bluuebunny/crossref_metadata_2025 huggingface dataset:
SpikeShip: A method for fast, unsupervised discovery of high-dimensional neural spiking patterns
Authors: Sotomayor-Gómez Boris , Battaglia Francesco P. , Vinck Martin
Published: June 2020

Neural coding and memory formation depend on temporal spiking sequences that span high-dimensional neural ensembles. The unsupervised discovery and characterization of these spiking sequences requires a suitable dissimilarity measure to spiking patterns, which can then be used for clustering and decoding. Here, we present a new dissimilarity measure based on optimal transport theory called SpikeShip, which compares multineuron spiking patterns based on all the relative spike-timing relationships among neurons. SpikeShip computes the optimal transport cost to make all the relative spike-timing relationships (across neurons) identical between two spiking patterns. We show that this transport cost can be decomposed into a temporal rigid translation term, which captures global latency shifts, and a vector of neuron-specific transport flows, which reflect inter-neuronal spike timing differences. SpikeShip can be effectively computed for high-dimensional neuronal ensembles, has a low (linear) computational cost that has the same order as the spike count, and is sensitive to higher-order correlations. Furthermore SpikeShip is binless, can handle any form of spike time distributions, is not affected by firing rate fluctuations, can detect patterns with a low signal-to-noise ratio, and can be effectively combined with a sliding window approach. We compare the advantages and differences between SpikeShip and other measures like SPIKE and Victor-Púrpura distance. We applied SpikeShip to large-scale Neuropixel recordings during spontaneous activity and visual encoding. We show that high-dimensional spiking sequences detected via SpikeShip reliably distinguish between different natural images and different behavioral states. These spiking sequences carried complementary information to conventional firing rate codes. SpikeShip opens new avenues for studying neural coding and memory consolidation by rapid and unsupervised detection of temporal spiking patterns in high-dimensional neural ensembles.
Glutamatergic adaptation to stress in medial prefrontal cortex underlies risk and resilience for pessimistic beliefs
Authors: Cooper Jessica A. , Nuutinen Makiah R. , Lawlor Victoria M. , DeVries Brittany A. M. , Barrick Elyssa M. , Hossein Shabnam , Cole Daniel C. , Leonard Chelsea V. , Teer Andrew P. , Shields Grant S. , Slavich George M. , Ongur Dost , Jensen J. Eric , Du Fei , Pizzagalli Diego A. , Treadway Michael T.
Published: June 2020

Stress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.
Confidence in action: differences between perceived accuracy of decision and motor response
Authors: Siedlecka Marta , Koculak Marcin , Paulewicz Borysław
Published: June 2020

Each of our decisions is associated with a degree of confidence. This confidence can change once we have acted as we might start doubting our choice or even become convinced that we made a mistake. In this study, we explore the relations between action and our confidence that our decision was correct or erroneous. Fifty-six volunteers took part in a perceptual decision task in which their decisions could either lead to action or not. At the end of each trial, participants rated their confidence that their decision was correct, or they reported that they had made an error. The main results showed that when given after a response, confidence ratings were higher and more strongly related to decision accuracy, and post-response reports of errors more often indicated actual errors. The results support the view that error awareness and confidence might be partially based on post-action processing.
Do male and female heterogamety really differ in expression regulation? Lack of global dosage balance in pygopodid geckos
Authors: Rovatsos Michail , Gamble Tony , Nielsen Stuart V. , Georges Arthur , Ezaz Tariq , Kratochvíl Lukáš
Published: June 2020

Differentiation of sex chromosomes is thought to have evolved with cessation of recombination and subsequent loss of genes from the degenerated partner (Y and W) of sex chromosomes, which in turn leads to imbalance of gene dosage between sexes. Based on work with traditional model species, theory suggests that unequal gene copy numbers lead to the evolution of mechanisms to counter this imbalance. Dosage compensation, or at least achieving dosage balance in expression of sex-linked genes between sexes, has largely been documented in lineages with male heterogamety (XX/XY sex determination), while ZZ/ZW systems are assumed to be usually associated with the lack of chromosome-wide gene dose regulatory mechanisms. Here we document that although the pygopodid geckos evolved male heterogamety with a degenerated Y chromosome 32-72 million years ago, one species in particular, Burton’s legless lizard (Lialis burtonis), does not possess dosage balance in the expression of genes in its X-specific region. We summarize studies on gene dose regulatory mechanisms in animals and conclude that there is in them no significant dichotomy between male and female heterogamety. We speculate that gene dose regulatory mechanisms are likely to be related to the general mechanisms of sex determination instead of type of heterogamety.
Pitfalls in SARS-CoV-2 PCR diagnostics
Authors: Wernike Kerstin , Keller Markus , Conraths Franz J. , Mettenleiter Thomas C. , Groschup Martin H. , Beer Martin
Published: June 2020

