bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial extracellular polysaccharide production and aggregate stability controlled by Switchgrass (Panicum virgatum) root biomass and soil water potential
Authors: Sher Yonatan , Baker Nameer R. , Herman Don , Fossum Christina , Hale Lauren , Zhang Xing-Xu , Nuccio Erin , Saha Malay , Zhou Jizhong , Pett-Ridge Jennifer , Firestone Mary
Published: August 2019

Deep-rooting perennial grasses are promising feedstock for biofuel production, especially in marginal soils lacking organic material, nutrients, and/or that experience significant water stress. Perennial grass roots can alter surrounding soil conditions and influence microbial activities, particularly the production of extracellular polymeric substances composed primarily of extracellular polysaccharides (EPS). These polymers can alleviate cellular moisture and nutrient stress, and enhance soil characteristics through improved water retention and aggregate stability, the latter of which may in turn enhance carbon persistence. In this study we used a13CO2tracer greenhouse experiment to examine the effect of switchgrass cultivation on the production and origin of EPS in a marginal soil with five fertilization/water treatments (control, +N, +NP, +P, low water). Soils with both added nitrogen and phosphorus had the highest root biomass, EPS and percentage of water-stable soil aggregates. Multiple linear regression analyses revealed root biomass was the most important determinant for soil EPS production, potentially by controlling carbon supply and diurnal changes in soil water potential. Path analysis highlighted the role of soil water potential were and EPS on with water-stable soil aggregates, indicating that EPS concentration and soil aggregation have similar drivers in this soil. High mannose content confirmed the microbial origin of EPS.13CO2labeling indicated that 0.18% of newly fixed plant carbon was incorporated into EPS. Analysis of field samples suggests that EPS is significantly enhanced under long-term switchgrass cultivation. Our results demonstrate that switchgrass cultivation can promote microbial production of EPS, providing a mechanism to enhance sustainability of marginal soils.
Adaptation is influenced by the complexity of environmental change during evolution in a dynamic environment
Authors: Boyer Sébastien , Hérissant Lucas , Sherlock Gavin
Published: August 2019

The environmental conditions of microorganisms’ habitats may fluctuate in unpredictable ways, such as changes in temperature, carbon source, pH, and salinity to name a few. Environmental heterogeneity presents a challenge to microorganisms, as they have to adapt not only to be fit under a specific condition, but they must also be robust across many conditionsand be able to deal with the switch between conditions itself. While experimental evolution has been used to gain insight into the adaptive process, this has largely been in either unvarying or consistently varying conditions. In cases where changing environments have been investigated, relatively little is known about how such environments influence the dynamics of the adaptive process itself, as well as the genetic and phenotypic outcomes. We designed a systematic series of evolution experiments where we used two growth conditions that have differing timescales of adaptation and varied the rate of switching between them. We used lineage tracking to follow adaptation, and whole genome sequenced adaptive clones from each of the experiments. We find that both the switch rate and the order of the conditions influences adaptation, and that switching can both speed up and slow down adaptation, depending on those parameters. We also find different adaptive outcomes, at both the genetic and phenotypic levels, even when populations spent the same amount of total time in the two different conditions, but the order and/or switch rate differed. Thus, in a variable environment adaptation depends not only on the nature of the conditions and phenotypes under selection, but also on the complexity of the manner in which those conditions are combined to result in a given dynamic environment.
Genomic adaptations in information processing underpin trophic strategy in a whole-ecosystem nutrient enrichment experiment
Authors: Okie Jordan G. , Poret-Peterson Amisha T. , Lee Zarraz M.P. , Richter Alexander , Alcaraz Luis D. , Eguiarte Luis E. , Siefert Janet L. , Souza Valeria , Dupont Chris L. , Elser James J.
Published: August 2019

Several universal genomic traits affect the capacity, cost, and efficiency of biochemical information processing underpinning metabolism and reproduction. We analyzed their role in mediating planktonic microbial community responses to nutrient enrichment in an oligotrophic, phosphorus-deficient pond in Cuatro Ciénegas, Mexico—one of the first whole-ecosystem experiments involving replicated metagenomic assessments. As predicted assuming oligotrophy favors lower information-processing costs whereas copiotrophy favors higher processing rates, mean bacteria genome size was higher in the fertilized treatment, as were GC content, total number of tRNA genes, total number of rRNA genes and codon usage bias in ribosomal protein sequences. However, contrasting changes in trait variances also suggested differences between traits in mediating assembly under oligotrophic versus copiotrophic conditions. Tradeoffs in information-processing traits are apparently sufficiently pronounced to play a role in community assembly and all different components of metabolism— information, energy, and nutrient requirements—are fine-tuned to an organism’s growth and trophic strategy.
Anxiety, avoidance, and sequential evaluation
Authors: Zorowitz Samuel , Momennejad Ida , Daw Nathaniel D.
Published: August 2019

