bluuebunny/crossref_metadata_2025_split huggingface dataset:
Build a better bootstrap and the RAWR shall beat a random path to your door: phylogenetic support estimation revisited
Authors: Wang Wei , Hejasebazzi Ahmad , Zheng Julia , Liu Kevin J 
Published: April 2021

AbstractMotivationThe standard bootstrap method is used throughout science and engineering to perform general-purpose non-parametric resampling and re-estimation. Among the most widely cited and widely used such applications is the phylogenetic bootstrap method, which Felsenstein proposed in 1985 as a means to place statistical confidence intervals on an estimated phylogeny (or estimate ‘phylogenetic support’). A key simplifying assumption of the bootstrap method is that input data are independent and identically distributed (i.i.d.). However, the i.i.d. assumption is an over-simplification for biomolecular sequence analysis, as Felsenstein noted.ResultsIn this study, we introduce a new sequence-aware non-parametric resampling technique, which we refer to as RAWR (‘RAndom Walk Resampling’). RAWR consists of random walks that synthesize and extend the standard bootstrap method and the ‘mirrored inputs’ idea of Landan and Graur. We apply RAWR to the task of phylogenetic support estimation. RAWR’s performance is compared to the state-of-the-art using synthetic and empirical data that span a range of dataset sizes and evolutionary divergence. We show that RAWR support estimates offer comparable or typically superior type I and type II error compared to phylogenetic bootstrap support. We also conduct a re-analysis of large-scale genomic sequence data from a recent study of Darwin’s finches. Our findings clarify phylogenetic uncertainty in a charismatic clade that serves as an important model for complex adaptive evolution.Availability and implementationData and software are publicly available under open-source software and open data licenses at: https://gitlab.msu.edu/liulab/RAWR-study-datasets-and-scripts.
Weakly supervised learning of RNA modifications from low-resolution epitranscriptome data
Authors: Huang Daiyun , Song Bowen , Wei Jingjue , Su Jionglong , Coenen Frans , Meng Jia 
Published: April 2021

AbstractMotivationIncreasing evidence suggests that post-transcriptional ribonucleic acid (RNA) modifications regulate essential biomolecular functions and are related to the pathogenesis of various diseases. Precise identification of RNA modification sites is essential for understanding the regulatory mechanisms of RNAs. To date, many computational approaches for predicting RNA modifications have been developed, most of which were based on strong supervision enabled by base-resolution epitranscriptome data. However, high-resolution data may not be available.ResultsWe propose WeakRM, the first weakly supervised learning framework for predicting RNA modifications from low-resolution epitranscriptome datasets, such as those generated from acRIP-seq and hMeRIP-seq. Evaluations on three independent datasets (corresponding to three different RNA modification types and their respective sequencing technologies) demonstrated the effectiveness of our approach in predicting RNA modifications from low-resolution data. WeakRM outperformed state-of-the-art multi-instance learning methods for genomic sequences, such as WSCNN, which was originally designed for transcription factor binding site prediction. Additionally, our approach captured motifs that are consistent with existing knowledge, and visualization of the predicted modification-containing regions unveiled the potentials of detecting RNA modifications with improved resolution.Availability implementationThe source code for the WeakRM algorithm, along with the datasets used, are freely accessible at: https://github.com/daiyun02211/WeakRMSupplementary informationSupplementary data are available at Bioinformatics online.
Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation
Authors: Neudorfer Clemens , Elias Gavin J B , Jakobs Martin , Boutet Alexandre , Germann Jürgen , Narang Keshav , Loh Aaron , Paff Michelle , Horn Andreas , Kucharczyk Walter , Deeb Wissam , Salvato Bryan , Almeida Leonardo , Foote Kelly D , Rosenberg Paul B , Tang-Wai David F , Anderson William S , Mari Zoltan , Ponce Francisco A , Wolk David A , Burke Anna D , Salloway Stephen , Sabbagh Marwan N , Chakravarty M Mallar , Smith Gwenn S , Lyketsos Constantine G , Okun Michael S , Lozano Andres M 
Published: April 2021

