bluuebunny/crossref_metadata_2025 huggingface dataset:
Anipose: a toolkit for robust markerless 3D pose estimation
Authors: Karashchuk Pierre , Rupp Katie L. , Dickinson Evyn S. , Walling-Bell Sarah , Sanders Elischa , Azim Eiman , Brunton Bingni W. , Tuthill John C.
Published: May 2020

Abstract

Quantifying movement is critical for understanding animal behavior. Advances in computer vision now enable markerless tracking from 2D video, but most animals live and move in 3D. Here, we introduce Anipose, a Python toolkit for robust markerless 3D pose estimation. Anipose is built on the popular 2D tracking method DeepLabCut, so users can easily expand their existing experimental setups to obtain accurate 3D tracking. It consists of four components: (1) a 3D calibration module, (2) filters to resolve 2D tracking errors, (3) a triangulation module that integrates temporal and spatial regularization, and (4) a pipeline to structure processing of large numbers of videos. We evaluate Anipose on four datasets: a moving calibration board, fruit flies walking on a treadmill, mice reaching for a pellet, and humans performing various actions. By analyzing 3D leg kinematics tracked with Anipose, we identify a key role for joint rotation in motor control of fly walking. We believe this open-source software and accompanying tutorials (anipose.org) will facilitate the analysis of 3D animal behavior and the biology that underlies it.
Response to “No support for the adaptive hypothesis of lagging-strand encoding in bacterial genomes”
Authors: Merrikh Houra , Merrikh Christopher
Published: May 2020

Several previous studies by our group suggest that positive selection can drive certain (not all) genes to be retained in the lagging strand orientation2,5,6. This is likely the result of multiple factors including accelerated evolution through replication-transcription conflicts. Liu and Zhang challenge this view, and claim that our method for detecting gene inversions is flawed. Below, we provide empirical evidence that their criticisms are largely unfounded, and show that our original analysis and conclusions are well supported. Though the GC skew method does have a detection limit, we provide new evidence that the fundamental assumptions of our model are accurate, and introduce an improved GC skew calculation which correctly identified 100% of the authors’ gene inversions. Our new findings indicate that the trends we originally identified are stronger than they initially appeared: across species, 89-96% of lagging strand genes appear to be natively leading strand genes that changed orientation. Our statistical analyses offer further support for the notion that for some genes, the lagging strand orientation can be adaptive.
Identification of HIV-Transmitting Sub-Epithelial Mononuclear Phagocytes in Human Anogenital and Colorectal Tissues
Authors: Rhodes Jake W , Botting Rachel A , Bertram Kirstie M , Rana Hafsa , Baharlou Heeva , Longmuir-Vine Erica E , Vegh Peter , Fletcher James , O’Neil Thomas R , Parnell Grant P , Graham J Dinny , Nasr Najla , Lim Jake J K , Barnouti Laith , Haertsch Peter , Gosselink Martijn P , Di Re Angelina , Ctercteko Grahame , Jenkins Gregory J , Brooks Andrew J , Patrick Ellis , Byrne Scott N , Haniffa Muzlifah A , Cunningham Anthony L , Harman Andrew N
Published: May 2020

Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. They are the first cells of the immune system to encounter HIV and play a key role in transmission as they deliver the virus to CD4 T cells, which are the primary HIV target cell in which the virus undergoes replication. Most studies have investigated the role that epithelial MNPs play in HIV transmission but, as mucosal trauma and inflammation are strongly associated with HIV transmission, it is also important to examine the role that sub-epithelial MNPs play. Sub-epithelial MNPs are present in a diverse array of subsets which differ in their function and the pathogens they detect. Understanding how specific subsets interact with HIV and deliver the virus to CD4 T cells is therefore of key importance to vaccine and microbicide development. In this study we have shown that, after topical application, HIV can penetrate to interact with sub-epithelial resident myeloid cells in anogenital explants and defined the full array of MNP subsets that are present in all the human anogenital and colorectal sub-epithelial tissues that HIV may encounter during sexual transmission. In doing so we have identified two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+CD11c+monocyte-derived dendritic cells and langerin-expressing dendritic cells 2 (DC2).
Inference of Diagnostic Markers and Therapeutic Targets from CSF proteomics for the Treatment of Hydrocephalus
Authors: Horowitz Arie , Saugier-Veber Pascale , Gilard Vianney
Published: May 2020

