搜索结果：Biology of sex differences

Lateralization is a fundamental feature of the human brain, where sex differences have been observed. Conventional studies in neuroscience on sex-specific lateralization are typically conducted on univariate statistical comparisons between male and female groups. However, these analyses often lack effective validation of group specificity. Here, we formulate modeling sex differences in lateralization of functional networks as a dual-classification problem, consisting of first-order classification for left vs. right functional networks and second-order classification for male vs. female models. To capture sex-specific patterns, we develop the Group-Specific Discriminant Analysis (GSDA) for first-order classification. The evaluation on two public neuroimaging datasets demonstrates the efficacy of GSDA in learning sex-specific models from functional networks, achieving a significant improvement in group specificity over baseline methods. The major sex differences are in the strength of lateralization and the interactions within and between lobes. The GSDA-based method is generic in nature and can be adapted to other group-specific analyses such as handedness-specific or disease-specif

Although numerous studies report significant sex differences in functional connectivity, these differences do not sufficient to reveal specific functional disparities among brain regions or the topological differences in brain networks. Meanwhile, individual differences could potentially bias the understanding of these sex differences. To address these challenges, we propose a consensus rank-based method to quantify sex differences in four node centrality ranking within the functional brain network. This method aggregates individuals' nodal centrality rankings into a consensus or "average" ranking, minimizing the impact of outliers and enhancing the robustness of the findings. By analyzing resting-state functional MRI data from 1,948 healthy young adults (aged 18-27 years, 1,163 females), we find significant sex differences in the topology of functional brain network, primarily attributed to biological sex rather than individual differences. Particularly, sex accounts for approximately 10% of the differences in nodal centrality consensus rankings. Using a rank difference index (RDI), we identify eight critical brain regions with the greatest rank differences, including the insula,

Over the last three decades, the human brain, and its role in determining behavior have been receiving a growing amount of attention in academia as well as in society more generally. Neuroscientific explanations of human behavior or other phenomena are often especially appealing to lay people. Therefore, neuroscientific explanations that can affect individuals, groups, or social relations in general should be formulated in a careful and responsible way. One field in which especially feminist scholars request more caution is the neuroscientific examination of sex or gender differences. Feminist scholars have described various ways in which sexist bias might be present in neuroscientific research on sex or gender differences. In this context, they coined the term "neurosexism" to describe the entanglement between neuroscientific work and sexist ideology, and "neurofeminism" as a response to that. Here, we aim to give an overview over the contemporary neurofeminist literature. In the first part, common levels of analysis in the neurofeminist literature are presented and the research level is explored in more detail. In the second part, some common developments in more recent neurofemi

Sex chromosomes have independently evolved in species with separate sexes in most lineages across the tree of life. However, the well-accepted canonical model of sex chromosome evolution is not universally supported. There is no single trajectory for sex chromosome formation and evolution across the tree of life, suggesting the underlying mechanisms and evolutionary forces are diverse and lineage specific. We review the diversity of sex chromosome systems, describe the canonical model of sex chromosome evolution, and summarize studies challenging various aspects of this model. They include evidence that many lineages experience frequent sex chromosome turnovers or maintain homomorphic sex chromosomes over long periods of time, suggesting sex chromosome degeneration is not inevitable. Sometimes the sex-limited Y/W chromosomes expand before they contract in size. Both transposable elements and gene gains could contribute to this size expansion, which further challenges gene loss being the hallmark of sex chromosome degeneration. Finally, empirical support for the role of sexually antagonistic selection as a driver of recombination suppression on sex chromosomes remains elusive. We su

Sex-based differences in cardiovascular disease are well documented, yet the precise nature and extent of these discrepancies in cardiac anatomy remain incompletely understood. Traditional scaling models often fail to capture the interplay of age, blood pressure, and body size, prompting a more nuanced investigation. Here, we employ statistical shape modeling in a healthy subset (n=456) of the UK Biobank to explore sex-specific variations in biventricular anatomy. We reconstruct 3D meshes and perform multivariate analyses of shape coefficients, controlling for age, blood pressure, and various body size metrics. Our findings reveal that sex alone explains at least 25 percent of morphological variability, with strong discrimination between men and women (AUC=0.96-0.71) persisting even after correction for confounders. Notably, the most discriminative modes highlight pronounced differences in cardiac chamber volumes, the anterior-posterior width of the right ventricle, and the relative positioning of the cardiac chambers. These results underscore that sex has a fundamental influence on cardiac morphology, which may have important clinical implications for differing cardiac structural

