bluuebunny/crossref_metadata_2025_split huggingface dataset:
LSD1 represses a neonatal/reparative gene program in adult intestinal epithelium
Authors: Zwiggelaar Rosalie T. , Lindholm Håvard T. , Fosslie Madeleine , Pedersen Marianne T. , Ohta Yuki , Díez-Sánchez Alberto , Martín-Alonso Mara , Ostrop Jenny , Matano Mami , Parmar Naveen , Kvaløy Emilie , Spanjers Roos R. , Nazmi Kamran , Rye Morten , Drabløs Finn , Arrowsmith Cheryl , Dahl John Arne , Jensen Kim B. , Sato Toshiro , Oudhoff Menno J. 
Published: February 2020

ABSTRACTIntestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth cells, appear after birth in the neonatal period. We aimed to identify new regulators of neonatal intestinal epithelial development by testing a small library of epigenetic modifier inhibitors in Paneth cell-skewed organoid cultures. We found that Lysine-specific demethylase 1A (Kdm1a/Lsd1) is absolutely required for Paneth cell differentiation.Lsd1-deficient crypts, devoid of Paneth cells, are still able to form organoids without a requirement of exogenous or endogenous Wnt. Mechanistically, we find that LSD1 represses genes that are normally expressed in fetal and neonatal epithelium. This gene profile is similar to what is seen in repairing epithelium, and indeed, we find thatLsd1-deficient epithelium has superior regenerative capacities after irradiation injury. In summary, we found an important regulator of neonatal intestinal development and identified a druggable target to reprogram intestinal epithelium towards a reparative state.
Supervising the PhD: identifying common mismatches in expectations between candidate and supervisor to improve research training outcomes
Authors: Cardilini Adam P.A. , Risely Alice , Richardson Mark F. 
Published: February 2020

AbstractThe relationship between a PhD candidate and their supervisor is influential in not only successful candidate completion, but maintaining candidate satisfaction and mental health. We quantified potential mismatches between the PhD candidates and supervisors expectations as a potential mechanism that facilitates poor candidate experiences and research training outcomes. 114 PhD candidates and 52 supervisors ranked the importance of student attributes and outcomes at the beginning and end of candidature. In relation to specific attributes, supervisors indicated the level of guidance they expected to give the candidate and candidates indicated the level of guidance they expected to receive. Candidates also report on whether different aspects of candidature influenced their mental well-being. We identified differences between candidates and supervisors perceived supervisor teaching responsibility and influences on mental well-being. Our results indicate that the majority of candidates were satisfied overall with their supervision, and find alignment of many expectations between both parties. Yet, we find that candidates have much higher expectations of achieving quantitative outcomes than supervisors. Supervisors believed they give more guidance to candidates than candidates perceive they received, and supervisors often only provided guidance when the candidate explicitly asked. Personal expectations and research progress significantly and negatively influenced over 50% of candidate’s mental well-being. Our results highlight the importance of candidates and supervisors explicitly communicating the responsibilities and expectations of the roles they play in helping candidates develop research skills. We provide four suggestions to supervisors that may be particularly effective at increasing communication, avoiding potential conflict and promoting candidate success and wellbeing.
Evolution of the standard genetic code
Authors: Yarus Michael 
Published: February 2020

AbstractA near-universal Standard Genetic Code (SGC) implies a single origin for Earthly life. To study this unique event, I compute paths to the SGC, comparing different plausible histories. Notably, SGC-like coding emerges from traditional evolutionary mechanisms, and a superior path can be identified.To objectively measure evolution, progress values from 0 (random coding) to 1 (SGC-like) are defined: these measure fractions of random-code-to-SGC distance. Progress types arespacing/distance/deltaPolarRequirement, detecting space between identical assignments /mutational distance to the SGC/chemical order, respectively. A coding system was based on known RNAs performing aminoacyl-RNA synthetase reactions. Acceptor RNAs exhibit SGC-like wobble; alternatively, non-wobbling triplets uniquely encode 20 amino acids/start/stop. Triplets acquire 22 functions by stereochemistry, selection, coevolution, or randomly. Assignments also propagate to an assigned triplet’s neighborhood via single mutations, but can also decay.Futile evolutionary paths are plentiful due to the vast code universe. Thus SGC evolution is critically sensitive to disorder from random assignments. Evolution also inevitably slows near coding completion. Coding likely avoided these difficulties, and two suitable paths are compared. Inlate wobble, a majority of non-wobble assignments are made before wobble is adopted. Incontinuous wobble, a uniquely advantageous early intermediate supplies the gateway to an ordered SGC. Revised coding evolution (limited randomness, late wobble, concentration on amino acid encoding, chemically conservative coevolution with a chemically-ordered elite) produces varied full codes with excellent joint progress values. A population of only 600 independent coding tables includes SGC-like members; a Bayesian path toward more accurate SGC evolution is available.
Tree diversity effects on forest productivity increase through time because of spatial partitioning
Authors: Tatsumi Shinichi 
Published: February 2020