To combat the COVID-19 pandemic, millions of PCR tests are performed worldwide. Any deviation of the diagnostic sensitivity and specificity will reduce the predictive values of the test. Here, we report the occurrence of contaminations of commercial primers/probe sets with the SARS-CoV-2 target sequence of the RT-qPCR as an example for pitfalls during PCR diagnostics affecting diagnostic specificity. In several purchased in-house primers/probe sets, quantification cycle values as low as 17 were measured for negative control samples. However, there were also primers/probe sets that displayed very low-level contaminations, which were detected only during thorough internal validation. Hence, it appears imperative to pre-test each batch of reagents extensively before use in routine diagnosis, to avoid false-positive results and low positive predictive value in low-prevalence situations. As such, contaminations may have happened more widely, COVID-19 diagnostic results should be re-assessed retrospectively to validate the epidemiological basis for control measures.
Brief sensory deprivation triggers plasticity of dopamine-synthesising enzyme expression in genetically labelled olfactory bulb dopaminergic neurons
Authors: Byrne Darren J , Lipovsek Marcela , Crespo Andres , Grubb Matthew S
Published: June 2020

In the glomerular layer of the olfactory bulb, local dopaminergic interneurons play a key role in regulating the flow of sensory information from nose to cortex. These dual dopamine- and GABA-releasing cells are capable of marked experience-dependent changes in the expression of neurotransmitter-synthesising enzymes, including tyrosine hydroxylase (TH). However, such plasticity has most commonly been studied in cell populations identified by their expression of the enzyme being studied, and after long periods of sensory deprivation. Here, instead, we used brief 1- or 3-day manipulations of olfactory experience in juvenile mice, coupled with a conditional genetic approach that labelled neurons contingent upon their expression of the dopamine transporter (DAT-tdTomato). This enabled us to evaluate the potential for rapid changes in neurotransmitter-synthesising enzyme expression in an independently identified neuronal population. Our labelling strategy showed good specificity for olfactory bulb dopaminergic neurons, whilst revealing a minority sub-population of non-dopaminergic DAT-tdTomato cells that expressed the calcium-binding protein calretinin. Crucially, the proportions of these neuronal subtypes were not affected by brief alterations in sensory experience. Short-term olfactory manipulations also produced no significant changes in immunofluorescence or whole-bulb mRNA for the GABA-synthesising enzyme GAD67/Gad1. However, in bulbar DAT-tdTomato neurons brief sensory deprivation was accompanied by a transient, small drop in immunofluorescence for the dopamine-synthesising enzyme dopa decarboxylase (DDC), and a sustained decrease for TH. Deprivation also produced a sustained decrease in whole-bulbThmRNA. Careful characterisation of an independently identified, genetically labelled neuronal population therefore enabled us to uncover rapid experience-dependent changes in dopamine-synthesising enzyme expression.
Precision genetic cellular models identify therapies protective against endoplasmic reticulum stress
Authors: Lebedeva Irina V. , Wagner Michelle V. , Sahdeo Sunil , Lu Yi-Fan , Anyanwu-Ofili Anuli , Harms Matthew B. , Wadia Jehangir S. , Rajagopal Gunaretnam , Boland Michael J. , Goldstein David B.
Published: June 2020

Congenital disorders of glycosylation (CDG) and deglycosylation (CDDG) are a collection of rare pediatric disorders with symptoms that range from mild to life threatening. They typically affect multiple organ systems and usually present with neurological abnormalities including hypotonia, cognitive impairment, and intractable seizures. Several genes have been implicated in the thirty-six types of CDG, but currentlyNGLY1is the only known CDDG gene. A common biological mechanism among CDG types and in CDDG is endoplasmic reticulum (ER) stress. Here, we develop two isogenic human cellular models of CDG (PMM2, the most prevalent type of CDG, andDPAGT1) and of the only CDDG (NGLY1) in an effort to identify drugs that can alleviate ER stress. Systematic phenotyping identified elevated ER stress and autophagy levels among other cellular and morphological phenotypes in each of the cellular models. We screened a complex drug library for compounds able to correct aberrant morphological phenotypes in each of the models using an agnostic phenotypic cell painting assay based on >300 cellular features. The image-based screen identified multiple candidate compounds able to correct aberrant morphology, and we show a subset of these are able to correct cellular and molecular defects in each of the models. These results provide new directions for the treatment of rare diseases of glycosylation and deglycosylation and a framework for new drug screening paradigms for more common neurodegenerative diseases characterized by ER stress.

Summary sentence

Novel drug screening modality identifies compounds that correct aberrant molecular phenotypes in precision cellular models of glycosylation defects.
Reduced intra- and inter-individual diversity of semantic representations in the brains of schizophrenia patients
Authors: Nishida Satoshi , Matsumoto Yukiko , Yoshikawa Naganobu , Son Shuraku , Murakami Akio , Hayashi Ryusuke , Nishimoto Shinji , Takahashi Hidehiko
Published: June 2020