Anxiety disorders are characterized by a range of aberrations in the processing of and response to threat, but there is little clarity what core pathogenesis might underlie these symptoms. Here we propose that a particular set of unrealistically pessimistic assumptions can distort an agent’s behavior and underlie a host of seemingly disparate anxiety symptoms. We formalize this hypothesis in a decision theoretic analysis of maladaptive avoidance and a reinforcement learning model, which shows how a localized bias in beliefs can formally explain a range of phenomena related to anxiety. The core observation, implicit in standard decision theoretic accounts of sequential evaluation, is that the potential for avoidance should be protective: if danger can be avoided later, it poses less threat now. We show how a violation of this assumption — via a pessimistic, false belief that later avoidance will be unsuccessful — leads to a characteristic, excessive propagation of fear and avoidance to situations far antecedent of threat. This single deviation can explain a range of features of anxious behavior, including exaggerated threat appraisals, fear generalization, and persistent avoidance. Simulations of the model reproduce laboratory demonstrations of abnormal decision making in anxiety, including in situations of approach-avoid conflict and planning to avoid losses. The model also ties together a number of other seemingly disjoint phenomena in anxious disorders. For instance, learning under the pessimistic bias captures a hypothesis about the role of anxiety in the later development of depression. The bias itself offers a new formalization of classic insights from the psychiatric literature about the central role of maladaptive beliefs about control and self-efficacy in anxiety. This perspective also extends previous computational accounts of beliefs about control in mood disorders, which neglected the sequential aspects of choice.
LyophilizedB. subtilisZB183 Spores: 90-Day Repeat Dose Oral (Gavage) Toxicity Study In Wistar Rats
Authors: Naidu. B Appala , Kannan Kamala , Kumar D. P. Santhosh , Oliver John W.K. , Abbott Zachary D.
Published: August 2019

A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on lyophilized spores of the novel genetically modified strainB. subtilisZB183. Lyophilized spores at doses of 109, 1010, and 1011CFU/kg body weight/day were administered by oral gavage to Wistar rats for a period of 90 consecutive days.B.SubtilisZB183 had no effects on clinical signs, mortality, ophthalmological examinations, functional observational battery, body weights, body weight gains and food consumption in both sexes. There were no test item-related changes observed in haematology, coagulation, urinalysis, thyroid hormonal analysis, terminal fasting body weights, organ weights, gross pathology and histopathology. A minimal increase in the plasma albumin level was observed at 1010and 1011CFU/kg/day doses without an increase in total protein in males or females and was considered a non-adverse effect. The “No Observed Adverse Effect Level (NOAEL)” is defined at the highest dose of 1011CFU/kg body weight/day for lyophilizedB.SubtilisZB183 Spores under the test conditions employed.
Microbial genomes retrieved from High Arctic lake sediments encode for adaptation to cold and oligotrophic environments
Authors: Ruuskanen Matti O. , Colby Graham , St.Pierre Kyra A. , St.Louis Vincent L. , Aris-Brosou Stéphane , Poulain Alexandre J.
Published: August 2019

The Arctic is currently warming at an unprecedented rate, which may affect environmental constraints on the freshwater microbial communities found there. Yet, our knowledge of the community structure and functional potential of High Arctic freshwater microbes remains poor, even though they play key roles in nutrient cycling and other ecosystem services. Here, using high-throughput metagenomic sequencing and genome assembly, we show that sediment microbial communities in the High Arctic’s largest lake by volume, Lake Hazen, are phylogenetically diverse, ranging from Proteobacteria, Verrucomicrobia, Planctomycetes, to members of the newly discovered Candidate Phyla Radiation (CPR) groups. These genomes displayed a high prevalence of pathways involved in lipid chemistry, and a low prevalence of nutrient uptake pathways, which might represent adaptations to the specific, cold (~3.5°C) and extremely oligotrophic conditions in Lake Hazen. Despite these potential adaptations, it is unclear how ongoing environmental changes will affect microbial communities, the makeup of their genomic idiosyncrasies, as well as the possible implications at higher trophic levels.
Anastrozole mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: An initial perspective
Authors: Kumar Somesh , Ghosh Subhajit , Choudhary Neha , Faruq Mohammed , Inderganti Prem kumar , Singh Vikram , Saran Ravindra kumar , Sait Haseena , Kapoor Seema
Published: August 2019

Background

Mitochondrial permeability transmembrane pore [mPTP] plays a vital role in alteration of the structure and function of mitochondria. Cyclophillin D is a mitochondrial protein that regulates mPTP function and a known drug target for therapeutic studies involving mitochondria. While aromatase inhibitor’s role on mPTP has been previously studied, the role of anastrazole on mPTP is not completely elucidated.

Methods

The role of anastrozole in modulating the mPTP was evaluated by docking and molecular dynamics using human cyclophillin D data. Peripheral blood mononuclear cells [PBMCs] of patients with mitochondrial disorders and healthy controls were treated with anastrazole and evaluated for mean fluorescence by flow cytometer. Spectrophotometry was employed for total ATP level estimation.

Findings

Anastrozole – cyclophillin D complex is more stable when compared to cyclosporine A – cyclophillin D. Anastrozole performed better than cyclosporine in inhibiting mPTP pore. Additional effects included reduction in mitochondrial swelling and mitochondrial membrane depolarization, decreased super oxide generations, caspase 3 intrinsic activity and cellular apoptosis levels and increase in ATP levels.

