bluuebunny/crossref_metadata_2025_split huggingface dataset:
A bounded accumulation model of temporal generalization outperforms existing models and captures modality differences and learning effects
Authors: Ofir Nir , Landau Ayelet N. 
Published: October 2024

AbstractMultiple systems in the brain track the passage of time and can adapt their activity to temporal requirements (Paton & Buonomano, 2018). While the neural implementation of timing varies widely between neural substrates and behavioral tasks, at the algorithmic level many of these behaviors can be described as bounded accumulation (Balcı & Simen, 2024). So far, from the range of temporal psychophysical tasks, the bounded accumulation model has only been applied to temporal bisection, in which participants are requested to categorize an interval as “long” or “short” (Balcı & Simen, 2014; Ofir & Landau, 2022). In this work, we extend the model to fit performance in the temporal generalization task, in which participants are required to categorize an interval as being the same or different compared to a standard, or reference, duration (Wearden, 1992). Previous models of performance in this task focused on either the group level or performance of highly trained animals (Birngruber et al., 2014; Church & Gibbon, 1982; Wearden, 1992). Whether the same models can fit performance from a few hundreds of trials of single participants, necessary for comparing performance across experimental manipulations, has not been tested. A drift-diffusion model with two decision boundaries fits the data of single participants better than the previous models. We ran two experiments, one comparing performance between vision and audition and another examining the effect of learning. We found that decision boundaries can be modified independently: While the upper boundary was higher in vision compared to audition, the lower boundary decreased with learning in the task.
Saving the Dinaric lynx: multidisciplinary monitoring and stakeholder engagement support large carnivore restoration in human-dominated landscape
Authors: Krofel Miha , Fležar Urša , Černe Rok , Hočevar Lan , Konec Marjeta , Skrbinšek Aleksandra Majić , Skrbinšek Tomaž , Wilson Seth , Bele Bernarda , Črtalič Jaka , Gomerčić Tomislav , Hvala Tilen , Kubala Jakub , Kvapil Pavel , Mavec Meta , Molinari-Jobin Anja , Molinari Paolo , Pazhenkova Elena , Potočnik Hubert , Sin Teodora , Sindičić Magda , Topličanec Ira , Oliveira Teresa 
Published: October 2024

AbstractTranslocations are central to large carnivore restoration efforts, but inadequate monitoring often inhibits effective conservation decision-making. Extinctions, reintroductions, poaching and high inbreeding levels of the Central European populations of Eurasian lynx (Lynx lynx) typify the carnivore conservation challenges in the Anthropocene. Recently, several conservation efforts were initiated to improve the genetic and demographic status, but were met with variable success. Here, we report on a successful, stakeholder-engaged translocation effort to reinforce the highly-inbred Dinaric lynx population and create a new stepping-stone subpopulation in the Southeastern Alps. We used multidisciplinary and internationally-coordinated monitoring using systematic camera- trapping, non-invasive genetic sampling, GPS-tracking of translocated and remnant individuals, recording of reproductive events and interspecific interactions, as well as the simultaneous tracking of the public and stakeholders’ support of carnivore conservation before, during and after the translocation process across the three countries. Among the 22 translocated wild-caught Carpathian lynx, 68% successfully integrated into the population and local ecosystems and at least 59% reproduced. Probability of dispersing from the release areas was 3-times lower when soft-release rather than hard-release method was used. Translocated individuals had lower natural mortality, higher reproductive success and similar ungulate kill rates compared to the remnant lynx. Cooperation with local hunters and protected area managers enabled us to conduct multi-year camera-trapping and non-invasive genetic monitoring across a 12,000-km2transboundary area. Results indicate a reversal in population decline, as the lynx abundance increased for >40% during the 4-year translocation period. Effective inbreeding decreased from 0.32 to 0.08-0.19, suggesting a 2- to 4-fold increase in fitness. Furthermore, successful establishment of a new stepping-stone subpopulation represents an important step towards restoring the Central European lynx metapopulation. Robust partnerships with local communities and hunters coupled with transparent communication helped maintain high public and stakeholder support for lynx conservation throughout the translocation process. Lessons learned about the importance of stakeholder involvement and multidisciplinary monitoring conducted across several countries provide a successful example for further efforts to restore large carnivores in human-dominated ecosystems.
Background optic flow modulates responses of multiple descending interneurons to object motion in locusts
Authors: Zhang Sinan , Gray John R. 
Published: October 2024