ABSTRACTBackgroundExperimental manipulations of tree diversity have often found overyielding in mixed-species plantations. While most experiments are still in the early stages of stand development, the impacts of tree diversity are expected to accumulate over time. Here, I present findings from a 31-year-old tree diversity experiment (as of 2018) in Japan.ResultsI find that the net diversity effect on stand biomass increased linearly through time. The species mixture achieved 64% greater biomass than the average monoculture biomass 31 years after planting. The complementarity effect was positive and increased exponentially with time. The selection effect was negative and decreased exponentially with time. In the early stages (≤3 years), the positive complementarity effect was explained by enhanced growths of early- and mid-successional species in the mixture. Later on (≥15 years), it was explained by their increased survival rates owing to vertical spatial partitioning — i.e., alleviation of self-thinning via canopy stratification. The negative selection effect resulted from suppressed growths of late-successional species in the bottom layer.ConclusionsThe experiment provides pioneering evidence that the positive impacts of diversity-driven spatial partitioning on forest biomass can accumulate over multiple decades. The results indicate that forest biomass production and carbon sequestration can be enhanced by multispecies afforestation strategies.
Methods for Running a Successful Women-in-STEM Organization on an Academic Campus
Authors: Rupert Deborah D. , Nowlan Alexandra C. , Tam Oliver H. , Hammell Molly Gale 
Published: February 2020

AbstractThe current academic culture facing women in science, technology, engineering, and math (STEM) fields in the United States has sparked the formation of grassroots advocacy groups to empower female scientists-in-training. However, the impact of these initiatives often goes unmeasured and underappreciated. Our Women in Science and Engineering (WiSE) organization serves post-doctoral researchers, graduate students, and research technicians (trainees) at a private research institute for biological sciences. Here we propose the following guidelines for cultivating a successful women-in-STEM-focused group based upon survey results from our own scientific community as well as the experience of our WiSE group leaders. We hope these recommendations can provide guidance to advocacy groups at other research and academic organizations that wish to strengthen their efforts. While our own group specifically focuses on the underrepresented state of women in science, we hope these guidelines may be adapted and applied to groups that advocate for any minority group within the greater scientific community (i.e. those of gender, race/ethnicity, socioeconomic background, sexual orientation, etc.).
Molecular epidemiology of third-generation cephalosporin-resistant Enterobacteriaceae from Southeast Queensland, Australia
Authors: Stewart AG , Price EP , Schabacker K , Birikmen M , Harris PNA , Choong K , Subedi S , Sarovich DS 
Published: February 2020

SynopsisThird-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae represent a major threat to human health. Here, we captured 288 3GC-R Enterobacteriaceae clinical isolates from 264 patients presenting at a regional Australian hospital over a 14-month period. Alongside routine mass spectrometry speciation and antibiotic sensitivity testing, isolates were examined using rapid (∼40 min) real-time PCR assays targeting the most common extended spectrum β-lactamases (ESBLs; CTX-M-1 and CTX-M-9 groups, plus TEM, SHV, and an internal 16S ribosomal DNA control). AmpC CMY β-lactamase prevalence was also examined.Escherichia coli(80.2%) andKlebsiella pneumoniae(17.0%) were dominant, withKlebsiella oxytoca, Klebsiella aerogenesandEnterobacter cloacaeinfrequently identified. Ceftriaxone and cefoxitin resistance were identified in 97.0% and 24.5% ofE. coli andK. pneumoniae isolates, respectively. Consistent with global findings in Enterobacteriaceae, most (98.3%) isolates harbored at least one β-lactamase gene, with 144 (50%) encodingblaCTX-M-1group, 92 (31.9%)blaCTX-M-9group, 48 (16.7%)blaSHV, 133 (46.2%)blaTEM, and 34 (11.8%)blaCMY. A subset of isolates (n=98) were subjected to whole-genome sequencing (WGS) to identify the presence of cryptic resistance determinants, and to verify genotyping accuracy. WGS of β-lactamase negative or carbapenem-resistant isolates identified uncommon ESBLs and carbapenemases, includingblaNDMandblaIMP, and confirmed all PCR-positive genotypes. We demonstrate that our PCR assays enable the rapid and cost-effective identification of ESBLs in the hospital setting, which has important infection control and therapeutic implications.
QMaker: Fast and accurate method to estimate empirical models of protein evolution
Authors: Minh Bui Quang , Dang Cuong Cao , Vinh Le Sy , Lanfear Robert 
Published: February 2020