Interpretation

These results highlights the potency of anastrozole as a promising agent in ameliorating the phenotype by inhibiting the opening of mPTP pore. However, larger functional studies are required to validate the efficacy of this molecule as a therapeutic agent in mitochondrial disorders.
Pedigree-based measurement of thede novomutation rate in the gray mouse lemur reveals a high mutation rate, few mutations in CpG sites, and a weak sex bias
Authors: Campbell C. Ryan , Tiley George P. , Poelstra Jelmer W. , Hunnicutt Kelsie E. , Larsen Peter A. , Lee Hui-Jie , Thorne Jeffrey L. , dos Reis Mario , Yoder Anne D.
Published: August 2019

Spontaneous germline mutations are the raw material on which evolution acts, and knowledge of their frequency and genomic distribution is crucial for understanding how evolution operates at both long and short timescales. At present, the rate and spectrum ofde novomutations have been directly characterized in only a few lineages. It is therefore critical to expand the phylogenetic scope of these studies to gain a more general understanding of observed mutation rate patterns. Our study provides the first direct mutation rate estimate for a strepsirrhine (i.e., the lemurs and lorises), which comprise nearly half of the primate clade. Using high-coverage linked-read sequencing for a focal quartet of gray mouse lemurs (Microcebus murinus), we estimated the mutation rate to be 1.64 × 10−8(95% credible interval: 1.41 × 10−8to 1.98 × 10−8) mutations/site/generation. This estimate is higher than those measured for most previously characterized mammals. Further, we found an unexpectedly low count of paternal mutations, and only a modest overrepresentation of mutations at CpG-sites. Given the surprising nature of these observations, we conducted an independent analysis of context-dependent substitution types for gray mouse lemur and five additional primate species. This analysis yielded patterns consistent with the mutation spectrum from the pedigree mutation-rate analysis, which provides confidence in our ability to accurately identifyde novomutations with our data and bioinformatic filters.
HOTAIR promotes an epithelial-to-mesenchymal transition through relocation of the histone demethylase Lsd1
Authors: Jarroux Julien , Bertrand Claire , Gabriel Marc , Foretek Dominika , Saci Zohra , Londoño-Valejo Arturo , Pinskaya Marina , Morillon Antonin
Published: August 2019

Epithelial-to-mesenchymal transition (EMT) drives a loss of epithelial traits by neoplastic cells enabling metastasis and recurrence in cancer. HOTAIR emerged as one of the most renowned long noncoding RNAs promoting EMT mostly as a scaffold for PRC2 and repressive histone H3 Lys27 methylation at gene promoters. In addition to PRC2, HOTAIR interacts with the Lsd1 lysine demethylase, a known epigenetic regulator of cell fate during development and differentiation. However, Lsd1 role in HOTAIR function is still poorly understood. Here, through expression of truncated variants of HOTAIR, we revealed that, in contrast to PRC2, its Lsd1-interacting domain is essential for acquisition of migratory properties by epithelial cells. HOTAIR induces Lsd1 relocation from its inherent genomic loci hence reprogramming the epithelial transcriptome. Our results uncovered an unexpected role of HOTAIR in EMT as an Lsd1 effector and pointed to the importance of Lsd1 as a guardian of the epithelial identity.
Genomic prediction for commercial traits using univariate and multivariate approaches in Nile tilapia (Oreochromis niloticus)
Authors: Joshi Rajesh , Skaarud Anders , de Vera Mayet , Alvarez Alejandro Tola , Ødegård Jørgen
Published: August 2019

Background

Over the past three decades, Nile tilapia industry has grown into a significant aquaculture industry spread over 120 tropical and sub-tropical countries around the world accounting for 7.4% of global aquaculture production in 2015. Across species, genomic selection has been shown to increase predictive ability and genetic gain, also extending into aquaculture. Hence, the aim of this paper is to compare the predictive abilities of pedigree- and genomic-based models in univariate and multivariate approaches, with the aim to utilize genomic selection in a Nile tilapia breeding program. A total of 1444 fish were genotyped (48,960 SNP loci) and phenotyped for body weight at harvest (BW), fillet weight (FW) and fillet yield (FY). The pedigree-based analysis utilized a deep pedigree, including 14 generations. Estimated breeding values (EBVs and GEBVs) were obtained with traditional pedigree-based (PBLUP) and genomic (GBLUP) models, using both univariate and multivariate approaches. Prediction accuracy and bias were evaluated using 5 replicates of 10-fold cross-validation with three different cross-validation approaches. Further, impact of these models and approaches on the genetic evaluation was assessed based on the ranking of the selection candidates.

