bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of the Follow-Up Discourse Observation Protocol (FUDOP) for characterizing instructor active-learning follow-up behaviors
Authors: Cen Xinjian , Kight Maci , Lee Rachel , Kranzfelder Petra , Lo Stanley M. , Maloy Jeffrey , Owens Melinda T. 
Published: August 2024

AbstractInstructors can provide feedback to their class in multiple ways. One way is through their follow-up behaviors, which are the specific strategies instructors implement after active learning activities. These behaviors could play an important role in student learning as students can receive feedback from the instructor. However, there is little research on the effects of different types of follow-up behaviors. Follow-up after active learning can be seen as a form of discourse between the instructor and the entire class. Previous researchers developed the Classroom Discourse Observation Protocol (CDOP) to analyze discourse between the instructor and individual students or small groups. We used CDOP as a starting point to develop and validate a new protocol, the Follow-Up Discourse Observation Protocol (FUDOP), to characterize instructional follow-up behaviors to the entire class after active-learning activities. We then used FUDOP to characterize follow-up behaviors of multiple instructors in introductory biology courses at three different universities. We measured consistent differences in these behaviors across instructors but not within instructors, demonstrating that instructors may engage in consistent follow-up behaviors. FUDOP could allow instructors and researchers to better measure and analyze follow-up behaviors and their effects, which could in turn provide guidance to instructors and faculty developers.
The transcription factor BATF pioneers the differentiation program of cytolytic effector CD8+T cells through the direct interaction with IRF4
Authors: Fujisawa Sotaro , Tanabe Yamato , Hojo Arisa , Shiga Ryotaro , Kurachi Junko , Koura Miki , Tamai Toshikatsu , Miyanari Yusuke , Wherry Edward John , Kurachi Makoto 
Published: August 2024

AbstractThe transcription factor BATF plays critical roles in the differentiation of various immune cells, including CD8+T cells. Here, we demonstrated that BATF controls epigenomic and transcriptomic reprogramming of CD8+T cells at an early phase of acute viral infection, thereby promoting the differentiation of cytolytic effector CD8+T cells. Loss of BATF drastically perturbed gene expression, chromatin accessibility, and the bindings of key transcription factors including Jun, T-bet, and IRF4. The direct interaction with IRF4 was essential for BATF-mediated effector differentiation, as the BATF mutant lacking this interaction failed to induce proper chromatin remodeling and proliferation of antigen-specific CD8+T cells. Notably, IRF4 binding was exhaustively dependent on BATF, whereas BATF retained binding capacity even in IRF4-deficient CD8+T cells. Furthermore, BATF initiated chromatin remodeling in the absence of IRF4, whereas subsequent dynamic epigenomic reorganization required IRF4. Our data proposed that BATF serves as a “pioneer transcription factor” spearheading the reorganization of chromatin architecture upon antigen encounter, followed by further rearrangement of epigenomic and transcriptomic landscapes through the cooperation with IRF4.
Voltage-gated calcium channels generate blastema Ca2+fluxes restraining zebrafish fin regenerative outgrowth
Authors: Le Bleu Heather K. , Kioussi Rea G. , Henner Astra L. , Lewis Victor M. , Stewart Scott , Stankunas Kryn 
Published: August 2024

