bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Epidemiology, Diagnostics and Mechanisms of Antibiotic Resistance inMycobacterium tuberculosiscomplex in Africa: A Systematic Review of Current Reports
Authors: Sekyere John Osei , Reta Melese Abate , Maningi Nontuthuko Excellent , Fourie Petrus Bernard 
Published: October 2019

AbstractBackgroundTuberculosis (TB) remains a main global public health problem. However, a systematic review of TB resistance epidemiology in Africa is wanting.MethodsA comprehensive systematic search of PubMed, Web of Science and ScienceDirect for English research articles reporting on the molecular epidemiology ofMycobacterium tuberculosiscomplex resistance in Africa from January 2007 to December 2018 was undertaken.Results and conclusionQualitative and quantitative synthesis were respectively undertaken with 232 and 186 included articles, representing 32 countries. TB monoresistance rate was highest for isoniazid (59%) and rifampicin (27%), particularly in Zimbabwe (100%), Swaziland (100%), and Sudan (67.9%) whilst multidrug resistance (MDR) rate was substantial in Zimbabwe (100%), Sudan (34.6%), Ivory Coast (24.5%) and Ethiopia (23.9%). Resistance-conferring mutations were commonly found inkatG(n=3694),rpoB(n=3591),rrs(n=1272),inhA(n=1065),pncA(n=1063) andembB(n=705) in almost all included countries: S315G/I/N/R/T, V473D/F/G/I, Q471H/Q/R/Y, S303C/L etc. inkatG;S531A/F/S/G, H526A/C/D/G, D516A/E/G etc. inrpoB;A1401G, A513C etc. inrrs;C15T, G17A/T, -A16G etc. ininhA;Ins456C, Ins172G, L172P, C14R, Ins515G etc inpncA. Commonest lineages and families such as T (n=8139), LAM (n=5243), Beijing (n=5471), Cameroon (n=3315), CAS (n=2021), H (n=1773) etc., with the exception of T, were not fairly distributed; Beijing, Cameroon and CAS were prevalent in South Africa (n=4964), Ghana (n=2306), and Ethiopia/Tanzania (n=799/635) respectively. Resistance mutations were not lineage-specific and sputum (96.2%) were mainly used for diagnosing TB resistance using the LPA (38.5%), GeneXpert (17.2%), whole-genome sequencing (12.3%) and PCR/amplicon sequencing (9%/23%). Intercountry spread of strains were limited while intra-country dissemination was common. TB resistance and its diagnosis remain a major threat in Africa, necessitating urgent action to contain this global menace.
Diagnosing Cornelia de Lange syndrome and related neurodevelopmental disorders using RNA-sequencing
Authors: Rentas Stefan , Rathi Komal S. , Kaur Maninder , Raman Pichai , Krantz Ian D. , Sarmady Mahdi , Tayoun Ahmad Abou 
Published: October 2019

ABSTRACTPurposeNeurodevelopmental phenotypes represent major indications for children undergoing clinical exome sequencing. However, 50% of cases remain undiagnosed even upon exome reanalysis. Here we show RNA sequencing (RNA-seq) on human B lymphoblastoid cell lines (LCL) is highly suitable for neurodevelopmental Mendelian gene testing and demonstrate the utility of this approach in suspected cases of Cornelia de Lange syndrome (CdLS).MethodsGenotype-Tissue Expression project transcriptome data for LCL, blood, and brain was assessed for neurodevelopmental Mendelian gene expression. Detection of abnormal splicing and pathogenic variants in these genes was performed with a novel RNA-seq diagnostic pipeline and using a validation CdLS-LCL cohort (n=10) and test cohort of patients who carry a clinical diagnosis of CdLS but negative genetic testing (n=5).ResultsLCLs share isoform diversity of brain tissue for a large subset of neurodevelopmental genes and express 1.8-fold more of these genes compared to blood (LCL, n=1706; whole blood, n=917). This enables testing of over 1000 genetic syndromes. The RNA-seq pipeline had 90% sensitivity for detecting pathogenic events and revealed novel diagnoses such as abnormal splice products in NIPBL and pathogenic coding variants in BRD4 and ANKRD11.ConclusionThe LCL transcriptome enables robust frontline and/or reflexive diagnostic testing for neurodevelopmental disorders.
APOE interacts with tau PET to influence memory independently of amyloid PET
Authors: Weigand Alexandra J. , Thomas Kelsey R. , Bangen Katherine J. , Eglit Graham M.L. , Delano-Wood Lisa , Gilbert Paul E. , Brickman Adam M. , Bondi Mark W. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