Results

GBLUP univariate models were found to increase the prediction accuracy and reduce bias of prediction compared to other PBLUP and multivariate approaches. Relative to pedigree-based models, prediction accuracy increased by ∼20% for FY, >75% for FW and >43% for BW. GBLUP models caused major re-ranking of the selection candidates, with no significant difference in the ranking due to univariate or multivariate GBLUP approaches. The heritabilities using multivariate GBLUP models for BW, FW and FY were 0.19 ± 0.04, 0.17 ± 0.04 and 0.23 ± 0.04 respectively. BW showed very high genetic correlation with FW (0.96 ± 0.01) and a slightly negative genetic correlation with FY (−0.11 ± 0.15).

Conclusion

Predictive ability of genomic prediction models is substantially higher than for classical pedigree-based models. Genomic selection is therefore beneficial to the Nile tilapia breeding program, and it is recommended in routine genetic evaluations of commercial traits in the Nile tilapia breeding nucleus.
Metagenomes in the borderline ecosystems of the Antarctic cryptoendolithic communities
Authors: Coleine Claudia , Albanese Davide , Onofri Silvano , Tringe Susannah G. , Pennacchio Christa , Donati Claudio , Stajich Jason E. , Selbmann Laura
Published: August 2019

Antarctic cryptoendolithic communities are microbial ecosystems dwelling inside rocks of ice-free areas in Continental Antarctica. In Antarctica, these ecosystems were first described from the McMurdo Dry Valleys, accounted as the best analogous of the Martian environment on Earth and thought to be devoid of life until the discovery of these cryptic life-forms. Our results present the first shotgun metagenomes of Antarctic cryptoendolithic lichen-dominated communities from 18 differently sun-exposed rock samples collected during the XXXI Italian Antarctic Expedition (2015-16), along an altitudinal transect from 834 up to 3100 m a.s.l. Here, we provide the raw data obtained with Illumina Novaseq sequencer, followed by initial functional and taxonomic analysis.

Our results extend understanding of the microbial diversity and biological processes in the Antarctic desert and represent an invaluable resource for the scientific community as a base-line for further studies of this kind to examine the mechanisms and pathways necessary for life to adapt and evolve in the extremes.
Reward prediction errors create event boundaries in memory
Authors: Rouhani Nina , Norman Kenneth A. , Niv Yael , Bornstein Aaron M.
Published: August 2019

We remember when things change. Particularly salient are experiences where there is a change in rewards, eliciting reward prediction errors (RPEs). This feature of memory may be useful because it can help us find greater rewards and avoid lesser ones in the future. How do RPEs influence our memory of those experiences? One idea is that this signal directly enhances the encoding of memory. Another, not mutually exclusive, idea is that the RPE signals a deeper change in the environment, and leads to the mnemonic separation of subsequent experiences from what came before, thereby creating a new latent context and a more separate memory trace. We tested this in four experiments in which participants learned to predict rewards associated with a series of images within visually-distinct “rooms.” High magnitude RPEs indicated a change in the underlying distribution of rewards. To test whether these large RPEs created a new latent context, we first assessed recognition priming for sequential pairs that contained or did not contain a high-RPE event, as well as out-of-sequence pairs (Exp. 1: n=27 & Exp. 2: n=83). We found evidence of recognition priming for both sequential pair types, including the pair with the high-RPE event, indicating that the high-RPE event is bound to its predecessor in memory. Given that high-RPE events are themselves preferentially remembered (Rouhani et al, 2018), we next tested recognition priming for pairs that had one item in between them (i.e. the pairs were either across a high-RPE event or not), where none of the tested items were high-RPE items (Exp. 3: n=85). Here, sequential pairs across a high-RPE no longer showed recognition priming whereas pairs within the same latent reward state did, providing initial evidence for an RPE-modulated event boundary. We then investigated whether RPE event boundaries disrupt temporal memory of those events (Exp. 4). After reward learning, we asked participants to order and estimate the distance between two events that had either included a high-RPE event between them, or not. We found (n=49) and replicated (n=77) worse sequence memory for events across a high-RPE event. Altogether, these findings demonstrate that high-RPE events are both more strongly encoded and act as event boundaries that interrupt the sequential integration of events. We captured these effects in a variant of the Context Maintenance and Retrieval model (CMR; Polyn, Norman & Kahana, 2009), modified to incorporate RPEs into the encoding process.
Spatial and temporal control of CRISPR/Cas9-mediated gene editing delivered via a light-triggered liposome system
Authors: Aksoy Yagiz Alp , Chen Wenjie , Goldys Ewa M , Deng Wei
Published: August 2019

The CRISPR-Cas9 and related systems offer a unique genome editing tool allowing facile and efficient introduction of heritable and locus-specific sequence modifications in the genome. Despite its molecular precision, temporal and spatial control of gene editing with CRISPR-Cas9 system is very limited. We developed a light-sensitive liposome delivery system that offers a high degree of spatial and temporal control of gene editing with CRISPR/Cas9 system. We demonstrated its high transfection efficiency, by assessing the targeted knockout of eGFP gene in human HEK293 cells (52.8% knockout). We further validated our results at a single-cell resolution using an in vivo eGFP reporter system in zebrafish (77% knockout). To the best of our knowledge we reported the first proof-of-concept of spatio-temporal control of CRISPR/Cas9 by using light-triggered liposomes in bothin vitroandin vivoenvironment.
Metadata-Guided Visual Representation Learning for Biomedical Images
Authors: Spiegel Stephan , Hossain Imtiaz , Ball Christopher , Zhang Xian
Published: August 2019

Motivation

The clustering of biomedical images according to their phenotype is an important step in early drug discovery. Modern high-content-screening devices easily produce thousands of cell images, but the resulting data is usually unlabelled and it requires extra effort to construct a visual representation that supports the grouping according to the presented morphological characteristics.