AbstractAnimals flying within natural environments are constantly challenged with complex visual information. Therefore, it is necessary to understand the impact of the visual background on the motion detection system. Locusts possess a well-identified looming detection pathway, compromised of the lobula giant movement detector (LGMD) and the descending contralateral movement detector (DCMD). The LGMD/DCMD pathway responds preferably to objects on a collision course, and the response of this pathway is affected by the background complexity. However, multiple other neurons are also responsive to looming stimuli. In this study, we presented looming stimuli against different visual backgrounds to a rigidly-tethered locust, and simultaneously recorded the neural activity with a multichannel electrode. We found that the number of discriminated units that responded to looms was not affected by the visual background. However, the peak times of these units were delayed, and the rise phase was shortened in the presence of a flow field background. Dynamic factor analysis (DFA) revealed that fewer types of common trends were present among the units responding to looming stimuli against the flow field background, and the response begin time was delayed among the common trends as well. These results suggest that background complexity affects the response of multiple motion-sensitive neurons, yet the animal is still capable of responding to potentially hazardous visual stimuli.
What’s in it for the dogs? Assessing the outcomes of a prison-based dog training program from an animal behavior and welfare perspective
Authors: Baria-Unwalla Parizad , Munhoz Morello Gabriela , Queiroz Maria , Olsson I. Anna S. , Vieira de Castro Ana Catarina 
Published: October 2024

AbstractPrison-Based Dog Training Programs (PBDTPs) are gaining popularity across the world for their benefits to inmates in terms of mental and emotional health, and reduced recidivism. However, research on the implications for the dogs is limited. The aim of the present study was to assess the outcomes of a PBDTP from an animal behavior and welfare perspective. Shelter dogs (N=42) were transported to and from the prisons twice a week where they received training from inmates for a total duration of 12 weeks. Dogs were tested for potential improvements in socialization and handling skills and basic training skills using standard tests (Temperament Test and Basic Education Test). Dog welfare was assessed using behavioral, physiological, and cognitive measures, namely stress-related behaviors and overall behavior states during training sessions, salivary cortisol levels, and cognitive bias tests. Results showed that participating in the PBDTP improved the dogs’ sociability towards humans and increased playful behavior, and improved basic training skills including not jumping on people, walking on a leash without pulling, responding to commands (sit, down, and staying in place) and staying calm when separated from the handler. Furthermore, behaviors indicative of stress were generally rare during training sessions and no impact of the PBDTP was found on the levels of salivary cortisol nor on the dogs’ affective states (as measured with cognitive bias tests). In conclusion, the present study suggests that PBDPTs are beneficial for dogs, with animals showing no indicators of compromised welfare while displaying improved behavior skills, which will likely facilitate their future rehoming.
Optimization of citric acid production from sugarcane molasses usingAspergillus nigerby submerged Fermentation
Authors: Amin Al , Ahmmed Hd. Razu , Ismail Mohammad , Islam Tajreen Naziba , Mohasin Mohammed 
Published: October 2024

