Current research in physiology最新文献

Background

Abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) has been linked to airway smooth muscle abnormalities including bronchial hyperresponsiveness. However, a role for CFTR in other types of smooth muscle, including myometrium, remains largely unexplored. As CF life expectancy and the number of pregnancies increases, there is a need for an understanding of the potential role of CFTR in myometrial function.

Methods

We investigated the role of CFTR in human and mouse myometrium. We used immunofluorescence to identify CFTR expression, and carried out contractility studies on spontaneously contracting term pregnant and non-pregnant mouse myometrium and term pregnant human myometrial biopsies from caesarean sections.

Results

CFTR was found to be expressed in term pregnant mouse myometrium. Inhibition of CFTR, with the selective inhibitor CFTR_inh-172, significantly reduced contractility in pregnant mouse and human myometrium in a concentration-dependent manner (44.89 ± 11.02 term pregnant mouse, 9.23 ± 4.75 term-pregnant human; maximal effect at 60 μM expressed as a percentage of the pre-treatment control period). However, there was no effect of CFTR_inh-172 in non-pregnant myometrium.

Conclusion

These results demonstrate decreased myometrial function when CFTR is inhibited, which may have implications on pregnancy and labour outcome and therapeutic decisions for labour in CF patients.

Cardiac glycogen-autophagy (‘glycophagy’) is disturbed in cardiometabolic pathologies. The physiological role of cardiac glycophagy is unclear. Exercise induces transient cardiac glycogen accumulation. Thus, this study experimentally examined glycophagy involvement during recovery from an exhaustive exercise protocol. Peak myocardial glycogen accumulation in mice was evident at 2 h post-exercise, preceded by transient activation of glycogen synthase. At 4 and 16 h post-exercise, glycogen degradation was associated with decreased STBD1 (glycophagy tagging protein) and increased GABARAPL1 (Atg8 protein), suggesting that glycophagy activity was increased. These findings provide the first evidence that glycophagy is involved in cardiac glycogen physiologic homeostasis post-exercise.

This study investigated the effects of aerobic exercise during recovery from eccentric contraction (EC) on muscular performance, oxidative stress, and inflammation. Nineteen male subjects between 18 and 29 years were divided into unexercised (control, n = 9) and exercised (n = 10) groups. Initially, the subjects performed EC as 3 sets until exhaustion with elbow flexion and extension on the Scott bench at 80% in 1RM, followed by four aerobic exercise sessions. The results obtained indicated (p > 0.05) that aerobic physical exercise during the recovery period does not improve muscle performance (isometric strength and muscular fatigue), oxidative stress parameters (lipid peroxidation, protein oxidation and antioxidant enzyme activity), and inflammatory cytokines (IL-1β, TNF-α, IL-10). In conclusion, the aerobic exercise during the recovery period does not alter the parameters of performance, oxidative stress and inflammation induced by the EC.

Synaptic vesicles specific to inhibitory GABA-releasing neurons are critical for regulating neuronal excitability. To study the specific molecular composition, architecture, and function of inhibitory synaptic vesicles, we have developed a new method to isolate and purify GABA synaptic vesicles from mouse brains. GABA synaptic vesicles were immunoisolated from mouse brain tissue using an engineered fragment antigen-binding region (Fab) against the vesicular GABA transporter (vGAT) and purified. Western blot analysis confirmed that the GABA synaptic vesicles were specifically enriched for vGAT and largely depleted of contaminants from other synaptic vesicle types, such as vesicular glutamate transporter (vGLUT1), and other cellular organelles. This degree of purity was achieved despite the relatively low abundance of vGAT vesicles compared to the total synaptic vesicle pool in mammalian brains. Cryo-electron microscopy images of these isolated GABA synaptic vesicles revealed intact morphology with circular shape and protruding proteinaceous densities. The GABA synaptic vesicles are functional, as assessed by a hybrid (ex vivo/in vitro) vesicle fusion assay, and they undergo synchronized fusion with synthetic plasma membrane mimic vesicles in response to Ca²⁺-triggering, but, as a negative control, not to Mg²⁺-triggering. Our immunoisolation method could also be applied to other types of vesicles.

Introduction

Methods

Results

Conclusion

Citation bias receives scant attention in discussions of ethics. However, inaccurate citation may lead to significant distortions in scientific understanding. Although ethnical and gender citation disparities have been proposed as critical aspects, there are other contributors to citation distortions, like region-based citation bias, that, although less recognized within the scientific community, are equally important. While the foundations of scientific citation include acknowledging pioneers, giving credit to related work, and providing background reading, other more subjective or even questionable criteria are often used when constructing a reference lists. Here, we discuss the potential causes and ethical concerns of citation bias, emphasizing the role of international- or region-based citation bias as one of the most harmful aspects of this ethical breach. We argue that the international scientific community should be aware of this problem and recognize its consequences, which include hindering the accurate dissemination of science, marginalizing underrepresented voices in academia, and impeding scientific progress. We advocate that scientists should compile their reference lists with the same seriousness and integrity they apply to all other aspects of their research.