Results

We introduce a novel approach to visual representation learning that is guided by metadata. In high-context-screening, meta-data can typically be derived from the experimental layout, which links each cell image of a particular assay to the tested chemical compound and corresponding compound concentration. In general, there exists a one-to-many relationship between phenotype and compound, since various molecules and different dosage can lead to one and the same alterations in biological cells.

Our empirical results show that metadata-guided visual representation learning is an effective approach for clustering biomedical images. We have evaluated our proposed approach on both benchmark and real-world biological data. Furthermore, we have juxtaposed implicit and explicit learning techniques, where both loss function and batch construction differ. Our experiments demonstrate that metadata-guided visual representation learning is able to identify commonalities and distinguish differences in visual appearance that lead to meaningful clusters, even without image-level annotations.

Note

Please refer to the supplementary material for implementation details on metadata-guided visual representation learning strategies.
Cholesterol is a strong promotor of an α-Synuclein membrane binding mode that accelerates oligomerization
Authors: Jakubec Martin , Bariås Espen , Furse Samuel , Govasli Morten L. , George Vinnit , Turcu Diana , Iashchishyn Igor , Morozova-Roche Ludmilla , Halskau Øyvind
Published: August 2019

Dysregulation of the biosynthesis of cholesterol and other lipids has been implicated in neurological diseases, including Parkinson's disease, where the misfolding of membraneassociated α-Synuclein is a key molecular event. Recent research also suggests that α-Synuclein aggregation is influenced by the lipid environment. The exact molecular mechanisms responsible for cholesterol’s effect on α-Synuclein binding to lipids and how this binding may affect α-Synuclein oligomerization and fibrillation remain elusive, as does the relative importance of cholesterol versus other lipid factors. We probed the interactions and fibrillation behaviour of α-Synuclein using SMA nanodiscs, containing zwitterionic and anionic lipid model systems with and without cholesterol. SPR and ThT fluorescence assays were then employed to monitor α-Synuclein binding, as well as fibrillation in the absence and presence of membrane models.1H-15N correlated NMR was used to monitor the fold of α-Synuclein in response to nanodisc binding, and we determined individual residue apparent affinities for the nanodisc-contained bilayers. Cholesterol inhibited α-Synuclein interaction with lipid bilayers. We also find that cholesterol significantly promotes α-Synuclein fibrillation, with a more than 20-fold reduction of lag-times before fibrillation onset. When α-Synuclein-bilayer interactions were analysed for individual residues by solution-state NMR, we observed two different effects of cholesterol. In nanodiscs made of DOPC, cholesterol modulated the NAC part of α-Synuclein, leading to stronger interaction of this region with the lipid bilayer. In contrast, in the nanodiscs comprising DOPC, DOPE and DOPG, the NAC part was mostly unaffected by cholesterol, while the binding of the N-terminal and the C-terminal were both inhibited.
HspA1BIs a Prognostic Biomarker and Correlated With Immune Infiltrates in different subtypes of Breast Cancers
Authors: He Jian , Wang Hui
Published: August 2019

Background

Heat shock A1B, also known as HSP70kDa protein 1B, encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family.HspA1Bis a critical gene which related to many type of diseases by involving in the ubiquitin-proteasome pathway. However, the correlations ofHspA1Bto prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear.

Methods

HspA1Bexpression was evaluated on the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We analyzed the influence ofHspA1Bon clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations betweenHspA1Band cancer immune infiltrates was investigated via TIMER. In addition, correlations betweenHspA1Bexpression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.

Results

Three cohorts (GSE9195, GSE9893, GSE3494-GPL96)) of breast cancer patients showed that highHspA1Bexpression was associated with poorer overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). In addition, highHspA1Bexpression was significantly correlated with poor OS and progression-free survival (PFS) in bladder cancer, brain cancer and skin cancer. Moreover,HspA1Bsignificantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA).HspA1Bexpression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) indifferent subtypes of Breast cancer.HspA1Bexpression showed strong correlations with diverse immune marker sets in BRCA-Luminal.