ABSTRACTThe potentiality of citric acid on economy is high because of its multi-purpose uses, particularly in the food and pharmaceutical industries. Bangladesh spent more than million US dollars to import citric acid mostly from India and China. Its consumption is increasing 3.5–4%, annually, indicating the need for better manufacturing alternatives. Globally, citric acid is primarily produced through microbial fermentation withAspergillus niger. To support the massive scale of production of citrate, the manufacturing process must be eco-friendly which should be inexpensive and available raw materials for maintaining high yielding in a cost-effective manner. In Bangladesh prospective, the current study has undertaken to optimize citric acid production using one of the most abundant raw materials sugarcane molasses. Moreover, the aim of this study was to determine the optimum conditions to produce citric acid from sugarcane molasses usingAspergillus niger (F-81)by submerged fermentation. The amount of citric acid production was determined by Marier-Boulet colorimetric method. The optimization data suggested that 10% substrate (from processed cane molasses), 4% inoculum size ofA. niger, and initial pH 6.0 allowed to produce around 25.8 g/L citric acid. Further study is warranted to assess the feasibility of citrate production in an industrial level as well as improvement of microbial strains is needed to further enhance citric acid production.
Coma pattern-based autofocusing unlocks superior performance in unravelling single-cell dynamics during bacterial cold shock response
Authors: Li Sihong , Ma Zhixin , Yu Yue , Wang Jinjuan , Shen Yaxin , Cui Xiaodong , Fu Xiongfei , Huang Shuqiang 
Published: October 2024

AbstractCutting-edge studies in live cell dynamics place increasing demands on microscopy imaging, and focus stability during acquisition is a critical factor in obtaining high-quality image data. Current autofocusing solutions are limited to focusing precision and range, thus impeding their application in high-accuracy research. Here, we introduce LUNA (locking under nanoscale accuracy), an innovative autofocusing method that leverages the coma pattern of detection light to characterize focus drift. LUNA improves the focusing precision down to 3 nm and extends the focusing range to at least 40 times the objective depth-of-focus. These advancements enable us to investigate how bacteria adapt to temperature change at the single-cell level, revealing a series of novel insights into bacterial cold shock response mechanisms. This approach addresses the complexities of growth dynamics, growth mode transition, division synchronization, and size regulation during the adaptation period, which present significant challenges for traditional analytical methods. Notably, the controversies between the growth lag of batch culture and continuous growth at the single-cell level are successfully explained based on scattering theory. LUNA shows enhanced performance in improving existing advanced microscopy technologies and demonstrates excellent potential for expanding state-of-the-art research in biology.
Systematic annotation of hyper-variability hotspots in phage genomes and plasmids
Authors: Egorov Artyom A. , Hauryliuk Vasili , Atkinson Gemma C. 
Published: October 2024

AbstractBacterial and bacteriophage genomes contain genomic regions of hyper-variability (diversity hotspots) caused by insertions of mobile genetic elements (MGEs), non-homologous recombination events and non-horizontal hypermutation. Accessory genes encoded in the diversity hotspots are involved in anti-MGE defence and counter-defence, virulence and antimicrobial resistance (AMR), thus playing key roles in interactions amongst phages, MGEs, bacteria and eukaryotic hosts. To date the majority of research has been focused on either individual hotspots or on relatively limited sets of hotspots in a small set of genomes, typically from a single species. A global understanding of hotspot diversity and dynamics still lacking. To address this gap, we developed iLund4u, an algorithm for the systematic annotation of hotspots across millions of sequences. Using a proteome composition approach, iLund4u detects proteome communities, annotates accessory proteins and identifies hotspots. By analysing 873K phage genomes and 696K plasmid sequences we identified 13.7K hotspots and 171K diverse protein families encoded there as cargo. Furthermore, iLund4u allows for protein search and proteome annotation functions versus a precomputed iLund4u database. In the protein search mode iLund4u identifies all hotspots that encode homologues of a query protein. In the proteome annotation mode iLund4u annotates hotspots by searching for communities of similar proteomes. Detailed documentation, user guide and the source code are available at the iLund4u home page: art-egorov.github.io/ilund4u.
Are you my mother?: When host genetics and gut microbiota tell different phylogenetic stories in the Africanized honey bee hybrid (Apis mellifera scutellatax sspp.)
Authors: Soares Kilmer Oliveira , de Oliveira Celso José Bruno , Villegas Luis Eduardo Martínez , Vasconcelos Priscylla Carvalho , Rodrigues Adriana Evangelista , Madden Christopher , Hale Vanessa L. 
Published: October 2024

