bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating intraspecific variation into population dynamics reveals how interacting species persist in mutualistic communities
Authors: Arroyo-Correa Blanca , Bartomeus Ignasi , Jordano Pedro , Cagua E. Fernando , Stouffer Daniel B. 
Published: September 2024

ABSTRACTMutualistic interactions among organisms are fundamental to the origin and maintenance of bio-diversity. Yet, the study of community dynamics often relies on species-level values, ignoring the effects of intraspecific variation. We propose a theoretical framework for evaluating the extent to which variation within populations can influence species’ persistence in mutualistic systems. Next, drawing from detailed empirical data on plant–pollinator interactions and plant fitness, we quantify intraspecific variation in the mutualistic benefits received by plants and incorporate this variation into estimations of structural stability, a robust theoretical measure of species’ likelihood of persistence. Through explicit consideration of intraspecific variation, we demonstrate that, in the absence of heterospecific plant competitors, plant populations composed of specialized individuals promote the persistence of the plant species they belong to and their associated pollinator community. However, these positive effects do not hold when plant species compete with a broader plant community. In this case, having more heterogeneous mixtures of plant individuals (i.e., both specialized and generalized) is more beneficial for a population’s persistence. By integrating the proposed framework with empirical data, we are able to explicitly account for individual-level variation, opening the door to a better understanding of the mechanisms promoting biodiversity in mutualistic communities.
Genetic diversity during selective sweeps in non-recombining populations
Authors: Kaushik Sachin , Jain Kavita , Johri Parul 
Published: September 2024

AbstractSelective sweeps, resulting from the spread of beneficial, neutral, or deleterious mutations through a population, shape patterns of genetic variation at linked neutral sites. While many theoretical, computational, and statistical advances have been made in understanding the genomic signatures of selective sweeps in recombining populations, substantially less is understood in populations with little/no recombination. We present a mathematical framework based on diffusion theory for obtaining the site frequency spectrum (SFS) at linked neutral sites immediately post and during the fixation of moderately or strongly beneficial mutations. We find that when a single hard sweep occurs, the SFS decays as 1/xfor low derived allele frequencies (x), similar to the neutral SFS at equilibrium, whereas at higher derived allele frequencies, it follows a 1/x2power law. These power laws are universal in the sense that they are independent of the dominance and inbreeding coefficient, and also characterize the SFS during the sweep. Additionally, we find that the derived allele frequency where the SFS shifts from the 1/xto 1/x2law, is inversely proportional to the selection strength: thus under strong selection, the SFS follows the 1/x2dependence for most allele frequencies, resembling a rapidly expanding neutral population. When clonal interference is pervasive, the SFS immediately post-fixation becomes U-shaped and is better explained by the equilibrium SFS of selected sites. Our results will be important in developing statistical methods to infer the timing and strength of recent selective sweeps in asexual populations, genomic regions that lack recombination, and clonally propagating tumor populations.
From Monomers to Oligomers: Structural Mechanism of Receptor-Triggered MyD88 Assembly in Innate Immune Signaling
Authors: Kasai Kazuki , Imamura Kayo , Uno Masatoshi , Sekiyama Naotaka , Miyata Tomoko , Makino Fumiaki , Yamada Ryusei , Takahashi Yoshiki , Kodera Noriyuki , Namba Keiichi , Ohnishi Hidenori , Narita Akihiro , Konno Hiroki , Tochio Hidehito 
Published: September 2024

SummaryMyD88 plays a pivotal role in Toll-like receptor (TLR) and interleukin-1 family signaling through its oligomerization upon receptor activation, leading to downstream protein recruitment. The Toll/interleukin-1 receptor domain of MyD88 (TIRMyD88) is responsible for this receptor-mediated oligomerization, but the detailed mechanism involved remains elusive. We investigated the structure of TIRMyD88oligomers and their interactions with TLRs. Cryoelectron microscopy revealed that tandemly arrayed TIRMyD88subunits formed an antiparallel double-stranded filament that could further form rings and cylindrical filaments. Moreover, the self-assembly of TIRMyD88in vitrowas markedly accelerated by dimeric rather than monomeric receptor TIRs, possibly reflecting the signal initiation stepin vivo. High-speed atomic force microscopy further captured the dynamic processes of oligomerization of TIRMyD88, in addition to its direct interaction with the receptor TIRs. Based on these results, a novel regulatory mechanism of TIRMyD88oligomerization underlying the signal initiation step was revealed.
Medin Induces Pro-Inflammatory Activation of Human Brain Vascular Smooth Muscle Cells
Authors: Karamanova Nina , Morrow Kaleb T. , Maerivoet Alana , Madine Jillian , Li Ming , Migrino Raymond Q. 
Published: September 2024