Conclusions

Our findings suggest thatHspA1Bis correlated with prognosis and immune infiltrating levels of, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in colon and gastric cancer patients. In addition,HspA1Bexpression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest thatHspA1Bcan be used as a prognostic biomarker for determining prognosis and immune infiltration in BRCA-Luminal subtype.
Cytochrome P450 26b1-mediated specification of vestibular striola and central zones is required for transient responses in linear acceleration
Authors: Ono Kazuya , Keller James , Ramírez Omar López , Garrido Antonia González , Zobeiri Omid , Chang Vanessa , Vijayakumar Sarath , Ayiotis Andrianna , Duester Gregg , Della Santina Charles C. , Jones Sherri M. , Cullen Kathleen , Eatock Ruth Anne , Wu Doris K.
Published: August 2019

Each vestibular sensory epithelia of the inner ear is divided into two zones, the striola and extrastriola in maculae of otolith organs and the central and peripheral zones in cristae of semicircular canals, that differ in morphology and physiology. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)-mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, the identities of the striolar/central zones were compromised, including abnormal innervating neurons and otoconia in otolith organs. Vestibular evoked potentials (VsEP) in response to jerk stimuli were largely absent. Vestibulo-ocular reflexes and standard motor performances such as forced swimming were unaffected, but mutants had head tremors and deficits in balance beam tests that were consistent with abnormal vestibular input. Thus, degradation of RA during embryogenesis is required for patterning highly specialized regions of the vestibular sensory epithelia that may provide acute feedback about head motion.
Spatiotemporal characterization of periocular mesenchyme heterogeneity during anterior segment development
Authors: Van Der Meulen Kristyn L. , Vöcking Oliver , Weaver Megan L. , Famulski Jakub K.
Published: August 2019

Establishment of the ocular anterior segment (AS) is a critical event during development of the vertebrate visual system. Failure in this process leads to Anterior Segment Dysgenesis (ASD), which is characterized by congenital blindness and predisposition to glaucoma. The anterior segment is largely formed via a neural crest-derived population, the Periocular Mesenchyme (POM). In this study, we aimed to characterize POM behaviors and identities during zebrafish AS development. POM distributions and migratory dynamics were analyzed using transgenic zebrafish embryos (Tg[foxC1b:GFP], Tg[foxD3:GFP], Tg[pitx2:GFP], Tg[lmx1b.1:GFP], and Tg[sox10:GFP] throughout the course of early AS development (24-72hpf).In vivoimaging analysis revealed unique AS distribution and migratory behavior among the reporter lines, suggesting AS mesenchyme (ASM) is a heterogenous population. This was confirmed using doublein situhybridization. Furthermore, we generated ASM transcriptomic profiles from our reporter lines and using a four-way comparison analysis uncovered unique ASM subpopulation expression patterns. Taken together, our data reveal for the first time that AS-associated POM is not homogeneous but rather comprised of several unique subpopulations identifiable by their distributions, behaviors, and transcriptomic profiles.
Skill learning can be independent of speed and accuracy instructions
Authors: Vékony Teodóra , Marossy Hanna , Must Anita , Vécsei László , Janacsek Karolina , Nemeth Dezso
Published: August 2019

A crucial question in skill learning research is how instruction affects the performance or the underlying representations. However, a little is known about its effect on one critical aspect of skill leaning, namely, picking-up statistical regularities. More specifically, how pre-learning speed vs. accuracy instructions affect the acquisition of non-adjacent second-order dependencies. Here, we trained two groups of participants on an implicit probabilistic sequence learning task: one group focusing on being fast and the other on being accurate. As expected, we detected strong instruction effect: accuracy instruction resulted in a nearly errorless performance, while speed instruction caused short reaction times. Despite the differences in the average reaction times and accuracy scores, we found a similar level of statistical learning in the training phase. After the training phase, we tested the two groups under the same instruction (focusing on both speed and accuracy), and they showed comparable performance, suggesting a similar level of underlying statistical representations. Our findings support that skill learning can result in robust representations, and they highlight that this form of knowledge may appear with almost errorless performance.
Biased connectivity of brain-wide inputs to ventral subiculum output neurons
Authors: Wee RWS , MacAskill AF
Published: August 2019

The ventral subiculum (vS) of the mouse hippocampus coordinates diverse behaviours through heterogeneous populations of projection neurons. These neurons transmit signals to multiple brain regions by integrating thousands of local and long-range synaptic inputs. However, whether each population is selectively innervated by different afferent input remains unknown. To address this question, we employed projection-specific rabies tracing to study the input-output relationship of vS output neurons. Analysis of brain-wide inputs reveals quantitative input differences that can be explained by the spatial location of postsynaptic neurons along the proximal-distal axis of vS and the identity of the downstream target. Further, the input from nucleus reuniens, an area thought to underlie vS and prefrontal cortex (PFC) reciprocal connectivity, is unexpectedly biased away from PFC-projecting vS neurons. Overall, we reveal prominent heterogeneity in brain-wide inputs to the vS parallel output circuitry, providing a basis for the selective control of individual projections during behaviour.
In-host population dynamics ofM. tuberculosisduring treatment failure
Authors: Vargas Roger , Freschi Luca , Marin Maximillian , Epperson L. Elaine , Smith Melissa , Oussenko Irina , Durbin David , Strong Michael , Salfinger Max , Farhat Maha Reda
Published: August 2019

Background

Tuberculosis (TB) is a leading cause of death globally from an infectious agent. Understanding the population dynamics of TB’s causative agentMycobacterium tuberculosis(Mtb) in-host is vital for understanding the efficacy of antibiotic treatment. Here we use longitudinally collected clinical Mtb isolates that underwent Whole-Genome Sequencing (WGS) from the sputa of 307 subjects to investigate Mtb diversity during the course of active TB disease.