Schizophrenia patients often manifest semantic processing deficits. It has been proposed that these deficits stem from disorganized semantic representations in the brain. However, no study has yet examined the neural correlates of semantic disorganization by directly evaluating semantic representations in the brain. We used voxelwise modeling on functional magnetic resonance imaging signals to evaluate the semantic representations associated with several thousand words in individual patient brains. We then compared the structural properties of semantic representations to those in healthy controls. The variability of semantic representations was smaller both within individual patients and across patients compared to controls. Surrogate data analysis suggests that the observed reduction in representational variability is associated with disorganization of categorical information. To our knowledge, these findings provide the first evidence for sematic disorganization in schizophrenia at the level of brain representations.
Microdiversity and phylogeographic diversification of bacterioplankton in pelagic freshwater systems revealed through long-read amplicon sequencing
Authors: Okazaki Yusuke , Fujinaga Shohei , Salcher Michaela M. , Callieri Cristiana , Tanaka Atsushi , Kohzu Ayato , Oyagi Hideo , Tamaki Hideyuki , Nakano Shin-ichi
Published: June 2020

Freshwater ecosystems are inhabited by members of cosmopolitan bacterioplankton lineages despite the disconnected nature of these habitats. The lineages are delineated based on >97% 16S rRNA gene sequence similarity, but their intra-lineage microdiversity and phylogeography, which are key to understanding the eco-evolutional processes behind their ubiquity, remain unresolved. Here, we applied long-read amplicon sequencing targeting nearly full-length 16S rRNA genes and the adjacent ribosomal internal transcribed spacer sequences to reveal the intra-lineage diversities of pelagic bacterioplankton assemblages in 11 deep freshwater lakes in Japan and Europe. Our single nucleotide-resolved analysis, which was validated using shotgun metagenomic sequencing, uncovered 7–101 amplicon sequence variants for each of the 11 predominant bacterial lineages and demonstrated sympatric, allopatric, and temporal microdiversities that could not be resolved through conventional approaches. Clusters of samples with similar intra-lineage population compositions were identified, which consistently supported genetic isolation between Japan and Europe. At a regional scale (up to hundreds of kilometers), dispersal between lakes was unlikely to be a limiting factor, and environmental factors were potential determinants of population composition. The extent of microdiversification varied among lineages, suggesting that highly diversified lineages (e.g., Iluma-A2 and acI-A1) achieve their ubiquity by containing a consortium of genotypes specific to each habitat, while less diversified lineages (e.g., CL500-11) may be ubiquitous due to a small number of widespread genotypes. The lowest extent of intra-lineage diversification was observed among the dominant hypolimnion-specific lineage (CL500-11), suggesting that their dispersal among lakes is not limited despite the hypolimnion being a more isolated habitat than the epilimnion. Our novel approach complemented the limited resolution of short-read amplicon sequencing and limited sensitivity of the metagenome assembly-based approach, and highlighted the complex ecological processes underlying the ubiquity of freshwater bacterioplankton lineages.
Systems-level immunomonitoring from acute to recovery phase of severe COVID-19
Authors: Rodriguez Lucie , Pekkarinen Pirkka , Lakshmikanth Tadepally , Tan Ziyang , Consiglio Camila Rosat , Pou Christian , Chen Yang , Mugabo Constantin Habimana , Quoc Anh Nguyen , Nowlan Kirsten , Strandin Tomas , Levanov Lev , Mikes Jaromir , Wang Jun , Kantele Anu , Hepojoki Jussi , Vapalahti Olli , Heinonen Santtu , Kekäläinen Eliisa , Brodin Petter
Published: June 2020

The immune response to SARS-CoV2 is under intense investigation, but not fully understood att this moment. Severe disease is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5–7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Systems-level analyses are required to simultaneously capture all immune cell populations and the many protein mediators by which cells communicate. Since every patient analyzed will be captured at different stages of his or her infection, longitudinal monitoring of the immune response is critical. Here we report on a systems-level blood immunomonitoring study of 39 adult patients, hospitalized with severe COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNγ – Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.

HIGHLIGHTS

Systems-level immunomonitoring from acute to recovery in severe COVID-19

An IFNγ - Eosinophil axis involved in lung hyperinflammation

Cell-cell coregulation differ during four disease stages

Basophils and hyperinflammation modulate humoral responses

A shared trajectory of immunological recovery in severe COVID-19
Coronavirus Disease 2019 (COVID-19) Dynamics Considering the Influence of Hospital Infrastructure
Authors: Pacheco Pedro M.C.L. , Savi Marcelo A. , Savi Pedro V.
Published: June 2020