The purpose of this mini-review is to examine if publicly available cerebrospinal fluid (CSF) proteomics data sets can be exploited to provide insight into the etiology of hydrocephalus, into the character of the injury inflicted on the parenchyma by ventriculomegaly, and into the response of the brain to this condition. While this undertaking was instigated by reanalysis of recent comparative proteomics of CSF collected from the brain of healthy andMpdzknockout (KO) mice (Yang et al., 2019), it is an opportunity to survey previously published CSF proteomics data sets to determine if they can be pooled together to that end. The overabundance of extracellular matrix (ECM) proteins, complement factors, and apolipoproteins in the CSF ofMpdzKO mice was taken to indicate that the hydrocephalic brain underwent ischemia, inflammation, and demyelination. The overabundance of five cytokine-binding proteins could be linked uniquely to insulin-like growth factor (IGF) secretion and signaling. The overabundance of two serpins, angiotensinogen and pigment epithelium-derived factor (PEDF) was considered as a biomarker of anti-angiogenic negative-feedback mechanisms to reduce CSF production. These findings raise the intriguing propositions that CSF proteomics can identify biomarkers of case-specific injuries, and that IGF signaling and angiogenesis pathways can serve as therapeutic targets. It appears, however, that the currently available proteomics data is not amenable to comparison of CSF from normal and hydrocephalic patients and cannot be used test the premise of those propositions.
A Rarefaction-Based Extension of the LDM for Testing Presence-Absence Associations in the Microbiome
Authors: Hu Yi-Juan , Lane Andrea , Satten Glen A.
Published: May 2020

Background

Many methods for testing association between the microbiome and covariates of interest (e.g., clinical outcomes, environmental factors) assume that these associations are driven by changes in the relative abundance of taxa. However, these associations may also result from changes in which taxa are present and which are absent. Analyses of such presence-absence associations face a unique challenge: confounding by library size (total sample read count), which occurs when library size is associated with covariates in the analysis. It is known thatrarefaction(subsampling to a common library size) controls this bias, but at the potential cost of information loss as well as the introduction of a stochastic component into the analysis. Currently, there is a need for robust and efficient methods for testing presence-absence associations in the presence of such confounding, both at the community level and at the individual-taxon level, that avoid the drawbacks of rarefaction.

Methods

We have previously developed the linear decomposition model (LDM) that unifies the community-level and taxon-level tests into one framework. Here we present an extension of the LDM for testing presence-absence associations. The extended LDM is a non-stochastic approach that repeatedly applies the LDM toallrarefied taxa count tables, averages the residual sum-of-squares (RSS) terms over the rarefaction replicates, and then forms anF-statistic based on these average RSS terms. We show that this approach compares favorably to averaging theF-statistic fromRrarefaction replicates, which can only be calculated stochastically. The flexible nature of the LDM allows discrete or continuous traits or interactions to be tested while allowing confounding covariates to be adjusted for.

Results

Our simulations indicate that our proposed method is robust to any systematic differences in library size and has better power than alternative approaches. We illustrate our method using an analysis of data on inflammatory bowel disease (IBD) in which case samples have systematically smaller library sizes than controls.

Conclusions

The rarefaction-based extension of the LDM performs well for testing presenceabsence associations and should be adopted even when there is no obvious systematic variation in library size.
Characterization of accessory genes in coronavirus genomes
Authors: Michel Christian J. , Mayer Claudine , Poch Olivier , Thompson Julie D.
Published: May 2020

The Covid19 infection is caused by the SARS-CoV-2 virus, a novel member of the coronavirus (CoV) family. CoV genomes code for a ORF1a / ORF1ab polyprotein and four structural proteins widely studied as major drug targets. The genomes also contain a variable number of open reading frames (ORFs) coding for accessory proteins that are not essential for virus replication, but appear to have a role in pathogenesis. The accessory proteins have been less well characterized and are difficult to predict by classical bioinformatics methods. We propose a computational tool GOFIX to characterize potential ORFs in virus genomes. In particular, ORF coding potential is estimated by searching for enrichment in motifs of theXcircular code, that is known to be over-represented in the reading frames of viral genes. We applied GOFIX to study the SARS-CoV-2 and related genomes including SARS-CoV and SARS-like viruses from bat, civet and pangolin hosts, focusing on the accessory proteins. Our analysis provides evidence supporting the presence of overlapping ORFs 7b, 9b and 9c in all the genomes and thus helps to resolve some differences in current genome annotations. In contrast, we predict that ORF3b is not functional in all genomes. Novel putative ORFs were also predicted, including a truncated form of the ORF10 previously identified in SARS-CoV-2 and a little known ORF overlapping the Spike protein in Civet-CoV and SARS-CoV. Our findings contribute to characterizing sequence properties of accessory genes of SARS coronaviruses, and especially the newly acquired genes making use of overlapping reading frames.
Nested species distribution models ofChlamydialesin tick hostIxodes ricinusin Switzerland
Authors: Rochat Estelle , Vuilleumier Séverine , Aeby Sebastien , Greub Gilbert , Joost Stéphane
Published: May 2020

The tickIxodes ricinusis the vector of various pathogens, includingChlamydialesbacteria, potentially causing respiratory infections. In this study, we modelled the spatial distribution ofI. ricinusand associatedChlamydialesover Switzerland from 2009 to 2019. We used a total of 2293 ticks and 186Chlamydialesoccurrences provided by a Swiss Army field campaign, a collaborative smartphone application and a prospective campaign. For each tick location, we retrieved from Swiss federal datasets the environmental factors reflecting the topography, climate and land cover. We then used the Maxent modelling technique to estimate the suitability forI. ricinusand to subsequently build the nested niche ofChlamydialesbacteria. Results indicate thatI. ricinushigh habitat suitability is determined by higher temperature and vegetation index (NDVI) values, lower temperature during driest months and a higher percentage of artificial and forests areas. The performance of the model was increased when extracting the environmental variables for a 100 m-radius buffer around the sampling points and when considering the data over the two years previous sampling date. ForChlamydialesbacteria, the suitability was favoured by lower percentage of artificial surfaces, driest conditions, high precipitation during coldest months and short distances to wetlands. From 2009 to 2018, we observed an extension of tick andChlamydialessuitable areas, associated with a shift towards higher altitude. The importance to consider spatio-temporal variations of the environmental conditions for obtaining better prediction was also demonstrated.

