Browse Articles

Higher-order interactions in neuronal function: From genes to ionic currents in biophysical models

Neuronal firing patterns are the consequence of precise variations in neuronal membrane potential, which are themselves shaped by multiple ionic currents. In this study, we use biophysical models, statistical methods, and information theory to explore the interaction between these ionic currents and neuron electrophysiological phenotype. We created numerous electrical models with diverse firing patterns. By analyzing these models, we identified intricate relationships between model parameters and electrical features. Our findings show that neuronal activity is often influenced by multiple biophysical model parameters, in a nonadditive (i.e. synergistic) fashion. When comparing this with single-cell RNAseq data, we found a contrasting structure: gene expression profiles were dominated by redundancy, reflecting differences in regulatory constraints and sampling diversity. This research sheds light on the complex links between biophysical parameters and neuronal phenotypes.

Layer-dependent spin-orbit torque switching of Néel vector in a van der Waals antiferromagnet

A SCG-YOLOv8n potato counting framework with efficient mobile deployment

It’s cool to be green

Metabolic interplay drives population cycles in a cross-feeding microbial community

Changes in the vaginal microbiome in female patients with condyloma acuminatum and its impact on persistent HPV infection

Influence of the protein corona on hematopoietic stem and progenitor cell uptake and macrophage clearance of membrane-wrapped nanoparticles

The ideal delivery of therapeutic nanoparticles (NPs) to specific sites requires evading immune clearance and selectively binding target cells. Wrapping NPs in cell-derived membranes has shown promise in improving targeted delivery, but the mechanisms underlying this phenomenon are not fully understood. Protein corona (PC) formation on NPs can significantly alter their biological identity to influence biodistribution, making its characterization on membrane-wrapped NPs (MWNPs) and unwrapped NPs crucial. In this study, we compared MWNPs incorporating membranes derived from megakaryoblastic CHRF-288-11 cells, which can accumulate in bone marrow (BM) and preferentially bind hematopoietic stem and progenitor cells (HSPCs), with unwrapped NPs. We investigated differences in PC composition, macrophage uptake, target cell uptake, and biodistribution in wild type (WT) mice and knockout mice that have low or absent expression of different opsonin proteins. In vitro, MWNPs with a PC exhibited increased target cell uptake and decreased macrophage uptake compared to unwrapped NPs with a PC. Proteomics revealed apolipoprotein B as the dominant opsonin on both NP types after incubation in mouse, bovine, or human serum, with other proteins like complement, immunoglobulins, and apolipoproteins also being present. Biodistribution studies indicated a complex interplay between the PC and targeting/clearance, where complement component 3 and immunoglobulin G adsorption on MWNPs led to macrophage clearance but also enabled HSPC targeting. Meanwhile, apolipoprotein E adsorption facilitated hepatocyte clearance but reduced immune cell uptake in the liver. Future research on PCs could determine whether these mechanisms are generalizable to other types of MWNPs, potentially revealing strategies to enhance their effectiveness as delivery systems.

Perinatal vitamin A excess impacts vitamin A and lipid metabolism in rat offspring

Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism

T cells can recognize a few molecules of cognate antigen among vastly outnumbering noncognate ligands. The T cell receptor (TCR) differentiates antigens based on antigen–TCR binding dwell time through a kinetic proofreading process. Historically, this has been modeled as the ligated receptor undergoing a series of reactions before producing a signal. In such a sequential mechanism, the number of steps is a key determinant of discrimination fidelity. Here, we consider two features of the molecular mechanism of TCR activation that diverge from a sequential process and suggest that an alternative kinetic proofreading mechanism may be at play. First, activation processes of multiple ITAM domains of the TCR represent parallel reaction sequences taking place on a single TCR molecule. Second, the states of the parallel proofreading reactions are integrated to produce a binary output from each TCR in the form of a discrete LAT condensation event, which may or may not occur. We examine a revised kinetic proofreading scheme based on parallel reactions followed by an integration step (multithread scheme) and compare its performance with the sequential scheme in a stochastic setting. A distinct difference in a multithread scheme is that multiplicity of the parallel reaction threads provides an additional means to increase discrimination fidelity. This relieves the need for fine-tuned kinetics among chemically distinct reaction steps, which is a major hurdle for physical implementation of a sequential mechanism. Lastly, we reinterpret previously reported experimental observations and find that various proofreading behaviors are well described as proofreading through parallel reaction threads.