ABSTRACTAdult zebrafish fins regenerate to their original size regardless of damage extent, providing a tractable model of organ size and scale control. Gain-of-function of voltage-gated K+channels expressed in fibroblast-lineage blastema cells promotes excessive fin outgrowth, leading to a long-finned phenotype. Similarly, inhibition of the Ca2+-dependent phosphatase calcineurin during regeneration causes dramatic fin overgrowth. However, Ca2+fluxes and their potential origins from dynamic membrane voltages have not been explored or linked to fin size restoration. We used fibroblast-lineage GCaMP imaging of regenerating adult fins to identify widespread, heterogeneous Ca2+transients in distal blastema cells. Membrane depolarization of isolated regenerating fin fibroblasts triggered Ca2+spikes dependent on voltage-gated Ca2+channel activity. Single cell transcriptomics identified the voltage-gated Ca2+channelscacna1c(L-type channel),cacna1ba(N-type), andcacna1g(T-type) as candidate mediators of fibroblast-lineage Ca2+signaling. Small molecule inhibition revealed L- and/or N-type voltage-gated Ca2+channels act during regenerative outgrowth to restore fins to their original scale. Strikingly,cacna1ghomozygous mutant zebrafish regenerated extraordinarily long fins due to prolonged outgrowth. The regenerated fins far exceeded their original length but with otherwise normal ray skeletons. Therefore,cacna1gmutants uniquely provide a genetic loss-of-function long-finned model that decouples developmental and regenerative fin outgrowth. Live GCaMP imaging of regenerating fins showed T-type Cacna1g channels enable Ca2+dynamics in distal fibroblast-lineage blastemal mesenchyme during the outgrowth phase. We conclude “bioelectricity” for fin size control likely entirely reflects voltage-modulated Ca2+dynamics in fibroblast-lineage blastemal cells that specifically and steadily decelerates outgrowth at a rate tuned to restore the original fin size.
Adult male Lar gibbon sings the female great-call: A case study of inter-sex song production in a non-human primate
Authors: Varkevisser Judith , Berger Stijn , van der Loo Judith , Kriengwatana Buddhamas Pralle , Spierings Michelle 
Published: August 2024

AbstractGibbons are known as one of the most vocal non-human primates. They vocally advertise and reinforce their pair-bonds by singing complex duets, in which both the male and female perform a predetermined sex-specific set of song phrases, including the loud and elongated great-calls. Only females and sub-adult male gibbons have been previously observed performing great-calls. Once a male gibbon matures, he normally stops great-call production completely but continues singing other and less high-pitched song phrases. This case study describes a fully adult, castrated male lar gibbon (Hylobates lar, 32 years old, zoo-housed) who performs both male phrases of the duet, including the female great-call. The male regularly produced great-calls despite being in a, relatively weak, pair bond with a female conspecific. His great-calls adhered to the general structure of typical female great-calls but were shorter and had a lower maximum frequency. Notably, he produced these great-calls predominantly when the female was absent, especially when she was in their inside enclosure whilst he was outside. Behavioural observations indicate that the occurrence of great-calls by the male cannot be predicted based on pre-song behaviour or his interaction with the female. The recurrence of sub-adult singing behaviour in a fully grown adult is most likely due to his reduced testosterone levels. This study sheds light on the intricate dynamics of duetting and the unique occurrence of cross-sex song production in gibbons, emphasizing the complexity of pair-bond communication in this species.
Aging and viral evolution impair immunity against dominant pan-coronavirus-reactive T cell epitope
Authors: Loyal Lucie , Jürchott Karsten , Reimer Ulf , Meyer-Arndt Lil , Henze Larissa , Mages Norbert , Kostrzanowski Jak , Reus Bernhard , Mangold Maike , Kruse Beate , Dingeldey Manuela , Sawitzki Birgit , Michel Janine , Grossegesse Marica , Schnatbaum Karsten , Wenschuh Holger , Nitsche Andreas , Lachmann Nils , Timmermann Bernd , Giesecke-Thiel Claudia , Braun Julian , Kern Florian , Thiel Andreas 
Published: August 2024

AbstractImmune evasion by escape mutations subverts immunity against SARS-CoV-2. A role of pan-coronavirus immunity for more durable protection is being discussed but has remained understudied. We here investigated the effects of age, mutations, and homo-/heterologous vaccination regimens on the dominant pan-coronavirus-specific cellular and humoral epitope iCope after SARS-CoV-2 infection and vaccination in detail. In the older, quantitatively, and qualitatively reduced iCope-reactive CD4+T cell responses with narrow TCR repertoires could not be enhanced by vaccination and were further compromised by emerging spike mutations. In contrast pan-coronavirus-reactive humoral immunity was affected only by mutations and not by age. Our results reveal a distinct deficiency of the dichotomous layer of pan-coronavirus immunity in the older, critical for long-term protection against SARS-CoV-2 variants.One-Sentence SummaryAging and viral evolution impair dominant pan-coronavirus immunity, a hallmark of efficient and broad immune competence against SARS-CoV-2
Large serine integrases utilise scavenged phage proteins as directionality cofactors
Authors: Alsaleh Abdulrazak , Pena Reyes Tania , Baksh Aron , Taiwo-Aiyerin Oluwateniola T. , Holland Alexandria , Pigli Ying , Rice Phoebe A. , Olorunniji Femi J. 
Published: August 2024

