The elucidation of the molecular architecture of cell membranes is a central goal for cell biology, as structure lies at the heart of function. The erythrocyte plasma membrane has long provided a favored testing ground for this inquiry. Human red blood cells are readily available, relatively homogeneous, and relevant to medicine. Their plasma membranes can be easily isolated intact and essentially free of contamination from other cells, organelles, and cytoplasmic contents. This membrane is complex enough to be interesting and, to some degree, representative, yet it is simple enough to be analyzed as a whole. These circumstances make it likely that the human red cell plasma membrane will be the first whose molecular anatomy is known in any degree of satisfying detail. The literature concerning the proteins of erythrocyte membranes and membranes in general has been the subject of repeated review (1 9). This article will focus on the localization and modes of association of individual major polypeptides within the human red cell membrane.
I defend a view of the species category, pluralistic realism, which is designed to do justice to the insights of many different groups of systematists. After arguing that species are sets and not individuals, I proceed to outline briefly some defects of the biological species concept. I draw the general moral that similar shortcomings arise for other popular views of the nature of species. These shortcomings arise because the legitimate interests of biology are diverse, and these diverse interests are reflected in different legitimate approaches to the classification of organisms. In the final section, I show briefly how the pluralistic approach can help to illuminate some areas of biological and philosophical dispute.
Abstract Objective To analyze the regularities and clinical features of sintilimab-related autoimmune myocarditis, and to summarize the differential diagnosis key points between sintilimab-related autoimmune myocarditis and acute myocardial infarction. Methods The case reports about sintilimab-related autoimmune myocarditis were searched on databases from the establishment of the database to April 1st 2024. The relevant medical records were searched on the hospital information system of Beijing Hospital of Traditional Chinese Medicine in the past 3 years. The case reports and medical records were collected for statistical analysis. Result Twenty three cases were collected including 22 case reports and 1 case record. Most of the sintilimab-related autoimmune myocarditis were in elderly men aged 60–75 years old and occurred between the end of the first dose of treatment to the beginning of the second dose. The symptom was nonspecific such as chest tightness and palpitation, sometimes with symptom of myasthenia as muscle weakness or myositisand as muscle soreness. Elevated cardiac biomarkers and changes in electrocardiogram were common, and decreased left ventricular ejection fraction was rarely seen in echocardiography. 9 cases underwent coronary angiography or computed coronary tomography angiography, and 3 cases underwent cardiovascular magnetic resonance. Conclusion The manifestations of sintilimab-related autoimmune myocarditis are not specific. The medication history and concomitant symptoms are of warning value. Coronary angiography or coronary computed coronary tomography angiography can be helpful when ruling out acute myocardial infarction. Cardiovascular magnetic resonance and myocardial biopsy can confirm the diagnosis. Cardiac biomarkers and the electrocardiogram can assist in diagnosis and prognosis assessment.
Introduction: Heavy metal pollution including lead (Pb) has become one of the serious global issues threatening food security, human health, and the ecosystem. Exogenous application of astaxanthin (ATX), a potent natural antioxidant, has been shown to enhance plant tolerance to various abiotic stresses. However, the role of endogenous ATX in alleviating Pb stress and the underlying molecular mechanisms remain poorly understood. Objectives: This study aimed to systematically investigate the effects and mechanism of endogenous ATX in biofortified tobacco (T-ATX) in promoting plant growth, particularly enhancing plant tolerance to Pb toxicity and blocking Pb pollution. Methods: Pot experiments were employed to investigate plant growth and Pb tolerance as well as Pb absorption and translocation in T-ATX and wild-type (SNN) tobacco seedlings subjected to various doses of Pb stress. Multiple physiological and cellular examinations were conducted, followed by integrated omics approaches in this study. Results: T-ATX plants exhibited an increased plant height, root length, leaf area, and biomass compared to SNN under Pb stress. T-ATX displayed higher levels of chlorophyll, photosynthetic efficiency, antioxidant enzyme activities, and non-enzymatic antioxidants, with improved integrity of subcellular structures. Remarkably, Pb content in various organs and Pb translocation coefficient were significantly reduced in T-ATX. Multiple genes and metabolites associated with antioxidant defense mechanisms, detoxification pathways, carotenoid metabolism, Pb ion transport, and plant hormone signal transduction were significantly upregulated in T-ATX tobacco plants. Conclusion: Endogenous ATX enriched in the T-ATX genotype significantly confers plant healthy performance and high tolerance to Pb stress by enhancing the antioxidant defense system, maintaining cellular structural integrity, reducing Pb absorption and translocation, upregulating detoxification and the related signaling pathways. These findings provide new insights into the endogenous ATX-mediated molecular mechanisms to promote plant growth and mitigate Pb toxicity, establishing a foundation for using ATX-fortified crops for green control technology of heavy metal pollution.
