Current Opinion in Physiology最新文献

This review examines how the experience of being a parent affects hippocampal plasticity throughout the lifespan, in both male and female rodents. The hippocampus is a unique region capable of producing new neurons throughout adulthood in numerous mammals. When transitioning into parenthood, there is a significant impact on hippocampal neurogenesis and other forms of plasticity in female and male rodents. However, research on the regulation and functional implications (such as cognitive abilities and anxiety regulation) is limited and mixed. Studies have been conducted across sexes, ages, and species. The effects of motherhood on the hippocampus are well-documented in monoparental laboratory rats, while research on fatherhood is more limited. Biparental species provide an opportunity to study this experience in both sexes. We review the current knowledge and propose future research questions to increase our understanding of the short- and long-term consequences of parenthood in both sexes.

Endothelial caveolae are essential for a wide range of physiological processes and have emerged as key players in vascular biology. Our understanding of caveolar biology in endothelial cells has expanded dramatically since their discovery, revealing critical roles in mechanosensation, signal transduction, eNOS regulation, lymphatic transport, and metabolic disease progression. Furthermore, caveolae are involved in the organization of membrane domains, regulation of membrane fluidity, and endocytosis which contribute to endothelial function and integrity. Additionally, recent advances highlight the impact of caveolae-mediated signaling pathways on vascular homeostasis and pathology. Together, the diverse roles of caveolae discussed here represent a breadth of cellular functions presenting caveolae as a defining feature of endothelial form and function. In light of these new insights, targeting caveolae may hold potential for the development of novel therapeutic strategies to treat a range of vascular diseases.

The complex and hierarchical vascular network of arteries, veins, and capillaries features considerable endothelial heterogeneity, yet the regulatory pathways directing arteriovenous specification, differentiation, and identity are still not fully understood. Recent advances in analysis of endothelial-specific gene-regulatory elements, single-cell RNA sequencing, and cell lineage tracing have both emphasized the importance of transcriptional regulation in this process and shed considerable light on the mechanism and regulation of specification within the endothelium. In this review, we discuss recent advances in our understanding of how endothelial cells acquire arterial and venous identity and the role different transcription factors play in this process.

In the human heart, adrenaline activates the β₂-adrenoceptor (β₂AR) to cause powerful increases in contractile force and acceleration of contraction. This is explained by tight coupling of the β₂AR to the Gsα-protein–cyclic AMP–PKA signaling pathway with phosphorylation of proteins, including the L-type Ca²⁺ channel, ryanodine receptor, phospholamban, and sarcomeric proteins troponin I and C-protein. Experimentally, it has been shown that activation of β₂ARs is arrhythmogenic in the human failing heart. From cell- and animal model-based experiments, there is increased awareness of the broader signaling repertoire of the β₂AR. The β₂AR has the ability to couple simultaneously to Gsα- and Giα-proteins and activate β-arrestin signaling pathways. In addition to the orthosteric binding site, modes of conformation stabilization exist through the allosteric binding site and with pepducins. Beneficial effects, including cardioprotection, have been observed, waiting for translation to the human diseased heart and fuelling optimism for advancement of therapeutics for heart disease.

Adrenergic receptors (ARs) and catalytic receptors (CRs), two major classes of cell-surface receptors, play essential roles in a wide range of physiological and pathological processes. Studies over the years have revealed that ARs and CRs, along with their associated signaling transduction pathways, are not isolated in the cells. Instead, there exists functional crosstalk, involving either activation or inhibition, among specific members of ARs and CRs. Although the dynamics and mechanism of individual receptors within each family have been extensively studied, we have just begun to understand the spatiotemporal dynamics, functional consequences, and underlying mechanisms of the crosstalk between ARs and CRs. In this review, we will provide a concise overview of recent progress in identifying and elucidating the crosstalk, either unidirectional or bidirectional, between ARs and CRs.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. PCOS is diagnosed by the presence of two of the following three characteristics: hyperandrogenemia and/or hyperandrogenism, oligo-/amenorrhea, and polycystic ovarian morphology. PCOS is associated with reproductive and nonreproductive complications, including obesity, insulin resistance and diabetes, dyslipidemia, and increased blood pressure. There is an urgent need for biomarkers that address both the reproductive and nonreproductive aspects of this complex syndrome. This review focuses on biomarkers, or potential ones, associated with the reproductive and nonreproductive aspects of PCOS, including anthropometric and clinical biomarkers, insulin and the insulin-like growth factor 1 system, lipids, anti-Müllerian hormone and gonadotropins, steroids, inflammatory and renal injury biomarkers, oxidative stress, and noncoding RNAs. We expect that this review will bring some light on the recent updates in the field and encourage researchers to join the exciting and promising field of PCOS biomarkers.

It is well-established that mechanosensitive (MS) ion channels differentially respond to membrane tension, bilayer thinning, and curvature. The thesis that the lipid bilayer acted as the terminal transducer of force directly to the channel became known as the force-from-lipids gating paradigm (also less frequently referred to as the ‘bilayer model’). This principle allows cells to detect and respond to mechanical forces in their environment, which is important for various physiological processes, including blood pressure regulation, touch sensation, and many others. Our understanding of how mechanical force drives MS channel gating has been greatly enhanced by new insights into the molecular interactions between the lipid bilayer and channel proteins. In this short review, we revisit the role of the force-from-lipids principle within the current understanding of MS channel gating and focus on its molecular underpinnings.

High endothelial venules (HEVs), high-walled cuboidal blood vessels, through their expression of adhesion molecules and chemokines, allow the entrance of lymphoid cells into primary, secondary, and tertiary lymphoid structures (TLSs) (aka tertiary lymphoid organs). HEV heterogeneity exists between various lymphoid organs in their expression of peripheral node addressin and mucosal vascular addressin adhesion molecule 1. Transcriptomic analyses reveal extensive heterogeneity, plasticity, and regulation of HEV gene expression in ontogeny, acute inflammation, and chronic inflammation within and between lymphoid organs. Rules regulating HEV development are flexible in inflammation. HEVs in tumor TLSs are diagnostic of favorable clinical outcome and response to immunotherapy, including immune checkpoint blockade. Immunotherapy induces HEVs and provides an entrance for naive, central memory, and effector cells and a niche for stem-like precursor cells. Understanding HEV regulation will permit their exploitation as routes for drug delivery to autoimmune lesions, rejecting organs, and tumors.