ABSTRACTRecombination directionality factors (RDFs) for large serine integrases (LSIs) are cofactor proteins that control the directionality of recombination to favor excision over insertion. Although RDFs are predicted to bind their cognate LSIs in similar ways, there is no overall common structural theme across LSI RDFs, leading to the suggestion that some of them may be moonlighting proteins with other primary functions. To test this hypothesis, we searched for characterized proteins with structures similar to the predicted structures of known RDFs. Our search shows that the RDFs for two LSIs, TG1 integrase and Bxb1 integrase, show high similarities to a single stranded DNA binding (SSB) protein and an editing exonuclease, respectively. We present experimental data to show that TG1 RDF is a functional SSB protein. We used mutational analysis to validate the integrase-RDF interface predicted by AlphaFold2 multimer for TG1 integrase and its RDF, and establish that control of recombination directionality is mediated via protein-protein interaction at the junction of recombinase’s second DNA binding domain and the base of the coiled coil domain.
Investigation of pair-wise single-cell interactions by statistically interpreting spatial cell state correlation learned by self-supervised graph inductive bias transformer
Authors: Xiao Xiao 
Published: August 2024

AbstractImage-based spatial transcriptomics (ST) offers spatial gene expression profile at the single-cell resolution and provides information to understand intercellular communication that is critical for maintaining tissue development and organ function. Disruption of normal cell-cell interactions (CCI) can lead to disease onset and progression. Current CCI analysis methods face several limitations, including subjection to the number of measured ligand-receptor genes in image-based spatial transcriptomics, limited graph encoding power, inadequate use of spatial information, and low interpretability. Here, we present GITIII, an interpretable self-supervised graph transformer- based language model that treats cells as words (nodes) and their cell neighborhood as a sentence to explore the communications among cells. Enhanced by multilayer perceptron-based distance scaler, physics-informed attention mechanism, and a state-of-the-art, expressive, and lightweight graph transformer model, GITIII infers CCI by investigating how the state of a cell is influenced by the spatial organization, ligand expression, cell types and states of neighboring cells. With its interpretable architecture, GITIII can be used to understand how the sender cell influences target genes in the receiver cell, visualize the spatial pattern and utility of CCI, identify significant CCI networks, perform CCI-informed cell subtyping, and compare CCI strength between disease groups. Applications to four ST datasets from several species, organs, and platforms, GITIII effectively identified and quantitatively interpreted key CCI patterns driving within-sample heterogeneity and disease progression, thus improving our understanding of brain structures, tumor microenvironments, and the interplay among different cell types responding to neighboring CCIs.
Spatial population dynamics of bacterial colonies with social antibiotic resistance
Authors: Denk-Lobnig Marlis K. , Wood Kevin B. 
Published: August 2024