ABSTRACTBackgroundMedin is one of the most common amyloidogenic proteins and accumulates in the vasculature with aging. Vascular medin accumulation is associated with Alzheimer’s disease, vascular dementia and aortic aneurysms. Medin impairs smooth muscle-dependent vasodilation in isolated human brain cerebral arteries. The role of medin in vascular smooth muscle (VSMC) activation is unknown. We aim to evaluate the effects of medin on human brain VSMC activation.MethodsVSMCs were exposed to physiologic doses of medin (0.5, 1 and 5 µM) without or with small molecule nuclear factor-κB (NFκB) inhibitor RO106-9920 (10 µM) for 20 hours. Polymerase chain reaction, Western blot/enzyme-linked immunosorbent assay were used to quantify gene and protein expressions/secretions, respectively, of pro-inflammatory factors (interleukin (IL)-6, IL-8 and monocyte chemoattractant protein (MCP)-1) and structural and enzyme proteins associated with VSMC phenotypic transformation (smooth muscle actin alpha 2 (ACTA2), myosin heavy chain 11 (MYH11) and NADPH oxidase 4 (NOX4)).ResultsMedin exposure increased VSMC gene expression and protein secretion of IL-6, IL-8 and MCP-1 (protein secretion 46.0±12.8x, 20.2±4.1x and 8.7±3.1x, respectively, medin 5 µM versus vehicle, all p<0.05). There was no change in gene or protein expressions of ACTA2, MYH11 and NOX4. Co-treatment with RO106-9920 reduced medin-induced increases in IL-6 and IL-8 and a trend towards reduced MCP-1 secretion.ConclusionsMedin induced pro-inflammatory activation of human brain VSMCs that is mediated, at least in part, by NFκB. Acute medin treatment did not alter structural proteins involved in VSMC phenotypic transformation. The findings support medin as a potential novel mediator of and therapeutic target for vascular aging pathology.
Developing a virtual Endoscopic Surgery Planning system to optimize surgical outcomes
Authors: Hittle Bradley , Odeh Ahmad , Maza Guillermo , Shen Brenda , Otto Bradley A , Stredney Don , Wiet Gregory J. , Zhao Kai 
Published: September 2024

AbstractObjectivePlanning and predicting functional outcomes of endoscopic sinus surgeries (e.g., nasal airflow) based solely on visualizing Computerized Tomography (CT) or endoscopy poses a challenge to produce optimal clinical outcomes.Study designTechnology development, retrospective case report.MethodsA virtual surgery planning (VSP) tool is developed that can load any patient’s CT data and allow surgeons to remove obstructive tissue using both visual and haptic feedback endoscopically. Pre-calculated airflow resistance, wall shear stress, pressure drop are displayed on the anatomy to identify potential sites of obstruction. After each virtual surgery, changes in nasal airflow can be computed, and the process is reiterated until an optimal result is reached.ResultsAs proof-of-concept, a series of isolated or combined procedures were performed on CT of one patient, who had olfactory losses that may involve obstructions blocking the air/odor flow to the olfactory fossa (OF). For this patient, an isolated medial partial middle turbinectomy (PMT) demonstrated the best outcome, better than traditionally performed lateral PMT, while septal body reduction worsened air/odor flow to OF.ConclusionThis proof of concept case report demonstrates the potential usefulness of VSP in preoperative planning based on objective benchmarks and could be a valuable tool for optimizing future surgical outcomes.
Mutant p53 Misfolding and Aggregation Precedes Transformation into High-Grade Serous Ovarian Carcinoma
Authors: Sartini Sara , Omholt Lexi , Moatamed Neda A. , Soragni Alice 
Published: September 2024