AbstractObjectiveApolipoprotein E (APOE) interacts with AD pathology to promote disease progression. Studies of APOE risk primarily focus on amyloid, however, and little research has assessed its interaction with tau pathology independent of amyloid. The current study investigated the moderating effect of APOE genotype on independent associations of amyloid and tau PET with cognition.MethodsParticipants included 297 older adults without dementia from the Alzheimer’s Disease Neuroimaging Initiative. Regression equations modeled associations between cognitive domains and (1) cortical Aβ PET levels adjusting for tau PET and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aβ PET, including interactions with APOE ε4 carrier status.ResultsAdjusting for tau PET, Aβ was not associated with cognition and did not interact with ε4 status. In contrast, adjusting for Aβ PET, MTL tau PET was significantly associated with all cognitive domains. Further, there was a moderating effect of ε4 status on MTL tau and memory with the strongest negative associations in ε4 carriers and at high levels of tau. This interaction persisted even among only Aβ negative individuals.InterpretationAPOE ε4 genotype strengthens the negative association between MTL tau and memory independently of Aβ, although the converse is not observed, and this association may be particularly strong at high levels of tau. These findings suggest that APOE may interact with tau independently of Aβ and that elevated MTL tau confers negative cognitive consequences in Aβ negative ε4 carriers.
Evolution of crab eye structures and the utility of ommatidia morphology in resolving phylogeny
Authors: Luque Javier , Allison W. Ted , Bracken-Grissom Heather D. , Jenkins Kelsey M. , Palmer A. Richard , Porter Megan L. , Wolfe Joanna M. 
Published: October 2019

ABSTRACTImage-forming compound eyes are such a valuable adaptation that similar visual systems have evolved independently across crustaceans. But if different compound eye types have evolved independently multiple times, how useful are eye structures and ommatidia morphology for resolving phylogenetic relationships? Crabs are ideal study organisms to explore these questions because they have a good fossil record extending back into the Jurassic, they possess a great variety of optical designs, and details of eye form can be compared between extant and fossil groups. True crabs, or Brachyura, have been traditionally divided into two groups based on the position of the sexual openings in males and females: the so-called ‘Podotremata’ (females bearing their sexual openings on the legs), and the Eubrachyura, or ‘higher’ true crabs (females bearing their sexual openings on the thorax). Although Eubrachyura appears to be monophyletic, the monophyly of podotreme crabs remains controversial and therefore requires exploration of new character systems. The earliest podotremous lineages share the plesiomorphic condition of ‘mirror’ reflecting superposition eyes with most shrimp, lobsters, and anomurans (false crabs and allies). The optical mechanisms of fossil and extant podotreme groups more closely related to Eubrachyura, however, are still poorly investigated. To better judge the phylogenetic utility of compound eye form, we investigated the distribution of eye types in fossil and extant podotreme crabs. Our findings suggest the plesiomorphic ‘mirror’ eyes—seen in most decapod crustaceans including the earliest true crabs—has been lost in several ‘higher’ podotremes and in eubrachyurans. We conclude that the secondary retention of larval apposition eyes has existed in eubrachyurans and some podotremes since at least the Early Cretaceous, and that the distribution of eye types among true crabs supports a paraphyletic podotreme grade, as suggested by recent molecular and morphological phylogenetic studies. We also review photoreceptor structure and visual pigment evolution, currently known in crabs exclusively from eubrachyuran representatives. These topics are critical for future expansion of research on podotremes to deeply investigate the homology of eye types across crabs.
Molecular and histologic outcomes following spinal cord injury in spiny mice,Acomys cahirinus
Authors: Streeter K.A. , Sunshine M.D. , Brant J.O. , Sandoval M. A.G.W. , Maden M. , Fuller D.D. 
Published: October 2019

