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<i>Cdc42</i> defect reveals insights into microvilli organization and function in T cell immunity
Microvilli on T cells differ from those on epithelial cells, exhibiting filopodia-like characteristics that facilitate the clustering of molecules essential for sensing and cell migration. Recently, they have also been recognized as the structures from which T cell immunological synaptosomes (TIS) are released. In this study, we examined a key determinant of microvilli organization during T cell development and explored the functional roles of these structures, particularly in relation to T cell behaviors. During thymocyte maturation, single-positive thymocytes were found to develop more and longer microvilli than double-positive thymocytes. However, the deletion or inhibition of Cdc42, a small Rho family protein, significantly reduced both the number and length of microvilli in single-positive thymocytes, leading to decreased cell mass. This reduction in microvilli correlates with a decrease in antigen recognition, leading to diminished T cell activation and adhesion, as well as reduced TIS production, while intrinsic migratory properties remain unaffected. These findings highlight the filopodia-like characteristics of T cell microvilli. In this context, Cdc42 contributes significantly to microvilli formation, thereby shaping T cell function.
Design of a novel robust adaptive fractional-order model predictive controller for boost converter using grey wolf optimization algorithm
The prognostic importance of neuronatin positivity as immunohistochemical in patients with lung adenocarcinoma in the development of brain metastasis
Time to death and its predictors among neonates with seizure in North West Ethiopia
Abstract Neonatal seizures were associated with significant rates of mortality; in which about one-third of the neonates with seizure ending up with death. Despite this, the time to death and its predictors among neonates with seizure has not been investigated; especially in Ethiopia. To determine the time to death and its predictors among neonates with seizure in public hospitals of Awi zone, Northwest Ethiopia. A multicenter prospective follow-up study was conducted in public hospitals of Awi zone on 263 neonates with seizure. Descriptive statistics, Kaplan–Meier curve, Nelson–Aalen curves, and log-rank tests were employed to describe the time to death and to assess the risk of mortality among different covariates. The Cox proportional hazards model was used to identify the predictors of time to death. AHR with 95% CI was used to identify significant predictor variables, and a statistical significance was declared at p-value < 0.05. A total of 263 neonates with seizure were followed for a total of 1334.3 person-days, and the incidence of mortality was found to be 22.5 per 1000 person-day observations (95% CI = 14.0–29.6). The median time to death was 3 days (IQR = 2–5 days). Birth trauma (AHR = 3.9, 95% CI = 1.5–10.6), neonatal sepsis (AHR = 3.4, 95% CI = 1.1–10.8), hypoglycemia (AHR = 3.2, 95% CI = 1.1–9.3), and tonic type seizure (AHR = 4.5, 95% CI = 1.3–15.6) were statistically significant predictors of early mortality in neonates with seizure. This study revealed that the incidence of in-hospital mortality among neonates with seizure to be high and the median time to death to be short; and the predictors of early mortality were identified. Early detection and appropriate management of neonates having birth trauma, sepsis, and hypoglycemia might be helpful.
Trigger factor accelerates nascent chain compaction and folding
Conformational control of nascent chains is poorly understood. Chaperones are known to stabilize, unfold, and disaggregate polypeptides away from the ribosome. In comparison, much less is known about the elementary conformational control mechanisms at the ribosome. Yet, proteins encounter major folding and aggregation challenges during translation. Here, using selective ribosome profiling and optical tweezers with correlated single-molecule fluorescence, with dihydrofolate reductase (DHFR) as a model system, we show that the Escherichia coli chaperone trigger factor (TF) accelerates nascent chain folding. TF scans nascent chains by transient binding events, and then locks into a stable binding mode as the chain collapses and folds. This interplay is reciprocal: TF binding collapses nascent chains and stabilizes partial folds, while nascent chain compaction prolongs TF binding. Ongoing translation controls these cooperative effects, with TF-accelerated folding depending on the emergence of a peptide segment that is central to the core DHFR beta-sheet. The folding acceleration we report here impacts processes that depend on folding occurring cotranslationally, including cotranslational protein assembly, protein aggregation, and translational pausing, and may be relevant to other domains of life.
An artificial intelligence model to predict mortality among hemodialysis patients: A retrospective validated cohort study
Involvement of hypoxia-inducible factor1-alpha in the protective effect of rivaroxaban against testicular ischemia-reperfusion in rats
Abstract This study investigated the protective effects of Rivaroxaban (RVX) against testicular ischemia-reperfusion (IR) injury in rats with a secondary aim of studying the involvement of hypoxia-inducible factor1-alpha testicular protection against ischemic insults. Twenty-four male rats were divided into four groups: sham control, testicular IR, and two RVX treatment groups (7 and 14 mg/kg) administered for one week prior to IR. Testicular IR led to significant impairment in testicular function, evidenced by an 86.5% reduction in testosterone levels and marked oxidative stress with an 189.3% increase in malondialdehyde (MDA). IR injury also triggered substantial elevations in apoptotic markers (271% increase in Bax (Bcl2-associated X protein) and 65.9% decrease in BCL2 (B-cell lymphoma 2), and inflammatory mediators (285.7% increase in NFκB (nuclear factor-kappa B). Additionally, angiogenic markers showed dramatic increases, with VEGF (vascular endothelial growth factor) and HIF-1 (Hypoxia inducible factor-1) rising by 431.8% and 519%, respectively. RVX treatment demonstrated dose-dependent protective effects, with the 14 mg/kg dose showing superior outcomes compared to 7 mg/kg. The higher dose significantly improved hormonal function (486.8% increase in testosterone), reduced oxidative stress (51.8% reduction in MDA), modulated apoptotic markers (68.3% decrease in BAX, 159.1% increase in BCL2), and normalized angiogenic factors (71.8% reduction in HIF-1). In conclusion, RVX demonstrated significant therapeutic potential in protecting against testicular IR injury, with the 14 mg/kg dose showing optimal protective effects. Reduction in HIF-1α and VEGF protein expression mediated RVX’s anti-oxidant, anti-inflammatory, and anti-apoptotic effect in rats subjected to testicular IR.