AbstractBacteria frequently inhabit surface-attached communities where rich “social” interactions can significantly alter their population-level behavior, including their response to antibiotics. Understanding these collective effects in spatially heterogeneous communities is an ongoing challenge. Here, we investigated the spatial organization that emerges from antibiotic exposure in initially randomly distributed communities containing antibiotic-resistant and -sensitive strains ofE. faecalis, an opportunistic pathogen. We identified that a range of complex spatial structures emerged in the population homeland—the inoculated region that microbes inhabit prior to range expansion—, which depended on initial colony composition and antibiotic concentration. We found that these arrangements were explained by cooperative interactions between resistant and sensitive subpopulations with a variable spatial scale, the result of dynamic zones of protection afforded to sensitive cells by growing populations of enzyme-producing resistant neighbors. Using a combination of experiments and mathematical models, we explored the complex spatiotemporal interaction dynamics that create these patterns, and predicted spatial arrangements of sensitive and resistant subpopulations under new conditions. We illustrated how spatial population dynamics in the homeland affect subsequent range expansion, both because they modulate the composition of the initial expanding front, and through long-range cooperation between the homeland and the expanding region. Finally, we showed that these spatial constraints resulted in populations whose size and composition differed markedly from matched populations in well-stirred (planktonic) cultures. These findings underscore the importance of spatial structure and cooperation, long-studied features in theoretical ecology, for determining the fate of bacterial communities under antibiotic exposure.SignificanceInteractions between bacteria are common, particularly in the crowded surface-associated communities that occur anywhere from natural ecosystems to the human body to medical devices. Antibiotic resistance can be influenced by these “social” interactions, making it difficult to predict how spatial communities respond to antibiotic. Here, we show that complex spatial arrangements emerge when initially randomly distributed populations of antibiotic-resistant and -sensitiveE. faecalis, a microbial pathogen, are exposed to antibiotic. Using mathematical models and experiments, we show how local competition and dynamic-range cross-protection drive pattern formation. As a result, these spatially structured populations respond differently to antibiotics than well-mixed communities. Our findings elucidate how “social” antibiotic resistance affects spatially structured bacterial communities, a step towards predicting and controlling resistance.
Facial and body colouration is linked to social rank in the African cichlidAstatotilapia burtoni
Authors: Peroš M. , Chang A. , Martashvili A. , Alvarado S.G. 
Published: August 2024

AbstractAnimal colouration is fundamentally important for social communication within conspecifics to advertising threat to competitors or fitness to possible mates. Social status and animal colouration are covarying traits that are plastic in response to dynamic environments. In the African cichlid,Astatotilapia burtoni, body colouration and behaviour have been extensively reported to vary with social rank. However, the nature of the interaction between these two traits is poorly understood. We hypothesise that pigmentation patterns could be linked to the behavioural repertoires underlying social status and can be resolved to regions on the cichlid body plan. To test this hypothesis, we generated Territorial (T) and Non-territorial (NT) males and employed computer vision tools to quantify and visualise patterns/colour enrichment associated with stereotyped T/NT male behaviour. We report colour-behaviour interactions localised in specific areas of the body and face for two colour morphs illustrating a more nuanced view of social behaviour and pigmentation. Since behavioural and morphological variation are key drivers of selection in the East African Great Rift Lakes, we surmise our data may be translatable to other cichlid lineages and underline the importance of trait covariance in sexual selection and male competition.
Unsupervised domain classification of AlphaFold2-predicted protein structures
Authors: Barone Federico , Laio Alessandro , Punta Marco , Cozzini Stefano , Ansuini Alessio , Cazzaniga Alberto 
Published: August 2024

AbstractThe release of the AlphaFold database, which contains 214 million predicted protein structures, represents a major leap forward for proteomics and its applications. However, lack of comprehensive protein annotation limits its accessibility and usability. Here, we present DPCstruct, an unsupervised clustering algorithm designed to provide domain-level classification of protein structures. Using structural predictions from AlphaFold2 and comprehensive all-against-all local alignments from Foldseek, DPCstruct identifies and groups recurrent structural motifs into domain clusters. When applied to the Foldseek Cluster database, a representative set of proteins from the AlphaFoldDB, DPCstruct successfully recovers the majority of protein folds catalogued in established databases such as SCOP and CATH. Out of the 28,246 clusters identified by DPCstruct, 24% have no structural or sequence similarity to known protein families. Supported by a modular and efficient implementation, classifying 15 million entries in less than 48 hours, DPCstruct is well suited for large-scale proteomics and metagenomics applications. It also facilitates the rapid incorporation of updates from the latest structural prediction tools, ensuring that the classification remains up-to-date. The DPCstruct pipeline and associated database are freely available in a dedicated repository, enhancing the navigation of the AlphaFoldDB through domain annotations and enabling rapid classification of other protein datasets.
Epigenetic and transcriptional regulation of ovarian development altered inErβKOovaries
Authors: Mohamadi Ryan , Vo Kevin , Sharma Yashica , Mohamadi Amelia , Bahadursingh Elizabeth S. , Fields Patrick E. , Karim Rumi M. A. 
Published: August 2024

