bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory diversity contributes to a divergent transcriptional response to dietary changes in mammals
Authors: Costello Kevin R. , Shin Heon , Trac Candi , Varlamov Oleg , Schones Dustin E. 
Published: November 2020

AbstractBACKGROUNDRegulatory innovation is central to the evolution of species. Different nutritional sources are one environmental pressure that can lead to selection for novel regulatory elements. Dietary composition changes, including exposure to “western” diets with excess fat and sugar content, can lead to transcriptional regulatory changes in the liver. In order to investigate how transcriptional regulatory changes in response to a high fat diet diverge across species, we profiled chromatin accessibility, histone modifications and the transcriptome in livers of rhesus macaques and mice fed high fat and normal diets.RESULTSWhile the majority of elements exhibiting changes in chromatin accessibility in response to a high fat diet are enriched for similar transcription factors across species, the loci that change are mostly species specific. These unique responsive regulatory elements are largely derived from transposable elements and are enriched for liver-specific transcription factors, such as HNF4α. Furthermore, the majority of genes that respond to a high fat diet in rhesus macaques do not have a shared response in mice and are proximal to regulatory elements that display changes in chromatin accessibility only in rhesus macaques.CONCLUSIONSOur study demonstrates that most of the liver regulatory elements that exhibit changes in chromatin accessibility in response to a high fat diet do so in a species-specific manner. These findings illustrate how a similar environmental stimulus can drive a divergent chromatin and transcriptional responses in evolutionary distinct mammalian species.
Climate warming weakens local adaptation
Authors: Bontrager M. , Muir C. D. , Mahony C. , Gamble D. E. , Germain R. M. , Hargreaves A. L. , Kleynhans E. J. , Thompson K. A. , Angert A. L. 
Published: November 2020

AbstractAnthropogenic climate change is generating mismatches between the environmental conditions that populations historically experienced and those in which they reside. Understanding how climate change affects population performance is a critical scientific challenge. We combine a quantitative synthesis of field transplant experiments with a novel statistical approach based in evolutionary theory to quantify the effects of temperature and precipitation variability on population performance. We find that species’ average performance is affected by both temperature and precipitation, but populations show signs of local adaptation to temperature only. Contemporary responses to temperature are strongly shaped by the local climates under which populations evolved, resulting in performance declines when temperatures deviate from historic conditions. Adaptation to other local environmental factors is strong, but temperature deviations as small as 2°C erode the advantage that these non-climatic adaptations historically gave populations in their home sites.One sentence summaryClimate change is pulling the thermal rug out from under populations, reducing average performance and eroding their historical home-site advantage.
Phylogenomic insights into distribution and adaptation of Bdellovibrionota in marine waters
Authors: Li Qing-Mei , Zhou Ying-Li , Wei Zhan-Fei , Wang Yong 
Published: November 2020

AbstractBdellovibrionota is composed of obligate predators that can consume some gram-negative bacteria inhabiting various environments. However, whether genomic traits influence their distribution and marine adaptation remains to be answered. In this study, we performed phylogenomics and comparative genomics studies on 82 Bdellovibrionota genomes along with five metagenome-assembled genomes (MAGs) from deep sea zones. Four phylogenetic groups, Oligoflexia, Bdello-group1, Bdello-group2 and Bacteriovoracia, were revealed by constructing a phylogenetic tree, of which 53.84% of Bdello-group2 and 48.94% of Bacteriovoracia were derived from ocean. Bacteriovoracia was more prevalent in deep sea zones, whereas Bdello-group2 was largely distributed in the epipelagic zone. Metabolic reconstruction indicated that genes involved in chemotaxis, flagellar (mobility), type II secretion system, ABC transporters and penicillin-binding protein were necessary for predatory lifestyle of Bdellovibrionota. Genes involved in glycerol metabolism, hydrogen peroxide (H2O2) degradation, cell wall recycling and peptide utilization were ubiquitously present in Bdellovibrionota genomes. Comparative genomics between marine and non-marine Bdellovibrionota demonstrated that betaine as an osmoprotectant is probably widely used by marine Bdellovibrionota, meanwhile, all the marine genomes have a number of related genes for adapting marine environment. The chitinase and chitin-binding protein encoding genes were identified for the first time in Oligoflexia, which implied that Oligoflexia may prey a wider spectrum of microbes. This study expanded our knowledge on adaption strategies of Bdellovibrionota inhabiting deep sea and their potential usage for biological control.ImportanceBdellovibrionota can prey gram-negative bacteria proposed as biocontrol agent. Available Bdellovibrionota genomes showed that most are from marine environment. However, vertical distribution and adaption of Bdellovibrionota in deep sea has not been reported. Our study of Bdellovibrionota revealed four groups (Oligoflexia, Bdello-group1, Bdello-group2 and Bacteriovoracia) and their distribution pattern in oceans. We also identified the genes for different phases of predation and adaptation in deep-sea environment. Moreover, Oligoflexia genomes contain more genes for carbohydrates utilization and particularly those encoding chitin-binding protein and chitinase. Our analyses of Bdellovibrionota genomes may help understand their special lifestyle and deep-sea adaptation.
“High resolution discovery of regulatory DNA with synthetic wild-type and ablated genome constructs”
Authors: Holmes Benjamin , Lin Lin , Sherwood Richard , Gifford David 
Published: November 2020