Integration of Google Earth Engine, Sentinel-2 images, and machine learning for temporal mapping of total dissolved solids in river systems
Abstract One of the important indicators of water quality (WQ) in inland water systems is total dissolved solids (TDS). Collecting and maintaining in situ TDS data with high spatial and temporal resolution is time and money-consuming. This study highlights an advanced approach integrating Google Earth Engine (GEE), remote sensing techniques using Sentinel-2 imagery, and machine learning algorithms to map TDS in a spatially explicit manner. We extracted relevant spectral indices and used them to train machine learning models, specifically Random Forest (RF) and Support Vector Machines (SVM), to classify TDS levels across the stretch of the Little Miami River (LMR). We analyzed TDS for August, September, October, and November, and over three years, from 2020 to 2023. Results showed RF to be more effective than SVM in mapping TDS levels, with overall accuracies and Kappa coefficients up to 0.88 and 0.85, respectively, for November 2021. Further, TDS levels remained a concern, particularly in the midstream LMR sections. Temporal rainfall variations corresponded with elevated TDS levels. Areas with higher percentages of natural cover (forests and wetlands) showed greater resilience to TDS fluctuations (r = -0.632) compared with developed or barren lands (r = 0.298). Our findings provide spatial insight into the current state of TDS as well as the success of management steps taken to manage and prevent eutrophic problems in the LMR.
Effects of the gut microbiota on placental angiogenesis and intrauterine growth in gnotobiotic mice
Environmental causes of intrauterine growth restriction (IUGR) remain poorly characterized. Here, we compare germ-free (GF) and conventionally raised (CONV-R) mice to assess the effects of the gut microbiota on placental/fetal development at embryonic day (E)11.5 (end of placentation) and E17.5 (near term). Pregnancy- and microbiota-associated changes in gene expression occur along the gut, including those related to angiogenesis, while bacterial composition and fermentation activity remain stable. Placental weights at E11.5 and fetal weights at E17.5 are significantly reduced in GF animals. Compared to CONV-R dams, the GF maternal decidua exhibits similar vascular histomorphometric features at E11.5 and E17.5, and numbers of uterine NK-cells (effectors of vascular remodeling) at E11.5. In contrast, angiogenesis is disturbed in the GF fetal-derived placental compartment (junctional and/or labyrinth zones) at E11.5, as judged by i) increased levels of proangiogenic proteins (angiopoietin-2, FGF-2, follistatin, SDF-1, VEGF-A, VEGF-C); ii) increased levels of phos-VEGFR2 and phos-p38-MAPK yet reduction in phos-ERK1/2; and iii) reduced expression of junctional zone glycoprotein genes associated with angiogenesis and fetal growth, resulting in reduced endothelial cell density at the labyrinth zone at E17.5. Colonization of GF mice before pregnancy with cecal microbiota from CONV-R animals rescues fetal growth and altered transcriptomic, proteomic, and immunohistochemical features in the fetal GF placental compartment. Single-nucleus RNA-sequencing demonstrated increased expression of mitochondrial and ribosomal-associated oxidative stress genes in endothelial cell clusters in the GF fetal placental compartment (E11.5, E17.5), mimicking oxidative stress signatures in human IUGR. These results provide a rationale for seeking microbial targets for treating/preventing IUGR.
Frequency domain characterisation of the sound insulation performance of wooden doors and optimal design of high performance wooden doors
How publics in small-island states view climate change and international responses to it
Climate change caused by carbon pollution from the world’s largest economies poses an existential threat to small-island states and territories this century. These places bear virtually no responsibility for climate change but will face sea-level rise, fresh water resource degradation, and intensified storms that will kill or dislocate exposed publics, and damage local economies. To alleviate this crisis, the global community has begun discussing who is responsible for climate mitigation and adaptation costs for those affected by climate change, in addition to continued debates around the distribution of responsibility for climate change. Missing from this analysis, however, are systematic efforts to elicit the preferences and perceptions of publics in these threatened small-island states and territories. Here, we report results from a large-sample (n = 14,710) cross-national survey of publics living in climate-vulnerable states and territories, conducted in June–July 2022. By quota sampling through Facebook’s ad platform, we generate survey samples at the national or territorial level for publics in 55 small-island states, territories, and subnational regions in the South Pacific, Indian Ocean, and Caribbean. We find widespread awareness and concern about the threat posed by climate change and sea-level rise, in contrast to what existing research finds in the Global North. We also find that climate-vulnerable publics believe their home governments, large polluters, and former colonial powers are all responsible for helping to manage the climate crisis, irrespective of these actors’ relative carbon emissions. These findings fill an important gap by depicting climate beliefs among the communities at the frontlines of climate change.