AbstractThe spiny mouse (Acomys cahirinus)appears to be unique among mammals by showing little scarring or fibrosis after skin or muscle injury, but theAcomysresponse to spinal cord injury (SCI) is unknown. We tested the hypothesis thatAcomyswould have molecular and immunohistochemical evidence of reduced spinal inflammation and fibrosis following SCI as compared to C57BL/6 mice (Mus), which similar to all mammals studied to date exhibits spinal scarring following SCI. Initial experiments used two pathway-focused RT-PCR gene arrays (“wound healing” and “neurogenesis”) to evaluate tissue samples from the C2-C6 spinal cord 3-days after a C3/C4 hemi-crush injury (C3Hc). Based on the gene array, specific genes were selected for RT-qPCR evaluation using species-specific primers. The results supported our hypothesis by showing increased inflammation and fibrosis related gene expression (Serpine 1, Plau, Timp1)inMusas compared toAcomys(P<0.05). RT-qPCR also showed enhanced stem cell and axonal guidance related gene expression(Bmp2, GDNF, Shh)inAcomyscompared toMus(P<0.05). Immunohistochemical evaluation of the spinal lesion at 4-wks post-injury indicated reduced collagen IV immunostaining inAcomys(P<0.05). Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1(IBA1) immunostaining indicated morphological differences in the appearance of astrocytes and macrophages/microglia inAcomys. Collectively, the molecular and histologic results support the hypothesis thatAcomyshas reduced spinal inflammation and fibrosis following SCI. We suggest thatAcomysmay be a useful comparative model to study adaptive responses to SCI.HighlightsSpiny mice (Acomys cahirinus)and C57BL/6 (Mus) were studied after spinal injuryRT-PCR gene arrays suggested different molecular response inAcomysRTq-PCR with species-specific primers showed increased neurogenesis-related signalingHistology indicates reduced scarring and fibrosis inAcomysAcomysmay be a useful comparative model to study SCI
The first fossil skull of an anteater (Vermilingua, Myrmecophagidae) from northern South America, a taxonomic reassessment ofNeotamanduaand a discussion of the myrmecophagid diversification
Authors: Jiménez-Lara Kevin , González Jhon 
Published: October 2019

AbstractThe evolutionary history of the South American anteaters, Vermilingua, is incompletely known as consequence of the fragmentary and geographically biased nature of the fossil record of this group.Neotamandua borealisis the only recorded extinct species from northern South America, specifically from the Middle Miocene of La Venta area, southwestern Colombia. A new genus and species of myrmecophagid for La Venta, Gen. et sp. nov., is here described based on a new partial skull. Additionally, given that the co-occurrent species of Gen. et sp. nov.,N. borealis, was originally referred to asNeotamandua, the taxonomic status of this genus is revised. The morphological and taxonomic analyses of these taxa indicate that Gen. et sp. nov. may be related toTamanduaand that the justification of the generic assignments of the species referred to asNeotamanduais weak or insufficient. Two species previously referred to asNeotamandua(N. magnaandN.?australis) were designated asspecies inquirendaeand new diagnostic information for the redefined genus and its type species,N. conspicua, is provided. Together, these results suggest that the diversification of Myrmecophagidae was taxonomically and biogeographically more complex than what has been proposed so far. Considering the new evidence, it is proposed a synthetic model on the diversification of these xenartrans during the late Cenozoic based on the probable relationships between their intrinsic ecological constraints and some major abiotic changes in the Americas.
Exact calculation of stationary solution and parameter sensitivity analysis of stochastic continuous time Boolean models
Authors: Koltai Mihály , Noel Vincent , Zinovyev Andrei , Calzone Laurence , Barillot Emmanuel 
Published: October 2019

AbstractMotivationSolutions to stochastic Boolean models are usually estimated by Monte Carlo simulations, but as the state space of these models can be enormous, there is an inherent uncertainty about the accuracy of Monte Carlo estimates and whether simulations have reached all asymptotic solutions. Moreover, these models have timescale parameters (transition rates) that the probability values of stationary solutions depend on in complex ways that have not been analyzed yet in the literature. These two fundamental uncertainties call for an exact calculation method for this class of models.ResultsWe show that the stationary probability values of the attractors of stochastic (asynchronous) continuous time Boolean models can be exactly calculated. The calculation does not require Monte Carlo simulations, instead it uses an exact matrix calculation method previously applied in the context of chemical kinetics. Using this approach, we also analyze the under-explored question of the effect of transition rates on the stationary solutions and show the latter can be sensitive to parameter changes. The analysis distinguishes processes that are robust or, alternatively, sensitive to parameter values, providing both methodological and biological insights.Contactmihaly.koltai@curie.froremmanuel.barillot@curie.frSupplementary informationSupplementary data available atbioRxivonline.Availability and implementationThe calculation method described in the article is available as the ExaStoLog MATLAB package on GitHub athttps://github.com/sysbio-curie/exact-stoch-log-mod
Differential polysaccharide utilization is the basis for a nanohaloarchaeon : haloarchaeon symbiosis
Authors: La Cono Violetta , Messina Enzo , Rohde Manfred , Arcadi Erika , Ciordia Sergio , Crisafi Francesca , Denaro Renata , Ferrer Manuel , Giuliano Laura , Golyshin Peter N. , Golyshina Olga V. , Hallsworth John E. , La Spada Gina , Mena Maria C. , Shevchenko Margarita A. , Smedile Francesco , Sorokin Dimitry Y. , Toshchakov Stepan V. , Mushegian Arcady , Yakimov Michail M. 
Published: October 2019

