bluuebunny/crossref_metadata_2025_split huggingface dataset:
Honey bee flights under ethanol-exposure show changes in body and wing kinematics
Authors: Ahmed Ishriak , Abramson Charles I. , Faruque Imraan A. 
Published: January 2022

AbstractFlying social insects can provide model systems for inflight interactions in computationally-constrained aerial robot swarms, whose interactions may be chemically modulated under recent measurement advancements provide a capability to simultaneously make precise measurements of insect wing and body motions. This paper presents the first quantitative measurements of ethanol-exposed honey bee flight body and wing kinematic parameters. Four high speed cameras (9000 fps) were used to track the wing and body motions of insects (Apis mellifera). Digitization, consisting of data association, hull reconstruction, and segmentation, achieved the first high speed measurements of ethanol exposed honey bees’ wing and body motions. Kinematic changes induced by exposure to ethanol concentrations from 0% to 5% were studied using statistical analysis tools. Analysis considered trial wide mean and maximum values and gross wingstroke parameters, and tested deviations for statistical significance using Welch’s t-test and Cohen’s d test. The results indicate a decrease in maximal heading and pitch rates of the body, and that roll rate is affected at high concentrations (5%). The wingstroke effects include a stroke frequency decrease, stroke amplitude increase, stroke inclination angle increase, and a more planar wingstroke. These effects due to ethanol exposure are valuable tools to separate from interaction effects.
Pareto-optimal trade-off for phenotypic switching of populations in a stochastic environment
Authors: Dinis L. , Unterberger J. , Lacoste D. 
Published: January 2022

AbstractFinding optimal survival strategies of living systems embedded in fluctuating environments generally involves a balance between phenotypic diversification and sensing. If we neglect sensing mechanisms, it is known that slow, resp. fast, environmental transitions favor a regime of heterogeneous, resp. homogeneous, phenotypic response.We focus here on the simplest non-trivial case, i.e. two randomly switching phenotypes subjected to two stochastically switching environments. The optimal asymptotic (long term) growth rate of this model was studied elsewhere; we further expand these results by discussing finite time growth rate fluctuations. An exact asymptotic expression for the variance, alongside with approximations valid in different regimes, are tested numerically in details. Our simulations of the dynamics suggest a close connection between this variance and the extinction probability, understood as risk for the population. Motivated by an earlier trade-off analysis between average capital growth rate and risk in Kelly’s gambling model, we study the trade-off between the average growth rate and the variance in the present model. Despite considerable differences between the two models, we find similar optimal trade-off curves (Pareto fronts), suggesting that our conclusions are robust, and broadly applicable in various fields ranging from biology/ecology to economics.
BrainStat: a toolbox for brain-wide statistics and multimodal feature associations
Authors: de Wael Reinder Vos , Bayrak Şeyma , Benkarim Oualid , Herholz Peer , Larivière Sara , Rodriguez-Cruces Raul , Paquola Casey , Hong Seok-Jun , Misic Bratislav , Evans Alan C. , Valk Sofie L. , Bernhardt Boris C. 
Published: January 2022

AbstractAnalysis and interpretation of neuroimaging datasets has become a multidisciplinary endeavor, relying not only on statistical methods, but increasingly on associations with respect to other brain-derived features such as gene expression, histological data, and functional as well as cognitive architectures. Here, we introduce BrainStat - a toolbox for (i) univariate and multivariate linear models in volumetric and surface-based brain imaging datasets, and (ii) multidomain feature association of results with respect to spatial maps of post-mortem gene expression and histology, task-based fMRI meta-analysis, as well as resting-state fMRI motifs across several common surface templates. The combination of statistics and feature associations into a turnkey toolbox streamlines analytical processes and accelerates cross-modal research. The toolbox is implemented in both Python and MATLAB, two widely used programming languages in the neuroimaging and neuroinformatics communities. BrainStat is openly available and complemented by an expandable documentation.
High-resolution map of plastid encoded polymerase binding patterns demonstrates a major role of transcription in chloroplast gene expression
Authors: Palomar V. Miguel , Jaksich Sarah , Fujii Sho , Kuciński Jan , Wierzbicki Andrzej T. 
Published: January 2022