This paper deals with the mathematical modeling and numerical simulations related to the coronavirus dynamics. A description is developed based on the framework of susceptible-exposed-infectious-removed model. Removed population is split into recovered and death populations allowing a better comprehension of real situations. Besides, total population is reduced based on the number of deaths. Hospital infrastructure is also included into the mathematical description allowing the consideration of collapse scenarios. Initially, a model verification is carried out calibrating system parameters with data from China outbreak that is considered a benchmark due the availability of data for the entire cycle. Afterward, numerical simulations are performed to analyze COVID-19 dynamics in Brazil. Results show several scenarios showing the importance of social isolation. System dynamics has a strong sensitivity to transmission rate showing the importance of numerical simulations to guide public health decision strategies.
Integrated genomic view of SARS-CoV-2 in India
Authors: Kumar Pramod , Pandey Rajesh , Sharma Pooja , Dhar Mahesh S , Vivekanand A , Uppili Bharathram , Vashisht Himanshu , Wadhwa Saruchi , Tyagi Nishu , Fatihi Saman , Sharma Uma , Singh Priyanka , Lall Hemlata , Datta Meena , Gupta Poonam , Saini Nidhi , Tewari Aarti , Nandi Bibhash , Kumar Dhirendra , Bag Satyabrata , Deepanshi  , Rathore Surabhi , Jatana Nidhi , Jaiswal Varun , Gogia Hema , Madan Preeti , Singh Simrita , Singh Prateek , Dash Debasis , Bala Manju , Kabra Sandhya , Singh Sujeet , Mukerji Mitali , Thukral Lipi , Faruq Mohammed , Agrawal Anurag , Rakshit Partha
Published: June 2020

India first detected SARS-CoV-2, causal agent of COVID-19 in late January-2020, imported from Wuhan, China. March-2020 onwards; importation of cases from rest of the countries followed by seeding of local transmission triggered further outbreaks in India. We used ARTIC protocol based tiling amplicon sequencing of SARS-CoV-2 (n=104) from different states of India using a combination of MinION and MinIT from Oxford Nanopore Technology to understand introduction and local transmission. The analyses revealed multiple introductions of SARS-CoV-2 from Europe and Asia following local transmission. The most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, here, proposed as A4-clade based on its divergence within A-cluster. The viral haplotypes may link their persistence to geo-climatic conditions and host response. Despite the effectiveness of non-therapeutic interventions in India, multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic.
Induction of Muscle Regenerative Multipotent Stem Cells from Human Adipocytes by PDGF-AB and 5-Azacytidine
Authors: Yeola Avani , Subramanian Shruthi , Oliver Rema A. , Lucas Christine A. , Thoms Julie A. I. , Yan Feng , Olivier Jake , Chacon Diego , Tursky Melinda L. , Hung Tzongtyng , Power Carl , Hardy Philip , Ma David D. , McCarroll Joshua , Kavallaris Maria , Hesson Luke B. , Beck Dominik , Curtis David J. , Wong Jason W.H. , Hardeman Edna C. , Walsh William R. , Mobbs Ralph , Chandrakanthan Vashe , Pimanda John E.
Published: June 2020

Terminally differentiated murine osteocytes and adipocytes can be reprogrammed using platelet-derived growth factor–AB and 5-Azacytidine into multipotent stem cells with stromal cell characteristics. To generate a product that is amenable for therapeutic application, we have modified and optimised culture conditions to reprogram human adipocytes into induced multipotent stem cells (iMS) and expand them in vitro. The basal transcriptomes of adipocyte-derived iMS cells and matched adipose-tissue-derived mesenchymal stem cells were remarkably similar. However, there were distinct changes in histone modifications and CpG methylation at cis-regulatory regions consistent with an epigenetic landscape that was primed for tissue development and differentiation. In a non-specific tissue injury xenograft model, iMS cells contributed directly to new muscle, bone, cartilage and blood vessels with no evidence of teratogenic potential. In a cardiotoxin muscle injury model, iMS cells contributed specifically to satellite cells and myofibres without ectopic tissue formation. Taken together, human adipocyte derived iMS cells regenerate tissues in a context dependent manner without ectopic or neoplastic growth.
Providing recombinant gonadotropin-based therapies that induce complete oogenesis and produce viable larvae from an immature teleost, flathead grey mullet (Mugil cephalus)
Authors: Ramos-Júdez Sandra , Chauvigné François , González-López Wendy Ángela , Rosenfeld Hanna , Cerdà Joan , Giménez Ignacio , Duncan Neil
Published: June 2020

Under intensive captive conditions, wild-caught flathead grey mullet (Mugil cephalus) females remained arrested at early gonad development and no sperm could be obtained from males. With the aim to induce and complete oogenesis, induce the release of sperm and obtain fertilized eggs, adult female and male grey mullet were treated with M. cephalus single-chain recombinant gonadotropins (rGths), follicle-stimulating (rFsh) and luteinizing (rLh) hormones. In Experiment 1, fish were treated with a weekly dose of rFsh (15 μg kg−1), which in females significantly (P < 0.001) increased plasma concentration of 17β-estradiol and induced vitellogenic oocyte growth up to a maximum mean diameter of 425 ± 19 μm after 9 weeks of treatment. In Experiment 2, fish were treated with weekly injections of both rFsh and rLh at different doses (from 2.5 to 12 μg kg−1). Oocyte diameter reached 609 ± 5 μm, from which final oocyte maturation and ovulation was induced with 30 μg kg−1 of rLh and 40 mg kg−1 of progesterone. Good quality sperm (> 75% motile spermatozoa) was obtained from males in both experiments, and in Exp. 2 the addition of rLh induced the production of higher quantities of sperm that were used to fertilise the eggs. Although fertilisation was low (0.4 %), these fertilized eggs with embryo development produced viable larvae (71% hatching rate). This is the first report in a teleost species, to obtain larvae from eggs that were from immature females induced through to maturation with rGths. In comparison, control females remained arrested as immature fish and control males did not produce sperm. The study demonstrated that both rGths are effective to induce the entire process of oogenesis in sexually immature female grey mullet and to obtain flowing sperm from males, adding more data to confirm the roles of the Gths in teleost gametogenesis. This advance provides the bases of a therapy for the use in the aquaculture of teleost of commercial interest or the conservation of endangered species.
Explaining #TheShoe based on the optimal color hypothesis: The role of chromaticity vs. luminance distribution in ambiguous image
Authors: Morimoto Takuma , Fukuda Kazuho , Uchikawa Keiji
Published: June 2020