Importance

Ixodes ricinusis the vector of pathogens, including the agent of Lyme disease, the tick borne encephalitis virus and the less knownChlamydialesbacteria at the origin of some respiratory infections. In this study, we identified the environmental factors influencing the presence ofI. ricinusandChlamydialesin Switzerland and generated maps of their distribution from 2009 to 2018. We found an important expansion of suitable areas for both the tick and the bacteria during the last decade. Results provided also the environmental factors that determine the presence ofChlamydialeswithin ticks. Distribution maps as generated here are expected to bring valuable informations for decision-makers to control tick-borne diseases in Switzerland and establish prevention campaigns. The methodological framework presented could be used to predict the distribution and spread of other host-pathogen couples, to identify environmental factors driving their distribution and to develop control or prevention strategies accordingly.
Comparative co-occurrence network analyses of the cichlid fish gut microbiota: community conservation and diet-associated shifts
Authors: Lluís Riera Joan , Baldo Laura
Published: May 2020

Co-occurrence networks of bacteria associations are a powerful approach to explore ecologically relevant aspects of the gut microbiota structure, beyond community composition alone. Here we exploit the remarkable diversity of cichlid fishes and their multiple lake assemblages to investigate a) network features and patterns of microbial associations that were robust to major phylogeographical variables, and b) community structure changes along cichlid dietary shifts. We tackled these objectives using the large gut microbiota sequencing dataset available (nine lakes from Africa and America), building geographical and diet-specific networks and performing comparative analyses. Major findings indicated that lake and continental networks were highly resembling in global topology and node taxonomic composition, suggesting important constraints in the cichlid gut community assembling. A small fraction of the observed co-occurrence pairwises was conserved across all lake assemblages; while the origin and ecological relevance of these core associations remains unclear, their persistence suggests a potential functional role in the cichlid gut. Comparison of carnivores and herbivores-specific networks as well as mapping of diet-specific values on the African Lake Tanganyika network revealed a clear community shift as a function of diet, with an increase in complexity and node taxonomic diversity from carnivores-omnivores-plantkivores to herbivores. More importantly, diet-associated nodes in herbivores formed complex modules of positive interactions. By intersecting results from association patterns and experimental trials, future studies will be directed to test the strength of these microbial associations and predict the outcome of community alterations driven by diet.

Importance

The gut microbiota is a complex community of interacting bacteria. Predicting patterns of co-occurrence among microbes can help understanding key ecological aspects driving community structure, maintenance and dynamics. Here we showed a powerful application of co-occurrence networks to explore gut bacteria interactions in a primary model system to study animal diversification, the cichlid fishes. Taking advantage of the large scale of phylogeographical and ecological diversity of this fish family, we built gut microbiota networks from distinct lake and continental fish assemblages and performed extensive comparative analyses to retrieve conserved and trait-specific patterns of bacteria associations. Our results identified network features that were independent from the fish biogeography and that indicated an important host selection effect on gut community assembling. Focusing on a single lake assemblage, and therefore excluding the major geographical effect, we observed that the gut microbiota structure dramatically shifted from carnivore to herbivore fishes, with a substantial increase in the number and complexity of microbial interactions.
ExtensiveIn SilicoAnalysis of the Functional and Structural Consequences of SNPs in HumanARXGene
Authors: Mustafa Mujahed I. , Murshed Naseem S. , Abdelmoneim Abdelrahman H. , Makhawi Abdelrafie M.
Published: May 2020

Early infantile epileptic encephalopathy 1 (EIEE1) is a rare but devastating neurologic disorder that displays concomitant cognitive and motor impairment, and is often presented in the first months of life with severe intellectual disability. The objective of this study is to classify the most deleterious nsSNPs inARXgene that may cause EIEE1 disease. Despite the reported association ofARXgene mutations with vulnerability to several neurologic condition, there is lack of in silico analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of theARXat protein level. Therefore, the pathogenic nsSNPs in the humanARXobtained from NCBI were analyzed for their functional and structural impact using bioinformatics tools like SIFT, Polyphen, PROVEAN, I-Mutant, and MUPro. The effects of the mutations on tertiary structure of the human ARX protein were predicted using RaptorX and visualized by UCSF Chimera while STRING was used to investigate its protein–protein interaction. Our extensivein silicoanalysis revealed 11 mutations that will significantly alter the structure of human ARX protein; that may disturb the domain which will affect the function of the protein. Extensivein silicoanalysis of the functional and structural consequences of SNPs in human ARX gene revealed 11 mutations (L535Q, R528S, R380L, V374D, L343Q, T333N, T333S, R332H, R330H, G34R and L33P) that may cause EIEE1.Therefore, can be used as diagnostic markers for EIEE1.
Exogenously applied ABA induced changes in physio-biochemical attributes in selected rice varieties under osmotic stress
Authors: Dash Goutam Kumar , Geda Chaitanya Kumar , Sahoo Soumya Kumar , Baig Mirza Jaynul , Swain Padmini
Published: May 2020