ABSTRACTGenomic enhancer elements play a role in modulating gene expression by interacting with effector proteins known as transcription factors. We present a new computational method, “STARR-scan”, which identifies transcription factor motif appearances in synthetic DNA constructs that are correlated with enhancer activity. Using a tiled STARR-seq assay, we demonstrate that STARR-scan can suggest the biological function of transcription factors previously suspected to activate the APOBEC-3B gene. Using the same methodology, STARR-scan can suggest transcription factors with previously unknown biological activity which may regulate the APOBEC-3B gene. These novel factors may have biological significance in our understanding of cancer biology.
Novel nuclear role of HDAC6 in prognosis and therapeutic target for colorectal cancer
Authors: García-Domínguez Daniel J. , Hontecillas-Prieto Lourdes , Kaliszczak Maciej , He Miaomiao , Burguillos Miguel Angel , Bekay Rajaa , Abdul-Salam Vahitha B. , Khozoie Combiz , Shah Khalid , O’Neill Kevin , de Álava Enrique , Silver Andrew , Syed Nelofer , Aboagye Eric O. , Hajji Nabil 
Published: November 2020

AbstractHistone deacetylase 6 (HDAC6) inhibition is a potential treatment of a wide range of cancer typesviathe acetylation of diverse proteins in the cytoplasm. However, the regulation of histone acetylation and the maintenance of higher-order chromatin structure remains unidentified. Here, we investigated the effect of selective inhibition of HDAC6 by histone acetylation, chromatin relaxation assays, co-immunoprecipitation, acetylome peptide array andin vivoRNA microarray. Our data shows that nuclear HDAC6 physically interacts with the Histone 4 lysine 12 residue, and that HDAC6 inhibition increases acetylation specifically at this residue in several cancer types. Inhibition induces major chromatin structure modulation, but has no equivalent effect on knockout HDAC6-/-MEF cells. We identified several novel HDAC6-deacetylated substrates and high expression of HDAC6 in colorectal cancer (CRC) tissue association with reduced levels of H4K12ac and independent of the key CRC driver mutations, but positively associated withEGFRexpression. Furthermore,in vivoHDAC6 inhibition induces significant tumor regression in a CRC xenograft mice model with significant changes in the expression of functional nuclear genes. We also demonstrated that a DNA damaging agent in combination with selective HDAC6 inhibition is effective and acts synergistically, inducing chromatin relaxation and increased cell death in CRC cells. CRC tissues (Normal versus tumor; n=58 matched pairs) together with TCGA data analysis of 467 CRC patients showed that high HDAC6 expression is associated with metastasis, overall and disease-free survival, and is an independent risk factor of CRC stage progression. Our findings designate a new role for nuclear HDAC6 both in cancer prognosis and as a new therapeutic target for CRC and other types of cancer.HighlightHistone deacetylases 6 activity; Chromatin relaxation; Histone modifications; Gene array; DOX: doxorubicin; OXA: oxaliplatin; 5-FU: fluorouracil; Ac: acetylation; MNase: Micrococal nuclease.
A Two-Step Bioreactor for Lung Recellularization
Authors: Young Bethany , Antczak Leigh-Ann M. , Shankar Keerthana , Heise Rebecca L. 
Published: November 2020

