bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Biomarkers and Trajectories of Prostate Cancer Progression: A Bioinformatics Fusion of Weighted Correlation Network Analysis and Machine Learning
Authors: Sheibani-Tezerji Raheleh , Pérez Malla Carlos Uziel , Wasinger Gabriel , Misura Katarina , Haase Astrid , Malzer Anna , Kalla Jessica , Tran Loan , Egger Gerda 
Published: March 2023

AbstractBackgroundProstate cancer diagnosis and prognosis is currently limited by the availability of sensitive and specific biomarkers. There is an urgent need to develop molecular biomarkers that allow for the distinction of indolent from aggressive disease, the sensitive detection of heterogeneous tumors, or the evaluation of micro-metastases. The availability of multi-omics datasets in publicly accessible databases provides a valuable foundation to develop computational workflows for the identification of suitable biomarkers for clinical management of cancer patients.ResultsWe combined transcriptomic data of primary localized and advanced prostate cancer from two cancer databases. Transcriptomic analysis of metastatic tumors unveiled a distinct overexpression pattern of genes encoding cell surface proteins intricately associated with cell-matrix components and chemokine signaling pathways. Utilizing an integrated approach combining machine learning and weighted gene correlation network modules, we identified the EZH2-TROAP axis as the main trajectory from initial tumor development to lethal metastatic disease. In addition, we identified and independently validated 58 promising biomarkers that were specifically upregulated in primary localized or metastatic disease. Among those biomarkers, 22 were highly significant for predicting biochemical recurrence. Notably, we confirmed TPX2 upregulation at the protein level in an independent cohort of primary prostate cancer and matched lymph node metastases.ConclusionsThis study demonstrates the effectiveness of using advanced bioinformatics approaches to identify the biological factors that drive prostate cancer progression. Furthermore, the targets identified show promise as prognostic biomarkers in clinical settings. Thus, integrative bioinformatics methods provide both deeper understanding of disease dynamics and open the doors for future personalized interventions.
Adaptive dynamics of memory-1 strategies in the repeated donation game
Authors: LaPorte Philip , Hilbe Christian , Nowak Martin A. 
Published: March 2023

AbstractSocial interactions often take the form of a social dilemma: collectively, individuals fare best if everybody cooperates, yet each single individual is tempted to free ride. Social dilemmas can be resolved when individuals interact repeatedly. Repetition allows individuals to adopt reciprocal strategies which incentivize cooperation. The most basic model to study reciprocity is the repeated donation game, a variant of the repeated prisoner’s dilemma. Two players interact over many rounds, in which they repeatedly decide whether to cooperate or to defect. To make their decisions, they need a strategy that tells them what to do depending on the history of previous play. Memory-1 strategies depend on the previous round only. Even though memory-1 strategies are among the most elementary strategies of reciprocity, their evolutionary dynamics has been difficult to study analytically. As a result, most previous work relies on simulations. Here, we derive and analyze their adaptive dynamics. We show that the four-dimensional space of memory-1 strategies has an invariant three-dimensional subspace, generated by the memory-1 counting strategies. Counting strategies record how many players cooperated in the previous round, without considering who cooperated. We give a partial characterization of adaptive dynamics for memory-1 strategies and a full characterization for memory-1 counting strategies.Author summaryDirect reciprocity is a mechanism for evolution of cooperation based on the repeated interaction of the same players. In the most basic setting, we consider a game between two players and in each round they choose between cooperation and defection. Hence, there are four possible outcomes: (i) both cooperate; (ii) I cooperate, you defect; (ii) I defect, you cooperate; (iv) both defect. A memory-1 strategy for playing this game is characterized by four quantities which specify the probabilities to cooperate in the next round depending on the outcome of the current round. We study evolutionary dynamics in the space of all memory-1 strategies. We assume that mutant strategies are generated in close proximity to the existing strategies, and therefore we can use the framework of adaptive dynamics, which is deterministic.
Antimicrobial peptides originating from expression libraries ofAurelia auritaandMnemiopsis leidyiprevent biofilm formation of opportunistic pathogens
Authors: Ladewig Lisa , Gloy Leon , Langfeldt Daniela , Pinnow Nicole , Weiland-Bräuer Nancy , Schmitz Ruth A. 
Published: March 2023