Abstarct
Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied—at multiple international centres—58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer’s disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation—including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear—were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.
Prion potentiation after life-long dormancy in mice devoid of PrP
Authors: Martin Davy , Reine Fabienne , Herzog Laetitia , Igel-Egalon Angélique , Aron Naima , Michel Christel , Moudjou Mohammed , Fichet Guillaume , Quadrio Isabelle , Perret-Liaudet Armand , Andréoletti Olivier , Rezaei Human , Béringue Vincent 
Published: April 2021

Abstract
Prions are neurotropic pathogens composed of misfolded assemblies of the host-encoded prion protein PrPC which replicate by recruitment and conversion of further PrPC by an autocatalytic seeding polymerization process. While it has long been shown that mouse-adapted prions cannot replicate and are rapidly cleared in transgenic PrP0/0 mice invalidated for PrPC, these experiments have not been done with other prions, including from natural resources, and more sensitive methods to detect prion biological activity. Using transgenic mice expressing human PrP to bioassay prion infectivity and RT-QuIC cell-free assay to measure prion seeding activity, we report that prions responsible for the most prevalent form of sporadic Creutzfeldt–Jakob disease in human (MM1-sCJD) can persist indefinitely in the brain of intra-cerebrally inoculated PrP0/0 mice. While low levels of seeding activity were measured by RT-QuIC in the brain of the challenged PrP0/0 mice, the bio-indicator humanized mice succumbed at a high attack rate, suggesting relatively high levels of persistent infectivity. Remarkably, these humanized mice succumbed with delayed kinetics as compared to MM1-sCJD prions directly inoculated at low doses, including the limiting one. Yet, the disease that did occur in the humanized mice on primary and subsequent back-passage from PrP0/0 mice shared the neuropathological and molecular characteristics of MM1-sCJD prions, suggesting no apparent strain evolution during lifelong dormancy in PrP0/0 brain. Thus, MM1-sCJD prions can persist for the entire life in PrP0/0 brain with potential disease potentiation on retrotransmission to susceptible hosts. These findings highlight the capacity of prions to persist and rejuvenate in non-replicative environments, interrogate on the type of prion assemblies at work and alert on the risk of indefinite prion persistence with PrP-lowering therapeutic strategies.
Household Exposure to Severe Acute Respiratory Syndrome Coronavirus 2 and Association With Coronavirus Disease 2019 Severity: A Danish Nationwide Cohort Study
Authors: Broccia Marcella , de Knegt Victoria Elizabeth , Mills Elisabeth Helen Anna , Møller Amalie Lykkemark , Gnesin Filip , Fischer Thea K , Zylyftari Nertila , Blomberg Stig Nikolaj , Andersen Mikkel Porsborg , Schou Morten , Fosbøl Emil , Kragholm Kristian , Christensen Helle Collatz , Polcwiartek Laura Bech , Phelps Matthew , Køber Lars , Torp-Pedersen Christian 
Published: April 2021

Abstract

Background
Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severity of coronavirus disease 2019 (COVID-19) is likely associated with the infectious dose of SARS-CoV-2 exposure. We therefore aimed to assess the association between SARS-CoV-2 exposure within households and COVID-19 severity.

Methods
We performed a Danish, nationwide, register-based, cohort study including laboratory-confirmed SARS-CoV-2–infected individuals from 22 February 2020 to 6 October 2020. Household exposure to SARS-CoV-2 was defined as having 1 individual test positive for SARS-CoV-2 within the household. Cox proportional hazards models were used to estimate the association between “critical COVID-19” within and between households with and without secondary cases.

Results
From 15 063 multiperson households, 19 773 SARS-CoV-2–positive individuals were included; 11 632 were categorized as index cases without any secondary household cases; 3431 as index cases with secondary cases, that is, 22.8% of multiperson households; and 4710 as secondary cases. Critical COVID-19 occurred in 2.9% of index cases living with no secondary cases, 4.9% of index cases with secondary cases, and 1.3% of secondary cases. The adjusted hazard ratio for critical COVID-19 among index cases vs secondary cases within the same household was 2.50 (95% confidence interval [CI], 1.88–3.34), 2.27 (95% CI, 1.77–2.93) for index cases in households with no secondary cases vs secondary cases, and 1.1 (95% CI, .93–1.30) for index cases with secondary cases vs index cases without secondary cases.

