Discrete and continuous dynamical simulations of this network reveal its multistable behavior that can explain co-existence of four experimentally observed phenotypes. Analysis of the network topology uncovers that multistability emerges from two teams of players that mutually inhibit each other but members of a team activate one another, forming a ‘toggle switch’ between the two teams. Deciphering these topological signatures in cancer-related regulatory networks can unravel their ‘latent’ design principles and offer a rational approach to characterize phenotypic heterogeneity in a tumor.
Climate influences the response of community functional traits to local conditions
Authors: Guzman Laura Melissa , Trzcinski M. Kurtis , Barberis Ignacio M. , Céréghino Régis , Srivastava Diane S. , Gilbert Benjamin , Pillar Valério D. , de Omena Paula M. , MacDonald A. Andrew M. , Corbara Bruno , Leroy Céline , Bautista Fabiola Ospina , Romero Gustavo Q. , Kratina Pavel , Debastiani Vanderlei J. , Gonçalves Ana Z. , Marino Nicholas A.C. , Farjalla Vinicius F. , Richardson Barbara A. , Richardson Michael J. , Dézerald Olivier , Piccoli Gustavo C.O. , Jocqué Merlijn , Montero Guillermo
Published: November 2020

Functional traits determine an organism’s performance in a given environment and as such determine which organisms will be found where. Species respond to local conditions, but also to larger scale gradients, such as climate. Trait ecology links these responses of species to community composition and species distributions. Yet, we often do not know which environmental gradients are most important in determining community trait composition at either local or biogeographical scales, or their interaction. Here we quantify the relative contribution of local and climatic conditions to the structure and composition of functional traits found within bromeliad invertebrate communities. We conclude that climate explains more variation in invertebrate trait composition within bromeliads than does local conditions. Importantly, climate mediated the response of traits to local conditions; for example, invertebrates with benthic life-history traits increased with bromeliad water volume only under certain precipitation regimes. Our ability to detect this and other patterns hinged on the compilation of multiple fine-grained datasets, allowing us to contrast the effect of climate vs. local conditions. We suggest that, in addition to sampling communities at local scales, we need to aggregate studies that span large ranges in climate variation in order to fully understand trait filtering at local, regional and global scales.
Closing the research-implementation gap using data science tools: a case study with pollinators of British Columbia
Authors: Guzman Laura Melissa , Kelly Tyler , Morandin Lora , M’Gonigle Leithen , Elle Elizabeth
Published: November 2020

A challenge in conservation is the gap between knowledge generated by researchers and the information being used to inform conservation practice. This gap, widely known as the research-implementation gap, can limit the effectiveness of conservation practice. One way to address this is to design conservation tools that are easy for practitioners to use. Here, we implement data science methods to develop a tool to aid in conservation of pollinators in British Columbia. Specifically, in collaboration with Pollinator Partnership Canada, we jointly develop an interactive web app, the goal of which is two-fold: (i) to allow end users to easily find and interact with the data collected by researchers on pollinators in British Columbia (prior to development of this app, data were buried in supplements from individual research publications) and (ii) employ up to date statistical tools in order to analyse phenological coverage of a set of plants. Previously, these tools required high programming competency in order to access. Our app provides an example of one way that we can make the products of academic research more accessible to conservation practitioners. We also provide the source code to allow other developers to develop similar apps suitable for their data.
Hippocampus shape across the healthy lifespan and its relationship with cognition
Authors: Bussy Aurelie , Patel Raihaan , Plitman Eric , Tullo Stephanie , Salaciak Alyssa , Bedford Saashi A. , Farzin Sarah , Béland Marie-Lise , Valiquette Vanessa , Kazazian Christina , Tardif Christine L. , Devenyi Gabriel A. , Chakravarty Mallar
Published: November 2020