The image of #theShoe is a derivative image of #theDress which induced vastly different color experiences across individuals. The majority of people perceive that the shoe has grey leather with turquoise laces, but others report pink leather with white laces. We hypothesized #theShoe presents the problem of color constancy, where different people estimated different illuminants falling onto the shoe. The present study specifically aimed to understand what cues in the shoe image caused the ambiguity based on the optimal color hypothesis: our visual system knows the gamut of surface colors under various illuminants and applies the knowledge for illuminant estimation. The analysis showed that estimated illuminant chromaticity largely changes depending on the assumed intensity of the illuminant. When the illuminant intensity was assumed to be low, a high color temperature was estimated. In contrast, assuming high illuminant intensity led to the estimation of low color temperature. A simulation based on a von Kries correction showed that the subtraction of estimated illuminants from the original image shifts the appearance of the shoe towards the reported states (i.e. gray-turquoise or pink-white). These results suggest that the optimal color hypothesis provides a theoretical interpretation to the #theShoe phenomenon. Moreover, this luminance-dependent color-shift was observed in #theDress phenomenon, supporting the notion that the same trigger induced #theShoe.
DNMT3b Dysfunction Promotes DNA cleavages at Centromeric R-loops to Increase Centromere Instability
Authors: Shih Hsueh-Tzu , Chen Wei-Yi , Wang Hsin-Yen , Huang Hsien-Da , Chou Chih-Hung , Chang Zee-Fen
Published: June 2020

This study investigates how DNA methyltransferase 3b (DNMT3b) dysfunction causes genome instability. We showed that in DNMT3b deficient cells, R-loops contribute to prominent γH2AX signal, which was mapped to repetitive satellite sequences including centromere regions. By ChIP and DRIP analyses, our data revealed that centromeric R-loops in DNMT3b deficient cells are removed by XPG/XPF, thus generating DNA breaks in centromeres to increase mitotic aberration. In immunodeficiency-centromeric instability-facial anomalies (ICF) patient cells carrying the loss-of-function mutation atDNMT3b, knockdown of XPG/XPF in ICF cells also reduces DNA breaks in centromere while bringing up centromeric R-loop to the level similar to that in wild-type cells. These results suggest that DNMT3b has a critical function in preventing XPG/XPF-mediated cleavages at centromeric R-loop sites. Finally, we showed the involvement of non-homologous end-joining repair at centromeric sites in ICF cells. Thus, DNA cleavages at centromeric R-loops with error-prone repair undermine centromere stability in ICF cells.
Systematic analysis of mutational spectra associated with DNA repair deficiency inC. elegans
Authors: Meier B , Volkova NV , Hong Y , Bertolini S , González-Huici V , Petrova T , Boulton S , Campbell PJ , Gerstung M , Gartner A
Published: June 2020

Genome integrity is particularly important in germ cells to faithfully preserve genetic information across generations. As yet little is known about the contribution of various DNA repair pathways to prevent mutagenesis. Using theC. elegansmodel we analyse mutational spectra that arise in wild-type and 61 DNA repair and DNA damage response mutants cultivated over multiple generations. Overall, 44% of lines show >2-fold increased mutagenesis with a broad spectrum of mutational outcomes including changes in single or multiple types of base substitutions induced by defects in base excision or nucleotide excision repair, or elevated levels of 50-400 bp deletions in translesion polymerase mutantsrev-3(pol ζ) andpolh-1(pol η). Mutational signatures associated with defective homologous recombination fall into two classes: 1) mutants lackingbrc-1/BRCA1orrad-51/RAD51 paralogs show elevated base substitutions, indels and structural variants, while 2) deficiency for MUS-81/MUS81 and SLX-1/SLX1 nucleases, and HIM-6/BLM, HELQ-1/HELQ and RTEL-1/RTEL1 helicases primarily cause structural variants. Genome-wide investigation of mutagenesis patterns identified elevated rates of tandem duplications often associated with inverted repeats inhelq-1mutants, and a unique pattern of ‘translocation’ events involving homeologous sequences inrip-1paralog mutants.atm-1/ATM DNA damage checkpoint mutants harboured complex structural variants enriched in subtelomeric regions, and chromosome end-to-end fusions. Finally, while inactivation of thep53-like genecep-1did not affect mutagenesis, combinedbrc-1 cep-1deficiency displayed increased, locally clustered mutagenesis. In summary, we provide a global view of how DNA repair pathways prevent germ cell mutagenesis.
Mg2+Sensing by an RNA Fragment: Role of Mg2+Coordinated Water Molecules
Authors: Halder Antarip , Kumar Sunil , Valsson Omar , Reddy Govardhan
Published: June 2020

