bluuebunny/crossref_metadata_2025_split huggingface dataset:
Foraging specialization and body size in seabirds
Authors: Hernandez Juan , Arroyo José Ignacio 
Published: June 2023

AbstractBody size affects many biological processes since it predicts traits, timing, and biological rates. Some of these relationships are explained by the metabolic theory of ecology, which predicts that they should scale according to a power law with exponents multiples of. Here we study the relationships between foraging specialization, particularly the number of dietary categories and prey capture strategies, and seabird species size, based on a database of 342 species (representing more than 95 % of all species). In our analysis, we found a negative relationship between the number of dietary categories and the number of capture strategies with body size with exponents of -0.83±0.31 and -0.76±0.06. To explain these relationships in terms of first principles, we developed a simple model to explain the origin of this scaling based on well-established ecological scaling relationships. Our study suggests that foraging specialization is constrained by the energy used by an organism, providing a basis for future theoretical developments.
Massage and Exercise Increase Body Awareness in Healthy Adults: A Randomized Placebo Controlled Trial
Authors: Danner Ursula , Avian Alexander , Mittermaier Christian 
Published: June 2023

ABSTRACTObjectivePhysiotherapists are supposed to have a great impact on the body awareness of their clients through passive and active measures. The aim of this study was to investigate the effect of a single session of manual massage or exercise on body awareness.MethodsA three-arm randomized controlled study including 96 healthy volunteers (18 - 65 years) was conducted at the Institute of Physical Medicine & Rehabilitation, at the Kepler University Hospital in Linz/Austria. Anonymous questionnaire assessments and analysis with intention-to-treat approach were performed. Participants were assigned to a single intervention of massage (full-body massage with slow strokes and gentle kneading), exercise (moderate body workout, video-based exercise instructions) or lecture on medicinal herbs (video-based lecture, control group). Primary endpoints were the changes of body awareness recorded with the non-verbal Awareness Body Chart test. Secondary endpoints were the changes of body awareness scored with a German body awareness questionnaire (Kurzer Fragebogen zur Eigenwahrnehmung des Koerpers, KEKS) and changes in mood scored with a German questionnaire on mood (Befindlichkeitsfragebogen).ResultsThe Awareness Body Chart total score increased in both intervention groups but not in the control group with significant differences in the change between control group and both other groups (massage vs. control: +0.47, 95% CI 0.30 to 0.64; exercise vs. control: +0.31, 95% CI 0.15 to 0.45; massage vs. exercise: +0.19, 95% CI -0.02 to 0.34). An increase of the KEKS total score was found in the exercise in comparison to the control group. Mood significantly improved in both intervention groups compared to the control group.ConclusionsIn this study single session interventions of massage or exercise presented immediate positive impact on body awareness and furthermore on mood. The trial may serve as a prototype for further research on body awareness.Trial RegistrationRegistered in theclinicaltrials.govdatabase (NCT05004272)
Screening of leaf extraction and storage conditions for eco-metabolomics studies
Authors: Lang Jakob , Ramos Sergio E. , Smohunova Marharyta , Bigler Laurent , Schuman Meredith C. 
Published: June 2023

AbstractMass spectrometry-based plant metabolomics is frequently used to identify novel natural products or study the effect of specific treatments on a plant’s metabolism. Reliable sample handling is required to avoid artifacts, which is why most protocols mandate shock freezing of plant tissue in liquid nitrogen and an uninterrupted cooling chain. However, the logistical challenges of this approach make it infeasible for many ecological studies. Especially for research in the tropics, permanent cooling poses a challenge, which is why many of those studies use dried leaf tissue instead. We screened a total of ten extraction and storage approaches for plant metabolites extracted from maize leaf tissue across two cropping seasons to develop a methodology for agroecological studies in logistically challenging tropical locations. All methods were evaluated based on changes in the metabolite profile across a 2-month storage period at different temperatures with the goal of reproducing the metabolite profile of the living plant as closely as possible. We show that our newly developed on-site liquid-liquid extraction protocol provides a good compromise between sample replicability, extraction efficiency, material logistics, and metabolite profile stability. We further discuss alternative methods which showed promising results and feasibility of on-site sample handling for field studies.HighlightWe developed an on-site metabolite extraction method for leaf tissue samples from field studies in challenging logistical circumstances. We highlight extract stability and reproducibility compared to frozen or dried tissue.
Mixed structure- and sequence-based approach for protein graph neural networks with application to antibody developability prediction
Authors: Khade Pranav M. , Maser Michael , Gligorijevic Vladimir , Watkins Andrew 
Published: June 2023