The study of the hippocampus across the healthy adult lifespan has rendered inconsistent findings. While volumetric measurements have often been a popular technique for analysis, more advanced morphometric techniques have demonstrated compelling results that highlight the importance and improved specificity of shape-based measures. Here, the MAGeT Brain algorithm was applied on 134 healthy individuals aged 18-81 years old to extract hippocampal subfield volumes and hippocampal shape measurements, notably: local surface area (SA) and displacement. We used linear, second or third order natural splines to examine the relationships between hippocampal measures and age. In addition, partial least squares analyses were performed to relate measurements with cognitive and demographic information. Volumetric results indicated a relative preservation of the right cornus ammonis 1 with age and a global volume reduction linked with older age, female sex, lower levels of education and cognitive performance. Vertex-wise analysis demonstrated an SA preservation in the anterior hippocampus with a peak during the sixth decade, while the posterior hippocampal SA gradually decreased across lifespan. Overall, SA decrease was linked to older age, female sex and, to a lesser extent lower levels of education and cognitive performance. Outward displacement in the lateral hippocampus and inward displacement in the medial hippocampus were enlarged with older age, lower levels of cognition and education, indicating an accentuation of the hippocampal “C” shape with age. Taken together, our findings suggest that vertex-wise analyses have higher spatial specifity and that sex, education and cognition are implicated in the differential impact of age on hippocampal subregions throughout its antero-posterior and medial-lateral axes.
Oscillatory activity in alpha/beta frequencies coordinates auditory and prefrontal cortices during extinction learning
Authors: Gritton Howard J. , Nocon Jian C. , James Nicholas M. , Lowet Eric , Abdulkerim Moona , Sen Kamal , Han Xue
Published: November 2020

Cortical synchrony is theorized to contribute to communication between connected networks during executive functioning. To understand the functional role of neural synchrony in cognitive flexibility, we recorded from auditory cortex (AC) and medial prefrontal cortex (mPFC), while mice performed an auditory extinction learning task. We found that while animals gradually showed reduced responding to the unrewarded tone over hundreds of trials, the power of local field potential (LFP) oscillations (8-18 Hz, centered at alpha/beta frequencies) in AC and mPFC exhibited immediate and robust increases, prior to behavioral changes. The strength of LFP alpha/beta power in the mPFC, but not AC, was strongly correlated with the behavioral performance that mice would achieve later in the training session. Further, we found that coherence between AC and mPFC at 8-18Hz was selectively enhanced only after mice learned to suppress licking, and this LFP coherence increase coincided with a reduction in spiking rate for the unrewarded tone in AC. These results reveal that enhanced interactions between PFC and AC is an inherent property of auditory discrimination learning, and that coordinated alpha/beta oscillations contribute to cognitive flexibility.
A nonsense mutation inTFECis the likely cause of the recessive piebald phenotype in ball pythons (Python regius)
Authors: Garcia-Elfring Alan , Roffey Heather L. , Hendry Andrew P. , Barrett Rowan D. H.
Published: November 2020

Captive-bred ball pythons (Python regius) represent a powerful model system for studying the genetic basis of colour variation and Mendelian phenotypes in vertebrates. Although hundreds of Mendelian phenotypes (colour morphs) affecting colouration and patterning have been described for ball pythons, the genes causing these colour morphs remain unknown. Here, we used crowdsourcing of samples from commercial ball python breeders to investigate the genetic basis of a classic phenotype found in the pet trade, the piebald [characterized by dorsolateral patches of unpigmented (white) skin]. We used whole-genome sequencing of pooled samples followed by population genetic methods to delineate the genomic region containing the causal gene. We identifiedTFECof the MIT-family of transcription factors as a candidate gene. Functional annotation of SNPs identified a nonsense mutation inTFEC, which we conclude is the likely causal variant for the piebald phenotype. Our work shows that ball python colour morphs have the potential to be an excellent model system for studying the genetic basis of pigment variation in vertebrates, and highlights how collaborations with commercial breeders can accelerate discoveries.
Natural isotope correction improves analysis of protein modification dynamics
Authors: Dietze Jörn , van Pijkeren Alienke , Egger Anna-Sophia , Ziegler Mathias , Kwiatkowski Marcel , Heiland Ines
Published: November 2020