AbstractHigh Grade Serous Ovarian Cancer (HG-SOC), the most prevalent and aggressive gynecological malignancy, is marked by ubiquitous loss of functional p53, largely due to point mutations that arise very early in carcinogenesis. These mutations often lead to p53 protein misfolding and subsequent aggregation, yet the alterations in intracellular p53 dynamics throughout ovarian cancer progression remain poorly understood. HG-SOC originates from the fallopian tube epithelium, with a well-documented stepwise progression beginning with early pre-malignant p53 signatures. These signatures represent largely normal cells that express and accumulate mutant p53, which then transform into benign serous tubal intraepithelial lesions (STIL), progress into late pre-malignant serous tubal intraepithelial carcinoma (STIC), and ultimately lead to HGSOC. Here, we show that the transition from folded, soluble to aggregated mutant p53 occurs during the malignant transformation of benign precursor lesions into HGSOC. We analyzed fallopian tube tissue collected from ten salpingo-oophorectomy cases and determined the proportion of cells carrying soluble versus mis-folded/mutant p53 through conformation-sensitive staining and quantification. Misfolded p53 protein, prone to aggregation, is present in STICs and HG-SOCs, but notably absent from preneoplastic lesions and surrounding healthy tissue. Overall, our results indicate that aggregation of mutant p53 is a structural defect that distinguishes preneoplastic early lesions from late premalignant and malignant ones, offering a potential treatment window for targeting p53 aggregation and halting ovarian cancer progression.
Cortical connectivity supports motoric synchronization to both auditory and visual rhythms in a frontal-temporal network
Authors: Lu Yuhan , Yu Yanlin , Wang Xiaosha , Qin Lang , Gao Jia-Hong , Bi Yanchao , Tian Xing , Ding Nai 
Published: September 2024

AbstractSynchronizing motoric responses to metrical sensory rhythms is key to social activities, e.g., group singing and dancing. It remains elusive, however, whether there is a common neural network for motoric synchronization to metrical rhythms from different sensory modalities. Here, we separate sensorimotor responses from basic sensory responses by combining a metrical sensorimotor synchronization task with frequency-domain magnetoencephalography (MEG) analysis. A common frontal-temporal network, not including visual cortex, is observed during both visual- and auditory-motor synchronization, and the network remains in congenitally deaf participants during visual-motor synchronization, suggesting the network is formed by intrinsic cortical connections instead of auditory experience. Furthermore, activation of the left and right frontal-temporal areas, as well as the ipsilateral white matter connection, separately predict the precision of auditory and visual synchronization. These results reveal a common but lateralized frontal-temporal network for visual- and auditory-motor synchronization, which is generated based on intrinsic cortical connections.
Genomic Analysis of Human-infectingLeptospira borgpeterseniiisolates in Sri Lanka: expanded PF07598 gene family repertoire, less overall genome reduction than bovine isolates
Authors: Senavirathna Indika , Jayasundara Dinesha , Warnasekara Janith , Agampodi Suneth , Putz Ellie J. , Nally Jarlath E. , Bayles Darrell O. , Chaurasia Reetika , Vinetz Joseph M. 
Published: September 2024

AbstractLeptospira borgpeterseniicommonly causes human leptospirosis, including severe disease. The first published analysis ofL. borgpetersenii, performed on two strains of serovar Hardjo (L550 and JB197), concluded that theL. borgpeterseniigenome is in the process of genome decay with functional consequences leading to a more obligately host-dependent life cycle. Yet whole genome analysis has only been carried out on few strains ofL. borgpetersenii, with limited closed genomes and comprehensive analysis. Herein we report the complete, circularized genomes of seven non-HardjoLeptospira borgpeterseniiisolates from human leptospirosis patients in Sri Lanka. These isolates (all ST144) were found to be nearly identical by whole genome analysis; serotyping showed they are a novel serovar. We show that theL. borgpeterseniiisolated from humans in Sri Lanka are less genomically decayed than previously reported isolates: fewer pseudogenes (N=141) and Insertion Sequence (IS) elements (N=46) compared to N=248, N=270, and N=400 pseudogenes, and N=121 and N=116 IS elements in publishedL. borgpeterseniiHardjo genomes (L550, JB197 and TC112). Compared to previously publishedL. borgpeterseniiwhole genome analyses showing two to three VM proteins inL. borgpeterseniiisolates from cattle, rats and humans, we found that all of the humanL. borgpeterseniiisolates from Sri Lanka, including previously reported serovar Piyasena, have 4 encoded VM proteins, one ortholog ofL. interrogansCopenhageni LIC12339 and 3 orthologs of LIC12844. Our findings of fewer pseudogenes, IS elements and expansion of the LIC12844 homologs of the PF07598 family in these human isolates suggests that this newly identifiedL. borgpeterseniiserovar from Sri Lanka has unique pathogenicity. Comparative genome analysis and experimental studies of theseL. borgpeterseniiisolates will enable deeper insights into the molecular and cellular mechanisms of leptospirosis pathogenesis.Author SummaryLeptospirosis is an emerging bacterial zoonosis worldwide.Leptospira borgpeterseniipredominates as the cause of human leptospirosis in some agricultural contexts. We address here the relatively neglected comparative genome analysis ofL. borgpetersenii. We show here thatL. borgpeterseniiisolated from humans in Sri Lanka have less genome reduction compared to available cattle isolates and have novel virulence characteristics compared to isolates from other animals including cattle and rats.
Molecular dynamics simulations of human cohesin subunits identify DNA binding sites and their potential roles in DNA loop extrusion
Authors: Gu Chenyang , Takada Shoji , Brandani Giovani B. , Terakawa Tsuyoshi 
Published: September 2024

