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The kinesin-14 family motor protein KIFC2 promotes prostate cancer progression by regulating p65

Recursive Objective Space Exploration (ROSE): A computationally efficient deterministic approach for bi-objective optimization

Bi-objective optimization problems arise when a process needs to be optimized with respect to two conflicting objectives. Solving such problems produces a set of points called the Pareto front, where no objective can be improved without worsening at least one other objective. Existing deterministic methods for solving Multi-Objective Optimization Problems (MOOPs) include scalarization techniques, which transform the problem into a set of Single-Objective Optimization Problems (SOOPs) where each of them is to be solved independently to obtain a point on the Pareto front. In this paper, we propose an alternative strategy that tackles bi-objective optimization problems by exploring the objective space recursively at a reduced computational cost. Our approach is inspired by how plants efficiently explore physical space in search of light energy, balancing exploration and exploitation while minimizing biomass cost. The algorithm navigates the objective space without revisiting previously explored areas by solving intermediate SOOPs visualized as branches within this space. A trade-offs based stopping criterion enables the algorithm to focus on steep, information-rich segments of the Pareto front, creating denser branches to provide more detailed representation of the Pareto front. We benchmark the algorithm’s performance against a standard scalarization-based solution strategy from the literature, employing five case studies. Our strategy demonstrates that a holistic approach that structures the solution process within the objective space provides significant advantages. These include a more computationally efficient method for solving bi-objective optimization problems, an adaptive representation of the Pareto front based on trade-offs, and intuitive, straightforward parameterization guided by a user-oriented, trade-offs based stopping criterion.

Arylsulfatase B induces melanoma apoptosis by the ubiquitin ligase COP1

Expression of Concern: Ontological Differences in First Compared to Third Trimester Human Fetal Placental Chorionic Stem Cells

Inflamed endothelial cells express S1PR1 inhibitor CD69 to induce vascular leak

The porphyran degradation system is complete, phylogenetically and geographically diverse across the gut microbiota of East Asian populations

The human gut microbiota can acquire new catabolic functions by integrating genetic material coming from the environment, for example from food-associated bacteria. An illustrative example of that is the acquisition by the human gut microbiota of Asian populations of genes coming from marine bacteria living on the surface of red algae that are incorporated into their diet when eating maki-sushi. To better understand the function and evolution of this set of algal genes corresponding to a polysaccharide utilization locus (PUL) dedicated to the degradation of porphyran, the main polysaccharide of the red algae Porphyra sp ., we characterized it biochemically, assessed its genetic diversity and investigated its geographical distribution in large public worldwide datasets. We first demonstrated that both methylated and unmethylated fractions are catabolized without the help of external enzymes. By scanning the genomic data of more than 10,000 cultivated isolates as well as metagenomic data from more than 14,000 worldwide individuals, we found that the porphyran PUL is present in 17 different Phocaeicola / Bacteroides species (including 12 species that were not known to carry it), as well as in two Parabacteroides species and two genera from the Bacillota phylum, highlighting multiple lateral transfers within the gut microbiota. We then analyzed the prevalence of this porphyran PUL across 32 countries and showed that it exists in appreciable frequencies (>1%) only in East Asia (Japan, China, Korea). Finally, we identified three major PUL haplotypes which frequencies significantly differ between these East Asian countries. This geographic structure likely reflects the rate of bacterial horizontal transmission between individuals.

Targeted degradation of α-synuclein by arginine-based PROTACs

Loss of Ufsp1 does not cause major changes at the neuromuscular junction

UFMylation is a Ubiquitin-like post-translational modification involved in myriad of cellular processes. Enzymes involved in this pathway, including ligases and UFM1-specific proteases, are essential for development and homeostasis. Our previous transcriptomic analyses identified an enrichment of Ufsp1 at the neuromuscular junction of skeletal muscle cells. Ufsp1, one of the two UFM1 proteases, had been considered a pseudogene due to truncation of its catalytic domain in several species, including humans. However, recent findings revealed that Ufsp1 is translated from a non-canonical start codon in humans, yielding a catalytically active enzyme. This discovery has revived interest in studying Ufsp1’s role in vivo. We generated two mutant mouse models, one with a point mutation abolishing catalytic activity and another with complete knockout of the gene. Unlike other UFMylation pathway enzymes, both Ufsp1 mutants were born in normal ratios and did not exhibit gross phenotypic abnormalities. Despite the enrichment of Ufsp1 at neuromuscular junctions, only mild structural alterations of this synapse were detected, which did not impact overall muscle function. Our findings indicate that Ufsp1 is dispensable for normal development and homeostasis in mice, but further exploration of its function is needed in pathological conditions.