RETRACTED ARTICLE: Study on the spatial and temporal evolution characteristics and spatial influencing factors of carbon emission intensity in commercial land

Genetic, phenotypic, and environmental drivers of local adaptation and climate change–induced maladaptation in a migratory songbird

Understanding processes driving local adaptation in wild species is a key goal in evolutionary biology, but linking genotype to phenotype to environmental drivers of natural selection remains challenging. Even more rare are empirical examples of what happens when genotype and phenotype fail to keep pace with environmental change. Here, we explore these connections by conducting an integrative study on the breeding range of the yellow warbler ( Setophaga petechia ). Using genome-wide association studies (GWAS), we first identify loci associated with variation in bill morphology and individual quality. We then employ gene–environment association (GEA) analyses and find that precipitation is a key environmental driver of putative selection on bill shape. Finally, we test whether contemporary individuals whose bill shapes deviate from the historical relationship with precipitation experience increased stress (measured by telomere length) as a result of maladaptation. We also use historical DNA to test whether local populations have shifted their ranges over the past century, confirming that the observed changes are not due to range shifts. Our results align with predictions from GWAS and GEA analyses, indicating that birds with shallower bills in increasingly arid regions suffer higher stress (i.e., shorter telomeres) because of maladaptation. Overall, this study links genetic, phenotypic, and environmental data with stress biomarkers to improve understanding of the process of local adaptation and the consequence of failing to keep pace with changing climate conditions.

Quantification of head leakage radiation in CyberKnife robotic radiosurgery systems using a multimodal approach

Abstract This study aims to measure the head leakage radiation of a CyberKnife system (Model-S7 (without MLC)) in-patient and out-of-patient planes using optically stimulated luminescence dosimeters (OSLDs), vented ionization chambers, and a pressurized ionization chamber-based survey meter, and to compare the measured leakage levels with the limits specified by the International Electrotechnical Commission (IEC) standards. In this study, a CyberKnife LINAC equipped with a 6 MV flattening filter-free (FFF) beam and a maximum circular field size of 6 cm in diameter was utilized. Leakage radiation was assessed for both IRIS and FIXED collimators in their fully closed positions. Three independent measurement techniques were employed to quantify leakage: optically stimulated luminescence dosimeters (OSLDs), vented ionization chambers (ICs), and a pressurized ionization chamber–based survey meter (SM). Leakage measurement points were taken as per the IEC 60601-2-1 report both for in-patient plane and out-of-patient plane. The total number of monitor units (MU) delivered were 500 MU’s. The measured average in-patient plane leakage was 0.015% using IC, 0.100% using OSLD and 0.010% using SM, that is well within the tolerance limit of 0.1% according to IEC guidelines. The average leakage for out of patient plane was 0.037%, which is well within the limit of 0.5% as per IEC guidelines. The study measured head leakage radiation of the CyberKnife System using OSLD, ionization chambers, and a survey meter. Leakage levels for both in-patient and out-of-patient planes were significantly below the IEC 60601-2-1 standard limits. This confirms the system’s compliance with safety guidelines, ensuring minimal radiation exposure.

Hybrid beluga whale optimization based MPPT for photovoltaic powered open end winding induction motor drives

Long-term synchronous changes in body size among domesticated and wild species

Correction: In-vitro antimicrobial activity of Jatropha variegata Vahl. (Euphorbiaceae) against some pathogenic microbes isolated from clinical samples in Ibb City, Yemen

The role of innate immunity, antibiotics, and bacteriophages in the course of bacterial infections and their treatment

Critical to our understanding of infections and their treatment is the role the innate immune system plays in controlling bacterial pathogens. Nevertheless, many in vivo systems are made or modified such that they do not have an innate immune response. Use of these systems denies the opportunity to examine the synergy between the immune system and antimicrobial agents. In this study, we demonstrate that the larva of Galleria mellonella is an effective in vivo model for the study of the population and evolutionary biology of bacterial infections and their treatment. To do this, we test three hypotheses concerning the role of the innate immune system during infection. We show that i) sufficiently high densities of bacteria are capable of saturating the innate immune system, ii) bacteriostatic drugs and bacteriophages are as effective as bactericidal antibiotics in preventing mortality and controlling bacterial densities, and iii) minority populations of bacteria resistant to a treating antibiotic will not ascend. Using a highly virulent strain of Staphylococcus aureus and a mathematical computer-simulation model, we further explore how the dynamics of the infection within the short term determine the ultimate infection outcome. We find that immune activation in response to high densities of bacteria leads to a strong but short-lived immune response which ultimately results in a high degree of mortality. Overall, our findings illustrate the utility of the G. mellonella model system in conjunction with established in vivo models in studying infectious disease progression and treatment.