The new dynamical game theoretic model of sex ratio evolution emphasizes the role of males as passive carriers of sex ratio genes. This shows inconsistency between population genetic models of sex ratio evolution and classical strategic models. In this work a novel technique of change of coordinates will be applied to the new model. This will reveal new aspects of the modelled phenomenon which cannot be shown or proven in the original formulation. The underlying goal is to describe the dynamics of selection of particular genes in the entire population, instead of in the same sex subpopulation, as in the previous paper and earlier population genetics approaches. This allows for analytical derivation of the unbiased strategic model from the model with rigorous non-simplified genetics. In effect, an alternative system of replicator equations is derived. It contains two subsystems: the first describes changes in gene frequencies (this is an alternative unbiased formalization of the Fisher-Dusing argument), whereas the second describes changes in the sex ratios in subpopulations of carriers of genes for each strategy. An intriguing analytical result of this work is that fitness of a gen

The state of the art on the issue of sex differences in research efficiency agrees in recognizing higher performances for males, however there are divergences in explaining the possible causes. One of the causes advanced is that there are sex differences in the availability of aptitude at the "high end". By comparing sex differences in concentration and performance of Italian academic star scientists to the case in the population complement, this work aims to verify if star, or "high-end", scientists play a preponderant role in determining higher performance among males. The study reveals the existence of a greater relative concentration of males among star scientists, as well as a performance gap between male and female star scientists that is greater than for the rest of the population. In the latter subpopulation the performance gap between the two sexs is seen as truly marginal.

In vitro models play a crucial role in advancing our understanding of biological processes, disease mechanisms, and developing screening platforms for drug discovery. Kidneys play an instrumental role in transport and elimination of drugs and toxins. However, despite the well-established patient-to-patient differences in kidney function and disease manifestation, progression and prognostic, few studies take this variability into consideration. In particular, the discrepancies between female and male biology warrants a better representation within kidney in vitro models. The omission of sex as a biological variable poses the significant risk of overlooking sex-specific mechanisms in health and disease and potential differences in drug efficacy and toxicity between males and females. This review aims to highlight the importance of incorporating sex dimorphism in kidney in vitro models by examining the sexual characteristics in the context of the current state-of-the-art. Furthermore, this review underscores opportunities for improving kidney models by incorporating sex-specific traits. Ultimately, this roadmap to incorporating sex-dimorphism in kidney in vitro models will facilitate

This technical monograph provides a comprehensive overview of the field of quantum biology. It approaches quantum biology from a physical perspective with core quantum mechanical concepts presented foremost to provide a theoretical foundation for the field. An extensive body of research is covered to clarify the significance of quantum biology as a scientific field, outlining the field's long-standing importance in the historical development of quantum theory. This lays the essential groundwork to enable further advances in nanomedicine and biotechnology. Written for academics, biological science researchers, physicists, biochemists, medical technologists, and students of quantum mechanics, this text brings clarity to fundamental advances being made in the emerging science of quantum biology.

Understanding the biological mechanisms of disease is crucial for medicine, and in particular, for drug discovery. AI-powered analysis of genome-scale biological data holds great potential in this regard. The increasing availability of single-cell RNA sequencing data has enabled the development of large foundation models for disease biology. However, existing foundation models only modestly improve over task-specific models in downstream applications. Here, we explored two avenues for improving single-cell foundation models. First, we scaled the pre-training data to a diverse collection of 116 million cells, which is larger than those used by previous models. Second, we leveraged the availability of large-scale biological annotations as a form of supervision during pre-training. We trained the \model family of models comprising six transformer-based state-of-the-art single-cell foundation models with 70 million, 160 million, and 400 million parameters. We vetted our models on several downstream evaluation tasks, including identifying the underlying disease state of held-out donors not seen during training, distinguishing between diseased and healthy cells for disease conditions and