ABSTRACTPlastids are endosymbiotic organelles containing their own genomes, which are transcribed by two types of RNA polymerases. One of those enzymes is a bacterial-type, multi-subunit polymerase encoded by the plastid genome. The plastid encoded RNA polymerase (PEP) is required for efficient expression of genes encoding proteins involved in photosynthesis. Despite the importance of PEP, its DNA binding locations have not been studied on the genome-wide scale at high resolution. We established a highly specific approach to detect the genome-wide pattern of PEP binding to chloroplasts DNA using ptChIP-seq. We found that in mature Arabidopsis thaliana chloroplasts, PEP has a complex DNA binding pattern with preferential association at genes encoding rRNA, tRNA, and a subset of photosynthetic proteins. Sigma factors SIG2 and SIG6 strongly impact PEP binding to a subset of tRNA genes and have more moderate effects on PEP binding throughout the rest of the genome. PEP binding is commonly enriched on gene promoters, around transcription start sites. Finally, the levels of PEP binding to DNA are correlated with the levels of RNA accumulation, which allowed estimating the quantitative contribution of transcription to RNA accumulation.
An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation
Authors: Seuma Mireia , Lehner Ben , Bolognesi Benedetta 
Published: January 2022

AbstractMultiplexed assays of variant effects (MAVEs) guide clinical variant interpretation and reveal disease mechanisms. To date, MAVEs have focussed on a single mutation type - amino acid (AA) substitutions - despite the diversity of coding variants that cause disease. Here we use Deep Indel Mutagenesis (DIM) to generate the first comprehensive atlas of diverse variant effects for a disease protein, the amyloid beta (Aß) peptide that aggregates in Alzheimer’s disease (AD) and is mutated in familial AD (fAD). The atlas identifies known fAD mutations and reveals many variants beyond substitutions accelerate Aß aggregation and are likely to be pathogenic. Truncations, substitutions, insertions, single- and internal multi-AA deletions differ in their propensity to enhance or impair aggregation, but likely pathogenic variants from all classes are highly enriched in the polar N-terminus of Aß. This first comparative atlas highlights the importance of including diverse mutation types in MAVEs and provides important mechanistic insights into amyloid nucleation.
Comb-structured mRNA vaccine tethered with short double-stranded RNA adjuvants maximizes cellular immunity for cancer treatment
Authors: Tockary Theofilus A. , Abbasi Saed , Matsui-Masai Miki , Yoshinaga Naoto , Boonstra Eger , Wang Zheng , Fukushima Shigeto , Kataoka Kazunori , Uchida Satoshi 
Published: January 2022

ABSTRACTIntegrating antigen-encoding mRNA and immunostimulatory adjuvant into a single formulation is a promising approach to potentiating the efficacy of mRNA vaccines. Here, we developed a scheme based on RNA engineering to integrate adjuvancy directly into antigen-encoding mRNA strands without hampering the ability to express antigen proteins. Short double-stranded RNA (dsRNA) was designed to target retinoic acid-inducible gene-I (RIG-I), an innate immune receptor, for effective cancer vaccination and then tethered onto mRNA strand via hybridization. Tuning the dsRNA structure and microenvironment by changing its length and sequence enabled the determination of the structure of dsRNA-tethered mRNA efficiently stimulating RIG-I. Eventually, the formulation loaded with dsRNA-tethered mRNA of the optimal structure effectively activated mouse and human dendritic cells and drove them to secrete a broad spectrum of proinflammatory cytokines without increasing the secretion of anti-inflammatory cytokines. Notably, the immunostimulating intensity was tunable by modulating the number of dsRNA along mRNA strand, which prevents excessive immunostimulation. Versatility in the applicable formulation is a practical advantage of the dsRNA-tethered mRNA. Its formulation with three existing systems, i.e., anionic lipoplex, ionizable lipid-based lipid nanoparticles, and polyplex micelles, induced appreciable cellular immunity in the mice model. Of particular interest, dsRNA-tethered mRNA encoding ovalbumin (OVA) formulated in anionic lipoplex used in clinical trials exerted a significant therapeutic effect in the mouse lymphoma (E.G7-OVA) model. In conclusion, the system developed here provides a simple and robust platform to supply the desired intensity of immunostimulation in various formulations of mRNA cancer vaccines.
Loneliness is associated with mentalizing and emotion recognition abilities in schizophrenia, but only in a cluster of patients with social cognitive deficits
Authors: Okruszek Ł. , Jarkiewicz M. , Piejka A. , Chrustowicz M. , Krawczyk M. , Schudy A. , Harvey P.D. , Penn D.L. , Ludwig K. , Green M.F. , Pinkham A. 
Published: January 2022