Conclusions
We found no increased hazard ratio of critical COVID-19 among household members of infected SARS-CoV-2 index cases.
Continuous Leakage-Amplified Public-Key Encryption With CCA Security
Authors: Zhang Wenzheng , Qiao Zirui , Yang Bo , Zhou Yanwei , Zhang Mingwu 
Published: April 2021

Abstract
Secret key leakage has become a security threat in computer systems, and it is crucial that cryptographic schemes should resist various leakage attacks, including the continuous leakage attacks. In the literature, some research progresses have been made in designing leakage resistant cryptographic primitives, but there are still some remaining issues unsolved, e.g. the upper bound of the permitted leakage is fixed. In actual applications, the leakage requirements may vary; thus, the leakage parameter with fixed size is not sufficient against various leakage attacks. In this paper, we introduce some novel idea of designing a continuous leakage-amplified public-key encryption scheme with security against chosen-ciphertext attacks. In our construction, the leakage parameter can have an arbitrary length, i.e. the length of the permitted leakage can be flexibly adjusted according to the specific leakage requirements. The security of our proposed scheme is formally proved based on the classic decisional Diffie–Hellman assumption.
Predicting effects of warming requires a whole-of-life cycle perspective: a case study in the alpine herb Oreomyrrhis eriopoda
Authors: Satyanti Annisa , Liantoro Toton , Thomas Morgan , Neeman Teresa , Nicotra Adrienne B , Guja Lydia K 
Published: April 2021

Abstract
Global warming is affecting plant phenology, growth and reproduction in complex ways and is particularly apparent in vulnerable alpine environments. Warming affects reproductive and vegetative traits, as well as phenology, but seldom do studies assess these traits in concert and across the whole of a plant’s life cycle, particularly in wild species. Thus, it is difficult to extrapolate from such effects to predictions about the persistence of species or their conservation and management. We assessed trait variation in response to warming in Oreomyrrhis eriopoda, an Australian native montane herb, in which populations vary in germination strategy (degree of dormancy) and growth characteristics as a function of ecological factors. Warming accelerated growth in the early stages of development, particularly for populations with non-dormant seed. The differences in growth disappeared at the transition to reproduction, when an accelerating effect on phenology emerged, to varying degrees depending on germination strategy. Overall, warming reduced flower and seed production and increased mortality, indicating a reduction in reproductive opportunities, particularly for populations with dormant seed. Developmental condition affected germination strategy of the next generation seed, leading to increased degree of dormancy and slowed germination rate. But there were no whole-scale shifts in strategy or total germination percent. Following through the life cycle reveals that warming will have some potentially positive effects (early growth rates) and some negative effects (reduced reproductive output). Ultimately, warming impacts will depend on how those effects play out in the field: early establishment and an accelerated trajectory to seed maturity may offset the tradeoff with overall seed production. Small differences among germination strategies likewise may cascade to larger effects, with important implications for persistence of species in the alpine landscape. Thus, to understand and manage the response of wild species to warming takes a whole-of-life perspective and attention to ecologically significant patterns of within-species variation.
Supervised Obesity Reduction Trial for AF ablation patients: results from the SORT-AF trial
Authors: Gessler Nele , Willems Stephan , Steven Daniel , Aberle Jens , Akbulak Ruken Oezge , Gosau Nils , Hoffmann Boris A , Meyer Christian , Sultan Arian , Tilz Roland , Vogler Julia , Wohlmuth Peter , Scholz Susanne , Gunawardene Melanie A , Eickholt Christian , Lüker Jakob 
Published: April 2021

Abstract

Aims
Weight management seems to be beneficial for obese atrial fibrillation (AF) patients; however, randomized data are sparse. Thus, this study aimed to investigate the influence of weight reduction on AF ablation outcomes.