AbstractThere are hundreds of thousands of known proteins but significantly fewer unique protein folds. Furthermore, proteins often have conserved and even repeating geometric patterns, which can be captured by models of protein structure and function. In this work, we use Delaunay tessellations andα-shapes, which capture these conserved geometric patterns, to define graph adjacency in Graph Convolutional Networks (GCN). We demonstrate the utility of the resulting GCN model on antibody developability prediction. Compared to the frequently used graph adjacencies based on k-nearest-neighbors or a fixed cutoff radius, the Delaunay tessellation andα-shapes better capture residue-specific interactions at a lower computational cost for a given system size. The resulting models achieve state-of-the-art performance on an antibody developability prediction task. Finally, we propose an extension of the model which does not require known or predicted structures but uses an “archetypical” antibody structure to infer likely contacts.
Data-driven discovery of innate immunomodulators via machine learning-guided high throughput screening
Authors: Tang Yifeng , Kim Jeremiah Y. , IP Carman KM , Bahmani Azadeh , Chen Qing , Rosenberger Matthew G. , Esser-Kahn Aaron P. , Ferguson Andrew L. 
Published: June 2023

AbstractThe innate immune response is vital for the success of prophylactic vaccines and immunotherapies. Control of signaling in innate immune pathways can improve prophylactic vaccines by inhibiting unfavorable systemic inflammation and immunotherapies by enhancing immune stimulation. In this work, we developed a machine learning-enabled active learning pipeline to guidein vitroexperimental screening and discovery of small molecule immunomodulators that improve immune responses by altering the signaling activity of innate immune responses stimulated by traditional pattern recognition receptor agonists. Molecules were tested byin vitrohigh throughput screening (HTS) where we measured modulation of the nuclear factorκ-light-chain-enhancer of activated B-cells (NF-κB) and the interferon regulatory factors (IRF) pathways. These data were used to train data-driven predictive models linking molecular structure to modulation of the NF-κB and IRF responses using deep representational learning, Gaussian process regression, and Bayesian optimization. By interleaving successive rounds of model training andin vitroHTS, we performed an active learning-guided traversal of a 139,998 molecule library. After sampling only∼2% of the library, we discovered viable molecules with unprecedented immunomodulatory capacity, including those capable of suppressing NF-κB activity by up to 15-fold, elevating NF-κB activity by up to 5-fold, and elevating IRF activity by up to 6-fold. We extracted chemical design rules identifying particular chemical fragments as principal drivers of specific immunomodulation behaviors. We validated the immunomodulatory effect of a subset of our top candidates by measuring cytokine release profiles. Of these, one molecule induced a 3-fold enhancement in IFN-βproduction when delivered with a cyclic di-nucleotide stimulator of interferon genes (STING) agonist. In sum, our machine learning-enabled screening approach presents an efficient immunomodulator discovery pipeline that has furnished a library of novel small molecules with a strong capacity to enhance or suppress innate immune signaling pathways to shape and improve prophylactic vaccination and immunotherapies.
Opioidergic activation of descending pain inhibitory system underlies placebo analgesia
Authors: Neyama Hiroyuki , Wu Yuping , Nakaya Yuka , Kato Shigeki , Shimizu Tomoko , Tahara Tsuyoshi , Shigeta Mika , Inoue Michiko , Miyamichi Kazunari , Matsushita Natsuki , Mashimo Tomoji , Miyasaka Yoshiki , Watanabe Yasuyoshi , Kobayashi Masayuki , Kobayashi Kazuto , Cui Yilong 
Published: June 2023