Objectives: To examine sex differences in the associations between vascular risk factors and 6-year changes in the volume of white matter hyperintensities (WMH), and between changes in WMH volumes and changes in cognitive performance, in a cohort of non-demented older adults. Methods: WMH volumes at 3 time-points (baseline, and 2- and 6-year follow-up) were automatically quantified in participants of Sydney Memory and Ageing Study (N = 605; age range = 70-92 years; 54.78% female). Linear mixed models were applied to examine the effects of vascular risk factors and cognitive consequences of the progression of WMH, as well as the sex moderation effects in the associations. Results: Total (TWMH), periventricular (PVWMH), and deep (DWMH) WMH volumes increased by 9.47%, 7.70%, and 11.78% per year, respectively. No sex differences were found in WMH progression rates. After Bonferroni correction, increases in PVWMH volumes over time were associated with decline in global cognition, especially in visuospatial and memory domains. Men with more increases in PVWMH volumes over time had greater declines in visuospatial abilities. Moreover, higher average TWMH volumes across time-points were as

Executive function emerges late in development and displays different developmental trends in males and females. Sex differences in executive function in youth have been linked to vulnerability to psychopathology as well as to behaviors that impinge on health. Yet, the neurobiological basis of these differences is not well understood. Here we test the hypothesis that sex differences in executive function in youth stem from sex differences in the controllability of structural brain networks as they rewire over development. Combining methods from network neuroscience and network control theory, we characterize the network control properties of structural brain networks estimated from diffusion imaging data acquired in males and females in a sample of 882 youth aged 8-22 years. We summarize the control properties of these networks by estimating average and modal controllability, two statistics that probe the ease with which brain areas can drive the network towards easy- versus difficult-to-reach states. We find that females have higher modal controllability in frontal, parietal, and subcortical regions while males have higher average controllability in frontal and subcortical regions

Optimal sex allocation theory is one of the most intricately developed areas of evolutionary ecology. Under a range of conditions, particularly under population sub-division, selection favours sex being allocated to offspring non-randomly, generating non-binomial variances of offspring group sex ratios. Detecting non-binomial sex allocation is complicated by stochastic developmental mortality, as offspring sex can often only be identified on maturity with the sex of non-maturing offspring remaining unknown. We show that current approaches for detecting non-binomiality have limited ability to detect non-binomial sex allocation when developmental mortality has occurred. We present a new procedure using an explicit model of sex allocation and mortality and develop a Bayesian model selection approach (available as an R package). We use the double and multiplicative binomial distributions to model over- and under-dispersed sex allocation and show how to calculate Bayes factors for comparing these alternative models to the null hypothesis of binomial sex allocation. The ability to detect non-binomial sex allocation is greatly increased, particularly in cases where mortality is common. Th

Deep learning has been reported to achieve high performances in the detection of skin cancer, yet many challenges regarding the reproducibility of results and biases remain. This study is a replication (different data, same analysis) of a previous study on Alzheimer's disease detection, which studied the robustness of logistic regression (LR) and convolutional neural networks (CNN) across patient sexes. We explore sex bias in skin cancer detection, using the PAD-UFES-20 dataset with LR trained on handcrafted features reflecting dermatological guidelines (ABCDE and the 7-point checklist), and a pre-trained ResNet-50 model. We evaluate these models in alignment with the replicated study: across multiple training datasets with varied sex composition to determine their robustness. Our results show that both the LR and the CNN were robust to the sex distribution, but the results also revealed that the CNN had a significantly higher accuracy (ACC) and area under the receiver operating characteristics (AUROC) for male patients compared to female patients. The data and relevant scripts to reproduce our results are publicly available (https://github.com/ nikodice4/Skin-cancer-detection-sex-

A tumor often consists of multiple cell subpopulations (clones). Current chemo-treatments often target one clone of a tumor. Although the drug kills that clone, other clones overtake it and the tumor reoccurs. Genome sequencing and computational analysis allows to computational dissection of clones from tumors, while singe-cell genome sequencing including RNA-Seq allows to profiling of these clones. This opens a new window for treating a tumor as a system in which clones are evolving. Future cancer systems biology studies should consider a tumor as an evolving system with multiple clones. Therefore, topics discussed in Part 2 of this review include evolutionary dynamics of clonal networks, early-warning signals for formation of fast-growing clones, dissecting tumor heterogeneity, and modeling of clone-clone-stroma interactions for drug resistance. The ultimate goal of the future systems biology analysis is to obtain a whole-system understanding of a tumor and therefore provides a more efficient and personalized management strategies for cancer patients.

