bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortex deviates from criticality during action and deep sleep: a temporal renormalization group approach
Authors: Sooter J. Samuel , Fontenele Antonio J. , Ly Cheng , Barreiro Andrea K. , Shew Woodrow L. 
Published: June 2024

AbstractThe hypothesis that the brain operates near criticality explains observations of complex, often scale-invariant, neural activity. However, the brain is not static, its dynamical state varies depending on what an organism is doing. Neurons often become more synchronized (ordered) during unconsciousness and more desynchronized (disordered) in highly active awake conditions. Are all these states equidistant from criticality; if not, which is closest? The fundamental physics of how systems behave near criticality came from renormalization group (RG) theory, but RG for neural systems remains largely undeveloped. Here we developed a temporal RG (tRG) theory for analysis of typical neuroscience data. We mathematically identified multiple types of criticality (tRG fixed points) and developed tRG-driven data analytic methods to assess proximity to each fixed point based on relatively short time series. Unlike traditional methods for studying criticality in neural systems, our tRG approach allows time-resolved measurements of distance from criticality in experiments at behaviorally relevant timescales. We apply our approach to recordings of spike activity in mouse visual cortex, showing that the relaxed, awake state is closest to criticality. When arousal shifts away from this state – either increasing in more active awake states or decreasing in deep sleep – cortical dynamics deviate from criticality.
Benchmarking Deep Learning-based Image Retrieval of Oral Tumor Histology
Authors: Herdiantoputri Ranny Rahaningrum , Komura Daisuke , Ochi Mieko , Fukawa Yuki , Kayamori Kou , Tsuchiya Maiko , Kikuchi Yoshinao , Ushiku Tetsuo , Ikeda Tohru , Ishikawa Shumpei 
Published: June 2024

AbstractOral tumors necessitate a dependable computer-assisted pathological diagnosis system considering their rarity and diversity. A content-based image retrieval (CBIR) system using deep neural networks has been successfully devised for digital pathology. No CBIR system for oral pathology has been investigated because of the lack of an extensive image database and feature extractors tailored to oral pathology. This study uses a large CBIR database constructed from 30 categories of oral tumors to compare deep learning methods as feature extractors. The highest average area under the receiver operating curve (AUC) was achieved by models trained on database images using self-supervised learning (SSL) methods (0.900 with SimCLR; 0.897 with TiCo). The generalizability of the models was validated using query images from the same cases taken with smartphones. When smartphone images were tested as queries, both models yielded the highest mean AUC (0.871 with SimCLR and 0.857 with TiCo). We ensured the retrieved image result would be easily observed by evaluating the top-10 mean accuracy and checking for an exact diagnostic category and its differential diagnostic categories. Therefore, training deep learning models with SSL methods using image data specific to the target site is beneficial for CBIR tasks in oral tumor histology to obtain histologically meaningful results and high performance. This result provides insight into the effective development of a CBIR system to help improve the accuracy and speed of histopathology diagnosis and advance oral tumor research in the future.
Differential risk of healthcare workers versus the general population during outbreak, war and pandemic crises
Authors: Ioannidis John P.A. 
Published: June 2024

ABSTRACTHealthcare workers may have different risk for severe outcomes compared with the general population during diverse crises. This paper introduces the concept of healthcare worker versus population hazard (HPH), the risk of an outcome of interest in active healthcare workers compared with the general population they serve. HPH can be expressed with relative risk (HPH(r)) and absolute risk difference (HPH(a)) metrics. Illustrative examples are drawn from infectious outbreaks, war, and the COVID-19 pandemic on death outcomes. HPH can be extreme for lethal outbreaks (HPH(r)=30 to 143, HPH(a)=8 to 91 per 1000 for Ebola deaths in 3 Western African countries in 2013-5), and modestly high in relative terms and very high in absolute terms for protracted, major armed conflicts (HPH(r)=1.38 and HPH(a)=10.2 for Syria during 2011-2024). Conversely, healthcare workers had 8-12-fold lower risk than the population they served for pandemic excess deaths (physicians in USA) or COVID-19 deaths (physicians in Ontario, healthcare workers in Finland), while healthcare workers in Indonesia did not have this advantage for COVID-19 deaths versus the general population. HPH is susceptible to data inaccuracies in numbers of at-risk populations and of outcomes of interest. Importantly, inferences about healthcare worker risk can be misleading, if deaths of retired healthcare workers contaminate the risk calculations – as in the case of misleading early perceptions of exaggerated COVID-19 risk for healthcare professionals. HPH can offer useful insights for risk assessment to healthcare professionals, the general public, and policy makers and may be useful to monitor for planning and interventions during crises.
Shape-Biased Learning by Thinking Inside the Box
Authors: Müller Niklas , Snoek Cees G. M. , Groen Iris I. A. , Scholte H. Steven 
Published: June 2024