AbstractBioreactors for reseeding of decellularized lung scaffolds have evolved with a wide variety of advancements. These include biomimetic mechanical stimulation, constant nutrient flow, multi-output monitoring, and large mammal scaling. Although dynamic bioreactors are not new to the field of bioengineered lungs, ideal conditions during cell seeding have not been extensively studied or controlled. To address the lack of cell dispersal in traditional seeding methods, we have designed a two-step bioreactor. The first step rotates a seeded lung every 20 minutes at different angles to ensure 20 percent of cells are anchored to a particular location based on the known rate of attachment. The second step involves perfusion culture to ensure nutrient dispersion and cellular growth. Compared to statically seeded lungs followed by conventional perfusion, rotationally seeded lungs followed by perfusion had significantly increased dsDNA content and more uniform cellular distribution. This new bioreactor system will aid in recellularizing the lung and other geometrically complex organs for tissue engineering.
Small-scale commercial chicken production: A risky business for farmers in the Mekong Delta of Vietnam
Authors: Bao Truong Dinh , Van Cuong Nguyen , Phu Hoang Doan , Dung Nguyen Thi Thuy , Kiet Bach Tuan , Rushton Jonathan , Carrique-Mas Juan 
Published: November 2020

ABSTRACTSmall-scale farming of meat chicken flocks using local native breeds contributes to the economy of many rural livelihoods in Vietnam and many other low- and middle-income countries (LMICs). These systems are also the target of high levels of antimicrobial use (AMU); however little is known about the profitability and sustainability of such systems. Since small scale farms are commercial enterprises, this knowledge is essential in order to develop successful strategies aimed at curbing excessive AMU. Using longitudinal data from 203 randomly selected small-scale (100-2,000 chickens) native chicken flocks raised in 102 farms in Dong Thap province (Mekong Delta, Vietnam), we investigated the financial and economic parameters of such systems and the main constraints to their sustainability. Feed accounted for the largest financial cost (flock median 49.5% [Inter-quartile range (IQR) 41.5-61.8%]) of total costs, followed by day-old-chicks (DOCs) (median 30.3% [IQR 23.2-38.4%]), non-antimicrobial health-supporting products (median 7.1% [IQR 4.7-10.5%]), vaccines (median 3.1% [IQR 2.2-4.8%]), equipment (median 1.9% [IQR 0.0-4.9%]) and antimicrobials (median 1.9% [IQR 0.7-3.6%]). Excluding labor costs, farmers achieved a positive return on investment (ROI) from 120 (59.1%) flocks, the remainder generated a loss (median ROI 124% [IQR 36-206%]). Higher ROI was associated with higher flock size and low mortality. There was no statistical association between use of medicated feed and flock mortality or chicken bodyweight. The median daily income per person dedicated to raising chickens was 202,100 VND, lower than alternative rural labour activities in the Mekong Delta. In a large proportion of farms (33.4%), farmers decided to stop raising chickens after completing one cycle. Farmers who dropped off chicken production purchased more expensive feed (in 1,000 VND per kg) (11.1 [10.6-11.5] vs. 10.8 [10.4-11.3] for farms that continued production (p=0.039) and experienced higher chicken mortality (28.5% [12.0-79.0%] vs. 16 [7.5-33.0%] (p=0.004). The turnover of farmers raising chickens in such systems represents a challenge in targeting messages on appropriate AMU and on chicken health. In order to ensure sustainability of small-scale commercial systems, advisory services need to be available as farmer initiate new flocks, and support them in the early stages to help overcome their limited experience and skills. This targeted approach would support profitability whilst reducing risk of emergence of AMR and other disease problems from these systems.
The hourglass model of evolutionary conservation during embryogenesis extends to developmental enhancers with signatures of positive selection
Authors: Liu Jialin , Viales Rebecca R. , Khoueiry Pierre , Reddington James P. , Girardot Charles , Furlong Eileen E. M. , Robinson-Rechavi Marc 
Published: November 2020