AbstractPlacebo analgesia is caused by inactive treatment, implicating endogenous brain function involvement. However, the underlying neurobiological mechanisms remain unclear. We found that μ-opioid signals in the medial prefrontal cortex (mPFC) activate the descending pain inhibitory system to initiate placebo analgesia in neuropathic pain rats. Chemogenetic manipulation demonstrated that specific activation of μ-opioid receptor-positive (MOR+) neurons in the mPFC or suppression of the mPFC-ventrolateral periaqueductal gray (vlPAG) circuit inhibited placebo analgesia in rats. MOR+neurons in the mPFC are monosynaptically connected and directly inhibit L5 pyramidal neurons that project to the vlPAG via GABAAreceptors. Thus, intrinsic opioid signaling in the mPFC disinhibits excitatory outflow to the vlPAG by suppressing MOR+neurons, leading to descending pain inhibitory system activation that initiates placebo analgesia.One Sentence SummarySugar pills relieve pain by activating the intrinsic pain inhibitory system via opioidergic signals in the prefrontal cortex.
Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia
Authors: Wu Haoyang , Lv Peiyuan , Wang Jinyu , Bennett Brian , Wang Jiajia , Li Pishun , Peng Yi , Hu Guang , Lin Jiaji 
Published: June 2023

AbstractEpigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remains largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. We identified Prmt5 as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion bothin vitroandin vivo. Prmt5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that Prmt5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, we treated mice with middle cerebral artery occlusion (MCAO) with the Prmt5 inhibitor EPZ015666 and found that Prmt5 inhibition sustain protection against neuronal deathin vivo. Together, our findings revealed a novel epigenetic mechanism of Prmt5 in cerebral ischemia and uncovered a potential target for neuroprotection.
Dysregulated DnaB unwinding induces replisome decoupling and daughter strand gaps that are countered by RecA polymerization
Authors: Behrmann Megan S. , Perera Himasha M. , Welikala Malisha U. , Matthews Jacquelynn E. , Trakselis Michael A. 
Published: June 2023

ABSTRACTRepair of DNA damage begins with the elicitation of targeted cellular responses to restore the genome. InE. coli, major products of DNA damage result in the buildup of single-stranded DNA (ssDNA) that is rapidly bound by cooperative filamentation of RecA to initiate the SOS response. The replicative helicase, DnaB, is a central component of the replisome, unwinding duplex DNA in concert with Pol III template dependent synthesis. Interestingly, helicase unwinding is heavily regulated, and the unwinding rate can be reduced by over 10-fold if DnaB becomes decoupled from Pol III. However, if DnaB is dysregulated by mutations that enforce a faster more constricted conformation, unwinding can continue independently, generating excess ssDNA resulting in severe cellular stress. This surplus ssDNA can stimulate RecA recruitment for recombinational repair or activation of SOS to increase the available repair protein pool. To better understand the consequences of dysregulated unwinding, we combined targeteddnaBmutations with an inducible plasmid-based RecA filament inhibition strategy to examine the dependencies on RecA in counteracting decoupling. We find that RecA filamentation is instrumental for processing daughter strand gaps left behind from decoupled unwinding and synthesis to prevent DNA breaks. Without functional RecA filaments,dnaBmutant strains had a greater burden from endogenous damage but without a compensatory increase in mutagenesis. Overall, RecA plays a critical role in strain survival by processing DNA gaps and protecting from breaks caused by dysregulated or interrupted helicase activityin vivo.AUTHOR SUMMARYCoupled DNA unwinding and synthesis is a genomic protection strategy used during DNA replication to prevent excessive buildup of labile single-stranded DNA (ssDNA). The helicase and polymerase enzymes have evolved multidimensional regulation tactics to maintain this connection despite different individual kinetic rates and differential responses to genomic obstacles. For one, the DnaB helicase inE. colican alter its hexameric ring structure by dilating to slow down or constricting to speed up DNA unwinding. Here, we have utilized persistently constricted mutants of DnaBin vitroor genomically editeddnaB in vivoto induce decoupling in the replisome. Constricted DnaB mutants limit total leading strand synthesis by Pol III, indicating that lost kinetic regulation between these enzymes results in inefficient replication. Using an inducible plasmid-based system to disrupt Rad51 filamentation in vivo, we show that RecA is responsible for the increased mutagenesis, a filamented cellular phenotype, and mitigating DNA breaks from excess ssDNA caused by decoupling. These results reveal a role for RecA filamentation in mediating excess ssDNA resulting from decoupling to maintain survival and adaptation.
Beyond venomous fangs: Uloboridae spiders have lost their venom but not their toxicity
Authors: Peng Xiaojing , Dersch Ludwig , Dresler Josephine , Lüddecke Tim , Dederichs Tim , Michalik Peter , Peigneur Steve , Tytgat Jan , Hassan Afrah , Mucciolo Antonio , Robinson-Rechavi Marc , Zancolli Giulia 
Published: June 2023