AbstractThe demand for novel antimicrobial compounds is rapidly growing due to the rising appearance of antibiotic resistance in bacteria; accordingly, alternative approaches are urgently needed. Antimicrobial peptides (AMPs) are promising since they are a naturally occurring part of the innate immune system and display remarkable broad-spectrum activity and high selectivity against various microbes. Marine invertebrates are a primary resource of natural AMPs. Consequently, cDNA expression (EST) libraries from the Cnidarian moon jellyfishAurelia auritaand the Ctenophore comb jellyMnemiopsis leidyiwere constructed inEscherichia coli. Cell-free size-fractionated cell extracts (< 3 kDa) of the two libraries (each with 29,952 clones) were consecutively screened for peptides preventing the biofilm formation of opportunistic pathogens using the crystal violet assay. The 3 kDa fraction of ten individual clones demonstrated promising biofilm-preventing activities againstKlebsiella oxytocaandStaphylococcus epidermidis. Sequencing the respective activity-conferring inserts allowed the identification of small ORFs encoding peptides (10 – 22 aa), which were subsequently chemically synthesized to validate their inhibitory potential. Biofilm-preventing effects againstK. oxytoca, Pseudomonas aeruginosa, S. epidermidis, andS. aureuswere verified for five synthetic peptides in a concentration-dependent manner, with peptide BiP_Aa_5 showing the strongest effects. The impact of BiP_Aa_2, BiP_Aa_5, and BiP_Aa_6 on dynamic biofilm formation ofK. oxytocawas further validated in microfluidic flow cells, demonstrating a significant reduction in biofilm thickness and volume by BiP_Aa_2 and BiP_Aa_5. Overall, the structural characteristics of the marine invertebrate-derived AMPs, their physicochemical properties, and promising anti-biofilm effects highlight them as attractive candidates for discovering new antimicrobials.
A network medicine approach to elucidate mechanisms underlying menopause-induced knee osteoarthritis
Authors: Gilmer Gabrielle , Iijima Hirotaka , Jackson Natalie , Hettinger Zachary , Bean Allison C. , Bergmann Juliana , Evans Christopher , Thurston Rebecca C. , Ambrosio Fabrisia 
Published: March 2023

AbstractPost-menopausal women present with the highest incidence and morbidity of knee osteoarthritis (KOA), but no disease-modifying therapies are available. This treatment gap may be driven by the absence of menopause in preclinical studies, as rodents do not naturally maintain a menopausal phenotype. Here, we employed a chemically-induced menopause model to map the trajectory of KOA at the tissue and proteome levels and test therapeuticsin silico. Middle-aged female mice were randomized to sesame oil (non-menopause) or 4-vinycyclohexene diepoxide (menopause) injections. Following comprehensive validation of our model, knees were collected across perimenopause and menopause for histology, and cartilage samples were micro-dissected for mass spectrometry proteomics. Menopause mice displayed aggravated cartilage degeneration and synovitis relative to non-menopause mice. An unbiased pathway analysis revealed progesterone as a predominant driver of pathological signaling cascades within the cartilage proteome. Network medicine-based analyses suggested that menopause induction amplifies chondrocyte senescence, actin cytoskeleton-based stress, and extracellular matrix disassembly. We then usedin silicodrug testing to evaluate how restoration of sex hormones impacted the cartilage network. The greatest restoration was observed with combined estradiol/progesterone treatment (i.e., hormone therapy), althoughin silicotreatment with a senolytic drug also partially recovered the cartilage proteome. Taken together, our findings using a translatable female aging model demonstrate that menopausal aging induces progressive cartilage degeneration and amplifies age-related synovitis. These changes may be driven by a previously unappreciated role of progesterone loss and menopause-induced cellular senescence. Lastly,in silicotreatment suggests an estradiol/progesterone cocktail or senolytics may attenuate menopause-induced cartilage pathology.One Sentence SummaryMenopause induces cartilage degradation, senescence, and extracellular matrix disassembly, while hormone therapy restores the cartilage proteome.
Seasonal gene-expression signatures of delayed fertilization in Fagaceae
Authors: Satake Akiko , Ohta Kayoko , Takeda-Kamiya Noriko , Toyooka Kiminori , Kusumi Junko 
Published: March 2023