Stable isotope labelling in combination with high resolution mass spectrometry approaches are increasingly used to analyse both metabolite and protein modification dynamics. To enable correct estimation of the resulting dynamics it is critical to correct the measured values for naturally occurring stable isotopes, a process commonly called isotopologue correction or deconvolution. While the importance of isotopologue correction is well recognized in metabolomics, it has received far less attention in proteomics approaches. Although several tools exist that enable isotopologue correction of mass spectrometry data, the majority is tailored for the analysis of low molecular weight metabolites. We here present PICor which has been developed for isotopologue correction of complex isotope labelling experiments in proteomics or metabolomics and demonstrate the importance of appropriate correction for accurate determination of protein modifications dynamics, using histone acetylation as an example.
Evaluation of azithromycin or hydroxychloroquine plus azithromycin combination therapy on cardiac conduction and function in guinea pigs
Authors: Li Xiang , Tan Weijiang , Zheng Shuang , Sun Huan , Zhang Xiaoshen , Li Xiaohui , Chen Honghua , Ren Xuecong , He Tianzhen , Zhu Caiyi , Zhang Yu , Yang Feng Hua
Published: November 2020

Background

In the early stages of the coronavirus disease pandemic, the anti-malarial drug hydroxychloroquine (HCQ) and the antibiotic drug azithromycin (AZM) were widely used as emerging treatments. However, controversial cardiac toxicity results obtained from clinical trials and epidemic studies suggest that the cardiotoxicity of these two drugs should be re-evaluated. In the present study, we aimed to assess the impact of a short course of AZM or HCQ + AZM combination treatment on ECG and cardiac function in healthy guinea pigs.

Methods

Thirty-two male guinea pigs were randomly divided into four groups: control; AZM; HCQ; and HCQ + AZM groups. At 3, 6, and 9 days after treatment, electrocardiograms (ECGs) and echocardiographic techniques were used to determine important ECG parameters and cardiac functional parameters of the left ventricle (including posterior wall thickness, end systolic/end diastolic volume, ejection fraction, and fractional shortening).

Results

Although AZM decreased the heart rates of guinea pigs on day 9 (under anesthetized conditions), HCQ + AZM decreased heart rates on days 3, 6, and 9. The corrected QT intervals of guinea pigs after AZM and HCQ + AZM treatments were significantly increased, compared with CON and HCQ treatment respectively, on days 3, 6, and 9. However, QRS complex durations were not significantly different between the groups. AZM significantly decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) on days 3, 6, and 9, whereas HCQ + AZM only decreased LVEF and LVFS on day 9. Posterior wall thickness and of the left ventricle in the diastolic and systolic states were not significantly different between these groups. In addition, compared with CON, AZM and HCQ decreased the EDV. And, in comparison with HCQ treatment, HCQ + AZM treatment increased ESV on day 9.

Conclusions

According to our study, AZM significantly prolongs the QT interval and damages cardiac function. Moreover, HCQ + AZM treatment increased the risk of cardiac dysfunction compared with HCQ treatment.
Structural Basis of Stu2 Recruitment to Yeast Kinetochores
Authors: Zahm Jacob A. , Stewart Michael G. , Carrier Joseph S. , Harrison Stephen C. , Miller Matthew P.
Published: November 2020