RNA molecules selectively bind to specific metal ions to populate their functional active states making it important to understand their source of ion selectivity. In large RNA systems, metal ions interact with the RNA at multiple locations making it difficult to decipher the precise role of ions in folding. To overcome this complexity, we studied the role of different metal ions (Mg2+, Ca2+and K+) in the folding of a small RNA hairpin motif (5′-ucCAAAga-3′) using unbiased all-atom molecular dynamics simulations. The advantage in studying this small system is that it requires specific binding of a single metal ion to fold to its native state. We find that even for this small RNA, the folding free energy surface (FES) is multidimensional as different metal ions present in the solution can simultaneously facilitate folding. The FES shows that specific binding of a metal ion is indispensable for its folding. We further show that in addition to the negatively charged phosphate groups, spatial organization of electronegative nucleobase atoms drive the site specific binding of the metal ion. Even though the binding site cannot discriminate between different metal ions, RNA folds efficiently only in Mg2+solution. We show that the rigid network of Mg2+coordinated water molecules facilitate the formation of important interactions in the transition state. The other metal ions such as K+and Ca2+cannot facilitate the formation of such interactions. These results allow us to hypothesize possible metal sensing mechanisms in large metallo-riboswitches and they also provide useful insights for the design of appropriate collective variables for studying large RNA molecules using enhanced sampling methods.
Assessing the re-introduction ofAedes aegyptiin Europe. Will the Yellow Fever Mosquito colonize the Old World?
Authors: Da Re Daniele , Montecino-Latorre Diego , Vanwambeke Sophie O. , Marcantonio Matteo
Published: June 2020

Aedes aegyptiare feared invasive mosquitoes as they transmit pathogens which cause debilitating diseases in humans. Although mainland Europe has not yet witnessed re-establishment and diffusion ofAe. aegyptipopulations, several urban areas along coastlines represent suitable habitats for the species. In addition, European coastal areas are characterized by a high exotic species propagule pressure, due to the dense international ship traffic.

Here, we applied a process-based population dynamical model to simulate both the life cycle and dispersal ofAe. aegyptiat the local scale after its introduction through ship traffic. We selected five European ports along a gradient of latitude by considering both environmental conditions and the economical importance of ports: Algeciras and Barcelona in Spain; Venice and Genoa in Italy and Rotterdam in the Netherlands. The model was informed using parameters relevant forAe. aegyptibiology, fine-scale temperature time-series, urban structures and road networks.

According to model results, the introduction of small quantities ofAe. aegyptieggs, from 10 to 1000, has the potential to cause species establishment, high local densities and slow initial dispersal in the two southernmost study areas, Algeciras and Barcelona, whereas Genoa may be considered only close to suitability. Barcelona had the highest simulated mosquito densities (584 females/ha), whereas Algeciras densities were never more than 32 females/ha, but remained higher during winter. The spatial spread of the species varied between a few hundred meters to 2 km/year and was affected by the structure of the road network, topography and urban sprawl along the coast in the surrounding of the port of introduction. The study areas of Genoa, Venice and Rotterdam were found not suitable for establishment of this mosquito species, however climate change could create conditions forAe. aegyptiinvasion in these regions in the next decades.

It is commonly accepted that targeted monitoring and early control actions are the most effective methods to hinder the establishment of invasive species in new areas. Our findings and model framework may support surveillance initiatives for those European coastal urban areas which have a known high propagule pressure and a high modelled probability ofAe. aegyptiestablishment.

Highlights

European coasts present favourable conditions forAedes aegyptiestablishment

We assess the species introduction and establishment using a process-based model

We selected five ports: Algeciras, Barcelona, Venice, Genoa and Rotterdam

Algeciras and Barcelona were the most suitable areas for the species establishment

Climate change could make more suitable the northernmost study areas
Climate gradients, and patterns of biodiversity and biotic homogenization in urban residential yards
Authors: Bergey Elizabeth A. , Whipkey Benjamin E.
Published: June 2020