AbstractBackgroundLoneliness is a concern for patients with schizophrenia (SCZ). However, the correlates of loneliness in SCZ are unclear; thus, the aim of the study is to investigate neuro- and social cognitive (SC) mechanisms associated with loneliness in SCZ.MethodsData for the study were pooled from two cross-national samples (Poland/USA) and included 147 SCZ and 103 healthy controls (HC) overall. Data from clinical, neurocognitive, and SC assessments were examined as potential predictors of loneliness in HC and SCZ samples pooled across two sites. Furthermore, Latent Class Analysis (LCA) was used to cluster patients based on SC capacity. Next, the relationship between SC and loneliness was explored in each cluster of SCZ.ResultsSCZ reported higher levels of loneliness than HC. Loneliness was linked to increased negative and affective symptoms in patients. A negative association between loneliness and mentalizing and emotion recognition abilities was found in the patients with social-cognitive impairments, but not in those who performed at normative levels.ConclusionsWe have elucidated a novel mechanism which may explain previous inconsistent findings regarding the correlates of loneliness in SCZ. As decreased SC capacity may be linked with loneliness only in patients with observable SC impairments, SC heterogeneity in SCZ needs to be recognized while planning psychosocial interventions targeting loneliness in this group.
Dynamics and structural changes of calmodulin upon interaction with its potent antagonist calmidazolium
Authors: Léger Corentin , Pitard Irène , Sadi Mirko , Carvalho Nicolas , Brier Sébastien , Mechaly Ariel , Raoux-Barbot Dorothée , Davi Maryline , Hoos Sylviane , Weber Patrick , Vachette Patrice , Durand Dominique , Haouz Ahmed , Guijarro J. Iñaki , Ladant Daniel , Chenal Alexandre 
Published: January 2022

AbstractCalmodulin (CaM) is a eukaryotic multifunctional, calcium-modulated protein that regulates the activity of numerous effector proteins involved in a variety of physiological processes. Calmidazolium (CDZ) is a potent small molecule antagonist of CaM and one the most widely used inhibitors of CaM in cell biology. Here, we report the structural characterization of CaM:CDZ complexes using combined SAXS, X-ray crystallography, HDX-MS and NMR approaches. Our results provide molecular insights into the CDZ-induced dynamics and structural changes of CaM leading to its inhibition. CDZ-binding induces an open-to-closed conformational change of CaM and results in a strong stabilization of its structural elements associated with a reduction of protein dynamics over a large time range. These CDZ-triggered CaM changes mimic those induced by CaM-binding peptides derived from protein targets, despite their distant chemical nature. CaM residues in close contact with CDZ and involved in the stabilization of the CaM:CDZ complex have been identified. These results open the way to rationally design new CaM-selective drugs.Figure and text for the Table of Contents (ToC)Calmidazolium is a potent and widely used inhibitor of calmodulin, a major mediator of calcium-signaling in eukaryotic cells. Structural characterization of calmidazolium-binding to calmodulin reveals that it triggers open-to-closed conformational changes similar to those induced by calmodulin-binding peptides derived from enzyme targets. These results open the way to rationally design new and more selective inhibitors of calmodulin.
Nulliparity affects the expression of a limited number of genes and pathways in Day 8 equine embryos
Authors: Derisoud E. , Jouneau L. , Archilla C. , Jaszczyszyn Y. , Legendre R. , Daniel N. , Peynot N. , Dahirel M. , Auclair-Ronzaud J. , Duranthon V. , Chavatte-Palmer P. 
Published: January 2022