Study on the calculation of surface residual deformation in goaf based on the Gudermann time function
Bivalent interaction through an intrinsically disordered linker promotes transcription activation complex assembly in Notch signaling
The Notch signaling pathway regulates cellular differentiation by activating transcription through an unusual heterotrimeric complex comprising the Notch receptor’s intracellular domain (NICD), the DNA-binding protein CSL, and the coactivator MAML. NICD has two binding sites for CSL, a short motif in the RAM region and an ankyrin domain (ANK), connected by an intrinsically disordered linker and which form a bivalent ternary complex with CSL and MAML. Although bivalency is required for maximal transcription activation, the energetic contributions of bivalency and heterotrimer formation within this essential complex are unknown. To elucidate the energetics of bivalency, we first determine the free energy of the CSL-ANK-MAML heterotrimer, using isothermal titration calorimetry and developing an obligate heterotrimer model to analyze the data. By comparing this heterotrimerization reaction with binding reactions involving different regions of RAMANK, we determine the energetic contribution of bivalency to heterotrimer assembly. We show that bivalency through the disordered linker increases the effective concentration of ANK, and that the bivalent interaction enhances occupancy of RAM and ANK at their binding sites on CSL by about three orders of magnitude. By redefining the standard state to a lower, more physiological protein concentration, we reveal the importance of the RAMANK intrinsically disordered linker for assembly of the Notch transcription activation complex. This work provides a framework whereby the energetic contributions of intrinsically disordered linkers to higher-order multivalent assembly may be analyzed.
Histomorphometry variations of placenta and birth outcomes in preeclamptic and normotensive mothers at Arba minch general hospital Southern Ethiopia
Differential representations of spatial location by aperiodic and alpha oscillatory activity in working memory
Decades of research have shown working memory (WM) relies on sustained prefrontal cortical activity and visual extrastriate activity, particularly in the alpha (8 to 12 Hz) frequency range. This alpha activity tracks the spatial location of WM items, even when spatial position is task-irrelevant and no stimulus is currently being presented. Traditional analyses of putative oscillations using bandpass filters, however, conflate oscillations with nonoscillatory aperiodic activity. Here, we reanalyzed seven human electroencephalography visual WM datasets to test the hypothesis that aperiodic activity, which is thought to reflect the relative contributions of excitatory and inhibitory drive-plays a distinct role in visual WM from true alpha oscillations. To do this, we developed a time-resolved spectral parameterization approach to disentangle oscillations from aperiodic activity during WM encoding and maintenance. Across all seven tasks, totaling 112 participants, we captured the representation of spatial location from total alpha power using inverted encoding models (IEMs), replicating traditional analyses. We then trained separate IEMs to estimate the strength of spatial location representation from aperiodic-adjusted alpha (reflecting just the oscillatory component) and aperiodic activity and find that IEM performance improves for aperiodic-adjusted alpha compared to total alpha power that blends the two signals. We also identify a distinct role for aperiodic activity, where IEM performance trained on aperiodic activity is highest during stimulus presentation, but not during the WM maintenance period. Our results emphasize the importance of controlling for aperiodic activity when studying neural oscillations while uncovering a functional role for aperiodic activity in encoding visual WM information.
Recycling of sewage sludge ash in cold-bonded artificial lightweight aggregate for sustainable lightweight concrete
Seed dispersal disruption limits tropical forest regrowth
Identifying linkages between biodiversity loss and climate change is required for understanding the scope of these interconnected challenges and developing approaches to address them. One crucial yet underexplored aspect is the influence of seed-dispersing animals on forest carbon storage. Here, we show that 81% of tropical trees rely on animals for seed dispersal and that disruption of this process, due to declines in animal diversity and movement, significantly hampers the carbon accumulation potential of regrowing tropical forests. Using a synthesis of animal biodiversity, movement, and seed dispersal data covering thousands of animal species, we developed an index of seed dispersal disruption and modeled its relationship to carbon accumulation observed across 3,026 tropical regrowth plots. Naturally regrowing areas with lowest seed dispersal disruption had aboveground carbon accumulation rates four times higher than those with most severe disruption. Across areas identified as locations suitable for reforestation, current levels of seed dispersal disruption yield a 57% average reduction in local carbon accumulation potential. Tropical regrowth forests currently represent the largest land-based carbon sink; ongoing animal biodiversity losses diminish their ability to recover naturally from disturbances and therefore threaten their climate mitigation potential. These results advance understanding of animal biodiversity’s impact on carbon dynamics and emphasize the need to address biodiversity loss and climate change together.