Residential yards constitute a substantive biodiverse greenspace within urban areas. This biodiversity results from a combination of native and non-native species and can contribute to biotic homogenization. Geographical climatic patterns affect the distribution of native species and may differently affect non-native species. In this study, we examined biodiversity and biotic homogenization patterns of yard-dwelling land snails across 12 towns in Oklahoma and Kansas (USA). The 3 × 4 array of towns incorporated a N-S winter temperature gradient (mean low January temperature range = −8.4 to 0.1 °C) and an E-W annual rainfall gradient (annual rainfall range = 113.8 to 61.3 cm/yr). Ten yards per town were surveyed. We hypothesized that mild winter temperatures and greater annual rainfall would be associated with greater snail abundance and richness, and that the presence of non-native species would contribute to biotic homogenization. Non-native snails were present and often abundant in all towns. Snail communities varied with both rainfall and cold temperature. Contrary to our prediction, snail abundance was inversely related to annual rainfall – likely because drier conditions resulted in greater yard watering that both augmented rainfall and maintained moist conditions. Sørensen similarity between towns for the entire land snail community and for only non-native species both showed distance-decay patterns, with snail composition becoming less similar with increasing distance - patterns resulting from species turnover. The biotic homogenization index also showed a distance-decay pattern, such that closer towns were more likely to have biotic homogenization whereas more distant towns tended to have biotic differentiation. These results support the concept that biotic homogenization is more likely regionally and that climatic changes over distance result in species turnover and can reduce spatially broad biotic homogenization.
PROPER UTILIZATION OF IODIZED SALT AND ASSOCIATED FACTORS AMONG RURAL COMMUNITY OF HETOSA DISTRICT, OROMIA REGIONAL STATE, SOUTH EAST ETHIOPIA
Authors: Bulli Abu Tura , Aredo MeleseTadese , Fekadu Hailu , Regesu Ashenafi Habtamu
Published: June 2020

Introduction

Iodine is considered to be one of the most essential micronutrients for the normal physical and mental development of human beings. However, little is known about households’ use of iodized salt and associated factors.

Objectives

This study was to assess the proper utilization of iodized salt at the household level and associated factors in Hetosa District, Southeast Ethiopia, 2019.

Methods

A Community-based cross-sectional study was conducted from August 20 up to September 15/2019 in rural Hetosa District, Arsi Zone, and east-south Ethiopia. A total of 603 households were selected using a systematic random sampling technique. Data were collected employing structured and pre-tested questionnaires by face -to -face interview technique. The use of iodized salt at the household level was tested with the iodine rapid test kit. The data were checked, coded and entered into Epi Info Version 7 and export to SPSS version 21 for analysis.

Result

A total of 596 participants were included in this study. The availability of adequately iodized salt was 61.1%. The proportion of proper utilization of iodized salt at the household level was 38.4%.Formal Educational (AOR=1.688, 95%CI (1.002, 2.846)),Practice of iodized salt use (AOR= 3.352, 95%CI (2.160, 5.202)), Knowledge on use of iodized salt (AOR=2.320, 95%CI (1.437, 3.745)) and level of iodine content in salt (AOR= 1.668, 95%CI (1.071, 2.597)) were statistically significant to utilization of iodized salt.

Conclusion

Proper utilization of iodized salt remains very low, which was 38.4% in the district and does not meet the national goal. Educational status, level of iodized salt, good knowledge and good practice were significantly associated factors with proper utilization of adequately iodized salt in this study.
Woeseiales transcriptional response in Arctic fjord surface sediment
Authors: Buongiorno Joy , Sipes Katie , Wasmund Kenneth , Loy Alexander , Lloyd Karen G.
Published: June 2020

Distinct lineages of Gammaproteobacteria clade Woeseiales are globally-distributed in marine sediments, based on metagenomic and 16S rRNA gene analysis. Yet little is known about why they are dominant or their ecological role in Arctic fjord sediments, where glacial retreat is rapidly imposing change. This study combined 16S rRNA gene analysis, metagenome-assembled genomes (MAGs), and genome-resolved metatranscriptomics uncovered the in situ abundance and transcriptional activity of Woeseiales with burial in four shallow sediment sites of Kongsfjorden and Van Keulenfjorden of Svalbard (79°N). We present five novel Woeseiales MAGs and show transcriptional evidence for metabolic plasticity during burial, including sulfur oxidation with reverse dissimilatory sulfite reductase (dsrAB) down to 4 cm depth and nitrite reduction down to 6 cm depth. A single stress protein, spore protein SP21 (hspA), had a tenfold higher mRNA abundance than any other transcript, and was a hundredfold higher on average than other transcripts. At three out of the four sites, SP21 transcript abundance increased with depth, while total mRNA abundance and richness decreased, indicating a shift in investment from metabolism and other cellular processes to build-up of spore protein SP21. The SP21 gene in MAGs was often flanked by genes involved in membrane-associated stress response. The ability of Woeseiales to shift from sulfur oxidation to nitrite reduction with burial into marine sediments with decreasing access to overlying oxic bottom waters, as well as enter into a dormant state dominated by SP21, may account for its ubiquity and high abundance in marine sediments worldwide, including those of the rapidly shifting Arctic.
Pleiotropic effects of heterozygosity for theSERPINA1Z allele in the UK Biobank
Authors: Fawcett Katherine A , Song Kijoung , Qian Guoqing , Farmaki Aliki-Eleni , Packer Richard , John Catherine , Shrine Nick , Granell Raquel , Ring Sue , Timpson Nicholas J , Yerges-Armstrong Laura M , Eastell Richard , Wain Louise V , Scott Robert A , Tobin Martin D , Hall Ian P
Published: June 2020

