bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates
Authors: Cottrell Christopher A. , van Schooten Jelle , Bowman Charles A. , Yuan Meng , Oyen David , Shin Mia , Morpurgo Robert , van der Woude Patricia , van Breemen Marielle , Torres Jonathan L. , Patel Raj , Gross Justin , Sewall Leigh M. , Copps Jeffrey , Ozorowski Gabriel , Nogal Bartek , Sok Devin , Rakasz Eva G. , Labranche Celia , Vigdorovich Vladimir , Christley Scott , Carnathan Diane G. , Sather D. Noah , Montefiori David , Silvestri Guido , Burton Dennis R. , Moore John P. , Wilson Ian A. , Sanders Rogier W. , Ward Andrew B. , van Gils Marit J. 
Published: February 2020

AbstractThe induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several human-derived broadly neutralizing antibodies.
Effects of a postnatalAtrxconditional knockout in neurons on autism-like behaviours in male and female mice
Authors: Martin-Kenny Nicole , Bérubé Nathalie G. 
Published: February 2020

AbstractBackgroundAlpha-thalassemia/mental retardation, X-linked, orATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations ofATRXresult in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by whichATRXmutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatalAtrxinactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours.MethodsMale and female mice with a postnatal conditional knockout ofAtrxwere tested in a battery of behavioural tests that assess autistic features. We utilized paradigms that measure social behaviour, repetitive and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak’s multiple comparison test or unpaired Student’s T-tests as indicated.ResultsThe behaviour tests revealed no significant differences betweenAtrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits. We additionally observed sex-specific differences in sociability, vertical episodes, and acoustic startle response when results were analyzed by sex.ConclusionThe postnatal knockout ofAtrxin forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice.
A Multicenter Preclinical MRI Study: Definition of Rat Brain Relaxometry Reference Maps
Authors: Deruelle Tristan , Kober Frank , Perles-Barbacaru Adriana , Delzescaux Thierry , Noblet Vincent , Barbier Emmanuel L. , Dojat Michel 
Published: February 2020

ABSTRACTSimilarly to human population imaging, there are several well-founded motivations for animal population imaging, the most notable being the improvement of the validity of statistical results by pooling a sufficient number of animal data provided by different imaging centers. In this paper, we demonstrate the feasibility of such a multicenter animal study, sharing raw data from forty rats and processing pipelines between four imaging centers. As specific use case, we considered the estimation of T1 and T2 maps for the healthy rat brain at 7T. We quantitatively report about the variability observed across two data provider centers and evaluate the influence of image processing steps on the final maps, by using three fitting algorithms from three centers. Finally, to derive relaxation time values per brain area, two multi-atlas segmentation pipelines from different centers were executed on two different platforms. In this study, the impact of the acquisition was 2.21% (not significant) and 9.52% on T1 and T2 estimates while the impact of the data processing pipeline was not significant (1.04% and 3.33%, respectively). In addition, the computed normality values can serve as relaxometry reference maps to explore differences to animal models of pathologies.
PICH function is required for organization of SUMOylated proteins on mitotic chromosomes
Authors: Hassebroek Victoria A. , Park Hyewon , Pandey Nootan , Lerbakken Brooklyn T. , Aksenova Vasilisa , Arnaoutov Alexei , Dasso Mary , Azuma Yoshiaki 
Published: February 2020