Epilepsy is one of the most common neurological disorders in both children and adults, characterized by significant clinical heterogeneity and dynamic natural course. The pathophysiological roles of astrocytes in epilepsy have been increasingly recognized. Fluid biomarkers derived from astrocytes are actively studied in epileptic disorders, although their use remains limited in clinical practice. This review aims to compile and analyze clinical and experimental findings concerning astrocytic biomarkers in epilepsy and related conditions, with a focus on glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B). Herein we examine their roles in assessing seizure burden and temporal dynamics, explore their potential in distinguishing epileptic from psychogenic non-epileptic seizures, and discuss their therapeutic, prognostic, and mechanistic implications in the context of epileptic disorders.
Sjoerd J.D. Tjalsma, Niels J. Rinzema, Marjon J.A.M. Verstegen
et al.
Summary: Cell-type-specific gene activation is regulated by enhancers, sometimes located at large genomic distances from target gene promoters. Whether distal enhancers require specific factors to orchestrate gene regulation remains unclear. Here, we used enhancer distance-controlled reporter screens to find candidate factors. We depleted them and employed activity-by-contact predictions to genome-wide classify genes based on enhancer distance. Predicted distal enhancers typically control tissue-restricted genes and often are strong enhancers. We find cohesin, but also mediator, most specifically required for long-range activation, with cohesin repressing short-range gene activation and prioritizing distal over proximal HBB genes competing for shared enhancers. Long-range controlled genes are also most sensitive to perturbations of other regulatory proteins and to BET inhibitor JQ1, this being more a consequence of their distinct enhancer features than distance. Our work predicts that lengthening of intervening sequences can help limit the expression of target genes to specialized cells with optimal trans-factor environments.
Nobumitsu Hirai, Yuhei Miwa, Shunta Hattori
et al.
Biofilms cause a variety of problems, such as food spoilage, food poisoning, infection, tooth decay, periodontal disease, and metal corrosion, so knowledge on biofilm prevention and removal is important. A detailed observation of the three-dimensional structure of biofilms on the nanoscale is expected to provide insight into this. In this study, we report on the successful in situ nanoscale observations of a marine bacterial biofilm on glass in phosphate buffer solution (PBS) using both scanning ion conductance microscopy (SICM) and confocal laser scanning microscopy (CLSM) over the same area. By observing the same area by SICM and CLSM, we were able to clarify the three-dimensional morphology of the biofilm, the arrangement of bacteria within the biofilm, and the difference in local ion conductivity within the biofilm simultaneously, which could not be achieved by observation using a microscope alone.