AbstractVenom, one of nature’s most potent secretions, has played a crucial role in the evolutionary success of many animal groups, including spiders. However, Uloboridae spiders appear to lack venom and capture their prey, unlike venomous spiders, by extensive silk-wrapping and regurgitation of digestive fluids onto the entire prey. A prevailing hypothesis posits that toxins may have been reallocated from the venom to alternative secretions, like silk or digestive fluids. Yet, whether uloborids have retained venom toxins and the mechanisms underlying prey immobilisation remain unresolved. Here, we employed a multi-disciplinary approach to assess the absence of venom glands inUluborus plumipes, toxin gene expression and toxicity of digestive proteins. Our findings confirm thatU. plumipeslacks a venom apparatus, while neurotoxin-like transcripts were highly expressed in the digestive system. Midgut gland extract had comparable toxicity levels to that of the venomousParasteatoda tepidariorum. However, no inhibitory effects on sodium nor potassium channels were observed, indicating a different toxic mechanism. These findings support the hypothesis that Uloboridae spiders have lost their venom apparatus while retaining toxin-like genes. The potent toxicity of their digestive fluids, a trait conserved across spiders, likely compensate for the absence of venom, ensuring effective prey immobilisation and digestion.
Inference of Genomic Landscapes using Ordered Hidden Markov Models with Emission Densities (oHMMed)
Authors: Vogl Claus , Karapetiants Mariia , Yıldırım Burçin , Kjartansdóttir Hrönn , Kosiol Carolin , Bergman Juraj , Majka Michal , Mikula Lynette Caitlin 
Published: June 2023

AbstractBackgroundGenomes are inherently inhomogeneous, with features such as base composition, recombination, gene density, and gene expression varying along chromosomes. Evolutionary, biological, and biomedical analyses aim to quantify this variation, account for it during inference procedures, and ultimately determine the causal processes behind it. Since sequential observations along chromosomes are not independent, it is unsurprising that autocorrelation patterns have been observede.g.,in human base composition.In this article, we develop a class of Hidden Markov Models (HMMs) called oHMMed (ordered HMM with emission densities, the corresponding R package of the same name is available on CRAN): They identify the number of comparably homogeneous regions within autocorrelated observed sequences. These are modelled as discrete hidden states; the observed data points are realisations of continuous probability distributions with state-specific means that enable ordering of these distributions. The observed sequence is labelled according to the hidden states, permitting only neighbouring states that are also neighbours within the ordering of their associated distributions. The parameters that characterise these state-specific distributions are inferred.ResultsWe apply our oHMMed algorithms to the proportion of G and C bases (modelled as a mixture of normal distributions) and the number of genes (modelled as a mixture of poisson-gamma distributions) in windows along the human, mouse, and fruit fly genomes. This results in a partitioning of the genomes into regions by statistically distinguishable averages of these features, and in a characterisation of their continuous patterns of variation. In regard to the genomic G and C proportion, this latter result distinguishes oHMMed from segmentation algorithms based in isochore or compositional domain theory. We further use oHMMed to conduct a detailed analysis of variation of chromatin accessibility (ATAC-seq) and epigenetic markers H3K27ac and H3K27me3 (modelled as a mixture of poisson-gamma distributions) along the human chromosome 1 and their correlations.ConclusionsOur algorithms provide a biologically assumption-free approach to characterising genomic landscapes shaped by continuous, autocorrelated patterns of variation. Despite this, the resulting genome segmentation enables extraction of compositionally distinct regions for further downstream analyses.
Mutant analysis of Kcng4b reveals how the different functional states of the voltage-gated potassium channel regulate ear development
Authors: Jędrychowska Justyna , Vardanyan Vitya , Wieczor Milosz , Marciniak Antoni , Czub Jacek , Amini Razieh , Jain Ruchi , Shen Hongyuan , Choi Hyungwon , Kuznicki Jacek , Korzh Vladimir 
Published: June 2023