Methods and findings

We excluded cases suspected of reinfection or contamination to analyze data from 200 subjects, 167 of which met microbiological criteria for delayed culture conversion, treatment failure or relapse. Using technical and biological replicate samples, we defined an allele frequency threshold attributable to in-host evolution. Of the 167 subjects with unsuccessful treatment outcome, 27 (16%) developed new resistance mutations between sampling with 20/27 (74%) occurring in patients with pre-existing antibiotic resistance. Low abundance resistance variants at a purity of ≥19% in the first isolate predicts fixation of these variants in the subsequent sample with 27.0% sensitivity and 95.8% specificity. We identify significant in-host variation in seven genes associated with antibiotic resistance and twenty other genes, including metabolic genes and genes known to modulate host innate immunity by interacting with TLR2. We confirm Rv0095c, Rv1944c,PPE18, PPE54andPPE60to be under positive selection by assessing phylogenetic convergence across a global and genetically diverse independent sample of 20,352 isolates.

Conclusions

Our large sample provides a comprehensive picture of the mutational dynamicsin-hostduring active TB disease. We demonstrate a framework to study temporal changes in Mtb population diversity using average depth WGS data. We show that minor variants can be used to inform antibiotic treatment regimens in patients with TB. Furthermore, we detect a signature of positive selection in-host, possibly stemming from innate immune pressure and informing our understanding of host-pathogen interactions.
Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence
Authors: Haws Spencer A. , Yu Deyang , Ye Cunqi , Wille Coral K. , Nguyen Long C. , Krautkramer Kimberly A. , Tomasiewicz Jay L. , Yang Shany E. , Miller Blake R. , Liu Wallace H. , Igarashi Kazuhiko , Sridharan Rupa , Tu Benjamin P. , Cryns Vincent L. , Lamming Dudley W. , Denu John M.
Published: August 2019

S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate cellular epigenetic states. This metabolism-epigenome link enables the sensitization of chromatin methylation to altered SAM abundance. However, a chromatin-wide understanding of the adaptive/responsive mechanisms that allow cells to actively protect epigenetic information during life-experienced fluctuations in SAM availability are unknown. We identified a robust response to SAM depletion that is highlighted by preferential cytoplasmic and nuclear de novo mono-methylation of H3 Lys 9 (H3K9) at the expense of global losses in histone di- and tri-methylation. Under SAM-depleted conditions, de novo H3K9 mono-methylation preserves heterochromatin stability and supports global epigenetic persistence upon metabolic recovery. This unique chromatin response was robust across the mouse lifespan and correlated with improved metabolic health, supporting a significant role for epigenetic adaptation to SAM depletion in vivo. Together, these studies provide the first evidence for active epigenetic adaptation and persistence to metabolic stress.
Cells collectively reshape habitability of temperature by helping each other replicate
Authors: Laman Trip Diederik S. , Youk Hyun
Published: August 2019

How the rising global temperatures affect organisms is a timely question. The conventional view is that high temperatures cause microbes to replicate slowly or die, both autonomously. Yet, microbes co-exist as a population, raising the underexplored question of whether they can cooperatively combat rising temperatures. Here we show that, at high temperatures, budding yeasts help each other and future generations of cells replicate by secreting and extracellularly accumulating glutathione - a ubiquitous heat-damage-reducing antioxidant. Yeasts thereby collectively delay and can halt population extinctions at high temperatures. As a surprising consequence, even for the same temperature, a yeast population can either exponentially grow, never grow, or grow after unpredictable durations (hours-to-days) of stasis, depending on its population density. Despite the conventional theory stating that heat-shocked cells autonomously die and cannot stop population extinctions, we found that non-growing yeast-populations at high temperatures - due to cells cooperatively accumulating extracellular glutathione - continuously decelerate and can eventually stop their approach to extinction, with higher population-densities stopping faster. We show that exporting glutathione, but not importing, is required for yeasts to survive high temperatures. Thus, cooperatively eliminating harmful extracellular agents – not glutathione’s actions inside individual cells – is both necessary and sufficient for surviving high temperatures. We developed a mathematical model - which is generally applicable to any cells that cooperatively replicate by secreting molecules - that recapitulates all these features. These results show how cells can cooperatively extend boundaries of life-permitting temperatures.
Enviromicsin breeding: applications and perspectives on envirotypic-assisted selection
Authors: Resende Rafael T. , Piepho Hans-Peter , Silva-Junior Orzenil B. , Silva Fabyano F. e , de Resende Marcos Deon V. , Grattapaglia Dario
Published: August 2019