Accurate chromosome segregation during cell division requires engagement of the kinetochores of sister chromatids with microtubules emanating from opposite poles of the mitotic spindle. In yeast, these “bioriented” metaphase sister chromatids experience tension as the corresponding microtubules (one per sister chromatid) shorten. Spindle-assembly checkpoint signaling appears to cease from a kinetochore under tension, which also stabilizes kinetochore-microtubule attachment in single-kinetochore experiments in vitro. The microtubule polymerase, Stu2, the yeast member of the XMAP215/ch-TOG protein family, associates with kinetochores in cells and contributes to tension-dependent stabilization, both in vitro and in vivo. We show here that a C-terminal segment of Stu2 binds the four-way junction of the Ndc80 complex (Ndc80c) and that amino-acid residues conserved both in yeast Stu2 orthologs and in their metazoan counterparts make specific contacts with Ndc80 and Spc24. Mutations that perturb this interaction prevent association of Stu2 with kinetochores, impair cell viability, produce biorientation defects, and delay cell-cycle progression. Ectopic tethering of the mutant Stu2 species to the Ndc80c junction restores wild-type function. These findings show that the role of Stu2 in tension sensing depends on its association with kinetochores by binding with Ndc80c.
Structure of Gcn1 bound to stalled and colliding 80S ribosomes
Authors: Pochopien Agnieszka A. , Beckert Bertrand , Kasvandik Sergo , Berninghausen Otto , Beckmann Roland , Tenson Tanel , Wilson Daniel N.
Published: November 2020

Protein synthesis is essential to cells and requires a constant supply of nutrients. Amino acid starvation leads to accumulation of uncharged tRNAs that promote ribosomal stalling, which is sensed by the protein kinase Gcn2, together with its effector proteins, Gcn1 and Gcn20. Activation of Gcn2 phosphorylates eIF2, leading to a global repression of translation. Fine-tuning of this adaptive response is performed by the Rbg2/Gir2 complex, which is a negative regulator of Gcn2. Despite the wealth of biochemical data, structures of Gcn proteins on the ribosome have remained elusive. Here we present a cryo-electron microscopy structure of the yeast Gcn1 protein in complex with stalled and colliding 80S ribosomes. Gcn1 interacts with both 80S ribosomes within the disome, such that the Gcn1 HEAT repeats span from the P-stalk region on the colliding ribosome to the A-site region of the lead ribosome. The lead ribosome is stalled in a non-rotated state with peptidyl-tRNA in the A-site, uncharged tRNA in the P-site, eIF5A in the E-site, as well as Rbg2/Gir2 located in the A-site factor binding region. By contrast, the colliding ribosome adopts a rotated state with peptidyl-tRNA in a hybrid A/P-site, uncharged-tRNA in the P/E-site and Mbf1 bound adjacent to the mRNA entry channel on the 40S subunit. Collectively, our findings provide a structural basis for Rbg2/Gir2 repression of Gcn2, and also reveal that colliding disomes are the substrate for Gcn1 binding, which has important implications not only for Gcn2-activated stress responses, but also for general ribosome quality control (RQC) pathways.
CHARACTERISATION OF FUNGI OF STORED COMMON BEAN CULTIVARS GROWN IN MENOUA DIVISION, CAMEROON
Authors: Akwa Teh Exodus , Maingi John M , Birgen Jonah K.
Published: November 2020

Common bean is a legume grown globally especially in developing countries including Cameroon for human consumption. In Cameroon it is grown in a wide variety of agro ecological zones in quantities enough to last through the off growing season after harvest. Stored common bean after harvest in Cameroon are prone to fungal spoilage which contributes to post harvest losses. This study aimed at characterising storage fungi on cultivars of stored common bean using morphological and molecular techniques. Fungi were isolated from six stored cultivars of common bean; Kidney bean, Black bean, Navy bean, Pinto bean, Pea bean and Large seeded bean plated on potato dextrose agar media. Cultural, micro-morphological and molecular techniques were used to characterise the isolates. A total of four fungi isolates resulted. Homology matches of the gene sequences in the Genbank databases identified the isolates to be;Xylaria hypoxylon, Aspergillus flavus, Penicillium aethiopicumandFusarium oxysporium. Phylogenetic analysis and multiple sequence alignment showed these isolates were of distinct species. The species of fungi recovered from the stored cultivars signified poor preservation methods carried out after harvest. Effective management and control of these fungal species in common bean at storage will help reduce post-harvest losses and increase seed health.
Beauty and the brain: Investigating the neural and musical attributes of beauty during a naturalistic music listening experience
Authors: Brattico E. , Brusa A. , Dietz M.J. , Jacobsen T. , Fernandes H.M. , Gaggero G. , Toiviainen P. , Vuust P. , Proverbio A.M.
Published: November 2020