AbstractThe SMC complex cohesin mediates interphase chromatin structural formation in eukaryotic cells through DNA loop extrusion. Here, we sought to investigate its mechanism using molecular dynamics simulations. To achieve this, we first constructed the amino-acid-residue-resolution structural models of the cohesin subunits, SMC1, SMC3, STAG1, and NIPBL. By simulating these subunits with double-stranded DNA molecules, we predicted DNA binding patches on each subunit and quantified the affinities of these patches to DNA using their dissociation rate constants as a proxy. Then, we constructed the structural model of the whole cohesin complex and mapped the predicted high-affinity DNA binding patches on the structure. From the spatial relations of the predicted patches, we identified that multiple patches on the SMC1, SMC3, STAG1, and NIPBL subunits form a DNA clamping patch group. The simulations of the whole complex with double-stranded DNA molecules suggest that this patch group facilitates DNA bending and helps capture a DNA segment in the cohesin ring formed by the SMC1 and SMC3 subunits. In previous studies, these have been identified as critical steps in DNA loop extrusion. Therefore, this study provides experimentally testable predictions of DNA binding sites implicated in previously proposed DNA loop extrusion mechanisms and highlights the essential roles of the accessory subunits STAG1 and NIPBL in the mechanism.
GABAergic neurons in the dorsal raphe nucleus regulate social hierarchy in mice
Authors: Lu Lidi , Fan Yanzhu , Ge Shaoxiang , Wu Yue , Wang Zhiyue , Qing Tao , Shi Suxin , Fang Guangzhan 
Published: September 2024

AbstractSocial hierarchy serves as a fundamental organizational mechanism within most animal societies, exerting significant influence on health, survival, and reproductive success in both humans and animals. However, the neural mechanisms by which the brain regulates dominance hierarchies remain inadequately understood. Considering that GABAergic neurons in the dorsal raphe nucleus (DRN) exert substantial inhibitory control over serotonergic firing, which may be implicated in the acquisition of dominance, we hypothesized that DRN GABAergic neurons may play a pivotal role in regulating social hierarchy. To test this hypothesis, we employed a combination of optogenetics, chemogenetics, fiber photometry recordings, and behavioral assays in mice, to elucidate the functional contributions of these neurons. Our results revealed a biphasic activity pattern of DRN GABAergic neurons, characterized by increased firing during retreats and decreased firing during push-initiation in the tube test. Furthermore, the optogenetic and chemogenetic activation of DRN GABAergic neurons led to an increase in the number of retreats and a reduction in social rank, while inhibition of these neurons produced the opposite effects. These findings elucidate the bidirectional regulatory role of DRN GABAergic neurons in social hierarchies.
Variations in human trigeminal and facial nerve branches and foramina identified by dissection and microcomputed tomography
Authors: Grimes Hannah L. , Pizzuti Valentina , Wright Maria A. , Santarius Thomas , Jones Susan 
Published: September 2024