Background

Cervical spinal cord injury (CSI) often leads to impaired respiratory function, affecting the overall well-being of patients. This study aimed to investigate the influence of rib cage motion on inspiratory capacity in CSI patients.

Methods

We conducted a study with 11 CSI patients, utilising respiratory inductance plethysmography (RIP). We measured ventilatory volume by spirometry concurrently with RIP. Participants were instructed to perform maximal inspiratory efforts. Inspiratory capacity (IC) was calculated from spirometry waveforms. We converted the respiratory waveforms of the chest and abdomen into inspiratory volume measured by a spirometer. The inspiratory volume measured by the chest sensor was defined as V_{RIP-rib cage} (V_RIP-rc), and the inspiratory volume measured by the abdominal sensor was defined as V_RIP-abdomen (V_RIP-ab). Subsequently, the relationships of IC with V_RIP-rc and V_RIPab were assessed.

Results

The mean IC was 1.828 ± 0.459 L, with the mean V_RIP-rc at 1.343 ± 0.568 L and the mean V_RIP-ab at 0.485 ± 0.427 L. A significant correlation was observed between IC and V_RIP-rc (r = 0.67, p = 0.02), indicating that rib cage motion significantly influences IC in CSI patients.

Conclusion

This study highlights the importance of rib cage motion in assessing inspiratory capacity in patients with CSI.

Human monoamine transporters (MATs) are critical to regulating monoaminergic neurotransmission by translocating their substrates from the synaptic space back into the presynaptic neurons. As such, their primary substrate binding site S1 has been targeted by a wide range of compounds for treating neuropsychiatric and neurodegenerative disorders including depression, ADHD, neuropathic pain, and anxiety disorders. We present here a comparative study of the structural dynamics and ligand-binding properties of two MATs, dopamine transporter (DAT) and serotonin transporter (SERT), with focus on the allosteric modulation of their transport function by drugs or substrates that consistently bind a secondary site S2, proposed to serve as an allosteric site. Our systematic analysis of the conformational space and dynamics of a dataset of 50 structures resolved for DAT and SERT in the presence of one or more ligands/drugs reveals the specific residues playing a consistent role in coordinating the small molecules bound to subsites S2–I and S2-II within S2, such as R476 and Y481 in dDAT and E494, P561, and F556 in hSERT. Further analysis reveals how DAT and SERT differ in their two principal modes of structural changes, PC1 and PC2. Notably, PC1 underlies the transition between outward- and inward-facing states of the transporters as well as their gating; whereas PC2 supports the rearrangements of TM helices near the S2 site. Finally, the examination of cross-correlations between structural elements lining the respective sites S1 and S2 point to the crucial role of coupled motions between TM6a and TM10. In particular, we note the involvement of hSERT residues F335 and G338, and E493-E494-T497 belonging to these two respective helices, in establishing the allosteric communication between S1 and S2. These results help understand the molecular basis of the action of drugs that bind to the S2 site of DAT or SERT. They also provide a basis for designing allosteric modulators that may provide better control of specific interactions and cellular pathways, rather than indiscriminately inhibiting the transporter by targeting its orthosteric site.

This paper describes how lentils (Lens culinaris species) can positively affect health by reducing inflammation, providing antioxidants, and displaying antimicrobial properties. Lentils are rich in proteins, essential amino acids, minerals, and fibers, making them a valuable source of nutrition, particularly in low and middle-income countries. Lentils have many health benefits, including positive effects on diabetes management, support for cardiovascular health, and antioxidative properties. The antioxidative properties of lentils, attributed to their phenolic content, and their ability to inhibit inflammation-related enzymes are also discussed. We discuss the potential of lentils as a dietary tool in promoting immunity, reducing disease burdens, and preventing nutritional deficiencies. Overall, lentils are a highly nutritious food with various health benefits, including anti-inflammatory and antimicrobial effects. The fiber and protein content in lentils make them beneficial for weight management, blood sugar regulation, and supporting overall gut health. Furthermore, the slow rate at which lentils affect blood sugar levels, due to their low glycemic index, can be advantageous for individuals with diabetes.

Cosmos caudatus leaves are one of around 7500 types of plants that are known to have herbal or medicinal plant properties in Indonesia. This research determines the effectiveness of Cosmos caudatus as an antioxidant agent against cells, biomolecules, and bone density. Forty-three male rat aged 3–4 months were divided into four groups.Group P0 was only given distilled water. Group P1 was given kenikir leaf extract at a dose of 0.91 mg/kg. Group P2 was given kenikir leaf extract at a dose of 1.82 mg/kg. And group P3 was given kenikir leaf extract at 3.64 mg/kg ad libitum once a day for 28 days. The highest average SOD level was in the 1.82 mg/bb P2 conversion dose group (1.09 ± 1.76). The lowest mean CTX level was in the P2 group (8.30 ± 1.10). There was a significant increase in mean trabecular bone in the P2 group (43.33 ± 5.32). The number of osteoblast cells increased significantly at P2 (103.94 (SD 38.14)). The number of osteoclasts decreased from the control group (P0) to 0.60 (SD 0.43) at P2. Indicate that the Cosmos caudatus extract may have advantages as an antioxidant support agent for bone metabolism.