AbstractProper chromosome segregation is essential for faithful cell division and if not maintained results in defective cell function caused by abnormal distribution of genetic information. Polo-like kinase 1 interacting checkpoint helicase (PICH) is a DNA translocase essential in chromosome bridge resolution during mitosis. Its function in resolving chromosome bridges requires both DNA translocase activity and ability to bind chromosomal proteins modified by Small Ubiquitin-like modifier (SUMO). However, it is unclear how these activities are cooperating to resolve chromosome bridges. Here, we show that PICH specifically promotes the organization of SUMOylated proteins like SUMOylated TopoisomeraseIIα (TopoIIα) on mitotic chromosomes. Conditional depletion of PICH using the Auxin Inducible Degron (AID) system resulted in the retention of SUMOylated chromosomal proteins, including TopoIIα, indicating that PICH functions to control proper association of these proteins with chromosomes. Replacement of PICH with its mutants showed that PICH is required for the proper organization of SUMOylated proteins on chromosomes.In vitroassays showed that PICH specifically attenuates SUMOylated TopoIIα activity using its SUMO-binding ability. Taken together, we propose a novel function of PICH in remodeling SUMOylated proteins to ensure faithful chromosome segregation.Summary StatementPolo-like kinase interacting checkpoint helicase (PICH) interacts with SUMOylated proteins to mediate proper chromosome segregation during mitosis. The results demonstrate that PICH controls association of SUMOylated chromosomal proteins, including Topoisomerase IIα, and that function requires PICH translocase activity and SUMO binding ability.
Duplications drive diversity inBordetella pertussison an underestimated scale
Authors: Abrahams Jonathan S. , Weigand Michael R. , Ring Natalie , MacArthur Iain , Peng Scott , Williams Margaret M. , Bready Barrett , Catalano Anthony P. , Davis Jennifer R. , Kaiser Michael D. , Oliver John S. , Sage Jay M. , Bagby Stefan , Tondella M. Lucia , Gorringe Andrew R. , Preston Andrew 
Published: February 2020

AbstractBacterial genetic diversity is often described using solely base pair changes despite a wide variety of other mutation types likely being major contributors. Tandem duplications of genomic loci are thought to be widespread among bacteria but due to their often intractable size and instability, comprehensive studies of the range and genome dynamics of these mutations are rare. We define a methodology to investigate duplications in bacterial genomes based on read depth of genome sequence data as a proxy for copy number. We demonstrate the approach withBordetella pertussis, whose insertion sequence element-rich genome provides extensive scope for duplications to occur. Analysis of genome sequence data for 2430B. pertussisisolates identified 272 putative duplications, of which 94% were located at 11 hotspot loci. We demonstrate limited phylogenetic connection for the occurrence of duplications, suggesting unstable and sporadic characteristics. Genome instability was further described in-vitro using long read sequencing via the Nanopore platform. Clonally derived laboratory cultures produced heterogenous populations containing multiple structural variants. Short read data was used to predict 272 duplications, whilst long reads generated on the Nanopore platform enabled the in-depth study of the genome dynamics of tandem duplications inB. pertussis. Our work reveals the unrecognised and dynamic genetic diversity ofB. pertussisand, as the complexity of theB. pertussisgenome is not unique, highlights the need for a holistic and fundamental understanding of bacterial genetics.
Method forin vivoassessment of cancer tissue inhomogeneity and accurate histology-like morphological segmentation based on Optical Coherence Elastography
Authors: Plekhanov Anton A. , Sirotkina Marina A. , Sovetsky Alexander A. , Gubarkova Ekaterina V. , Kuznetsov Sergey S. , Matveyev Alexander L. , Matveev Lev A. , Zagaynova Elena V. , Gladkova Natalia D. , Zaitsev Vladimir Y. 
Published: February 2020

AbstractWe present a non-invasive method based on Optical Coherence Elastography (OCE) enabling thein vivosegmentation of morphological tissue constituents, in particular, monitoring of morphological alterations during both tumor development and its response to therapies. The method uses compressional OCE to reconstruct tissue stiffness map as the first step. Then the OCE-image is divided into regions, for which the Young’s modulus (stiffness) falls in specific ranges corresponding to the morphological constituents to be discriminated. These stiffness ranges (characteristic “stiffness spectra”) are initially determined by careful comparison of the “gold-standard” histological data and the OCE-based stiffness map for the corresponding tissue regions. After such precalibration, the results of morphological segmentation of OCE-images demonstrate a striking correlation with the histological results in terms of percentage of the segmented zones. To demonstrate high sensitivity of the OCE-method and its excellent correlation with conventional histological segmentation we present results obtainedin vivoon a murine model of breast cancer in comparative experimental study of the efficacy of two anti-tumor chemotherapeutic drugs with different mechanisms of action. The new technique allowedin vivomonitoring and quantitative segmentation of (i) viable, (ii) dystrophic, (iii) necrotic tumor cells and (iv) edema zones very similar to morphological segmentation of histological images. Numerous applications in other experimental/clinical areas requiring rapid, nearly real-time, quantitative assessment of tissue structure can be foreseen.
Rational arbitration between statistics and rules in human sequence processing
Authors: Maheu Maxime , Meyniel Florent , Dehaene Stanislas 
Published: February 2020