AbstractIn the family Fagaceae, fertilization is delayed by several weeks to one year after pollination, leading to one- or two-year fruiting species depending on whether fruiting occurs in the same or the next year after flowering. To investigate physiological responses underlying the regulation of delayed fertilization, we monitored seasonal changes in genome-wide gene expression in tissues including leaves and buds over two years under natural conditions in one- (Quercus glauca) and two-year fruiting species (Lithocarpus edulis). Genes associated with the responses to cold stress, photosynthesis, and cell proliferation, which are essential for survival and growth, showed highly conserved seasonal expression profiles regardless of species. However, seasonal expression profiles diverged between the one- and two-year fruiting species in genes associated with pollination, an important process contributing to the origin and maintenance of the reproductive barrier between plant species. By comparing seasonal progression of ovule development and gene expression in pistillate flowers, we revealed that ovules started developing after winter in the two-year fruiting species, which could be linked to the activation of genes involved in fertilization and female gametophyte development after winter. These findings suggest that the two-year fruiting species may have evolved a requirement of winter cold to prevent fertilization before winter and facilitate fertilization and embryo development in the following spring when temperature rises. This study offers new possibilities to explore the evolution of reproductive strategies in Fagaceae.
Differentiating shame- and guilt-proneness with heart rate variability in Chinese young adults
Authors: Ip Isaac N. , Ching Fiona N. Y. , Chiu Hey Tou , Keung Ariel H. Y. , Wong Savio W. H. 
Published: March 2023

AbstractA high proneness to experience shame and guilt has been associated with psychopathology. Despite their similarity, shame- and guilt-proneness have different psychological and neurobiological correlates. The present study aims to compare the physiological correlates between shame- and guilt-proneness. Resting heart rate variability (HRV), a peripheral biomarker of emotion dysregulation and psychopathology, was measured in a sample of 60 Chinese young adults with two sessions of electrocardiogram recording. Proneness to shame and guilt were measured by the Test of Self-Conscious Affect 3. Hierarchical linear modeling indicated that guilt-proneness was positively associated with HRV while shame-proneness was not. Our findings implied that shame- and guilt-proneness have different relations with HRV. The distinct physiological relations are discussed with respect to the adaptive/maladaptive nature of shame- and guilt-proneness.
The claustrum drives large-scale interactions of cortical circuits relevant to long-term memory
Authors: Mutel S. , Renfer JR. , Rodriguez I. , Carleton A. , Salazar RF. 
Published: March 2023

AbstractThe consolidation and recall of episodic memories rely on distributed cortical activity. The claustrum, a subcortical structure reciprocally connected to most of the cortex, may facilitate inter-areal communication necessary for these processes. We report here that the functional inhibition of claustral projection neurons affects directional interactions and the coordination of oscillatory neuronal patterns in the fronto-parietal network. Moreover, the inhibition of these neurons has a detrimental effect on concurrent oscillatory events relevant to the consolidation of contextual fear memory. Last, we demonstrate that biasing the directional flow of information between the latter two cortical areas enhances the retrieval of a remote contextual memory. We propose that the claustrum orchestrates inter-areal cortical interactions relevant to contextual memory processes by affecting the latency of neuronal responses.One-Sentence SummaryThe claustrum coordinates inter-areal cortical activity.
Response of adult carrion beetlesNecrodes littoralis(L.) (Staphylinidae: Silphinae) to selected cadaveric volatile organic compounds: laboratory and field tests
Authors: Mądra-Bielewicz Anna , Gruszka Joanna , Matuszewski Szymon 
Published: March 2023