AbstractAmino acid substitution models play a crucial role in phylogenetic analyses. Maximum likelihood (ML) methods have been proposed to estimate amino acid substitution models, however, they are typically complicated and slow. In this paper, we propose QMaker, a new ML method to estimate a general time-reversibleQmatrix from a large protein dataset consisting of multiple sequence alignments. QMaker combines an efficient ML tree search algorithm, a model selection for handling the model heterogeneity among alignments, and the consideration of rate mixture models among sites. We provide QMaker as a user-friendly function in the IQ-TREE software package (http://www.iqtree.org) supporting the use of multiple CPU cores so that biologists can easily estimate amino acid substitution models from their own protein alignments. We used QMaker to estimate new empirical general amino acid substitution models from the current Pfam database as well as five clade-specific models for mammals, birds, insects, yeasts, and plants. Our results show that the new models considerably improve the fit between model and data and in some cases influence the inference of phylogenetic tree topologies.
Consumption of a high energy density diet triggers microbiota dysbiosis, hepatic lipidosis, and microglia activation in the nucleus of the solitary tract in rats
Authors: Minaya Dulce M. , Turlej Anna , Joshi Abhinav , Nagy Tamas , Di Lorenzo Patricia , Hajnal Andras , Czaja Krzysztof 
Published: February 2020

AbstractObesity is a multifactorial chronic inflammatory disease. Consumption of high energy density (ED) diets is associated with hyperphagia, increased body weight and body fat accumulation, and obesity. Our lab has previously shown that short-term (4 weeks) consumption of a high ED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal communication. The aim of the current study was to investigate the effect of long-term (6 months) consumption of high ED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the Nucleus of the Solitary Tract, and the development of systemic inflammation. Male Sprague-Dawley rats were fed a low ED diet (5% fat) for two weeks and then switched to a high ED (45% fat) diet for 26 weeks. Twenty-four hour food intake, body weight, and body composition were measured twice a week. Blood serum and fecal samples were collected at baseline, and 1, 4, 8, and 26 weeks after introduction of the high ED diet. Serum samples were used to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were used for 16S rRNA genome sequencing. High ED diet induced microbiota dysbiosis within a week of introducing the diet. In addition, there was significant microglia activation in the intermediate NTS and marked hepatic lipidosis after four weeks of high ED diet. We further observed changes in the serum cytokine profile after 26 weeks of high ED feeding. These data suggest that microbiota dysbiosis is the first response of the organism to high ED diets and this, in turn, detrimentally affects liver fat accumulation, microglia activation in the brain, and circulating levels of inflammatory markers.
Plant SYP12 syntaxins mediate an evolutionarily conserved general immunity to filamentous pathogens
Authors: Rubiato Hector M. , Liu Mengqi , O’Connell Richard J. , Nielsen Mads E. 
Published: February 2020