AbstractDetecting and learning temporal regularities is essential to accurately predict the future. A long-standing debate in cognitive science concerns the existence of a dissociation, in humans, between two systems, one for handling statistical regularities governing the probabilities of individual items and their transitions, and another for handling deterministic rules. Here, to address this issue, we used finger tracking to continuously monitor the online build-up of evidence, confidence, false alarms and changes-of-mind during sequence processing. All these aspects of behaviour conformed tightly to a hierarchical Bayesian inference model with distinct hypothesis spaces for statistics and rules, yet linked by a single probabilistic currency. Alternative models based either on a single statistical mechanism or on two non-commensurable systems were rejected. Our results indicate that a hierarchical Bayesian inference mechanism, capable of operating over distinct hypothesis spaces for statistics and rules, underlies the human capability for sequence processing.
Probing the effect of glycosaminoglycan depletion on integrin interactions with collagen I fibrils in the native ECM environment
Authors: Roth Jonathan , Hoop Cody L. , Williams Jonathan K. , Hayes Robert , Baum Jean 
Published: February 2020

AbstractFibrillar collagen–integrin interactions in the extracellular matrix (ECM) regulate a multitude of cellular processes and cell signalling. Collagen I fibrils serve as the molecular scaffolding for connective tissues throughout the human body and are the most abundant protein building blocks in the ECM. The ECM environment is diverse, made up of several ECM proteins, enzymes, and proteoglycans. The contents of the ECM environment are modulated by disease and aging and may influence these critical collagen–integrin interactions. In particular, glycosaminoglycans (GAGs), anionic polysaccharides that decorate proteoglycans, become depleted in the ECM with natural aging and their mis-regulation has been linked to cancers and other diseases. The impact of GAG concentration in the ECM environment on collagen interactions is not well understood. Here, we integrate protein adhesion assays with liquid high resolution atomic force microscopy (AFM) to assess the affects of GAG depletion on the interaction of collagen I fibrils with the integrin α2I domain. Adhesion assays demonstrate that α2I preferentially binds to GAG-depleted collagen I fibrils. By amplitude modulated AFM in air and in solution, we find that GAG-depleted collagen I fibrils retain structural features of the native fibrils, including their characteristic D-banding pattern, a key structural motif. AFM fast force mapping in solution shows that GAG depletion reduces the stiffness of individual fibrils, lowering the indentation modulus by half compared to native fibrils. Together these results shed new light on how GAGs influence collagen I fibril– integrin interactions and may aid in strategies to treat diseases that result from GAG misregulation.Statement for broader audienceAging and disease result in mis-regulation of glycosaminoglycan (GAG) levels in the extracellular matrix (ECM), which may affect fibrillar collagen interactions that are vital for cellular processes. Here, we characterize the impact of GAG depletion on collagen–integrin α2I domain interactions and collagen fibril topography and stiffness. We show that GAG depletion increases collagen–α2I binding and reduces stiffness in comparison to native fibrils. These results may inform on strategies for treating GAG mis-regulation.
Widespread Recombination Suppression Facilitates Plant Sex Chromosome Evolution
Authors: Rifkin Joanna L. , Beaudry Felix E.G. , Humphries Zoë , Choudhury Baharul I. , Barrett Spencer C.H. , Wright Stephen I. 
Published: February 2020