AbstractDeep Neural Networks (DNNs) may surpass human-level performance on vision tasks such as object recognition and detection, but their model behavior still differs from human behavior in important ways. One prominent example of this difference, and the main focus of our paper, is that DNNs trained on ImageNet exhibit an object texture bias, while humans are consistently biased towards shape. DNN shape-bias can be increased by data augmentation, but next to being computationally more expensive, data augmentation is a biologically implausible method of creating texture-invariance. We present an empirical study on texture-shape-bias in DNNs showcasing that high texture-bias correlates with high background-object ratio. In addition, DNNs trained on tight object bounding boxes of ImageNet images are sub-stantially more biased towards shape than models trained on the full images. Using a custom dataset of high-resolution, object annotated scene images, we show that (I) shape-bias systematically varies with training on bounding boxes, (II) removal of global object shape as a result of commonly applied cropping during training increases texture bias, (III) shape-bias is negatively correlated with test accuracy on ImageNet while being positively correlated on cue-conflict images created using bounding boxes, following the trend of humans. Overall, we show that an improved supervision signal that better reflects the visual features that truly belong to the to-be-classified object increases the shape-bias of deep neural networks. Our results also imply that simultaneous human alignment on both classification accuracy and strategy can not be achieved on default ImageNet images, suggesting the need for new assessments of both shape-bias and behavioural alignment between DNNs and humans.
Benzylic Trifluoromethyl Accelerates 1,6-Elimination Toward Rapid Probe Activation
Authors: Wang Liming , Sivakumar Aditya , Zhang Rui , Cho Sarah , Kim Yuhyun , Aggarwal Tushar , Wang Lu , Izgu Enver Cagri 
Published: June 2024

ABSTRACTActivity-based detection of hydrogen sulfide in live cells can expand our understanding of its reactivity and complex physiological effects. We have discovered a highly efficient method for fluorescent probe activation, which is driven by H2S-triggered 1,6-elimination of an α-CF3-benzyl to release resorufin. In detecting intracellular H2S, 4-azido-(α-CF3)-benzyl resorufin offers significantly faster signal generation and improved sensitivity compared to 4-azidobenzyl resorufin. Computed free energy profiles for the 1,6-elimination process support the hypothesis that a benzylic CF3group can reduce the activation energy barrier toward probe activation. This novel probe design allows for near-real-time detection of H2S in HeLa cells under stimulation conditions.
Selection of sheep skin bacteria to reduce blood-feeding by biting midges under laboratory conditions
Authors: Brok Paula S. , Jost Stéphanie M. , Verhulst Niels O. 
Published: June 2024

AbstractBiting midges of the genus Culicoides (Diptera: Ceratopogonidae) are of huge veterinary importance, mainly as vectors of pathogens, such asBluetongue virus. Currently, there are no effective methods to protect animals against biting midges since insecticides have limited or short-lived efficacy. Biting midges are attracted to hosts by carbon dioxide and by their body odours, which are mainly produced by skin bacteria. In humans, it has been shown that differences in attractiveness between individuals to mosquitoes is mediated by these skin bacterial volatiles. This opens the possibility to protect individuals from biting insects by supplementing their skin microbiome with probiotics. In this study, we investigated this approach by culturing sheep skin bacteria on different media and assessed their effects against field-caught Culicoides (overwhelmingly Obsoletus group species) as well as laboratory-rearedCulicoides nubeculosus(Meigen).Aerococcus urinaeeequi,Bacillus safensis,Bacillus subtilis,Jeotgalicoccus psychrophilus,Micrococcussp. andStaphylococcus equorumwere selected to be tested in a dual-choice Y-tube olfactometer, assessing their behavioural effects towards biting midges. We revealed an avoidance effect towards laboratory-rearedC. nubeculosuswhen testingB. safensis(P ≤ 0.001) andB. subtilis(P ≤ 0.001).Bacillus safensis(P = 0.006) andMicrococcussp. (P ≤ 0.001) yielded significant repellent potential towards field-caught Culicoides. These two candidates were subsequently tested in a membrane blood feeding assay. When the bacterial speciesB. safensiswas applied to the membrane, a feeding reduction of 83 % was observed with field-caught Culicoides.
A bipartite interaction with the processivity clamp potentiates Pol IV-mediated TLS
Authors: Chang Seungwoo , Laureti Luisa , Thrall Elizabeth S. , Kay Marguerite S , Philippin Gaëlle , Jergic Slobodan , Pagès Vincent , Loparo Joseph J 
Published: June 2024