Defects in pipes adversely affect both the jacking construction process and long-term operational safety, yet their specific impacts on mechanical properties remain unclear. This study investigates pipe jacking segments under deflection, using the Changsha Meixi Lake project as a case study. Similar model tests combined with digital image correlation were employed to examine the evolution of stress and deformation under various deflection angles and defect conditions. The reliability of the laboratory tests was verified through theoretical stress calculations under the non-deflection condition. The credibility of the laboratory test results was further enhanced by employing a numerical model and normalized parameters. Key findings reveal that stress distribution characteristics are jointly determined by the deflection mode and load. Co-directional deflection exhibits a more significant stress concentration effect; under identical load and angle conditions, it results in higher stress levels due to a superposition effect, whereas diagonal deflection shows a weakening effect. Joint deformation progresses through three distinct stages. The linear growth stage exhibits an initial linear strain–load relationship under stable deflection (load < 2 kN). The accelerated deformation stage is characterized by nonlinear strain growth with a slowing deformation rate (2–4 kN). The deformation deceleration stage finally shows a slow linear strain increment (load > 4 kN). Increasing load and deflection angle significantly amplify axial deformation, particularly revealing a “thick-in-the-middle, thin-at-the-sides” compression characteristic in the 45° vault zones. Furthermore, segment defects markedly exacerbate stress non-uniformity. Defect angles ≥ 60° substantially increase the frequency and amplitude of compressive stress in the vault, accelerate the decay of tensile stress at the bottom, and critically reduce structural stability. These new findings provide significant insights for deflection control and structural safety assessment in pipe jacking engineering. The experimental framework provides fundamental insights into construction operations in upper-soft and lower-hard strata tunneling.
Kim-Marie A. Dam, Harry B. Gristick, Yancheng E. Li
et al.
Summary: HIV-1 broadly neutralizing antibodies (bNAbs) targeting the CD4-binding site (CD4bs) contain rare features that pose challenges to elicit these bNAbs through vaccination. The IOMA class of CD4bs bNAbs includes fewer rare features and somatic hypermutations (SHMs) to achieve broad neutralization, thus presenting a potentially accessible pathway for vaccine-induced bNAb development. Here, we created a library of IOMA variants in which each SHM was individually reverted to the inferred germline counterpart to investigate the roles of SHMs in conferring IOMA’s neutralization potency and breadth. Impacts on neutralization for each variant were evaluated, and this information was used to design minimally mutated IOMA-class variants (IOMAmin) that incorporated the fewest SHMs required for achieving IOMA’s neutralization breadth. A cryoelectron microscopy (cryo-EM) structure of an IOMAmin variant bound to Env was used to further interpret characteristics of IOMA variants to elucidate how IOMA’s structural features correlate with its neutralization mechanism, informing the design of IOMA-targeting immunogens.
Cadmium (Cd) contamination in soil poses a serious threat to plant growth and productivity, while arbuscular mycorrhizal (AM) fungi play a vital role in enhancing plant growth, improving tolerance to heavy metals, and restoring polluted ecosystems. To enhance the tolerance of <i>Astragalus sinicus</i> to Cd stress, a pot experiment was conducted to investigate the effects of inoculation and copper (Cu) addition on growth, Cd accumulation, and translocation under Cd-stressed soil conditions. The results showed that Cd inhibited the root growth of <i>A. sinicus</i>, and AM fungi inoculation and Cu + AM significantly increased root biomass and root volume (<i>p</i> < 0.05). Under Cd stress, AM fungi inoculation reduced Cd concentration by 72.40% in the shoots, while it increased by 92.69% in the roots. Both AM fungi inoculation and Cu + AM enhanced Cd uptake in the roots, while inhibiting Cd translocation to the shoots. After the application of Cu and inoculation with AM fungi, the roots have a strong absorption and enrichment ability for Cd; the bioconcentration factor of Cd in the roots of <i>A. sinicus</i> reached 1018.59% and 366.08%, respectively. Cu + AM increased the enrichment of Cd in the roots and restricted its translocation to the shoots. Moreover, the combination of AM fungi inoculation and Cu addition significantly increased soluble sugar (by 77.29%) and proline contents (by 445.62%) and reduced CAT activity (by 74.67%) under Cd stress. In summary, both Cu addition and AM fungi inoculation promoted the growth of <i>A. sinicus</i> under Cd stress, improved its physiological metabolism, and reduced Cd content in the soil, with the combined Cu and AM fungi treatment showing the most significant effect.