1SummaryClassical models suggest recombination rates on sex chromosomes evolve in a stepwise manner to localize the inheritance of sexually antagonistic variation in the sex where it is beneficial, thereby lowering rates of recombination between X and Y chromosomes. However, it is also possible that sex chromosome formation occurs in regions with pre-existing recombination suppression. To evaluate these possibilities, we constructed linkage maps and a chromosome-scale genome assembly for the dioecious plantRumex hastatulus, a species with a young neo-sex chromosome found in part of its geographical range. We found that the ancestral sex-linked region is located in a large region characterized by low recombination. Furthermore, comparison between the recombination landscape of the neo-sex chromosome and its autosomal homologue indicates that low recombination rates preceded sex linkage. Our findings suggest that ancestrally low rates of recombination have facilitated the formation and evolution of heteromorphic sex chromosomes.
Prochlorococcusphage ferredoxin: structural characterization and electron transfer to cyanobacterial sulfite reductases
Authors: Campbell Ian J. , Olmos Jose L. , Xu Weijun , Kahanda Dimithree , Atkinson Joshua T. , Sparks Othneil N. , Miller Mitchell D. , Phillips George N. , Bennett George N. , Silberg Jonathan J. 
Published: February 2020

AbstractMarine cyanobacteria are infected by phage whose genomes encode ferredoxin (Fd) electron carriers. While these Fds are thought to redirect the energy harvested from light to phage-encoded oxidoreductases that enhance viral fitness, it is not clear how the biophysical properties and partner specificities of phage Fds relate to those in photosynthetic organisms. Bioinformatic analysis using a sequence similarity network revealed that phage Fds are most closely related to cyanobacterial Fds that transfer electrons from photosystems to oxidoreductases involved in nutrient assimilation. Structural analysis of myovirus P-SSM2 Fd (pssm2-Fd), which infectsProchlorococcus marinus, revealed high similarity to cyanobacterial Fds (≤0.5 Å RMSD). Additionally, pssm2-Fd exhibits a low midpoint reduction potential (−336 mV vs. SHE) similar to other photosynthetic Fds, albeit lower thermostability (Tm= 28°C) than many Fds. When expressed in anEscherichia colistrain with a sulfite assimilation defect, pssm2-Fd complemented growth when coexpressed with aProchlorococcus marinussulfite reductase, revealing that pssm2-Fd can transfer electrons to a host protein involved in nutrient assimilation. The high structural similarity with cyanobacterial Fds and reactivity with a host sulfite reductase suggest that phage Fds evolved to transfer electrons to cyanobacterial-encoded oxidoreductases.
Measurement of the torque in braided DNAs using a thermodynamic Maxwell relation
Authors: Xiao Botao , Brahmachari Sumitabha , Liu Yang , Ding Ke , Marko John F. 
Published: February 2020

ABSTRACTBraided DNAs are significant structural intermediates in cellular processes, yet little has been experimentally demonstrated about their higher-order structure and twisting torques. We use magnetic tweezers to measure braid extensions at forces ranging from 0.3 to 8 piconewtons, and then apply a thermodynamic Maxwell relation to calculate the torque. Experimentally inferred torques in unbuckled braids take on values up to 76 pN·nm, which depends on force, and inter-tether distance. As predicted using a statistical mechanical model, the twist modulus of the braids increases with catenation prior to buckling or formation of plectoneme, and is comparable to that of single DNA.
Bumblebee worker castes show differences in allele-specific DNA methylation and allele-specific expression
Authors: Marshall H. , Jones A.R.C. , Lonsdale Z.N. , Mallon E.B. 
Published: February 2020