AbstractProcessivity clamps mediate polymerase switching for translesion synthesis (TLS). All threeE. coliTLS polymerases interact with the β2processivity clamp through a conserved clamp-binding motif (CBM), which is indispensable for TLS. Notably, Pol IV also makes a unique secondary contact with the clamp through non-CBM residues. However, the role of this “rim contact” in Pol IV-mediated TLS remains poorly understood. Here we show that the rim contact is critical for TLS past strong replication blocks. Inin vitroreconstituted Pol IV-mediated TLS, ablating the rim contact compromises TLS past 3-methyl dA, a strong block, while barely affecting TLS past N2-furfuryl dG, a weak block. Similar observations are also made inE. colicells bearing a single copy of these lesions in the genome. Within lesion-stalled replication forks, the rim interaction and ssDNA binding protein cooperatively poise Pol IV to better compete with Pol III for binding to a cleft through its CBM. We propose that this bipartite clamp interaction enables Pol IV to rapidly resolve lesion-stalled replication through TLS at the fork, which reduces damage induced mutagenesis.
X-linked multi-ancestry meta-analysis reveals tuberculosis susceptibility variants
Authors: Schurz Haiko , Kinnear Craig J , van Helden Paul D , Tromp Gerard , Hoal Eileen G ,   International Tuberculosis Host Genetics Consortium, Möller Marlo 
Published: June 2024

AbstractGlobally, tuberculosis (TB) presents with a clear male bias that cannot be completely accounted for by environment, behaviour, socioeconomic factors, or the impact of sex hormones on the immune system. This suggests that genetic and biological differences, which may be mediated by the X chromosome, further influence the observed male sex bias. The X chromosome is heavily implicated in immune function and yet has largely been ignored in previous association studies. Here we report the first multi-ancestry X chromosome specific meta-analysis on TB susceptibility. We identified X- linked TB susceptibility variants using seven genotyping data sets and 20,255 individuals from diverse genetic ancestries. Sex-specific effects were also identified in polygenic heritability between males and females along with enhanced concordance in direction of genetic effects for males but not females. These sex-specific genetic effects were supported by a sex-stratified and combined meta- analysis conducted using the X chromosome specific XWAS software and a multi-ancestry analysis using the MR-MEGA software. Seven significant associations were identified. Two in the overall analysis (rs6610096, rs7888114) and a second for the female specific analysis (rs4465088) including all data sets. For the ancestry specific meta-analysis three significant associations were identified for males in the Asian cohorts (rs1726176, rs5939510, rs1726203) and one in females for the African cohort (rs2428212). Several genomic regions previously associated with TB susceptibility were reproduced in this study, along with strong ancestry-specific effects. These results support the hypothesis that the X chromosome and sex-specific effects could significantly impact the observed male bias in TB incidence rates globally.
Genomic prediction of individual inbreeding levels for the management of genetic diversity in populations with small effective size
Authors: Forneris Natalia Soledad , Bosse Mirte , Gautier Mathieu , Druet Tom 
Published: June 2024

AbstractIn populations of small effective size (Ne), such as those in conservation programs, companion animals or livestock species, management of diversity and inbreeding is essential. Homozygosity-by-descent (HBD) segments provide relevant information in that context, as they allow efficient estimation of the inbreeding coefficient, provide locus-specific information and their length is informative about the “age” of inbreeding. Therefore, our objective was to evaluate tools for predicting HBD in future offspring based on parental genotypes, a problem equivalent to identifying segments identical-by-descent (IBD) among the four parental chromosomes. In total, we reviewed and evaluated 16 approaches using simulated and real data with small Ne. The methods included model-based approaches, mostly hidden Markov models (HMMs), which considered up to 15 IBD configurations among the four parental chromosomes, as well as more computationally efficient rule-based approaches. The accuracy of the methods was then evaluated, including with low-density marker panels, genotyping-by-sequencing data and small groups of individuals, typical features in such populations. Two HMMs performed consistently well, while two rule-based approaches proved efficient for genome-wide predictions. The model-based approaches were particularly efficient when information was reduced (low marker density, locus-specific estimation). Methods using phased data proved to be more efficient, while some approaches relying on unphased genotype data proved to be sensitive to the allele frequencies used. In some settings, pedigree information was competitive in predicting recent inbreeding levels. Finally, we showed that our evaluation is also informative about the accuracy of the methods for estimating relatedness and identifying IBD segments between pairs of individuals.
A hemispheric dome setup for naturalistic visual stimulation in head-fixed mice
Authors: Kautzky Magdalena , Peterreins Verena , Qiu Yongrong , Zhao Zhijian , Kotkat Ann H. , Katzner Steffen , Euler Thomas , Busse Laura 
Published: June 2024