AbstractNulliparous mares produce lighter and smaller foals compared to mares having previously foaled, with effects observed at least until 4 months of age. The need for a first gestation priming for the uterus to reach its full capacity has been proposed to explain this observation. Embryo developmental defects could be hypothesized but effects of maternal parity on the embryo have only been described once, in old mares, thus combining effects of parity and old age. The aim of this study was to determine effects of mare parity on embryo gene expression. Day-8 post ovulation blastocysts were collected from young (5/6 years old) nulliparous (YN, N=6) or multiparous (YM, N=4) non-nursing Saddlebred mares, inseminated with the semen of one stallion. Pure (TE_part) or inner-cell-mass-enriched (ICMandTE) trophoblast were obtained by embryo bisection for RNA sequencing (paired end, non-oriented, Illumina, NextSeq500). Deconvolution was performed on the ICMandTE dataset. Differential expression, with embryo sex and diameter as cofactors and gene set enrichment analysis (GO BP, KEGG, REACTOME databases) were performed using a false discovery rate <0.05 cutoff. Only a few genes were altered (ICM: n=18; TE: n=6) but several gene sets were perturbed (ICM: n=62; TE: n=50) by maternal parity. In YM, only pathways related to transcription, RNA processing and vesicle transport functions were enriched in the ICM whereas only pathways related to RNA localization were enriched in TE. In YN, while only gene sets related to ribosomes and extracellular matrix were enriched in the ICM, functions related to energy and lipid metabolism, lipid transport and interleukin-1 signaling were enriched in the TE. In conclusion, several genes and pathways are affected in embryos collected from nulliparous mares, with different effects on TE and ICM. Embryo development is altered in nulliparous mares, which could partially explain the term phenotype. Whether differences in gene expression result/induce poor embryo-maternal communication remains to be determined.
Context-Dependent Enhancer Function Revealed by Targeted Inter-TAD Relocation
Authors: Bolt Christopher Chase , Lopez-Delisle Lucille , Hintermann Aurélie , Mascrez Bénédicte , Rauseo Antonella , Andrey Guillaume , Duboule Denis 
Published: January 2022

ABSTRACTThe expression of genes with a key function during development is frequently controlled by large regulatory landscapes containing multiple enhancer elements. These landscapes often match Topologically Associating Domains (TADs) and sometimes integrate range of similar enhancers, thus leading to TADs having a global regulatory specificity. To assess the relative functional importance of enhancer sequences versus the regulatory domain they are included in, we set out to transfer one particular enhancer sequence from its native domain into a TAD with a closely related, yet different functional specificity. We used Hoxd genes and their biphasic regulation during limb development as a paradigm, since they are first activated in proximal limb cells by enhancers located in one TAD, which is then silenced at the time when the neighboring TAD starts to activate its enhancers in distal limb cells. We introduced a strong distal limb enhancer into the ‘proximal limb TAD’ and found that its new context strongly suppresses its distal specificity, even though it continues to be bound by HOX13 transcription factors, which normally are responsible for this activity. Using local genetic alterations and chromatin conformation measurements, we see that the enhancer is capable of interacting with target genes, with a pattern comparable to its adoptive neighborhood of enhancers. Its activity in distal limb cells can be rescued only when a large portion of the surrounding environment is removed. These results indicate that, at least in some cases, the functioning of enhancer elements is subordinated to the local chromatin context, which can exert a dominant control over its activity.
Phase separation driven by interchangeable properties in the intrinsically disordered regions of protein paralogs
Authors: Chiu Shih-Hui , Ho Wen-Lin , Sun Yung-Chen , Kuo Jean-Cheng , Huang Jie-rong 
Published: January 2022