AbstractAllele-specific expression is when one allele of a gene shows higher levels of expression compared to the other allele, in a diploid organism. Genomic imprinting is an extreme example of this, where some genes exhibit allele-specific expression in a parent-of-origin manner. Recent work has identified potentially imprinted genes in species of Hymenoptera. However, the molecular mechanism which drives this allelic expression bias remains unknown. In mammals DNA methylation is often associated with imprinted genes. DNA methylation systems have been described in species of Hymenoptera, providing a candidate imprinting mechanism. Using previously generated RNA-Seq and whole genome bisulfite sequencing from reproductive and sterile bumblebee (Bombus terrestris) workers we have identified genome-wide allele-specific expression and allele-specific DNA methylation. The majority of genes displaying allele-specific expression are common between reproductive castes and the proportion of allele-specific expression bias generally varies between colonies. We have also identified genome-wide allele-specific DNA methylation patterns in both castes. There is no significant overlap between genes showing allele-specific expression and allele-specific methylation. These results indicate that DNA methylation does not directly drive genome-wide allele-specific expression in this species. Only a small number of the genes identified may be ‘imprinted’ and it may be these genes which are associated with allele-specific DNA methylation. Future work utilising reciprocal crosses to identify parent-of-origin DNA methylation will further clarify the role of DNA methylation in parent-of-origin allele-specific expression.
Genetic basis of phenotypic plasticity and genotype x environment interaction in a multi-parental population
Authors: Diouf Isidore , Derivot Laurent , Koussevitzky Shai , Carretero Yolande , Bitton Frédérique , Moreau Laurence , Causse Mathilde 
Published: February 2020

AbstractDeciphering the genetic basis of phenotypic plasticity and genotype x environment interaction (GxE) is of primary importance for plant breeding in the context of global climate change. Tomato is a widely cultivated crop that can grow in different geographical habitats and which evinces a great capacity of expressing phenotypic plasticity. We used a multi-parental advanced generation intercross (MAGIC) tomato population to explore GxE and plasticity for multiple traits measured in a multi-environment trial (MET) design comprising optimal cultural conditions and water deficit, salinity and heat stress over 12 environments. Substantial GxE was observed for all the traits measured. Different plasticity parameters were estimated through the Finlay-Wilkinson and factorial regression models and used together with the genotypic means for quantitative trait loci (QTL) mapping analyses. Mixed linear models were further used to investigate the presence of interactive QTLs (QEI). The results highlighted a complex genetic architecture of tomato plasticity and GxE. Candidate genes that might be involved in the occurrence of GxE were proposed, paving the way for functional characterization of stress response genes in tomato and breeding for climate-adapted crop.HighlightThe genetic architecture of tomato response to several abiotic stresses is deciphered. QTL for plasticity and QTL x Environment were identified in a highly recombinant MAGIC population.
Cold-mediated regulation of systemic retinol transport controls adipose tissue browning
Authors: Fenzl Anna , Kulterer Oana Cristina , Spirk Katrin , Mitulović Goran , Marculescu Rodrig , Bilban Martin , Baumgartner-Parzer Sabina , Kautzky-Willer Alexandra , Kenner Lukas , Plutzky Jorge , Quadro Loredana , Kiefer Florian W. 
Published: February 2020

ABSTRACTBrowning of white fat reduces obesity in many preclinical models. Vitamin A metabolites (retinoids) have been linked to thermogenic programming of adipose tissue (AT), however the physiologic importance of systemic retinoid metabolism for AT browning is unknown. Here we show that cold stimulation in mice and humans increases circulating retinol and its plasma transporter, retinol binding protein (RBP). Cold exposure shifts retinol abundance from liver towards subcutaneous white AT which correlates with enhanced thermogenic gene transcription. Cold-mediated retinoid flux is abrogated in Rbp deficient (Rbp-/-) mice and AT browning is dramatically impaired, which renders Rbp-/-mice cold intolerant. Rbp deficiency attenuates cold-induced lipid clearance due to decreased oxidative capacity. In humans, cold-mediated retinol increase is associated with enhanced lipid utilization. Retinol stimulation in primary human adipocytes promotes thermogenic gene expression and mitochondrial respiration. In conclusion, coordinated retinol delivery is essential for cold-induced thermogenic programming of white fat.