Drought is the most catastrophic abiotic stress that affect plant growth and development. Plant initiates alterations at physiological, biochemical and molecular levels to combat deleterious effects of drought in which abscisic acid, play a pivotal role. The present investigation was conducted to investigate how abscisic acid modulates different biochemical traits under osmotic stress. Twenty-one days old seedlings were exposed to osmotic stress, exogenously applied abscisic acid and the combination of both osmotic stress and abscisic acid to study the influence of abscisic acid on biochemical traits under moisture stress. The results reveals that abscisic acid has no influence on leaf water potential, however, it has active role in increasing osmolytes like proline. Δ1-pyrroline-5-carboxylate reductase and proline dehydrogenase remained unresponsiveness to ABA that indicates ABA-independent regulation of these two enzymes but the activity of Δ1-pyrroline-5-carboxylate synthesase and Ornithine-δ-aminotransferase was enhanced (3 fold) in response to abscisic acid. Antioxidative enzymes increased (catalase-2.5 fold; peroxidase-3 fold and SOD-6 fold) in response to abscisic acid and osmotic stress, gave an insight of the regulation of these traits under the influence of abscisic acid. Aldehyde oxidase remained unresponsive to abscisic acid but showed enhanced expression when both abscisic acid and osmotic stress was applied suggest its ABA-independent regulation. The information provided here has significance in understanding the regulation of different catabolite that play important role in drought tolerance and can be implemented for the development of drought-tolerant varieties.
A rapid urban biodiversity blitz using aquatic environmental DNA
Authors: Hupało Kamil , Majaneva Markus , Czachur Molly Victoria , Sire Lucas , Marquina Daniel , Lijtmaer Darío A. , Ivanov Vladislav , Leidenberger Sonja , Čiampor Fedor , Čiamporová-Zaťovičová Zuzana , Mendes Izabela S. , Desiderato Andrea , Topstad Lasse , Meganck Kenny , Hariz Z. A. Danial , Kjærstad Gaute , Lin Xiao-Long , Price Benjamin , Stevens Mark , Ekrem Torbjørn , Deiner Kristy
Published: May 2020

Background

As global biodiversity declines, there’s an increasing need to create an educated and engaged society. Having people from all ages participate in measuring biodiversity where they live helps to create awareness. Recently, the use of environmental DNA (eDNA) for biodiversity surveys has gained momentum. Here, we test whether sampling eDNA and metabarcoding can be used for rapid urban biodiversity surveys for educational purposes.

Materials & Methods

We sampled 2×1 L of water from each of 15 locations in the city of Trondheim, Norway, including a variety of freshwater, marine and brackish habitats. DNA was extracted, amplified in triplicate for the COI gene and sequenced. The obtained data were analysed on the novel mBRAVE platform, an online open access software and computing resource.

Results

The water samples were collected in two days by two people and the lab analysis was completed in five days by one person. Overall, we detected the presence of 501 taxa identified as belonging to 435 species, representing 90 orders and 18 phyla. On average, only 5.4% of the taxa were shared among six replicates per site. Based on the observed diversity, three distinct clusters were detected and related to geographic distribution of sites. There were some taxa shared between the habitats, with a substantial presence of terrestrial biota.

Discussion

Our results match expected patterns of biodiversity in the landscape and show that with minimal sampling effort, hundreds of species can be detected. Thus, using eDNA analysis of water is promising for rapid biodiversity surveys, and it is likely that more detailed results could be obtained by optimising field and lab methods for particular groups of interest. We recommend that rapid eDNA surveys, with openly available services and softwares, can be used to raise awareness in the importance of biodiversity.
SS3D: Sequence similarity in 3D for comparison of protein families
Authors: Lima Igor , Cino Elio A.
Published: May 2020

Homologous proteins are often compared by pairwise sequence alignment, and structure superposition if the atomic coordinates are available. Unification of sequence and structure data is an important task in structural biology. Here, we present Sequence Similarity 3D (SS3D), a new method for integrating sequence and structure information for comparison of homologous proteins. SS3D quantifies the spatial similarity of residues within a given radius of homologous through-space contacts. The spatial alignments are scored using native BLOSUM and PAM substitution matrices. This work details the SS3D approach and demonstrates its utility through case studies comparing members of several protein families: GPCR, p53, kelch, SUMO, and SARS coronavirus spike protein. We show that SS3D can more clearly highlight biologically important regions of similarity and dissimilarity compared to pairwise sequence alignments or structure superposition alone. SS3D is written in C++, and is available with a manual and tutorial athttps://github.com/0x462e41/SS3D/.
Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing
Authors: Griffin Donald R. , Archang Maani M. , Kuan Chen H. , Weaver Westbrook M. , Weinstein Jason S. , Feng An Chieh , Ruccia Amber , Sideris Elias , Ragkousis Vasileios , Koh Jaekyung , Plikus Maksim V. , Di Carlo Dino , Segura Tatiana , Scumpia Philip O.
Published: May 2020