AbstractThe voltage gated (Kv) slow-inactivating delayed rectifier channel regulates the development of hollow organs of the zebrafish. The functional tetramer consists of an electrically active subunit (Kcnb1, Kv2.1) and a modulatory silent subunit (Kcng4b, Kv6.4). The two mutations in zebrafishkcng4b - kcng4b-C1andkcng4b-C2(Gasanov et al., 2021) - have been studied during ear development using electrophysiology, developmental biology andin silicostructural modelling.kcng4b-C1mutation causes a C-terminal truncation characterized by mild Kcng4b loss-of-function (LOF) manifested by failure of kinocilia to extend and formation of ectopic otoliths. In contrast, thekcng4b-C2-/-mutation causes the C-terminal domain to elongate and the ectopic seventh transmembrane (TM) domain to form, converting the intracellular C-terminus to an extracellular one. Kcng4b-C2 acts as a Kcng4b gain-of-function (GOF) allele. Otoliths fail to develop and kinocilia are reduced inkcng4b-C2-/-. These results show that different mutations of the silent subunit Kcng4 can affect the activity of the Kv channel and cause a wide range of developmental defects.
Proximity labelling and evolutionary evidence reveal insights into IL-1α nuclear networks and function
Authors: Wellens Rose , Tapia Victor S. , Bennett Hayley , Adamson Antony , Rivers-Auty Jack , Green Jack P. , Lopez-Castejon Gloria , Brough David , Hoyle Christopher 
Published: June 2023

AbstractInterleukin (IL)-1α is a suggested dual-function cytokine that diverged from IL-1β in mammals potentially by acquiring additional biological roles that relate to highly conserved regions in the pro-domain of IL-1α, including a nuclear localisation sequence (NLS) and histone acetyl transferase (HAT)-binding domains. Why evolution modified pro-IL-1α’s subcellular location and protein interactome, and how this shaped IL-1α’s intracellular role, is unknown. TurboID proximity labelling with pro-IL-1α suggested a nuclear role for pro-IL-1α that involved interaction with HATs, including EP300. We also identified and validated inactivating mutations in the pro-IL-1α NLS of multiple mammalian species. However, HAT-binding domains were also conserved in species that had lost pro-IL-1α nuclear localisation. Together, these data suggest that HAT binding and nuclear localisation occurred together, and that while some species lost the NLS in their pro-IL-1α, HAT binding was maintained. The NLS was lost from several distinct species at different evolutionary times, suggesting convergent evolution, and that the loss of the NLS confers some important biological outcome.
SALL3mediates the loss of neuroectodermal differentiation potential in human embryonic stem cells with chromosome 18q loss
Authors: Lei Yingnan , Al Delbany Diana , Krivec Nuša , Regin Marius , de Deckersberg Edouard Couvreu , Janssens Charlotte , Ghosh Manjusha , Sermon Karen , Spits Claudia 
Published: June 2023

AbstractHuman pluripotent stem cell (hPSC) cultures are prone to genetic drift, as cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but currently their functional consequences in differentiating cells are scarcely described. An accurate assessment of the risk associated with these genetic variants in both research and clinical settings is therefore lacking. In this work, we established that one of these recurrent abnormalities, the loss of chromosome 18q, impairs neuroectoderm commitment and affects the cardiac progenitor differentiation of hESCs. We show that downregulation ofSALL3, a gene located in the common 18q loss region, is responsible for failed neuroectodermal differentiation. Knockdown ofSALL3in control lines impaired differentiation in a manner similar to the loss of 18q, while transgenic overexpression ofSALL3in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show by gene expression analysis that loss of 18q and downregulation ofSALL3leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, including the WNT, NOTCH, JAK-STAT, TGF-beta and NF-kB pathways, suggesting that these cells are in an altered state of pluripotency.