AbstractCarrion insects need to quickly and accurately locate a suitable carcass to maximize their reproductive success. They are attracted by cadaveric volatile organic compounds (VOCs). However, very little is known about VOCs that attract insects at later stages of carrion decomposition. Here, we tested the response ofNecrodes littoralis(Linnaeus, 1758). (Staphylinidae: Silphinae), a Palearctic beetle that colonizes large carrion late in decomposition, to selected VOCs. First, in the laboratory choice tests we demonstrated that the beetles reveal no preference for meat with larval blow flies over meat alone. This finding indicates that both, the fly larvae and the feeding matrix they form on meat are not the source of specific attractants for the adult beetles ofNecrodesLeach, 1815. Therefore, we focused on VOCs that are related to carrion putrefaction. We tested the response of the beetles to benzyl butyrate, butan-1-ol, butyric acid, cadaverine, dimethyl disulfide (DMDS), dimethyl trisulfide, indole, phenol, putrescine and skatole in laboratory choice assays and field trapping tests. None of the compounds elicited the positive and significant response of the beetles under laboratory or field conditions, indicating that these VOCs are probably not the attractants ofN. littoralis. Moreover, in the field tests we found a significant attraction ofLucilia sericata(Meigen, 1826) (Diptera: Calliphoridae) to traps with DMDS. DMDS revealed also a positive (however insignificant) response ofSaprinusspp. (Coleoptera: Histeridae) andSarcophagaspp. (Diptera: Sarcophagidae).Sarcophagaflies were also attracted to traps with butyric acid. These findings expand the knowledge on chemoecology of carrion insects, highlighting the need to further search for VOCs that attract late-colonizers of carrion.
The proton-activated receptor TDAG8 is upregulated in oligodendrocytes during maturation and under acidic conditions
Authors: Opiełka Mikołaj , Caratis Fionä , Hausmann Martin , Velasco-Estevez Maria , de Vallière Cheryl , Seuwen Klaus , Rogler Gerhard , Karaszewski Bartosz , Rutkowska Aleksandra 
Published: March 2023

ABSTRACTAcidosis is one of the hallmarks of demyelinating central nervous system (CNS) lesions in multiple sclerosis (MS). Response to acidic pH is primarily mediated by a family of G protein-coupled proton-sensing receptors: OGR1, GPR4, and TDAG8. These receptors are inactive at alkaline pH, while at acidic pH they are maximally activated. Genome-wide association studies identified a locus within the TDAG8 gene to be associated with several autoimmune diseases including MS. Notably, we here found that TDAG8 expression is upregulated in MS plaques which prompted us to explore the expression and function of TDAG8 in the CNS in human MO3.13 oligodendrocytesin vitroandin vivoin the lipopolysaccharide-induced neuroinflammation model. We found that TDAG8 is upregulated in maturing oligodendrocytes and temporarily under acidic conditions. Acidic pH also induces oligodendrocyte branching, inhibits chemotaxis and affects the expression of oligodendrocyte maturation markers, PDGFRα and MBPin vitro. Even though myelination was not affected in the adult TDAG8-deficient mice, the expression of human and murine TDAG8 was strongly regulated upon inflammationin vivoin the brain andin vitroin lipopolysaccharide and pro-inflammatory cytokine-treated oligodendrocytes. Together these findings point toward a potential role of TDAG8 in oligodendrocyte biology, neuroinflammation and pathophysiology of MS and provide new directions for further scientific enquiry.
Investigating macroecological patterns in coarse-grained microbial communities using the stochastic logistic model of growth
Authors: Shoemaker William R. , Grilli Jacopo 
Published: March 2023