Biomaterial scaffolds represent a promising approach for material-based tissue regeneration. We previously developed microporous annealed particle (MAP) hydrogels - a flowable, microparticle-based hydrogel in which neighboring hydrogel particles are linkedin situto form a porous scaffold that accelerates wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow scaffold degradation by switching the chirality of the crosslinking peptides from L-peptides to D-peptides. Unexpectedly, despite showing the predicted slower enzymatic degradationin vitro, D-peptide crosslinked MAP hydrogel (D-MAP) hastened material degradationin vivoand imparted significant tissue regeneration to healed cutaneous wounds, including increased tensile strength and hair neogenesis. By themselves, D-chiral peptides were poor activators of macrophage innate immune signalingin vivo, but MAP particles elicit IL-33 type 2 myeloid cell recruitment which is amplifiedin vivoin the presence of D-peptides. Remarkably, D-MAP elicited significant antigen-specific immunity against the D-chiral peptides, and an intact adaptive immune system was required for the hydrogel-induced skin regeneration. These findings demonstrate that the generation of an adaptive immune response from a biomaterial is sufficient to induce cutaneous regenerative healing despite faster scaffold degradation.
Movement-related changes in pallidocortical synchrony differentiate action execution and observation in humans
Authors: Cross Katy A. , Malekmohammadi Mahsa , Choi Jeong Woo , Pouratian Nader
Published: May 2020

Suppression of local and network alpha (8-12 Hz) and beta (12-35 Hz) oscillations in the human basal ganglia-thalamocortical (BGTC) circuit is a prominent feature of movement. Local alpha/beta power, cross-region beta phase coupling, and phase-amplitude coupling (PAC) have all been shown to be suppressed during movement in multiple nodes of the BGTC. However, the specificity of these various movement-related changes to actual movement execution remains poorly understood. To differentiate signals that are specifically related to movement execution, we compared changes in globus pallidus internus (GPi) and motor cortical local oscillatory activity and coupling (cross-region phase coupling and local PAC) during movement execution and movement observation in 12 patients with Parkinson disease undergoing deep brain stimulator implantation. We hypothesized that network coupling is more directly related to movement execution than local power changes, given the putative role of pathological network coupling in movement disorders such as Parkinson disease. We observed suppression of alpha/beta power during action observation and execution in the globus pallidus and motor cortex during both action execution and action observation. In contrast, pallidocortical coherence and GPi and motor cortical alpha/beta-gamma PAC were significantly suppressed only during action execution. Our results demonstrate a functional dissociation within the BG-cortical network during action execution and observation in which suppression of BG-cortical functional connectivity and local phase amplitude coupling are features specifically of overt movement, suggesting a particularly important role in motor execution. This has implications for identification and use of intracranial signals for closed loop brain stimulation therapies.
Integrate Heterogeneous NGS and TGS Data to Boost Genome-free Transcriptome Research
Authors: Qin Yangmei , Lin Zhe , Shi Dan , Zhong Mindong , An Te , Chen Linshan , Wang Yiquan , Lin Fan , Li Guang , Ji Zhi-Liang
Published: May 2020

It is a long-term challenge to undertake reliable transcriptomic research under different circumstances of genome availability. Here, we newly developed a genome-free computational method to aid accurate transcriptome assembly, using the amphioxus as the example. Via integrating ten next generation sequencing (NGS) transcriptome datasets and one third-generation sequencing (TGS) dataset, we built a sequence library of non-redundant expressed transcripts for the amphioxus. The library consisted of overall 91,915 distinct transcripts, 51,549 protein-coding transcripts, and 16,923 novel extragenic transcripts. This substantially improved current amphioxus genome annotation by expanding the distinct gene number from 21,954 to 38,777. We consolidated the library significantly outperformed the genome, as well asde novomethod, in transcriptome assembly from multiple aspects. For convenience, we curated the Integrative Transcript Library database of the amphioxus (http://www.bio-add.org/InTrans/). In summary, this work provides a practical solution for most organisms to alleviate the heavy dependence on good quality genome in transcriptome research. It also ensures the amphioxus transcriptome research grounding on reliable data.
The role of sodium thiocyanate supplementation during dextran sodium sulphate-stimulated experimental colitis
Authors: Liu Yuyang (Anna) , Burton Thomas , Rayner Benjamin Saul , Gabriel Patrick San , Shi Han , Kazzi Mary El , Wang XiaoSuo , Dennis Joanne M , Ahmad Gulfam , Witting Paul Kenneth , Chami Belal
Published: May 2020