AbstractAfricanized honey bees (Apis mellifera scutellatax sspp.) originated in Brazil through the crossbreeding of African (A. mellifera scutellata) and European (A. melliferasspp.) honey bee subspecies. African genes came to dominate in these hybrid honey bees over time. Gut microbiota co-evolve with their hosts and generally reflect host phylogeny. To examine if this was true in Africanized honey bee hybrids, we compared the gut microbiota (16S rRNA) of 3 honey bee subspecies: African, European, and Africanized honey bees. Publicly available sequencing data from five honey bee studies were downloaded from NCBI. European bee samples (n=42) came from United Kingdom, Switzerland, and United States. African bee samples (n=82) came from Kenya. Africanized bee samples (n=10) came from Brazil. Unexpectedly, Africanized honey bee gut microbiota was far more similar to European bees than to African bees despite the closer host genetic relationship between African and Africanized bees. All three subspecies shared similar relative abundances of core taxa. We posit that the similarity in gut microbiota between Africanized and European honey bees arose from the nature of the crossbreeding, and the social / environmental transmission of gut microbiota within hives. Namely, African queens took over European hives. However, the hybrid offspring acquired their gut microbiota from European nurse bees and European hive materials, resulting in the stable transmission of European gut microbiota across generations. Our results provide an intriguing insight into the potential ecological, social, and environmental factors that shape the gut microbiota of the Africanized honey bee hybrid.ImportanceAfricanized honey bee hybrids originated in Brazil through the crossbreeding of African and European honey bee subspecies. In this study, we examined the gut microbiota of all 3 honey bee subspecies (African, European, Africanized). A few core microbiota were shared across all subspecies. Interestingly, while African honey bee genes dominated in the Africanized honey bee hybrids, their gut microbial composition was most similar to European bees. This is likely related to the way these bees were crossbred – with African queens taking over European hives, while gut microbial inoculation of hybrids came from European nurse bees and European hive matierals. Gut microbiota are critical to honey bee health, and studying the gut microbiota of closely related honey bee subspecies helps understand the factors that influence gut microbial composition. This is important for our broader understanding of honey bee health, conservation, and evolution.
The restricted N-glycome of neurons is programmed during differentiation
Authors: Kiwimagi Katherine , Noel Maxence , Cetinbas Murat , Sadreyev Ruslan I. , Wang Lei , Smoller Jordan W. , Cummings Richard D. , Weiss Ron , Mealer Robert G. 
Published: October 2024

AbstractThe protein glycome of individual cell types in the brain is unexplored, despite the critical function of these modifications in development and disease. In aggregate, the most abundant asparagine (N-) linked glycans in the adult brain are high mannose structures, and specifically Man5GlcNAc2(Man-5), which normally exits the ER for further processing in the Golgi. Mannose structures are uncommon in other organs and often overlooked or excluded in most studies. To understand cell-specific contributions to the unique brain N-glycome and its abundance of Man-5, we performed RNAseq and MALDI-MS TOF protein N-glycomics at several timepoints during differentiation of multiple cell types. To this end, homogeneous cultures of glutamatergic neurons, GABAergic neurons, and brain-specific endothelial cells were generated from monoclonal human inducible pluripotent stem cells (hiPSCs) through cellular reprogramming. Small molecule induction of stably integrated synthetic transcription units driving morphogen expression generated differentiated cells with distinct patterns mirroring intact tissue. Comparing uninduced hiPSCs for each cell type revealed identical transcriptomic and glycomic profiles before differentiation, with low quantities of Man-5. In differentiated glutamatergic and GABAergic neurons, the most abundant N-glycans became Man-5 and its immediate precursor Man-6, despite the presence of transcripts encoding enzymes for their subsequent modification. Differentiation to brain-specific endothelial cells showed an opposite effect, with the N-glycome displaying an abundance of complex N-glycans and terminal modifications of the late secretory pathway. These results confirm that the restricted N-glycome profile of brain is programmed into neuronal differentiation, with regulation independent of the transcriptome and under tight evolutionary constraint.
A Reproducibility Focused Meta-Analysis Method for Single-Cell Transcriptomic Case-Control Studies Uncovers Robust Differentially Expressed Genes
Authors: Nakatsuka Nathan , Adler Drew , Jiang Longda , Hartman Austin , Cheng Evan , Klann Eric , Satija Rahul 
Published: October 2024