AbstractNanohaloarchaeota, a clade of diminutive archaea, with small genomes and limited metabolic capabilities, are ubiquitous in hypersaline habitats, which they share with the extremely halophilic and phylogenetically distant euryarchaea. Some of these nanohaloarchaeota and euryarchaea appear to interact with each other. In this study, we investigate the genetic and physiological nature of their relationship. We isolated the nanohaloarchaeon Candidatus Nanohalobium constans LC1Nh and the haloarchaeon Halomicrobium sp. LC1Hm from a solar saltern, reproducibly co-cultivated these species, sequenced their genomes, and characterized their metabolic/trophic interactions. The nanohaloarchaeon is a magnesium-dependent aerotolerant heterotrophic anaerobe of the DPANN superphylum; it lacks respiratory complexes and its energy production relies on fermentative metabolism of sugar derivatives, obtained by depolymerizing alpha-glucans or by acquiring the chitin monomer N-acetylglucosamine from the chitinolytic haloarchaeal host. Halomicrobium is a member of the class Halobacteria and a chitinotrophic aerobe. The nanohaloarchaeon lacks key biosynthetic pathways and is likely to be provided with amino acids, lipids, nucleotides and cofactors via physical contact with its host Halomicrobium. In turn, the ability of Ca. Nanohalobium to hydrolyse alpha-glucans boosts the host’s growth in the absence of a chitin substrate. These findings suggest that at least some members of the nanohaloarchaea, previously considered ecologically unimportant given their limited metabolic potential, in fact may play significant roles in the microbial carbon turnover, food chains, and ecosystem function. The behaviour of Halomicrobium, which accommodates the colonization by Ca. Nanohalobium, can be interpreted as a bet-hedging strategy, maximizing its long-term fitness in a habitat where the availability of carbon substrates can vary both spatially and temporarily.
Activation and inhibition of nonsense-mediated mRNA decay controls the abundance of alternative polyadenylation products
Authors: Kishor Aparna , Fritz Sarah E. , Haque Nazmul , Ge Zhiyun , Yang Wenjing , Zhu Jun , Hogg J. Robert 
Published: October 2019

SUMMARYAlternative polyadenylation (APA) produces transcript 3’ untranslated regions (3’UTRs) with distinct sequences, lengths, stability, and functions. We show here that APA products include a class of cryptic nonsense-mediated mRNA decay (NMD) substrates with extended 3’UTRs that gene- or transcript-level analyses of NMD often fail to detect. Transcriptome-wide, the core NMD factor UPF1 preferentially recognizes long 3’UTR products of APA, leading to their systematic downregulation. Further, we find that many APA events consistently observed in multiple tumor types are controlled by NMD. Additionally, PTBP1, previously implicated in direct modulation of co-transcriptional polyA site choice, regulates the balance of short and long 3’UTR isoforms by inhibiting NMD. Our data suggest that PTBP1 binding near polyA sites can drive production of long 3’UTR APA products in the nucleus and/or protect them from decay in the cytoplasm. Together, our findings reveal a widespread role for NMD in shaping the outcomes of APA.
Gene Balance Predicts Transcriptional Responses Immediately Following Ploidy Change InArabidopsis thaliana
Authors: Potter Barney , Song Michael J. , Doyle Jeff J. , Coate Jeremy E. 
Published: October 2019