The role of medication timing and patient involvement in adherence to treatment for hypertension

Abstract Despite improvements in the effectiveness of medication for the treatment of hypertension, patient adherence to prescription regimens remains a challenge in clinical practice. This study examined the impact of two factors on improving medication adherence: medication timing (morning timing is considered as 06:00–10:00, and evening timing, as 20:00-midnight) and patient involvement. Following the STROBE guidelines, a cross-sectional survey design was undertaken at a university hospital between May and August 2023. Three hundred and four inpatients with a diagnosis of hypertension comprised the study sample. Data was gathered using the Control Preferences and Medication Adherence Report Scales. The results revealed that patients preferred to take a passive role in taking their medications (60.2%). However, more active patient participation in decision-making resulted from considering patients’ daily routines (80.9%) and positive attitudes from healthcare providers during communication (69.4%). Regression analyses indicated that patient involvement (OR:5.649, 95%CI [2.528–12.622]), rather than medication timing (OR:1.052, 95%CI [0.591-1.875]), predicted treatment adherence. Shared decision-making improved adherence to medication regimes compared with passive acceptance (81.0% vs. 50.8%; p  = .000). These findings underscore the significance of patient involvement. Given patients’ preference for a paternalistic approach, in which healthcare providers make the decisions, often without patients’ active involvement, promoting participation through strategies such as providing ample time for treatment discussions, offering information, and aligning treatment hours with patients’ daily routines are promising approaches for enhancing adherence.

Sustainable separation of rare earth elements from wastes

Rare earth elements (REEs) are indispensable in modern technologies, but their supply chain faces challenges due to limited geographical availability and political difficulties. Recycling REEs from industrial waste provides a sustainable alternative to mining, promoting a circular economy and reducing environmental impacts. The mainstay approaches for REE recovery, hydrometallurgical and pyrometallurgical methods, can be inefficient, consuming high energy and generating large aqueous and acid waste streams. Here, we introduce flash Joule heating (FJH) combined with chlorination (FJH-Cl 2 ) as an efficient method for REE separation and recovery by capitalizing on the free energies of formation (ΔG form ) of the metal chlorides and the boiling points of those metal chlorides. FJH-Cl 2 enables high-purity (>90%) and high-yield (>90%) REE recovery from waste magnets in a single step. Life cycle assessment and techno-economic analysis show that this process reduces the number of steps by 3× while reducing energy consumption by 87%, greenhouse gas emissions by 84%, and operating costs by 54% while eliminating water and acid use by 100% compared to traditional methods. This offers an environmentally friendly and economically viable pathway for sustainable REE recycling and recovery.

Significance of molecular and zymography profiling for accurate detection of infected sheep with Anaplasma marginale in South Sinai, Egypt

Abstract Anaplasma marginale is a significant tick-borne pathogen affecting ruminants; yet its prevalence and pathological impact in sheep remain underreported. This study aimed to investigate the prevalence of A. marginale in sheep from Southern Sinai, Egypt, along with its molecular characterization and the associated oxidative stress and immune responses. Microscopic examinations and PCR targeting the msp4 and msp5 genes were employed for detection, with sequencing and phylogenetic analysis performed on the msp5 gene. Oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH), were quantified using commercial kits. Inflammatory response was assessed via gelatin zymography for matrix metalloproteinase (MMP-2 and MMP-9). Expression levels of candidate genes, DNA methyltransferase 3 A (DNMT3a), IL-1β, and heat shock proteins (HSPs) were measured by qPCR. A high prevalence of A. marginale infection was observed, with 76% positivity by microscopy and 79.85% by PCR. Sequencing of the msp5 gene revealed 95.2–100% identity with global strains, clustering closely with the Florida (USA) strain in the phylogenetic tree. Infected sheep exhibited significantly elevated MDA levels (p < 0.05) and decreased SOD and GSH levels, indicating oxidative stress. MMP-2 and MMP-9 activities were also significantly increased, suggesting inflammatory involvement. Moreover, qPCR revealed significant upregulation of DNMT3a, IL-1β, and HSPs, highlighting transcriptional changes associated with infection. These findings provide valuable insights into molecular epidemiology and host response to A. marginale in sheep. The combination of msp5 sequencing, oxidative stress biomarkers, zymographic profiles, and gene expression analysis of DNMT3a, IL-1β, and HSPs suggests a potential panel of biomarkers for the diagnosis and monitoring of ovine anaplasmosis.

Molecular divergence and convergence of mammalian antibody responses to the influenza virus hemagglutinin stem

Antibody responses to the influenza virus hemagglutinin (HA) stem, a major target for broadly protective vaccine development, have been extensively characterized in humans. However, they remain largely elusive in other natural influenza hosts, including pigs, which are considered intermediate hosts for the emergence of pandemic strains. By leveraging single-cell variable, diversity, and joining (VDJ) sequencing, this study identified 25 porcine antibodies to the HA stem, including two cross-group bnAbs, 14-8 and 15-1, from vaccinated specific-pathogen-free pigs and unvaccinated domestic pigs. Cryogenic electron microscopy analysis showed that 14-8 targeted the well-characterized central stem epitope, whereas 15-1 bound to a linear epitope spanning the HA1/HA2 junction. Additionally, while some porcine and human bnAbs targeted the central stem epitope via convergent molecular signatures, our results revealed a pig-specific recurring binding motif. Overall, our findings provide important insights into the commonalities and uniqueness of antibody responses between different species, which have significant implications for vaccine development for nonhuman animals.