Genotype by Environment interaction (G × E) studies have focused mainly on estimating genetic parameters over a limited number of experimental trials. However, recent Geographic Information System (GIS) techniques have opened new frontiers for understanding and dealing with G × E. These advances allow increasing selection accuracy across all sites of interest, including those where experimental trials have not yet been deployed. Here, we introduce the term Enviromics under an envirotypic-assisted breeding framework and propose the GIS-GE method, i.e. a geospatial tool to maximize genetic gains by predicting the phenotypic performance of unobserved genotypes using “enviromic markers”. In summary, a particular site represents a set of envirotypes, each one representing a set of environmental factors that interact with the genetic background of genotypes, thus resulting in informative re-rankings to make decisions over different environments. Based on a simulated case study, we show that GIS-GE allows accurate (i) matching of genotypes to their most appropriate sites; (ii) definition of breeding areas that have high genetic correlation to ensure selection gains across environments; and (iii) indication of the best sites to carry out experiments for further analysis based on environments that maximize heritability. Envirotyping techniques provide a new class of markers for genetic studies, which are inexpensive, increasingly available and transferable across species. We envision a promising future for the integration of the Enviromics approach into breeding when coupled with next-generation genotyping/phenotyping and powerful statistical modeling of genetic diversity. Environmental scenarios can also be improved using information from strategic plans for biodiversity and genetic resources management, especially in the current perspective of dynamic climate change.

Key message

We propose the application ofEnviromicsto breeding practice, by which the similarity among sites assessed on an “omics” scale of environmental attributes drives the prediction of unobserved genotypes.
projectR: An R/Bioconductor package for transfer learning via PCA, NMF, correlation, and clustering
Authors: Sharma Gaurav , Colantuoni Carlo , Goff Loyal A , Fertig Elana J , Stein-O’Brien Genevieve
Published: August 2019

Motivation

Dimension reduction techniques are widely used to interpret high-dimensional biological data. Features learned from these methods are used to discover both technical artifacts and novel biological phenomena. Such feature discovery is critically import to large single-cell datasets, where lack of a ground truth limits validation and interpretation. Transfer learning (TL) can be used to relate the features learned from one source dataset to a new target dataset to perform biologically-driven validation by evaluating their use in or association with additional sample annotations in that independent target dataset.

Results

We developed an R/Bioconductor package, projectR, to perform TL for analyses of genomics data via TL of clustering, correlation, and factorization methods. We then demonstrate the utility TL for integrated data analysis with an example for spatial single-cell analysis.

Availability

projectR is available on Bioconductor and at https://github.com/genesofeve/projectR.

Contact

gsteinobrien@jhmi.edu; ejfertig@jhmi.edu
Inter-subject representational similarity analysis reveals individual variations in affective experience when watching erotic movies
Authors: Chen Pin-Hao A. , Jolly Eshin , Cheong Jin Hyun , Chang Luke J.
Published: August 2019

We spend much of our life pursuing or avoiding affective experiences. However, surprisingly little is known about how these experiences are represented in the brain and if they are shared across individuals. Here, we explore variations in the construction of an affective experience during a naturalistic viewing paradigm based on subjective preferences in sociosexual desire and self-control using intersubject representational similarity analysis (IS-RSA). We found that when watching erotic movies, intersubject variations in sociosexual desire preferences of 26 heterosexual males were associated with similarly structured fluctuations in the cortico-striatal reward, default mode, and mentalizing networks. In contrast, variations in the self-control preferences were associated with shared dynamics in the fronto-parietal executive control and cingulo-insula salience networks. Importantly, these results were specific to the affective experience, as we did not observe any relationship with variation in preferences when individuals watched neutral movies. Moreover, these results appear to require multivariate representations of preferences as we did not observe any significant results using single summary scores. Our findings demonstrate that multidimensional variations in individual preferences can be used to uncover unique dimensions of an affective experience, and that IS-RSA can provide new insights into the neural processes underlying psychological experiences elicited through naturalistic experimental designs.
High-density genetic linkage map construction and white rot resistance QTL mapping for Vitis based on restriction site-associated DNA sequencing
Authors: Su Kai , Guo Yinshan , Zhong Weihao , Lin Hong , Liu Zhendong , Li Kun , Guo Xiuwu
Published: August 2019

Grape white rot (Coniothyrium diplodiella) is a major fungal disease affecting grape yield and quality. The present study aimed to provide a foundation to improve future grape white rot resistance breeding. To this end, interspecific hybridization was conducted between a white rot resistance cultivar ‘Zhuosexiang’ (Vitus vinifera L. × Vitus labrusca L.), and a susceptible cultivar ‘Victoria’ (Vitus vinifera L.), using 177 hybrid offspring and two parents for restriction site-associated DNA sequencing (RAD-seq) and high-density genetic linkage mapping. Female, male, and integrated map marker numbers were 2501, 4110, and 6249, respectively. The average genetic distance of adjacent markers was 1.25 cM, 0.77 cM, and 0.50 cM. White rot resistance identification of the two parents and 177 individuals was conducted in July and August of 2017 and 2018. Additionally, white rot resistance quantitative trait locus (QTL) mapping was conducted. In total, nine QTLs were detected and located on linkage groups LG1, LG4, LG7, LG12, LG14, and LG15, with overlapping QTLs on LG7 and LG15. Further, three candidate genes that may be responsible for grape white rot resistance were screened. The results will provide an important theoretical reference for future grape white rot resistance breeding.