AbstractFilamentous fungal and oomycete plant pathogens that invade by direct penetration through the leaf epidermal cell wall, cause devastating plant diseases. Towards non-adapted filamentous pathogens, plant pre-invasive immunity is highly effective and durable. Pre- and post-invasive immunity correlates with the formation of evolutionarily conserved and cell-autonomous cell wall structures, named papillae and encasements. Yet, it is still unresolved how papillae/encasements are formed and whether these defense structures prevent pathogen ingress. Here we show that inArabidopsis, the two closely related members of the SYP12 clade of syntaxins (PEN1 and SYP122) are indispensable for the formation of papillae and encasements. Moreover, loss-of-function mutants were hampered in pre-invasive immunity towards a range of taxonomically distinct non-adapted filamentous pathogens, underlining the versatility and efficacy of this defense. Complementation studies using SYP12s from the early diverging land plant,Marchantia polymorpha, showed that the SYP12 clade immunity function has survived 470 My of independent evolution. These results suggest that ancestral land plants evolved the SYP12 clade to provide a broad and durable pre-invasive immunity to facilitate their life on land, and pave the way to a better understanding of how adapted pathogens overcome this ubiquitous plant defense strategy.
A novel protein complex that regulates active DNA demethylation inArabidopsis
Authors: Liu Pan , Nie Wen-Feng , Xiong Xiansong , Wang Yuhua , Jiang Yuwei , Huang Pei , Lin Xueqiang , Qin Guochen , Huang Huan , Niu Qingfeng , Du Jiamu , Lang Zhaobo , Lozano-Duran Rosa , Zhu Jian-Kang 
Published: February 2020

SUMMARYActive DNA demethylation is critical for altering DNA methylation patterns and regulating gene expression. The 5-methylcytosine DNA glycosylase/lyase ROS1 initiates a base excision repair pathway for active DNA demethylation and is required for the prevention of DNA hypermethylation at thousands of genomic regions inArabidopsis. How ROS1 is regulated and targeted to specific genomic regions is not well understood. Here, we report the discovery of anArabidopsisprotein complex that contains ROS1, regulatesROS1gene expression, and likely targets the ROS1 protein to specific genomic regions. ROS1 physically interacts with a WD40 domain protein (RWD40), which in turn interacts with a methyl-DNA binding protein (RMB1) as well as with a zinc finger and homeobox domain protein (RHD1). RMB1 binds to DNA that is methylated in any sequence context, and this binding is necessary for its functionin vivo.Loss-of-function mutations inRWD40, RMB1, orRHD1cause DNA hypermethylation at several tested genomic regions independently of the known ROS1 regulator IDM1. Because the hypermethylated genomic regions include the DNA methylation monitoring sequence in theROS1promoter, plants mutated inRWD40, RMB1, orRHD1show increasedROS1expression. Importantly, ROS1 binding to theROS1promoter requires RWD40, RMB1, and RHD1, suggesting that this complex dictates ROS1 targeting to this locus. Our results demonstrate that ROS1 forms a protein complex with RWD40, RMB1, and RHD1, and that this novel complex regulates active DNA demethylation at several endogenous loci inArabidopsis.
Sedation modulates fronto-temporal predictive coding circuits and the double surprise acceleration effect
Authors: Witon Adrien , Shirazibehehsti Amirali , Cooke Jennifer , Aviles Alberto , Adapa Ram , Menon David K. , Chennu Srivas , Bekinschtein Tristan , Lopez Jose David , Litvak Vladimir , Li Ling , Friston Karl , Bowman Howard 
Published: February 2020

AbstractTwo important theories in cognitive neuroscience are predictive coding and the global workspace theory. A key research task is to understand how these two theories relate to one another, and particularly, how the brain transitions from a predictive early state to the eventual engagement of a brain-scale state (the global workspace). To address this question, we present a source-localisation of EEG responses evoked by the local-global task – an experimental paradigm that engages a predictive hierarchy, which encompasses the global workspace. The results of our source reconstruction suggest three-phases of processing. The first phase involves the sensory (here auditory) regions of the superior temporal lobe and predicts sensory regularities over a short timeframe (as per the local effect). The third phase is brain-scale, involving inferior frontal, as well as inferior and superior parietal regions; consistent with a global neuronal workspace (as per the global effect). Crucially, our analysis suggests that there is an intermediate (second) phase, involving modulatory interactions between inferior frontal and superior temporal regions. Furthermore, sedation with propofol reduces modulatory interactions in the second phase. This selective effect is consistent with a predictive coding explanation of sedation, with propofol acting on descending predictions of the precision of prediction errors; thereby constraining access to the global neuronal workspace.
Tissue-specific volatile-mediated defense regulation in maize leaves and roots
Authors: van Doan Cong , Züst Tobias , Maurer Corina , Zhang Xi , Machado Ricardo A.R. , Mateo Pierre , Ye Meng , Schimmel Bernardus C.J. , Glauser Gaétan , Robert Christelle A.M. 
Published: February 2020