AbstractWe assessed the reproducibility of differentially expressed genes (DEGs) in previously published Alzheimer’s (AD), Parkinson’s (PD), Schizophrenia (SCZ), and COVID-19 scRNA-seq studies. While transcriptional scores from DEGs of individual PD and COVID-19 datasets had moderate predictive power for case-control status of other datasets (AUC=0.77 and 0.75), genes from individual AD and SCZ datasets had poor predictive power (AUC=0.68 and 0.55). We developed a non-parametric meta-analysis method, SumRank, based on reproducibility of relative differential expression ranks across datasets, and found DEGs with improved predictive power (AUC=0.88, 0.91, 0.78, and 0.62). By multiple other metrics, specificity and sensitivity of these genes were substantially higher than those discovered by dataset merging and inverse variance weighted p-value aggregation methods. The DEGs revealed known and novel biological pathways, and we validateBCAT1as down-regulated in AD mouse oligodendrocytes. Lastly, we evaluate factors influencing reproducibility of individual studies as a prospective guide for experimental design.
OpenASO: RNA Rescue — designing splice-modulating antisense oligonucleotides through community science
Authors: Tse Victor , Guiterrez Martin , Townley Jill , Romano Jonathan , Pearl Jennifer , Chacaltana Guillermo , Players Eterna , Das Rhiju , Sanford Jeremy R. , Stone Michael D. 
Published: October 2024

ABSTRACTSplice-modulating antisense oligonucleotides (ASOs) are precision RNA-based drugs that are becoming an established modality to treat human disease. Previously, we reported the discovery of ASOs that target a novel, putative intronic RNA structure to rescue splicing of multiple pathogenic variants ofF8exon 16 that cause hemophilia A. However, the conventional approach to discovering splice-modulating ASOs is both laborious and expensive. Here, we describe an alternative paradigm that integrates data-driven RNA structure prediction and community science to discover splice-modulating ASOs. Using a splicing-deficient pathogenic variant ofF8exon 16 as a model, we show that 25% of the top-scoring molecules designed in the Eterna OpenASO challenge have a statistically significant impact on enhancing exon 16 splicing. Additionally, we show that a distinct combination of ASOs designed by Eterna players can additively enhance the inclusion of the splicing-deficient exon 16 variant. Together, our data suggests that crowdsourcing designs from a community of citizen scientists may accelerate the discovery of splice-modulating ASOs with potential to treat human disease.
Modeling compound lipid homeostasis using stable isotope tracing
Authors: Wessendorf-Rodriguez Karl , Ruchhoeft Maureen L. , Ashley Ethan L. , Galvez Hector M. , Murray Christopher W. , Huang Yale , McGregor Grace H. , Kambhampati Shrikaar , Shaw Reuben J. , Metallo Christian M. 
Published: October 2024

SummaryLipids represent the most diverse pool of metabolites found in cells, facilitating compartmentation, signaling, and other functions. Dysregulation of lipid metabolism is linked to disease states such as cancer and neurodegeneration. However, limited tools are available for quantifying metabolic fluxes across the lipidome. To directly measure reaction fluxes encompassing compound lipid homeostasis, we applied stable isotope tracing, liquid chromatography-high-resolution mass spectrometry, and network-based isotopologue modeling to non-small cell lung cancer (NSCLC) models. Compound lipid metabolic flux analysis (CL-MFA) enables the concurrent quantitation of fatty acid synthesis, elongation, headgroup assembly, and salvage reactions within virtually any biological system. Here, we resolve liver kinase B1 (LKB1)-mediated regulation of sphingolipid recycling in NSCLC cells and precision-cut lung slice cultures. We also demonstrate that widely used tissue culture conditions drive cells to upregulate fatty acid synthase flux to supraphysiological levels. Finally, we identify previously uncharacterized isozyme specificity of ceramide synthase inhibitors. These results highlight the ability of CL-MFA to quantify lipid cycling in biological systems to discover biological function and elucidate molecular mechanisms in membrane lipid metabolism.