AbstractThe visual system of any animal species is adapted to its ecological niche. Thus, investigating visual function and behavior using naturalistic stimuli holds significant potential. In mice, these adaptations include a field of view of ∼280° and cone opsins sensitive to UV and green wavelengths. Such adaptations, however, cannot be probed with standard consumer displays. To present naturalistic visual stimuli to mice, we built a hemispheric dome setup, enabling the controlled projection of wide-field movies with UV-green spectral content. For our UV-green projection, we used a customized light engine with external high-power LEDs. We mitigated spatial distortions introduced by the projection through a geometry-independent calibration procedure. Additionally, we adapted a head-mounted eye tracking system to capture behavioral responses of head-fixed mice viewing these stimuli. We validated our setup by quantifying the pupillary light reflex to uniform stimuli and the optokinetic reflex to drifting gratings. Finally, in experiments with naturalistic movies, we investigated whether mice showed differential saccades and eye positions based on visual input. Comparing naturalistic movies to a uniform screen control condition, we observed that although head-fixed mice did not make targeted saccades during movies, their overall eye position consistently shifted towards more frontal regions of visual space. This indicates that mice adjust their eye position in a stimulus-dependent way, potentially to optimize visual processing of information ahead in the visual field. Together, our results highlight the utility of our setup for in vivo studies of the mouse visual system with more naturalistic visual stimulation.Significance StatementOver the past decades, mice have emerged as a prominent model for vision. Nonetheless, compared to primates, mice inhabit a different visual niche, featuring several species-specific adaptations, including a wide field of view and sensitivity to UV light. Both adaptations cannot be adequately studied using consumer displays commonly employed in vision research. We therefore built a hemispheric dome setup allowing the presentation of wide field movies with appropriate spectral content and tracking eye movements and pupil dynamics in head-fixed mice with minimal shadows. We provide a baseline assessment of the setup leveraging two well-established eye reflexes. We also showcase the setup’s utility by reporting adjustments in eye movements when mice viewed the naturalistic movies.
Generating human AMN and cALD iPSC-derived astrocytes with potential for modeling X-linked adrenoleukodystrophy phenotypes
Authors: Kaur Navtej , Singh Jaspreet 
Published: June 2024

AbstractX-adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder caused by mutations in the ABCD1 gene encoding the peroxisomal ABC transporter adrenoleukodystrophy protein (ALDP). Similar mutations in ABCD1 may result in a spectrum of phenotypes in males with slow progressing adrenomyeloneuropathy (AMN) and fatal cerebral adrenoleukodystrophy (cALD) dominating the majority of cases. Mouse model of X-ALD does not capture the phenotype differences and an appropriate model to investigate mechanism of disease onset and progress remains a critical need. Induced pluripotent stem cell (iPSC)-derived and cell models derived from them have provided useful tools for investigating cell-type specific disease mechanisms. Here, we generated induced pluripotent stem cell (iPSC) lines from skin fibroblasts of two each of apparently healthy control, AMN and cALD patients with non-integrating mRNA-based reprogramming. iPSC lines expanded normally and expressed pluripotency markers Oct4, SOX2, Nanog, SSEA and TRA-1-60. Expression of markers SOX17, brachyury, Desmin, Oxt2 and beta tubulin III demonstrated the ability of the iPSCs to differentiate into all three germ layers. iPSC-derived lines from CTL, AMN and cALD male patients were differentiated into astrocytes. Differentiated AMN and cALD astrocytes lacked ABCD1 expression and accumulated VLCFA, a hallmark of X-ALD. These patient astrocytes provide disease-relevant tools to investigate mechanism of differential neuroinflammatory response and metabolic reprogramming in X-ALD. Further these patient-derived human astrocyte cell models will be valuable for testing new therapeutics.
A newly-identified mini-hairpin shaped nascent peptide blocks translation termination by a novel mechanism
Authors: Ando Yushin , Kobo Akinao , Niwa Tatsuya , Yamakawa Ayako , Konoma Suzuna , Kobayashi Yuki , Nureki Osamu , Taguchi Hideki , Itoh Yuzuru , Chadani Yuhei 
Published: June 2024

AbstractProtein synthesis by ribosomes not only produces functional proteins but also serves diverse functions depending on the coding amino acid sequences. Certain nascent peptides interact with the ribosome exit tunnel to arrest translation and modulate the expression of downstream genes or themselves. However, a comprehensive understanding of the mechanisms of such ribosome stalling and its regulation remains elusive. In this study, we systematically screened for unidentified ribosome arrest peptides through phenotypic evaluation, proteomics, and MS analyses, leading to the discovery of novel arrest peptides PepNL and NanCL inE. coli. Our cryo-EM study on PepNL revealed a unique arrest mechanism, in which the N-terminus of PepNL folds back towards the tunnel entrance to prevent the catalytic GGQ motif of release factor from accessing the peptidyl transferase center, causing translation arrest at the UGA stop codon. Furthermore, unlike other sensory arrest peptides that require an arrest inducer, PepNL uses tryptophan as an arrest releaser, where Trp-tRNA reads through the stop codon. Our findings illuminate the mechanism and regulatory framework of nascent peptide-induced translation arrest, paving the way for exploring regulatory nascent peptides.