Ulcerative colitis is a condition characterised by the infiltration of leukocytes into the gastrointestinal wall. Leukocyte-MPO catalyses hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) formation from chloride (Cl-) and thiocyanous (SCN-) anions, respectively. While HOCl indiscriminately oxidises biomolecules, HOSCN primarily targets low-molecular weight protein thiols. Oxidative damage mediated by HOSCN may be reversible, potentially decreasing MPO-associated host tissue destruction. This study investigated the effect of SCN-supplementation in a model of acute colitis. Female mice were supplemented dextran sodium sulphate (DSS, 3% w/v) in the presence of 10 mM Cl-or SCN-in drinking waterad libitum, or with salts (NaCl and NaSCN only) or water only (controls). Behavioural studies showed mice tolerated NaSCN and NaCl-treated water with water-seeking frequency. Ion-exchange chromatography showed increased fecal and plasma SCN-levels in thiocyanate supplemented mice; plasma SCN-reached similar fold-increase for smokers. Overall there was no difference in weight loss and clinical score, mucin levels, crypt integrity and extent of cellular infiltration between DSS/SCN-and DSS/Cl-groups. Neutrophil recruitment remained unchanged in DSS-treated mice, as assessed by fecal calprotectin levels. Total thiol and tyrosine phosphatase activity remained unchanged between DSS/Cl-and DSS/SCN-groups, however, colonic tissue showed a trend in decreased 3-chlorotyrosine (1.5-fold reduction,p<0.051) and marked increase in colonic GCLC, the rate-limiting enzyme in glutathione synthesis. These data suggest that SCN-administration can modulate MPO activity towards a HOSCN-specific pathway, however, this does not alter the development of colitis within a DSS murine model.

Highlights

Sodium thiocyanate (SCN-) supplementation increased plasma and fecal SCN-level.

Thiocyanate supplementation diverted HOCl-mediated oxidative damage in mice colon.

Thiocyanate supplementation stimulated thiol synthesis in the DSS colitis model.

Thiocyanate provides no protection in an acute experimental model of UC.
Classification of the glyphosate target enzyme (5-enolpyruvylshikimate-3-phosphate synthase)
Authors: Leino Lyydia , Tall Tuomas , Helander Marjo , Saloniemi Irma , Saikkonen Kari , Ruuskanen Suvi , Puigbò Pere
Published: May 2020

Glyphosate is the most common broad-spectrum herbicide. It targets the key enzyme of the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which synthesizes three essential aromatic amino acids (phenylalanine, tyrosine and tryptophan) in plants. Because the shikimate pathway is also found in many prokaryotes and fungi, the widespread use of glyphosate may have unsuspected impacts on the diversity and composition of microbial communities, including the human gut microbiome. Here, we introduce the first bioinformatics method to assess the potential sensitivity of organisms to glyphosate based on the type of EPSPS enzyme. We have precomputed a dataset of EPSPS sequences from thousands of species that will be an invaluable resource to advancing the research field. This novel methodology can classify sequences from >90% of eukaryotes and >80% of prokaryotes. A conservative estimate from our results shows that 54% of species in the core human gut microbiome are sensitive to glyphosate.
The Homo-Edit Distance Problem
Authors: Brand Maren , Tran Nguyen Khoa , Spohr Philipp , Schrinner Sven , Klau Gunnar W.
Published: May 2020

We consider the homo-edit distance problem, which is the minimum number of homo-deletions or homo-insertions to convert one string into another. A homo-insertion is the insertion of a string of equal characters into another string, while a homo-deletion is the inverse operation. We show how to compute the homo-edit distance of two strings in polynomial time: We first demonstrate that the problem is equivalent to computing a common subsequence of the two input strings with a minimum number of homo-deletions and then present a dynamic programming solution for the reformulated problem.

2012 ACM Subject Classification

Applied computing → Bioinformatics; Applied computing → Molecular sequence analysis; Theory of computation → Dynamic programming
Patterns of microbiome variation among infrapopulations of permanent bloodsucking parasites
Authors: Doña Jorge , Herrera Stephany Virrueta , Nyman Tommi , Kunnasranta Mervi , Johnson Kevin P.
Published: May 2020

While interspecific variation in microbiome composition can often be readily explained by factors such as host species identity, there is still limited knowledge of how microbiomes vary at scales lower than the species level (e.g., between individuals or populations). Here, we evaluated variation in microbiome composition of individual parasites among infrapopulations (i.e., populations of parasites of the same species living on a single host individual). To address this question, we used genome-resolved and shotgun metagenomic data of 17 infrapopulations (balanced design) of the permanent, bloodsucking seal louseEchinophthirius horridussampled from individual Saimaa ringed sealsPusa hispida saimensis. Both genome-resolved and read-based metagenomic classification approaches consistently show that parasite infrapopulation identity is a significant factor that explains both qualitative and quantitative patterns of microbiome variation at the intraspecific level. This study contributes to the general understanding of the factors driving patterns of intraspecific variation in microbiome composition, especially of bloodsucking parasites, and has implications for understanding how well-known processes occurring at higher taxonomic levels, such as phylosymbiosis, might arise in these systems.
Optimizing the Electric Field Strength in Multiple Targets for Multichannel Transcranial Electric Stimulation
Authors: Saturnino Guilherme B. , Madsen Kristoffer H. , Thielscher Axel
Published: May 2020

Objective

Most approaches to optimize the electric field pattern generated by multichannel Transcranial Electric Stimulation (TES) require the definition of a preferred direction of the electric field in the target region(s). However, this requires knowledge about how the neural effects depend on the field direction, which is not always available. Thus, it can be preferential to optimize the field strength in the target(s), irrespective of the field direction. However, this results in a more complex optimization problem.