AbstractWe analyzed the transcriptome of wildtype and estrogen receptor β knockout (ErβKO) rat ovaries during the early postnatal period and detected remarkable changes in epigenetic regulators and transcription factors. Compared to postnatal day (PD) 4.5 wildtype ovaries, 17 differentially expressed epigenetic regulators (DEERs), and 23 differentially expressed transcription factors (DETFs) were detected in PD6.5 wildtype ovaries. Subsequently, compared to PD 6.5 wildtype ovaries, 24 DEERs and 68 DETFs were detected in PD8.5 ovaries. Changes in DEERs and DEFTs resulted in 581 differentially expressed downstream genes (DEDGs) in PD6.5 and 920 DEDGs in wildtype PD8.5 ovaries. The DEERs, DETFs, and DEDGs in wildtype ovaries represented primordial follicle activation (PFA) and development of the first-wave follicles because the second-wave follicles remain dormant during this period. However, the changes in DEERs, DETFs, and DEDGs during this postnatal period were markedly different in ErβKOrat ovaries, which suffered from increased PFA in both waves. Compared to 17 DEERs and 23 DETFs in wildtype, 46 DEERs and 55 DETFs were identified in PD 6.5 ErβKOovaries. The differences were more remarkable in PD 8.5 ErβKOovaries; compared to 24 DEERS and 68 DETFs in wildtype, only 8 DEERs and 10 DETFs were detected in ErβKOovaries. Such dysregulation resulted in altered DEDGs in PD 6.5 (581 vs. 744) and in PD8.5 (920 vs. 191) ErβKOovaries. These findings also suggest that the number of DEDGs depends directly on the numbers of DEERS and DETFs. In addition to the quantitative differences in DEERs and DETFs between the wildtype and ErβKOovaries, we detected distinct differences in the identities of the regulators. Our observations indicate that loss of ERβ dysregulates the epigenetic regulators and transcription factors in ErβKOovaries, which disrupts the downstream genes in ovarian follicles and increases follicle activation.
High-Intensity Interval Training Decreases Circulating HMGB1 in Individuals with Insulin Resistance; Plasma Lipidomics Identifies Associated Cardiometabolic Benefits
Authors: Bravo Gabriela Martinez , Paramasivam Prabu , Bellissimo Gabriella F. , Jacquez Quiteria , Zheng Huayu , Amorim Fabiano , Alvidrez Roberto Ivan Mota 
Published: August 2024

AbstractBackground:Exercise is a fundamental primary standard of care for cardiometabolic health. Body Weight (BW) High-Intensity Interval Training (HIIT) is an effective strategy for reducing cardiometabolic markers in individuals with insulin resistance and Type-2 diabetes (T2D). High-mobility group box 1 (HMGB1), a ubiquitous nuclear factor, plays an ample role beyond an alarmin in T2D development and progression. Our group has described this novel role previously, showing the beneficial effect of whole body HMGB1 silencing in decreasing hyperglycemia in diabetic mice. In the present study we tested the hypothesis that BW-HIIT as an effective exercise training modality will decrease cardiometabolic risk with a concomitant decrease in circulating HMGB1 more prominently in insulin resistant individuals compared to non-insulin resistant individuals contrasting to what we can evidence in a preclinical murine model of insulin resistance;Methods:Human and mouse pre- and post-exercise serum/plasma samples were analyzed for Lipidomics as well as Metabolic and Cytokine Multiplex assays. Standard of care, as well as cardiometabolic parameters, was also performed in human subjects;Results:insulin resistant individuals had the most positive effect, primarily with a decrease in the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). as an index of insulin resistance as well as decreased HMGB1 post-exercise. Lipidomic analysis illustrated the highly beneficial effect of exercise training using a modified HIIT program, showing an enhanced panel of circulating lipids post-exercise exclusively in insulin resistant individuals. Plasma multiplex revealed significant translational heterogeneity in our studies with distinct metabolic hormone responses to exercise conditioning with a decrease in inflammatory markers in insulin resistant individuals;Conclusions:The current study demonstrated that 6-week BW-HIIT training improves cardiometabolic, anti-inflammatory markers, metabolic hormones, and insulin sensitivity in humans, strongly associated with decreased circulating HMGB1. Overall, these experiments reinforce the potential of HMGB1 as a marker of changes in insulin resistance and the positive effect of exercise training on insulin resistance possibly preventing the development of T2D and associated complications.