AbstractThe aim of this study was to identify branches of the trigeminal and facial nerves relevant to surgical incisions and injections and the scalp block techniques in the frontotemporal region, and to determine their relationships with superficial vascular structures and bony landmarks. Half-heads from consenting embalmed donors (6 male, 2 female, mean age at death 78.4 years) were used in this study. Detailed dissection was carried out to identify the position of the auriculotemporal nerve (ATN) relative to the superior temporal artery (STA) and the facial nerve (FN) in six subjects (5 male, 1 female). The results provide a minimum safe distance of 5 mm between the STA and the frontotemporal branches of the FN at the level of the low edge of zygoma and 8mm between the low edge of zygoma and the FN trunk, providing a pre-auricular triangle of safety for incisions and injections. Variability between subjects was up to 60%. Microcomputed tomography (microCT) scans were taken from all eight subjects and the three-dimensional reconstructions were used to identify the supraorbital notch (SON), the zygomaticotemporal foramen (ZTF) and the zygomaticofacial foramen (ZFF). The volume and relative locations of these foramina were calculated for 5-8 subjects. The closest distance between ZTF and the FZS ranged from 9 to 21mm (26% variation); 3 subjects had a single ZTF while 5 subjects had two ZTF. The angle at the centre of the orbit between ZFF and the FZS ranged from 156 to 166 degrees (2.5% variation). These findings demonstrate that both traditional cadaveric dissection methods as well as contemporary microCT methods can be used to investigate the relative locations of nerves or their foramina in the human head. The findings provide anatomical considerations for fronto-temporal incisions and local anaesthesia.
Activation of 5-HT7receptors in the mouse dentate gyrus does not affect theta-burst-induced plasticity at the perforant path synapse
Authors: Siwiec Marcin , Bobula Bartosz , Kiełbiński Michał , Multan Nikola , Hess Grzegorz , Tokarski Krzysztof 
Published: September 2024

AbstractBackgroundThe study examined the effects of 5-HT7receptor activation on GABAergic transmission within the dentate gyrus and plasticity at the glutamatergic perforant path input.MethodsImmunofluorescence imaging was performed using transverse hippocampal slices from transgenic mice expressing green fluorescent protein (GFP) under the Htr7 promoter. This was followed by whole-cell patch clamp electrophysiological recordings assessing the effects of pharmacologically activating 5-HT7receptors on spontaneous inhibitory postsynaptic currents recorded from dentate granule cells and hilar mossy cells — two glutamatergic neuron types present in the dentate gyrus. Extracellular recordings of field excitatory postsynaptic potentials were then performed to assess whether 5-HT7receptor activation influenced theta-burst stimulation-evoked plasticity of the perforant path synaptic input.ResultsIt was found that parvalbumin and somatostatin interneurons in the dentate gyrus expressed GFP, which suggests they express 5-HT7receptors. However, activation of 5-HT7receptors had no effect on GABAergic transmission targeting mossy cells or granule cells. There was also no effect of 5-HT7receptor activation on perforant path plasticity either with intact or blocked GABAAreceptor signaling.ConclusionThe presence of 5-HT7receptors in a subset of parvalbumin and somatostatin interneurons in the mouse dentate gyrus could mean that they are involved in the inhibitory control of dentate gyrus activity. However, this potential effect was not evident in slice recordings of inhibitory transmission targeting principal cells and did not affect perforant path plasticity. Further experiments are needed to fully elucidate the functional role of these receptors in the dentate gyrus.
RCoxNet: deep learning framework for enhanced cancer survival prediction integrating random walk with restart with mutation and clinical data
Authors: Kumari Stuti , Gujral Sakshi , Panda Smruti , Gupta Prashant , Ahuja Gaurav , Sengupta Debarka 
Published: September 2024

AbstractCancer poses a significant global health challenge, characterized by a complex disease progression and disrupted growth regulation. A thorough understanding of cellular and molecular biological mechanisms is essential for developing novel treatments and improving the accuracy of patient survival predictions. While prior studies have leveraged gene expression and clinical data to forecast survival outcomes through current machine learning and deep learning approaches, gene mutation data—despite being a widely recognized metric—has rarely been incorporated due to its limited information, inadequate representation of gene relationships, and data sparsity, which negatively affects the robustness, effectiveness, and interpretability of current survival analysis approaches. To overcome the challenges of mutation data sparsity, we propose RCoxNet, a novel deep learning neural network framework that integrates the Random Walk with Restart (RWR) algorithm with a deep learning Cox Proportional Hazards model. By applying this framework to mutation data from cBioportal, our model achieved an average concordance index of 0.62 ± 0.05 across four cancer types, outperforming existing deep neural network models. Additionally, we identified clinical features critical for differentiating between predicted high- and low-risk patients, with the relevance of these features being partially supported by previous studies.