AbstractParalogs, arising from gene duplications, increase the functional diversity of proteins. Protein functions in paralog families have been extensively studied, but little is known about the roles of intrinsically disordered regions (IDRs), even though more than half of eukaryotic proteins have them. Using the RNA-binding protein Musashi family as an example, we applied multiple structural techniques and phylogenetic analysis to show how members in a paralog family have evolved their IDRs to different physicochemical properties but converge to the same function. In this example, the lower prion-like tendency of Musashi-1’s IDRs, rather than Musashi-2s’, is compensated by its higher α-helical propensity to assist their assembly. Without a folded structure to restraint, IDRs’ sequences mutate faster along with evolution. No matter how fast they change, our work suggests that IDRs evolve different traits to a converged function, such as liquid-liquid phase separation.
Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum ofShank3mutant mice
Authors: Allain-Thibeault Ferhat , Elisabeth Verpy , Anne Biton , Benoît Forget , de Chaumont Fabrice , Florian Mueller , Anne-Marie Le Sourd , Sabrina Coqueran , Julien Schmitt , Christelle Rochefort , Laure Rondi-Reig , Aziliz Leboucher , Anne Boland , Bertrand Fin , François Deleuze Jean , Boeckers Tobias M. , Elodie Ey , Thomas Bourgeron 
Published: January 2022

AbstractAutism is characterised by atypical social communication and stereotyped behaviours. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1-2% of patients with autism and intellectual disability (ID), but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterised the behaviour ofShank3Δ11/Δ11mice from three to twelve months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEG). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g.Grm2, Dlgap1), G-protein-signalling pathways (e.g.Gnal, Prkcg1, and Camk2g), as well as excitation/inhibition balance (e.g.Gad2). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs (Cnr1, Gnal1, Gad2, and Drd4) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded byGad2, we showed that the striosome compartment ofShank3Δ11/Δ11mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of SHANK3-deficient mice and strongly suggest, for the first time, that the impairment in behaviour of these mice are related to an imbalance striosomes/matrix.
Biochemistry and nanomechanical properties of human colon cells upon simvastatin, lovastatin and mevastatin supplementations – Raman imaging and AFM studies
Authors: Beton K. , Brożek-Płuska B. 
Published: January 2022

AbstractOne of the most important areas of medical science is oncology, which is responsible for both the diagnostics and treatment of cancer diseases. Over the years, there has been an intensive development of cancer diagnostics and treatment. This paper shows the comparison of normal (CCD-18Co) and cancerous (CaCo-2) cell lines of the human gastrointestinal tract on the basis of nanomechanical and biochemical properties in order to obtain information on the cancer biomarkers useful in oncological diagnostics. The research techniques used were: Atomic Force Microscopy and Raman spectroscopy and imaging. In addition, the studies included also the effect of the statins compounds: mevastatin, lovastatin and simvastatin and their influence on nanomechanical and biochemical changes of properties of cells tracking using AFM and Raman imaging techniques. The cytotoxicity of mevastatin and lovastatin was determined by using XTT tests.
Targeting SARS-CoV-2 infection through CAR-T like bispecific T cell engagers incorporating ACE2
Authors: Dogan Mikail , Kozhaya Lina , Placek Lindsey , Karabacak Fatih , Yigit Mesut , Unutmaz Derya 
Published: January 2022

SummaryDespite advances in antibody treatments and vaccines, COVID-19 caused by SARS-CoV-2 infection remains a major health problem resulting in excessive morbidity and mortality and the emergence of new variants has reduced the effectiveness of current vaccines. Here, as a proof-of-concept we engineered primary CD8 T cells to express SARS-CoV-2 Spike protein-specific CARs, using extracellular region of ACE2, and demonstrated their highly specific and potent cytotoxicity towards Spike-expressing target cells. To improve on this concept as a potential therapeutic, we developed a bispecific T cell engager combining ACE2 with an anti-CD3 scFv (ACE2-Bite) to target infected cells and the virus. Similar to CAR-T cell approach, ACE2-Bite endowed cytotoxic cells to selectively kill Spike-expressing targets. Furthermore, ACE2-Bite neutralized the pseudoviruses of SARS-CoV, SARS-CoV-2 wild-type and variants including Delta and Omicron, as a decoy protein. Remarkably, ACE2-Bite molecule showed a higher binding and neutralization affinity to Delta and Omicron variants compared to SARS-CoV-2 wild-type Spike proteins, suggesting the potential of this approach as a variant-proof, therapeutic strategy for future SARS-CoV-2 variants, employing both humoral and cellular arms of the adaptive immune response.