Evaluative beauty judgments are very common, but in spite of this commonality, are rarely studied in cognitive neuroscience. Here we investigated the neural and musical attributes of musical beauty using a naturalistic free-listening paradigm applied to behavioral and neuroimaging recordings and validated by experts’ judgments. In Study 1, 30 Western healthy adult participants rated continuously the perceived beauty of three musical pieces using a motion sensor. This allowed us to identify the passages in the three musical pieces that were inter-subjectively judged as beautiful or ugly. This informed the analysis for Study 2, where additional 36 participants were recorded with functional magnetic resonance imaging (fMRI) while they listened attentively to the same musical pieces as in Study 1. In Study 3, in order to identify the musicological features characterizing the passages that were consistently rated as beautiful or ugly in Study 1, we collected post-hoc questionnaires from 12 music-composition experts. Results from Study 2 evidenced focal regional activity in the orbitofrontal brain structure when listening to beautiful passages of music, irrespectively of the subjective reactions and individual listening biographies. In turn, the moments in the music that were consistently rated as ugly were associated with bilateral supratemporal activity. Effective connectivity analysis also discovered inhibition of auditory activation and neural communication with orbitofrontal cortex, especially in the right hemisphere, during listening to beautiful musical passages as opposed to intrinsic activation of auditory cortices and decreased coupling to orbitofrontal cortex during listening to ugly musical passages. Experts’ questionnaires indicated that the beautiful passages were more melodic, calm, sad, slow, tonal, traditional and simple than the ones negatively valenced. In sum, we identified a neural mechanism for inter-subjective beauty judgments of music in the supratemporal-orbitofrontal circuit, irrespectively of individual taste and listening biography. Furthermore, some invariance in objective musical attributes of beautiful and ugly passages was evidenced. Future studies might address the generalizability of the findings to non-Western listeners.
Fast inactivation of Na+current in rat adrenal chromaffin cells involves two independent inactivation pathways
Authors: Martinez-Espinosa Pedro L. , Neely Alan , Ding Jiuping , Lingle Christopher J.
Published: November 2020

Voltage-dependent sodium (Nav) current in adrenal chromaffin cells (CCs) is rapidly inactivating and TTX-sensitive. The fractional availability of CC Nav current has been implicated in regulation of action potential (AP) frequency and the occurrence of slow-wave burst firing. To ascertain whether features of CC Nav inactivation might influence AP firing, we recorded Nav current in rat CCs, primarily from adrenal medullary slices. A key feature of CC Nav current is that recovery from inactivation, even following brief (5 ms) inactivation steps, exhibits two exponential components of generally similar amplitude. Variations of standard paired pulse protocols support the view that entry into the fast and slower recovery processes result from largely independent, competing inactivation pathways, both of which occur with similar onset times at depolarizing potentials. Over voltages from −120 to −80 mV, faster recovery varies from ~3 to 30 ms, while slower recovery from about 50-400 ms. At strong activation voltages (+0 mV and more positive), the relative entry into slow or fast recovery pathways is similar and independent of voltage. Trains of brief inactivating steps result in cumulative increases in the slower recovery fraction. This supports idea that brief recovery intervals preferentially allow recovery of channels from fast recovery pathways, thereby increasing the fraction of channels in the slow recovery pathway with each subsequent inactivation step. This provides a mechanism whereby differential rates of recovery produce use-dependent accumulation in slower recovery pathways. Consistent with use-dependent accumulation of channels in slow recovery pathways, repetitive AP clamp waveforms at 1-10 Hz frequencies reduce Nav availability to 10-20% of initial amplitude dependent on holding potential. The results indicate that there are two distinct pathways of fast inactivation, one that leads to normal fast recovery and the other with a slower time course, which together are well-suited to mediate use-dependent changes in Nav availability.