AbstractThe structure and diversity of microbial communities is intrinsically hierarchical due to the shared evolutionary history of their constituents. This history is typically captured through taxonomic assignment and phylogenetic reconstruction, sources of information that are frequently used to group microbes into higher levels of organization in experimental and natural communities. Connecting community diversity to the joint ecological dynamics of the abundances of these groups is a central problem of community ecology. However, how microbial diversity depends on the scale of observation at which groups are defined has never been systematically examined. Here, we used a macroecological approach to quantitatively characterize the structure and diversity of microbial communities among disparate environments across taxonomic and phylogenetic scales. We found that measures of biodiversity at a given scale can be consistently predicted using a minimal model of ecology, the Stochastic Logistic Model of growth (SLM). This result suggests that the SLM is a more appropriate null-model for microbial biodiversity than alternatives such as the Unified Neutral Theory of Biodiversity. Extending these within-scale results, we examined the relationship between measures of biodiversity calculated at different scales (e.g., genus vs. family), an empirical pattern predicted by the Diversity Begets Diversity (DBD) hypothesis. We found that the relationship between richness estimates at different scales can be quantitatively predicted assuming independence among community members.Contrastingly, only by including correlations between the abundances of community members (e.g., as the consequence of interactions) can we predict the relationship between estimates of diversity at different scales. The results of this study characterize novel microbial patterns across scales of organization and establish a sharp demarcation between recently proposed macroecological patterns that are not and are affected by ecological interactions.
Feedback control of organ size precision is mediated by BMP2-regulated apoptosis in theDrosophilaeye
Authors: Navarro T. , Iannini A. , Neto M. , Campoy-Lopez A. , Muñoz-Garcia J. , Pereira P.S. , Ares S. , Casares F. 
Published: March 2023

SUMMARYBiological processes are intrinsically noisy and yet, the result of development –like the species-specific size and shape of organs– is usually remarkably precise. This precision suggests the existence of mechanisms of feedback control that ensure that deviations from a target size are minimized. Still, we have very limited understanding of how these mechanisms operate. Here, we investigate the problem of organ size precision using theDrosophilaeye. The size of the adult eye depends on the rates at which eye progenitor cells grow and differentiate. We first find that the progenitor net growth rate results from the balance between their proliferation and apoptosis, with this latter contributing to determining both final eye size and its variability. In turn, apoptosis of progenitor cells is hampered by Dpp, a BMP2/4 signaling molecule transiently produced by early differentiating retinal cells. Our genetic and computational experiments show how the status of retinal differentiation is communicated to progenitors through the differentiation-dependent production of Dpp which, by adjusting the rate of apoptosis, exerts a feedback control over the net growth of progenitors to reduce final eye size variability.
Done in 65 ms: Express visuomotor responses in upper limb muscles in Rhesus Macaques
Authors: Cecala Aaron L. , Kozak Rebecca A. , Pruszynski J. Andrew , Corneil Brian D. 
Published: March 2023

AbstractHow rapidly can the brain transform vision into action? Work in humans has established that the transformation for visually-guided reaching can be remarkably rapid, with the first phase of upper limb muscle recruitment, theexpress visuomotor response, beginning within less than 100 ms of visual target presentation. Such short-latency responses limit the opportunities for extensive cortical processing, leading to the hypothesis that they are generated via the subcortical tectoreticulospinal pathway. Here, we examine if non-human primates (NHPs) exhibit express visuomotor responses. Two male macaques made visually-guided reaches in a behavioral paradigm known to elicit express visuomotor responses in humans, while we acquired intramuscular recordings from the deltoid muscle. Across several variants of this paradigm, express visuomotor responses began within 65 ms (range 48–91 ms) of target presentation. Although the timing of the express visuomotor response did not co-vary with reaction time, larger express visuomotor responses tended to precede shorter latency reaches. Finally, the magnitude of the express visuomotor response was muted on trials where NHPs withheld a reach to one stimulus in order to move to a stimulus appearing 34 ms later in the opposite direction. Overall, the response properties and contextual control of express visuomotor responses in NHPs resemble those in humans. Our results establish a new benchmark for visuomotor transformations underlying visually-guided reaches, setting the stage for experiments that can directly compare the role of cortical and subcortical areas in reaching when time is of the essence.Significance statementExpress visuomotor responses in upper limb muscles are brief periods of recruitment preceding visually-guided reaches. Such responses begin ∼90 ms after visual target presentation in humans, and potentially arise from signaling along the tecto-reticulo-spinal pathway. Here, we show that express visuomotor responses in macaques upper limb muscles resemble those in humans, excepting that they evolve ∼65 ms after target onset, consistent with shorter responses latencies in macaques versus humans. Our results clock the completion of the visuomotor transformation for rapid reaching, and set the stage for experiments to directly test the underlying substrates.