Methods and results
SORT-AF is an investigator-sponsored, prospective, randomized, multicentre, and clinical trial. Patients with symptomatic AF (paroxysmal or persistent) and body mass index (BMI) 30–40 kg/m2 underwent AF ablation and were randomized to either weight-reduction (group 1) or usual care (group 2), after sleep–apnoea–screening and loop recorder (ILR) implantation. The primary endpoint was defined as AF burden between 3 and 12 months after AF ablation. Overall, 133 patients (60 ± 10 years, 57% persistent AF) were randomized to group 1 (n = 67) and group 2 (n = 66), respectively. Complications after AF-ablation were rare (one stroke and no tamponade). The intervention led to a significant reduction of BMI (34.9 ± 2.6–33.4 ± 3.6) in group 1 compared to a stable BMI in group 2 (P &lt; 0.001). Atrial fibrillation burden after ablation decreased significantly (P &lt; 0.001), with no significant difference regarding the primary endpoint between the groups (P = 0.815, odds ratio: 1.143, confidence interval: 0.369–3.613). Further analyses showed a significant correlation between BMI and AF recurrence for patients with persistent AF compared with paroxysmal AF patients (P = 0.032).

Conclusion
The SORT-AF study shows that AF ablation is safe and successful in obese patients using continuous monitoring via ILR. Although the primary endpoint of AF burden after ablation did not differ between the two groups, the effects of weight loss and improvement of exercise activity were beneficial for obese patients with persistent AF demonstrating the relevance of life-style management as an important adjunct to AF ablation in this setting.

Trial registration number
NCT02064114.
Divergent Gene Expression Following Duplication of Meiotic Genes in the Stick InsectClitarchus hookeri
Authors: Wu Chen , Twort Victoria G , Newcomb Richard D , Buckley Thomas R 
Published: April 2021

AbstractSome animal groups, such as stick insects (Phasmatodea), have repeatedly evolved alternative reproductive strategies, including parthenogenesis. Genomic studies have found modification of the genes underlying meiosis exists in some of these animals. Here we examine the evolution of copy number, evolutionary rate, and gene expression in candidate meiotic genes of the New Zealand geographic parthenogenetic stick insect Clitarchus hookeri. We characterized 101 genes from a de novo transcriptome assembly from female and male gonads that have homology with meiotic genes from other arthropods. For each gene we determined copy number, the pattern of gene duplication relative to other arthropod orthologs, and the potential for meiosis-specific expression. There are five genes duplicated in C. hookeri, including one also duplicated in the stick insect Timema cristinae, that are not or are uncommonly duplicated in other arthropods. These included two sister chromatid cohesion associated genes (SA2 and SCC2), a recombination gene (HOP1), an RNA-silencing gene (AGO2) and a cell-cycle regulation gene (WEE1). Interestingly, WEE1 and SA2 are also duplicated in the cyclical parthenogenetic aphid Acyrthosiphon pisum and Daphnia duplex, respectively, indicating possible roles in the evolution of reproductive mode. Three of these genes (SA2, SCC2, and WEE1) have one copy displaying gonad-specific expression. All genes, with the exception of WEE1, have significantly different nonsynonymous/synonymous ratios between the gene duplicates, indicative of a shift in evolutionary constraints following duplication. These results suggest that stick insects may have evolved genes with novel functions in gamete production by gene duplication.
REGULATORY MUTATIONS OF INOSITOL BIOSYNTHESIS IN YEAST: ISOLATION OF INOSITOL-EXCRETING MUTANTS
Authors: Greenberg Miriam L , Reiner Barry , Henry Susan A 
Published: April 2021