A kinetic model of copper homeostasis in Saccharomyces cerevisiae

Genotype distribution of human papillomavirus among women with cervical cancer stratified by HIV status in Tanzania

Background Cervical cancer (CC) is the leading cancer among women in Tanzania, especially among those between the ages of 15 and 44. The prevalence of high-risk Human papillomavirus (HR-HPV)-16/18 women in the general population at any given time is 3.3%. HR-HPVs 16 or 18 are the primary cause of CC. The distribution of HPV genotypes among women with CC according to HIV status is unknown in Tanzania. This study aimed to determine the HPV genotype distribution according to HIV status among women with CC in Tanzania. Methods This cross-sectional study was done at Ocean Road Cancer Institute (ORCI) in Tanzania among women with histologically confirmed CC. HIV serology testing was performed. Biopsy was taken from cervical lesions, and DNA was extracted. HPV DNA was amplified by using a previously validated multiplex HPV PCR assay targeting 14 high-risk HPV genotypes (16,18,30,31,33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) and two low‐risk HPV genotypes (6 and 11). Continuous variables were compared using either a student t-test or the Mann-Whitney U test. Fisher’s exact test was employed to compare discrete variables. A P-value less than 0.05 was considered statistically significant. Results We included 100 women with CC. The prevalence of HIV infection in this study was 42%. The prevalence of any HPV infection was 94%, ranging from 1–3 genotypes per woman. HPV. The median age for women living with HIV (WLWH) with CC patients was 45 years (IQR, 31–60), while the median age for HIV-uninfected women with CC patients was 57 years (IQR, 30–78). (p = 0.0001). WLWH and HIV-uninfected women had similar HPV prevalence, except for HPV 35, which was more common in WLWH. There was a trend of high prevalence of HPV 52 and HPV 58 in WLHH compared to HIV-uninfected women, but this difference was not statistically significant. The prevalence of HPV 16 and/or 18 infection in the entire sample was 85%. The combined prevalence of HPV 16 and/or 18 was 76% WLWH and 91% amongst HIV-uninfected women (p = 0.036).The majority of women (77.9%) had single-genotype HPV infection. There was no difference in the distribution of multiple or single HPV genotypes infection by HIV status (p = 0.25). Conclusion In this study, HIV positive women with CC presented at a significantly younger age (45 years) compared to the HIV-negative women (57 years). The prevalence of high-risk HPV is high among women with CC in Tanzania. Distribution of most high-risk HPV genotypes among women with CC was not significantly influenced by HIV status except for HPV 35, which appeared to be more in HIV positive women compared to HIV-negative women. While the majority of the high-risk HPV infections were with single HPV genotypes, the prevalence of multiple high-risk HPV infections was at 22%, with no significant difference between the two HIV statuses. A vaccination program that aptly targets HPV 16 and 18 could prevent up to 85% of CC cases in Tanzania, regardless of HIV. Keywords: Human papillomavirus, cervical cancer, HIV, Tanzania.

PERK and IRE1α promote exosome secretion via blocking lysosomal degradation of multiple vesicular body

Bayesian robust symmetric regression for medical data with heavy-tailed errors and censoring

Bayesian symmetric regression offers a principled framework for modeling data characterized by heavy-tailed errors and censoring, both of which are frequently encountered in medical research. Classical regression methods often yield unreliable results in the presence of outliers or incomplete observations, as commonly seen in clinical and survival data. To address these limitations, we develop a robust Bayesian regression model that incorporates symmetric error distributions such as the Student-t and Cauchy, providing improved resistance to extreme values. The model also explicitly accounts for both right and left censoring through its likelihood structure. Inference is performed using Markov Chain Monte Carlo (MCMC), allowing for accurate estimation of uncertainty. The proposed approach is validated through simulation studies and two real-world medical applications: lung cancer survival analysis and hospital stay duration modeling. Results indicate that the model consistently outperforms traditional methods when dealing with noisy, censored, and non-Gaussian data, highlighting its potential for broad use in medical statistics and health outcome research.