AbstractThe Gene Balance Hypothesis postulates that there is selection on gene copy number (gene dosage) to preserve stoichiometric balance among interacting proteins. This presupposes that gene product abundance is governed by gene dosage, and that the way in which gene product abundance is governed by gene dosage is consistent for all genes in a dosage-sensitive network or complex. Gene dosage responses, however, have rarely been quantified and the available data suggest that they are highly variable. We sequenced the transcriptomes of two synthetic autopolyploid accessions ofArabidopsis thalianaand their diploid progenitors, as well as one natural tetraploid and its synthetic diploid produced via haploid induction, to estimate transcriptome size and gene dosage responses immediately following ploidy change. We demonstrate that overall transcriptome size does not exhibit a simple doubling in response to genome doubling, and that individual gene dosage responses are highly variable in all three accessions, indicating that expression is not strictly coupled with gene dosage. Nonetheless, putatively dosage-sensitive gene groups (GO terms, metabolic networks, gene families, and predicted interacting protein pairs) exhibit both smaller and more coordinated dosage responses than do putatively dosage-insensitive gene groups, suggesting that constraints on dosage balance operate immediately following whole genome duplication. This supports the hypothesis that duplicate gene retention patterns are shaped by selection to preserve dosage balance.
Metagenomic discovery and co-infection of diverse wobbly possum disease viruses and novel hepaciviruses in Australian brushtail possums
Authors: Chang Wei-Shan , Eden John-Sebastian , Hartley William J. , Shi Mang , Rose Karrie , Holmes Edward C. 
Published: October 2019

AbstractBackgroundAustralian brushtail possums (Trichosurus vulpecula) are an introduced pest species in New Zealand, but native to Australia where they are protected for biodiversity conservation. Wobbly possum disease (WPD) is a fatal neurological disease of Australian brushtail possums described in New Zealand populations that has been associated with infection by the arterivirus (Arteriviridae) wobbly possum disease virus (WPDV-NZ). Clinically, WPD-infected possums present with chronic meningoencephalitis, choroiditis and multifocal neurological symptoms including ataxia, incoordination, and abnormal gait.MethodsWe conducted a retrospective investigation to characterise WPD in native Australian brushtail possums, and used a bulk meta-transcriptomic approach (i.e. total RNA-sequencing) to investigate its potential viral aetiology. PCR assays were developed for case diagnosis and full genome recovery in the face of extensive genetic variation.ResultsWe identified a distinct lineage of arteriviruses from archival tissues of WPD-infected possums in Australia, termed wobbly possum disease virus AU1 and AU2. Phylogenetically, WPDV-AU1 and WPDV-AU2 shared only ∼70% nucleotide similarity to each other and the WPDV-NZ strain, suggestive of a relatively ancient divergence. Notably, we identified a novel and divergent hepacivirus (Flaviviridae) - the first in a marsupial - in both WPD-infected and uninfected possums, indicative of virus co-infection.ConclusionsWe have identified a distinctive marsupial-specific lineage of arteriviruses in mainland Australia that is genetically distinct from that in New Zealand, in some cases co-infecting animals with a novel hepacivirus. Our study provides new insight into the hidden genetic diversity of arteriviruses, the capacity for virus co-infection, and highlights the utility of meta-transcriptomics for disease investigation and surveillance in a One Health context.
Late- but not early-onset blindness impairs the development of audio-haptic multisensory integration
Authors: Scheller Meike , Proulx Michael J. , de Haan Michelle , Dahlmann-Noor Annegret , Petrini Karin 
Published: October 2019

AbstractIntegrating different senses to reduce sensory uncertainty and increase perceptual precision can have an important compensatory function for individuals with visual impairment and blindness. However, how visual impairment and blindness impact the development of optimal multisensory integration in the remaining senses is currently unknown. Here we first examined how audio-haptic integration develops and changes across the life span in 92 sighted (blindfolded) individuals between 7 to 70 years of age by using a child-friendly size discrimination task. We assessed whether audio-haptic performance resulted in a reduction of perceptual uncertainty compared to auditory-only and haptic-only performance as predicted by maximum-likelihood estimation model. We then tested how this ability develops in 28 children and adults with different levels of visual experience, focussing on low vision individuals, and blind individuals that lost their sight at different ages during development. Our results show that in sighted individuals, adult-like audio-haptic integration develops around 13-15 years of age, and remains stable until late adulthood. While early blind individuals, even at the youngest ages, integrate audio-haptic information in an optimal fashion, late blind individuals do not. Optimal integration in low vision individuals follows a similar developmental trajectory as that of sighted individuals. These findings demonstrate that visual experience is not necessary for optimal audio-haptic integration to emerge, but that consistency of sensory information across development is key for the functional outcome of optimal multisensory integration.Research HighlightsAudio-haptic integration follows principles of statistical optimality in sighted adults, remaining stable until at least 70 years of lifeNear-optimal audio-haptic integration develops at 13-15 years in sighted adolescentsBlindness within the first 8 years of life facilitates the development of optimal audio-haptic integration while blindness after 8 years impairs such developmentSensory consistency in early childhood is crucial for the development of optimal multisensory integration in the remaining senses