Approach

We introduce and validate a novel optimization algorithm that maximizes focality while controlling the electric field strength in the target to maintain a defined value. It obeys the safety constraints, allows limiting the number of active electrodes and allows also for multi-target optimization.

Main Results

The optimization algorithm outperformed naïve search approaches in both quality of the solution and computational efficiency. Using the amygdala as test case, we show that it allows for reaching a reasonable trade-off between focality and field strength in the target. In contrast, simply maximizing the field strength in the target results in far more extended fields. In addition, by maintaining the pre-defined field strengths in the targets, the new algorithm allows for a balanced stimulation of two or more regions.

Significance

The novel algorithm can be used to automatically obtain individualized, optimal montages for targeting regions without the need to define preferential directions. It will automatically select the field direction that achieves the desired field strength in the target(s) with the most focal stimulation pattern.
Two-pass alignment using machine-learning-filtered splice junctions increases the accuracy of intron detection in long-read RNA sequencing
Authors: Parker Matthew T. , Knop Katarzyna , Barton Geoffrey J. , Simpson Gordon G.
Published: May 2020

Transcription of eukaryotic genomes involves complex alternative processing of RNAs. Sequencing of full-length RNAs using long reads reveals the true complexity of processing. However, the relatively high error rates of long-read sequencing technologies can reduce the accuracy of intron identification. Here we apply alignment metrics and machine-learning-derived sequence information to filter spurious splice junctions from long read alignments and use the remaining junctions to guide realignment in a two-pass approach. This method, available in the software package 2passtools (https://github.com/bartongroup/2passtools), improves the accuracy of spliced alignment and transcriptome assembly for species both with and without existing high-quality annotations.
The efficacy of a virtual reality exposure therapy treatment for fear of flying: A retrospective study
Authors: Gottlieb Amihai , Doniger Glen M. , Hussein Yara , Noy Shlomo , Plotnik Meir
Published: May 2020

Background

Fear of flying (FoF) is an anxiety disorder classified as a phobia. Its prevalence is estimated at 10–40% in the industrialized world, and it is accompanied by severe economic, social, vocational and emotional consequences. In recent years, virtual reality-based exposure therapy (VRET) for FoF has been introduced. One such FoF-VRET is offered as a paid clinical service at the Center of Advanced Technologies in Rehabilitation (CATR), Sheba Medical Center, Israel. Positive long-term efficacy of FoF-VRET has been found in several studies. However, these studies are limited by relatively small, non-representative samples and a lack of comparative pre/post functional efficacy outcome measures.

Methods

To address these limitations, we conducted a retrospective survey of self-referred individuals treated with FoF-VRET at CATR over the previous four years. The aim of the present study was to evaluate the efficacy of our FoF-VRET in this representative real-world sample. Of 274 individuals who received the treatment, 214 met inclusion/criteria, and 103 agreed to participate. The survey focused mainly on collecting information regarding flight activity before and after treatment. The primary outcome measures were: (1) number of flights per month (FpM); (2) number of flight hours per month (FHpM). For each participant, these outcomes were computed for the post-treatment period (≥6 months after FoF-VRET) and the corresponding pre-treatment period.

Results

FpM (mean±SD) increased from .05±.07 to .16±.07 flights (p<.0001). FHpM rose from.22±.41 to .80±.86 hours per month (p<.0001).

Conclusions

These results are indicative of FoF-VRET treatment efficacy. Future studies should evaluate long-term maintenance of the treatment effect and thus identify the optimal frequency for delivery of periodic booster treatments.
Mitochondrial dysfunction in skeletal muscle of fukutin deficient mice is resistant to exercise- and AICAR-induced rescue
Authors: Southern W. Michael , Nichenko Anna S. , Qualls Anita E. , Portman Kensey , Gidon Ariel , Beedle Aaron , Call Jarrod A.
Published: May 2020

Disruptions in the dystrophin-glycoprotein complex (DGC) are clearly the primary basis underlying various forms of muscular dystrophies and dystroglycanopathies, but the cellular consequences of DGC disruption are still being investigated. Mitochondrial abnormalities are becoming an apparent consequence and contributor to dystrophy disease pathology. Herein, we demonstrate that muscle-specific deletion of the fukutin gene [Myf5/fktn-KO mice (KO)], a model of secondary dystroglycanopathy, results in ~30% lower muscle strength (P<0.001) and 16% lower mitochondrial function (P=0.002) compared to healthy littermate controls (LM). We also observed ~80% lower PGC-1α signaling (P=0.004), a primary transcription factor for mitochondrial biogenesis, in KO mice that likely contributes to the mitochondrial defects. PGC-1α is post-translationally regulated via phosphorylation by AMPK. Treatment with the AMPK agonist AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) failed to rescue mitochondrial deficits in KO mice (P=0.458) but did have beneficial (~30% greater) effects on recovery of muscle contractility following injury in both LM and KO mice compared to saline treatment (P=0.006). The beneficial effects of AMPK stimulation via AICAR on muscle function may be partially explained by AMPK’s other role of regulating skeletal muscle autophagy, a cellular process critical for clearance of damaged and/or dysfunctional organelles. Two primary conclusions can be drawn from this data, 1) fukutin deletion produces intrinsic muscular metabolic defects that likely contribute to dystroglycanopathy disease pathology, and 2) AICAR treatment accelerates recovery of muscle function following injury suggesting AMPK signaling as a possible target for therapeutic strategies.
Network-enabled efficient image restoration for 3D microscopy of turbid biological specimens
Authors: Xiao Le , Fang Chunyu , Wang Yarong , Yu Tingting , Zhao Yuxuan , Zhu Dan , Fei Peng
Published: May 2020