SUMMARYPlant leaves that are exposed to herbivore induced plant volatiles (HIPVs) respond by increasing their defenses. Whether this phenomenon also occurs in the roots is unknown.Using maize (Zea mays), whose leaves respond strongly to leaf HIPVs, we measured the impact of root HIPVs, emanating from plants infested by the banded cucumber beetle (Diabrotica balteata), on constitutive and herbivore-induced levels of root soluble sugars, starch, total soluble proteins, free amino acids, volatile and non-volatile secondary metabolites, defense gene expression, growth and root herbivore resistance of neighboring plants.HIPV exposure did not alter constitutive or induced levels of any of the measured root traits. Furthermore, HIPV exposure did not reduce the performance and survival of banded cucumber beetle larvae on maize or teosinte. Cross-exposure experiments revealed that maize roots, in contrast to maize leaves, neither emit nor respond strongly to defense-regulating HIPVs.Together, these results demonstrate that volatile-mediated defense regulation is restricted to the leaves of maize and teosinte, a finding which is in line with the lower diffusibility of volatiles in the soil and the availability of other, potentially more efficient information conduits below ground.
Systematic functional analysis of Rab GTPases reveals limits of neuronal robustness inDrosophila
Authors: Kohrs Friederike E. , Daumann Ilsa-Maria , Pavlović Bojana , Jin Eugene Jennifer , Lin Shih-Ching , Port Fillip , Kiral F. Ridvan , Wolfenberg Heike , Mathejczyk Thomas F. , Chan Chih-Chiang , Boutros Michael , Hiesinger P. Robin 
Published: February 2020

SummaryRab GTPases are molecular switches that regulate membrane trafficking in all cells. Neurons have particular demands on membrane trafficking and express numerous Rab GTPases of unknown function. Here we report the generation and characterization of molecularly defined null mutants for all 26rabgenes inDrosophila. In addition, we created a transgenic fly collection for the acute, synchronous release system RUSH for all 26 Rabs. In flies, allrabgenes are expressed in the nervous system where at least half exhibit particularly high levels compared to other tissues. Surprisingly, loss of any of these 13 nervous-system enriched Rabs yields viable and fertile flies without obvious morphological defects. However, 9 of these 13 affect either developmental timing when challenged with different temperatures, or neuronal function when challenged with continuous stimulation. These defects are non-lethal under laboratory conditions, but represent sensitized genetic backgrounds that reveal limits of developmental and functional robustness to environmental challenges. Interestingly, the neuronalrab26was previously proposed to function in synaptic maintenance by linking autophagy and synaptic vesicle recycling and we identifiedrab26as one of sixrabmutants with reduced synaptic function under continuous stimulation conditions. However, we found no changes to autophagy or synaptic vesicle markers in therab26mutant, but instead a cell-specific role in membrane receptor turnover associated with cholinergic synapses in the fly visual system. Our systematic functional analyses suggest that several Rabs ensure robust development and function under varying environmental conditions. The mutant and transgenic fly collections generated in this study provide a basis for further studies of Rabs during development and homeostasisin vivo.
Gene expression has more power for predictingin vitrocancer cell vulnerabilities than genomics
Authors: Dempster Joshua M. , Krill-Burger John M. , McFarland James M. , Warren Allison , Boehm Jesse S. , Vazquez Francisca , Hahn William C. , Golub Todd R. , Tsherniak Aviad 
Published: February 2020

AbstractAchieving precision oncology requires accurate identification of targetable cancer vulnerabilities in patients. Generally, genomic features are regarded as the state-of-the-art method for stratifying patients for targeted therapies. In this work, we conduct the first rigorous comparison of DNA- and expression-based predictive models for viability across five datasets encompassing chemical and genetic perturbations. We find that expression consistently outperforms DNA for predicting vulnerabilities, including many currently stratified by canonical DNA markers. Contrary to their perception in the literature, the most accurate expression-based models depend on few features and are amenable to biological interpretation. This work points to the importance of exploring more comprehensive expression profiling in clinical settings.