AbstractInter-species comparisons of both morphology and gene expression within a phylum have revealed a period in the middle of embryogenesis with more similarity between species compared to earlier and later time-points. This ‘developmental hourglass’ pattern has been observed in many phyla, yet the evolutionary constraints on gene expression, and underlying mechanisms of how this is regulated, remains elusive. Moreover, the role of positive selection on gene regulation in the more diverged earlier and later stages of embryogenesis remains unknown. Here, using DNase-seq to identify regulatory regions in two distantDrosophilaspecies (D. melanogasterandD. virilis), we assessed the evolutionary conservation and adaptive evolution of enhancers throughout multiple stages of embryogenesis. This revealed a higher proportion of conserved enhancers at the phylotypic period, providing a regulatory basis for the hourglass expression pattern. Using anin silicomutagenesis approach, we detect signatures of positive selection on developmental enhancers at early and late stages of embryogenesis, with a depletion at the phylotypic period, suggesting positive selection as one evolutionary mechanism underlying the hourglass pattern of animal evolution.
Hindbrain neuropore tissue geometry determines asymmetric cell-mediated closure dynamics
Authors: Maniou Eirini , Staddon Michael F , Marshall Abigail , Greene Nicholas DE , Copp Andrew J , Banerjee Shiladitya , Galea Gabriel L 
Published: November 2020

AbstractGap closure is a common morphogenetic process. In mammals, failure to close the embryonic hindbrain neuropore (HNP) gap causes fatal anencephaly. We observed that surface ectoderm cells surrounding the mouse HNP assemble high-tension actomyosin purse-strings at their leading edge and establish the initial contacts across the embryonic midline. The HNP gap closes asymmetrically, faster from its rostral than caudal extreme, while maintaining an elongated aspect ratio. Cell-based physical modelling identifies two closure mechanisms sufficient to describe tissue-level HNP closure dynamics; purse-string contraction and directional cell crawling. Combining both closure mechanisms hastens gap closure and produces a constant rate of gap shortening. Purse-string contraction reduces, whereas crawling increases gap aspect ratio, and their combination maintains it. Closure rate asymmetry can be explained by embryo tissue geometry, namely a narrower rostral gap apex. At the cellular level, our model predicts highly directional cell migration with a constant rate of cells leaving the HNP rim. These behaviours are reproducibly live-imaged in mouse embryos. Thus, mammalian embryos coordinate cellular and tissue-level mechanics to achieve this critical gap closure event.
More rule than exception: Parallel evidence of ancient migrations in grammars and genomes of Finno-Ugric speakers
Authors: Santos Patrícia , Gonzalez-Fortes Gloria , Trucchi Emiliano , Ceolin Andrea , Cordoni Guido , Guardiano Cristina , Longobardi Giuseppe , Barbujani Guido 
Published: November 2020

AbstractTo reconstruct aspects of human demographic history, linguistics and genetics complement each other, reciprocally suggesting testable hypotheses on population relationships and interactions. Relying on a linguistic comparative method exclusively based on syntactic data, here we focus on the complex relation of genes and languages among Finno-Ugric (FU) speakers, in comparison to their Indo-European (IE) and Altaic (AL) neighbors. Syntactic analysis supports three distinct clusters corresponding to these three Eurasian families; yet, the outliers of the FU group show linguistic convergence with their geographical neighbors. By analyzing genome-wide data in both ancient and contemporary populations, we uncovered remarkably matching patterns, with north-western FU speakers linguistically and genetically closer in parallel degrees to their IE-speaking neighbors, and eastern FU speakers to AL-speakers. Therefore, our study indicates plausible secondary convergence in the syntax of languages of different families, providing evidence that such interference effects were accompanied, and possibly caused, by recognizable processes at the population level. In particular, based on the comparison of modern and ancient genomes, our analysis identified the Pontic-Caspian steppes as the possible origin of the demographic processes that led to the expansion of the FU into Europe.
Ancient evolution of hepadnaviral paleoviruses and their impact on host genomes
Authors: Lytras Spyros , Arriagada Gloria , Gifford Robert J. 
Published: November 2020