Dmrt1 is pivotal in testis formation and function by interacting with genes crucial for Sertoli cell differentiation. Dmrt1, or Sox9, forms a conserved antagonistic interaction with Foxl2 across mammals. Across 128 vertebrate species, Dmrt1 exhibits sexually dimorphic expression, implicating its role in master regulation of sex determination and gonadal sex differentiation. Dmrt1 emerges as a master/upstream sex-determining gene in one fish, frog, chicken and turtle. Recent studies suggest epigenetic regulation of Dmrt1 in its promoter methylation, and transposable element insertion introducing epigenetic modification to cis-regulatory elements of Dmrt1, alongside non-coding RNA involvement, in a wide spectrum of sex-determining mechanisms ranging from genetic factors, to interactions between genetic factors with the environment, to solely environmental factors. Additionally, alternative splicing of Dmrt1 was found in all major vertebrate groups except amphibians. Dmrt1 has evolved many lineage-specific isoforms (ranging from 2 to 10), and various isoforms showed sex, tissue or development-specific expression, which is in contrast to the highly conserved sex-specific splicing of it

This article frames the relation between biology and physics by characterizing the former as a subdiscipline rather than a special case of the latter. To do this, we posit biological physics as the science of living matter in contrast to classic biophysics, the study of organismal properties by physical techniques. At the scale of the individual cell, living matter is nonunitary, i.e., not composed of aggregated subunits, and has features (e.g., intracellular organizational arrangements and biomolecular condensates) that are unlike any materials of the nonliving world. In transiently or constitutively multicellular forms (social microorganisms, animals, plants), living matter sustains physical processes that are generic (shared with nonliving matter, e.g., subunit communication by molecular diffusion in cellular slime molds), biogeneric (analogous to nonliving matter but realized through cellular activities, e.g., subunit demixing in animal embryos) or nongeneric (pertaining to sui generis materials, e.g., budding of active solids in plants). This "forms of matter" perspective is philosophically situated in the dialectical materialism of Engels and Hessen and the multilevel physica

Musculoskeletal (MSK) models offer a non-invasive way to understand biomechanical loads on joints and tendons, which are difficult to measure directly. Variations in muscle strength, especially relative differences between muscles, significantly impact model outcomes. Typically, scaled generic MSK models use maximum isometric forces that are not adjusted for different demographics, raising concerns about their accuracy. This review provides an overview on experimentally derived strength parameters, including physiological cross-sectional area (PCSA), muscle mass (Mm), and relative muscle mass (%Mm), which is the relative distribution of muscle mass across the leg. We analysed differences by age and sex, and compared open-source lower limb MSK model parameters with experimental data from 57 studies. Our dataset, with records dating back to 1884, shows that uniformly increasing all maximum isometric forces in MSK models does not capture key muscle ratio differences due to age and sex. Males have a higher proportion of muscle mass in the rectus femoris and semimembranosus muscles, while females have a greater relative muscle mass in the pelvic (gluteus maximus and medius) and ankle mu

In a recent paper, Wilmes et al. demonstrated a qualitative integration of omics data streams to gain a mechanistic understanding of cyclosporine A toxicity. One of their major conclusions was that cyclosporine A strongly activates the nuclear factor (erythroid-derived 2)-like 2 pathway (Nrf2) in renal proximal tubular epithelial cells exposed in vitro. We pursue here the analysis of those data with a quantitative integration of omics data with a differential equation model of the Nrf2 pathway. That was done in two steps: (i) Modeling the in vitro pharmacokinetics of cyclosporine A (exchange between cells, culture medium and vial walls) with a minimal distribution model. (ii) Modeling the time course of omics markers in response to cyclosporine A exposure at the cell level with a coupled PK-systems biology model. Posterior statistical distributions of the parameter values were obtained by Markov chain Monte Carlo sampling. Data were well simulated, and the known in vitro toxic effect EC50 was well matched by model predictions. The integration of in vitro pharmacokinetics and systems biology modeling gives us a quantitative insight into mechanisms of cyclosporine A oxidative-stress