Microcurrent stimulation induces cell death in p53-mutant and 5-FU-resistant breast cancer

Scalable quality control on processing of large diffusion-weighted and structural magnetic resonance imaging datasets

Thorough quality control (QC) can be time consuming when working with large-scale medical imaging datasets, yet necessary, as poor-quality data can lead to erroneous conclusions or poorly trained machine learning models. Most efforts to reduce data QC time rely on quantitative outlier detection, which cannot capture every instance of algorithm failure. Thus, there is a need to visually inspect every output of data processing pipelines in a scalable manner. We design a QC pipeline that allows for low time cost and effort across a team setting for a large database of diffusion-weighted and structural magnetic resonance images. Our proposed method satisfies the following design criteria: 1.) a consistent way to perform and manage quality control across a team of researchers, 2.) quick visualization of preprocessed data that minimizes the effort and time spent on the QC process without compromising the condition/caliber of the QC, and 3.) a way to aggregate QC results across pipelines and datasets that can be easily shared. In addition to meeting these design criteria, we also provide a comparison experiment of our method to an automated QC method for a T1-weighted dataset of N=1560 images and an inter-rater variability experiment for several processing pipelines. The experiments show mostly high agreement among raters and slight differences with the automated QC method. While researchers must spend time on robust visual QC of data, there are mechanisms by which the process can be streamlined and efficient.

Failed cellular surveillance enables pathogenic matrix deposition in a COL2A1-related osteoarthritis

Study on bearing capacity of Mortise-tenon and joint-flange concrete assembled foundation of transmission line under combined load

Mortise-tenon and joint-flange assembled foundation has excellent application as a new type of slab concrete assembled foundation, but there is a lack of research on its bearing capacity. In order to explore the mechanical characteristics and bearing capacity of this type of foundation under combined load (uplift-horizontal load), which is different from the traditional cast-in-place foundation, the uplift bearing model of mortise-tenon and joint-flange assembled foundation and the uplift model of cast-in-place foundation with the same specification were established based on the actual geological environment by finite element software. The stress distribution, vertical and horizontal displacements, and uplift and horizontal bearing capacities of the foundations were simulated and calculated. This study found that the bearing capacity of the Mortise-tenon and joint-flange assembled foundation has not been fully utilized. Specifically, the deformation of the foundation mainly concentrates on the main column, and the load is unable to be transmitted to the lower structure through the flange. Under combined loading (uplift-horizontal load), the load-displacement relationship curve can be roughly divided into three stages: linear slow rise stage, plastic accelerated rise stage, and linear failure stage. During the pull-out process, the foundation demonstrates stress characteristics of segmented load transmission. After the concrete upper column yields, the mortise-tenon and joint-flange connection node receives the load transmitted by the upper column, and continues to transmit the load to the lower column of the foundation after the displacement of the node reaches its limit. When the uplift cumulative displacement of the foundation reaches approximately 13 mm and the horizontal cumulative displacement reaches around 10 mm, the foundation reaches its ultimate state. At this point, its ultimate bearing capacity surpasses that of the cast-in-place foundation of the same specification, with significant improvement. The ultimate uplift bearing capacity increases by 33.34%, while the ultimate horizontal bearing capacity increases by 48.09%.

GoLoco/GPR motif-dependent regulation of Rap1GAP1 by Gαo is disrupted by Gαo encephalopathy variants

Correction: Effects of a low-carbohydrate diet in adults with type 1 diabetes management: A single arm non-randomised clinical trial

Extensive citrullination of human serum albumin is physiological and not inherently immunogenic in rheumatoid arthritis

Divergent trends in structural landscape connectivity from historic and potential future grassland conversion in Alberta, Canada

Grasslands across the Canadian prairies are crucial for maintaining biodiversity and ensuring landscape connectivity. In Alberta, a large portion of natural grasslands has been converted to agricultural cropland or other land uses, while the remaining natural grasslands are mainly used as rangeland. However, with increasing crop demand and food security concerns, there is a potential risk of further grassland conversion to cropland, particularly in areas where climate change may enhance suitability for farming. Here, we (1) quantified the impact of the present state of grasslands on maintaining landscape permeability; and (2) determined how the conversion of remaining grasslands to croplands could affect structural landscape connectivity at multiple spatial scales. We simulated four progressive scenarios of grassland conversion to cropland, starting with grasslands identified as most suitable for farming. Our results revealed that structural landscape connectivity, quantified as mean normalized current density with resistance values based on naturalness, decreased by up to 43% in southwestern and central areas of the Parkland and Grassland regions with higher rates of conversion. Conversion scenarios introduced new areas with notably constrained ecological flow in the Grassland region in the southeastern part of the province. Conversely, increased current density was observed in the Rocky Mountain and Boreal regions, which appear to act as alternative pathways for redirected ecological flow. Future grassland conversion is expected to further shift current flow from the grasslands westward through the foothills of the Rocky Mountain and northward into the Parkland and Boreal regions. These findings underscore the critical role of grasslands in maintaining structural landscape connectivity across Alberta, which is essential for supporting biodiversity and gene flow among species. Simulated changes in connectivity were most pronounced at the finer spatial scale, revealing key areas of past and future permeability shifts. Incorporating local land management decisions is crucial for improving landscape permeability and effective connectivity planning province-wide.