ABSTRACT
The enzyme inositol-1-phosphate synthase (I-1-P synthase), product of the INO1 locus, catalyzes the synthesis of inositol-1-phosphate from the substrate glucose-6-phosphate. The activity of this enzyme is dramatically repressed in the presence of inositol. By selecting for mutants which overproduce and excrete inositol, we have identified mutants constitutive for inositol-1-phosphate synthase as well as a mutation in phospholipid biosynthesis. Genetic analysis of the mutants indicates that at least three loci (designated OPI1, OPI2 and OPI4) direct inositol-mediated repression of I-1-P synthase. Mutants of these loci synthesize I-1-P synthase constitutively. Three loci are unlinked to each other and to INO1, the structural gene for the enzyme. A mutant of a fourth locus, OPI3, does not synthesize I-1-P synthase constitutively, despite its inositol excretion phenotype. This mutant is preliminarily identified as having a defect in phospholipid synthesis.
THE Ah PHENOTYPE. SURVEY OF FORTY-EIGHT RAT STRAINS AND TWENTY INBRED MOUSE STRAINS
Authors: Nebert Daniel W , Jensen Nancy M , Shinozuka Hisashi , Kunz Heinz W , Gill Thomas J 
Published: April 2021

ABSTRACT
Forty-four inbred and four randombred rat strains and 20 inbred mouse strains were examined for their Ah phenotype by determining the induction of liver microsomal aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity (EC 1.14.14.1) by intraperitoneal treatment with either β-naphthoflavone or 3-methylcholanthrene. All 48 rat strains were found to be Ah-responsive. The maximally induced hydroxylase specific activities of the ALB/Pit, MNR/Pit, MR/Pit, SHR/Pit, and Sprague-Dawley strains were of the same order of magnitude as the basal hydroxylase specific activities of the ACI/Pit, F344/Pit, OKA/Pit, and MNR/N strains. Six of the 20 mouse strains were Ah-nonresponsive (i.e. lacking the normal induction response and presumably lacking detectable amounts of the Ah receptor). The basal hydroxylase specific activities of the BDL/N, NFS/N, STAR/N, and ST/JN mouse strains were more than twice as high as the maximally induced hydroxylase specific activity of the CBA/HT strain.——To date, 24 Ah-nonresponsive mouse strains have been identified, out of a total of 68 known to have been characterized. The reasons for not finding a single Ah-nonresponsive inbred rat strain—as compared with about one Ah-nonresponsive inbred mouse strain found for every three examined—remain unknown.
GENETIC DISSECTION OF CLONALLY INHERITED GENOMES OF POECILIOPSIS: II. INVESTIGATION OF A SILENT CARBOXYLESTERASE ALLELE
Authors: Spinella Dominic G , Vrijenhoek Robert C 
Published: April 2021

ABSTRACT
According to the ratchet mechanism hypothesis, deleterious mutations should accumulate in clonal genomes of unisexual fish of the genus Poeciliopsis. This study defines one such mutant, a silent carboxylesterase allele (Es-5o) which is found in the heterozygous condition in a particular population of P. monacha-occidentalis. An antiserum to purified Poeciliopsis carboxylesterase cross-reacts with the gene product of the Es-5o allele upon immunoelectrophoresis. This finding of cross-reacting material associated with the Es-5o allele provides a useful marker for the breeding of a carboxylesterase deficient strain.
ESTIMATES OF INBREEDING IN A NATURAL POPULATION: A COMPARISON OF SAMPLING PROPERTIES
Authors: Curie-Cohen Martin 
Published: April 2021

ABSTRACT
The average inbreeding coefficient f of a population can be estimated in several different ways based solely on the genotypic frequencies at a single locus. The means and variances of four different estimates have been compared. While the four estimates are equivalent when there are two alleles, the best estimates when there are three or more alleles are based upon total heterozygosity (see PDF) where x and y are the expected and observed number of heterozygotes) and the proportion of alleles that are homozygous (see PDF) where k = the number of alleles, aii = the number of AiAi homozygotes, and 2aij = the number of AiAj heterozygotes). Both are minimally biased estimates of f and have identical sampling variances when all alleles are equally frequent. However, when alleles have different frequencies, the choice between these two estimates depends on the gene frequencies and the true inbreeding coefficient of a population; f 2 is the best estimate when the true average inbreeding coefficient is suspected to be low or f = 0, while f 1 is best in populations with large average inbreeding coefficients. Approximate sampling variances of these two estimates are given for any f and any number of alleles with arbitrary gene frequencies; these approximations are accurate for samples as small as n = 100. The chi-square and maximum likelihood estimates of f are not as good for realistic sample sizes.