Though three-dimensional (3D) fluorescence microscopy has been an essential tool for modern life science research, the light scattering by biological specimens fundamentally prevents its more widespread applications in live imaging. We hereby report a deep-learning approach, termed ScatNet, that enables reversion of 3D fluorescence microscopy from high-resolution targets to low-quality, light-scattered measurements, thereby allowing restoration for a single blurred and light-scattered 3D image of deep tissue, with achieving improved resolution and signal-to-noise ratio. Our approach can computationally extend the imaging depth for current 3D fluorescence microscopes, without the addition of complicated optics. Combining ScatNet approach with cutting-edge light-sheet fluorescence microscopy, we demonstrate that the image restoration of cell nuclei in the deep layer of live Drosophila melanogaster embryos at single-cell resolution. Applying our approach to two-photon excitation microscopy, we could improve the signal and resolution of neurons in mouse brain beyond the photon ballistic region.
Genetic architecture and lifetime dynamics of inbreeding depression in a wild mammal
Authors: Stoffel M.A. , Johnston S.E. , Pilkington J.G. , Pemberton J.M
Published: May 2020

Inbreeding depression is ubiquitous, but we still know little about its genetic architecture and precise effects in wild populations. Here, we combine long-term life-history data with 417K imputed SNP genotypes for 5,952 wild Soay sheep to explore inbreeding depression on a key fitness component, annual survival. Inbreeding manifests in long runs of homozygosity (ROH), which make up nearly half of the genome in the most inbred individuals. The ROH landscape varies widely across the genome, with islands where up to 87% and deserts where only 4% of individuals have ROH. The fitness consequences of inbreeding are severe; a 10% increase in individual inbreeding FROHis associated with a 60% reduction in the odds of survival in lambs, though inbreeding depression decreases with age. Finally, a genome-wide association scan on ROH shows that many loci with small effects and five loci with larger effects contribute to inbreeding depression in survival.
bbsBayes: An R Package for Hierarchical Bayesian Analysis of North American Breeding Bird Survey Data
Authors: Edwards Brandon P.M. , Smith Adam C.
Published: May 2020

The North American Breeding Bird Survey (BBS) is the primary ecological monitoring program used to assess the population, status, and trend of North American birds. As such, accessible analysis of BBS data is crucial to wildlife conservation/management and ecological science in North America. The R packagebbsBayeswas developed as a wrapper for the analysis of BBS data using hierarchical Bayesian models, including the models currently used by the Canadian Wildlife Service and the United States Geological Survey. The goal ofbbsBayesis to provide an accessible package for anyone in the conservation community to estimate population trajectories (time-series) and trends (rates of change) for any of the 400+ bird species monitored by the BBS, and to allow more advance users to easily access the data and model-templates necessary to customize an analysis for their research.
De novo transcriptome assembly, functional annotation and characterization of the Atlantic bluefin tuna (Thunnus thynnus) larval stage
Authors: Luca Marisaldi , Danilo Basili , Giorgia Gioacchini , Oliana Carnevali
Published: May 2020

Over the last two decades, many efforts have been invested in attempting to close the life cycle of the iconic Atlantic bluefin tuna (Thunnus thynnus) and develop a true aquaculture-based market. However, the limited molecular resources nowadays available represent a clear limitation towards the domestication of this species. To fill such a gap of knowledge, we assembled and characterized a de novo larval transcriptome by taking advantage of publicly available databases with the final goal of better understanding the larval development. The assembled transcriptome comprised 37,117 protein-coding transcripts, of which 13,633 full-length (>80% coverage), with an Ex90N50 of 3,061 bp and 76% of complete and single-copy core vertebrate genes orthologues. Of these transcripts, 34,980 had a hit against the EggNOG database and 14,983 with the KAAS annotation server. By comparing our data with a set of representative fish species proteomes, it was found that 78.4% of the tuna transcripts were successfully included in orthologous groups. Codon usage bias was identified for processes such as translation, peptide biosynthesis, muscle development and ion transport, supporting the idea of mechanisms at play in regulating stability and translation efficiency of transcripts belonging to key biological processes during the larval growth. The information generated by this study on the Atlantic bluefin tuna represent a relevant improvement of the transcriptomic resources available to the scientific community and lays the foundation for future works aimed at exploring in greater detail physiological responses at molecular level in different larval stages.