Homozygosity for theSERPINA1Z allele causes alpha-1 antitrypsin deficiency, a rare condition that can cause lung and liver disease. However, the effects of Z allele heterozygosity on non-respiratory phenotypes, and on lung function in the general population, remain unclear. We conducted the largest population-based study to date to determine Z allele effects on >2,400 phenotypes using the UK Biobank study (N>303,353). We detected strong associations between heterozygosity and non-respiratory phenotypes including increased height, increased risk of gall bladder disease, reduced risk of heart disease and lower blood pressure, reduced risk of osteoarthritis and reduced bone mineral density, increased risk of headache and enlarged prostate, as well as with blood biomarkers of liver function. Heterozygosity was associated with higher lung function in non-smokers, but smoking appears to abolish this protective effect. Individuals heterozygous for the Z allele may therefore have altered risk of smoking-induced lung disease and other, non-respiratory conditions.
Clinical management and mortality among COVID-19 cases in sub-Saharan Africa: A retrospective study from Burkina Faso and simulated case analysis
Authors: Skrip Laura , Derra Karim , Kaboré Mikaila , Noori Navideh , Gansané Adama , Valéa Innocent , Tinto Halidou , Brice Bicaba W. , Van Gordon Mollie , Hagedorn Brittany , Hien Hervé , Althouse Benjamin M. , Wenger Edward A. , Ouédraogo André Lin
Published: June 2020

Background

Absolute numbers of COVID-19 cases and deaths reported to date in the sub-Saharan Africa (SSA) region have been significantly lower than those across the Americas, Asia, and Europe. As a result, there has been limited information about the demographic and clinical characteristics of deceased cases in the region, as well as the impacts of different case management strategies.

Methods

Data from deceased cases reported across SSA through May 10, 2020 and from hospitalized cases in Burkina Faso through April 15, 2020 were analyzed. Demographic, epidemiological, and clinical information on deceased cases in SSA was derived through a line-list of publicly available information and, for cases in Burkina Faso, from aggregate records at the Center Hospitalier Universitaire de Tengandogo in Ouagadougou. A synthetic case population was derived probabilistically using distributions of age, sex, and underlying conditions from populations of West African countries to assess individual risk factors and treatment effect sizes. Logistic regression analysis was conducted to evaluate the adjusted odds of survival for patients receiving oxygen therapy or convalescent plasma, based on therapeutic effectiveness observed for other respiratory illnesses.

Results

Across SSA, deceased cases for which demographic data are available have been predominantly male (63/103, 61.2%) and over 50 years of age (59/75, 78.7%). In Burkina Faso, specifically, the majority of deceased cases either did not seek care at all or were hospitalized for a single day (59.4%, 19/32); hypertension and diabetes were often reported as underlying conditions. After adjustment for sex, age, and underlying conditions in the synthetic case population, the odds of mortality for cases not receiving oxygen therapy was significantly higher than those receiving oxygen, such as due to disruptions to standard care (OR: 2.07; 95% CI: 1.56 – 2.75). Cases receiving convalescent plasma had 50% reduced odds of mortality than those who did not (95% CI: 0.24 – 0.93).

Conclusion

Investment in sustainable production and maintenance of supplies for oxygen therapy, along with messaging around early and appropriate use for healthcare providers, caregivers, and patients could reduce COVID-19 deaths in SSA. Further investigation into convalescent plasma is warranted, as data on its effectiveness specifically in treating COVID-19 becomes available. The success of supportive or curative clinical interventions will depend on earlier treatment seeking, such that community engagement and risk communication will be critical components of the response.
Dynamics of COVID-19 under social distancing measures are driven by transmission network structure
Authors: Nande Anjalika , Adlam Ben , Sheen Justin , Levy Michael Z. , Hill Alison L.
Published: June 2020

In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. Our simulations show that long delays between the adoption of control measures and observed declines in cases, hospitalizations, and deaths occur in many scenarios. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. We suggest limited conditions under which the formation of household “bubbles” can be safe. These findings can improve future predictions of the timescale and efficacy of interventions needed to control second waves of COVID-19 as well as other similar outbreaks, and highlight the need for better quantification and control of household transmission.

Author Summary

Social distancing is the main tool used to control COVID-19, and involves reducing contacts that could potentially transmit infection with strategies like school closures, work-from-home policies, mask-wearing, or lockdowns. These measures have been applied around the world, but in situations where they have suppressed infections, the effect has not been immediate or consistent. In this study we use a mathematical model to simulate the spread and control of COVID-19, tracking the different settings of person-to-person contact (e.g. household, school, workplace) and the different clinical stages an infected individual may pass through before recovery or death. We find that there are often long delays between when strong social distancing policies are adopted and when cases, hospitalizations, and deaths peak and begin to decline. Moreover, we find that the amount of transmission that happens within versus outside the household is critical to determining when social distancing can be effective and the delay until the epidemic peak. We show how the interaction between unmitigated households spread and residual external connections due to essential activities impacts individual risk and population infection levels. These results can be used to better predict the impact of future interventions to control COVID-19 or similar outbreaks