ABSTRACTHepadnaviruses (family Hepadnaviviridae) are reverse-transcribing animal viruses that infect vertebrates. Vertebrate genomes contain DNA sequences derived from ancient hepadnaviruses, and these ‘endogenous hepatitis B viruses’ (eHBVs) reveal aspects of the long-term coevolutionary relationship between hepadnaviruses and their vertebrate hosts. Here, we use a novel, data-oriented approach to recover and analyse the complete repertoire of eHBV elements in published animal genomes. We show that germline incorporation of hepadnaviruses is exclusive to a single vertebrate group (Sauria) and that the eHBVs contained in saurian genomes represent a far greater diversity of hepadnaviruses than previously recognised. Through in-depth characterisation of eHBV elements we establish the existence of four distinct subgroups within the genus Avihepadnavirus and trace their evolution through the Cenozoic Era. Furthermore, we provide a completely new perspective on hepadnavirus evolution by showing that the metahepadnaviruses (genus Metahepadnavirus) originated >300 million years ago in the Paleozoic Era, and has historically infected a broad range of vertebrates. We also show that eHBVs have been intra-genomically amplified in some saurian lineages, and that eHBVs located at approximately equivalent genomic loci have been acquired in entirely distinct germline integration events. These findings indicate that selective forces have favoured the accumulation of hepadnaviral sequences at specific loci in the saurian germline. Our investigation provides a range of new insights into the long-term evolutionary history of reverse-transcribing DNA viruses and demonstrates that germline incorporation of hepadnaviruses has played an important role in shaping the evolution of saurian genomes.
Growth and transgenerational acclimatization of juvenilePocillopora damicornis
Authors: Gerstle Lev 
Published: November 2020

AbstractGlobal carbon emissions and associated increase in ocean temperatures are understood to be the main driving force in the degradation of coral reefs. Elevated temperatures impact various life stages of scleractinian corals, from the free-floating planulae of brooding corals to older, sexually viable individuals. With global warming, questions have arisen over whether organismal adaptation will be enough to keep up with the pace of environmental change. Researchers have pursued investigations of whether or not rapid acclimatization, through transgenerational plasticity, can help protect populations until genetic adaptation occurs. Acclimatization in corals has been widely studied in all life stages of corals, with the important exception of recently settled juveniles. In this study, I built upon past research by exposing adultPocillopora damicorniscolonies to elevated (28.5°C) or ambient (25.5°C) temperatures and examining the settlement ability and growth of their planulaeex situ. Juveniles from preconditioned parents fared better in higher temperatures compared to their naïve counterparts. Lunar timing of planula release between treatments peaked at different times in the lunar cycle. Peak planula release occurred on lunar day 23 for prestressed corals and on lunar day 7 for corals from ambient temperature seawaters. While future projects should follow up on these preliminary trials within situexperiments to assess this phenomenon in the field, this study represents an important step in understanding how corals may be able to acclimatize and eventually adapt to climate change.
Do Support Vector Machines play a role in stratifying patient population based on cancer biomarkers?
Authors: Lanza Ben , Parashar Deepak 
Published: November 2020

AbstractBiomarkers are known to be the key driver behind targeted cancer therapies by either stratifying the patients into risk categories or identifying patient subgroups most likely to benefit. However, the ability of a biomarker to stratify patients relies heavily on the type of clinical endpoint data being collected. Of particular interest is the scenario when the biomarker involved is a continuous one where the challenge is often to identify cut-offs or thresholds that would stratify the population according to the level of clinical outcome or treatment benefit. On the other hand, there are well-established Machine Learning (ML) methods such as the Support Vector Machines (SVM) that classify data, both linear as well as non-linear, into subgroups in an optimal way. SVMs have proven to be immensely useful in data-centric engineering and recently researchers have also sought its applications in healthcare. Despite their wide applicability, SVMs are not yet in the mainstream of toolkits to be utilised in observational clinical studies or in clinical trials. This research investigates the very role of SVMs in stratifying the patient population based on a continuous biomarker across a variety of datasets. Based on the mathematical framework underlying SVMs, we formulate and fit algorithms in the context of biomarker stratified cancer datasets to evaluate their merits. The analysis reveals their superior performance for certain data-types when compared to other ML methods suggesting that SVMs may have the potential to provide a robust yet simplistic solution to stratify real cancer patients based on continuous biomarkers, and hence accelerate the identification of subgroups for improved clinical outcomes or guide targeted cancer therapies.