Search

The mutation-selection mechanism of Darwinian evolution gives rise not only to adaptation to environmental conditions but also to the enhancement of robustness against mutations. When two or more phenotypes have the same fitness value, the robustness distribution for different phenotypes can vary. Thus, we expect that some phenotypes are favored in evolution and that some are hardly selected because of a selection bias for mutational robustness. In this study, we investigated this selection bias for phenotypes in a model of gene regulatory networks (GRNs) using numerical simulations. The model had one input gene accepting a signal from the outside and one output gene producing a target protein, and the fitness was high if the output for the full signal was much higher than that for no signal. The model exhibited three types of responses to changes in the input signal: monostable, toggle switch, and one-way switch. We regarded these three response types as three distinguishable phenotypes. We constructed a randomly generated set of GRNs using the multicanonical Monte Carlo method originally developed in statistical physics and compared it to the outcomes of evolutionary simulations. One-way switches were strongly suppressed during evolution because of their lack of mutational robustness. By examining one-way switch GRNs in detail, we found that mutationally robust GRNs obtained by evolutionary simulations and non-robust GRNs obtained by McMC have different network structures. While robust GRNs have a common core motif, non-robust GRNs lack this motif. The bistability of non-robust GRNs is considered to be realized cooperatively by many genes, and these cooperative genotypes have been suppressed by evolution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Macoto Kikuchi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genomic prediction (GP) has been evaluated in durum wheat breeding programs for several years, but prediction accuracy (PA) remains insufficient for some traits. Recently, multivariate (MV) analysis has gained much attention due to its potential to significantly improve PA. In this study, PA was evaluated for several agronomic traits using a univariate (UV) model in durum wheat, subsequently, different multivariate genomic prediction models were performed to attempt to increase PA. The panel was phenotyped for 10 agronomic traits over two consecutive crop seasons and under two different field conditions: high nitrogen and well-watered (HNW), and low nitrogen and rainfed (LNR). Multivariate GP was implemented using two cross-validation (CV) schemes: MV-CV1, testing the model for each target trait using only the markers, and MV-CV2, testing the model for each target trait using additional phenotypic information. These two MV-CVs were applied in two different analyses: modelling the same trait under both HNW and LNR conditions, and modelling grain yield together with the five most genetically correlated traits. PA for all traits in HNW was higher than LNR for the same trait, except for the trait yellow index. Among all traits, PA ranged from 0.34 (NDVI in LNR) to 0.74 (test weight in HNW). In modelling the same traits in both HNW and LNR, MV-CV1 produced improvements in PA up to 12.45% (NDVI in LNR) compared to the univariate model. By contrast, MV-CV2 increased PA up to 56.72% (thousand kernel weight in LNR). The MV-CV1 scheme did not improve PA for grain yield when it was modelled with the five most genetically correlated traits, whereas MV-CV2 significantly improved PA by up to ~18%. This study demonstrated that increases in prediction accuracy for agronomic traits can be achieved by modelling the same traits in two different field conditions using MV-CV2. In addition, the effectiveness of MV-CV2 was established when grain yield was modelled with additional correlated traits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

The genus Prototheca (alga) comprises a unique group of achlorophyllic saprotrophic and mammalian pathogen species. Despite its rare occurrence in humans and animals, protothecosis is considered an emerging clinical entity with relevance in immunocompromised patients. In this study, the characterization of spherical structures with endospores recovered from a blood culture in an HIV patient was investigated using phenotypic and molecular methodologies. On 2% Sabouraud dextrose agar, the isolate displayed morphological and biochemical characteristics found on isolates identified as Prototheca wickerhamii. To validate these analyses, molecular phylogeny of the internal transcript space (ITS) partial gene confirmed the identity of the isolate as P. wickerhamii. This is the first case of systemic human protothecosis in Brazil. The present case of human Prototheca and those reported in the medical literature highlight the need for novel methodologies to identify pathogenic algae in the clinical laboratory, improving in this way the diagnosis and treatment of this group of neglected pathogens., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Duarte-Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Genome-wide association studies (GWAS) provide valuable insights into the genetic architecture of complex traits, yet interpreting their results remains challenging due to the polygenic nature of most traits. Gene set analysis offers a solution by aggregating genetic variants into biologically relevant pathways, enhancing the detection of coordinated effects across multiple genes. In this study, we present and evaluate a gene set prioritization approach utilizing Bayesian Linear Regression (BLR) models to uncover shared genetic components among different phenotypes and facilitate biological interpretation. Through extensive simulations and analyses of real traits, we demonstrate the efficacy of the BLR model in prioritizing pathways for complex traits. Simulation studies reveal insights into the model's performance under various scenarios, highlighting the impact of factors such as the number of causal genes, proportions of causal variants, heritability, and disease prevalence. Comparative analyses with MAGMA (Multi-marker Analysis of GenoMic Annotation) demonstrate BLR's superior performance, especially in highly overlapped gene sets. Application of both single-trait and multi-trait BLR models to real data, specifically GWAS summary data for type 2 diabetes (T2D) and related phenotypes, identifies significant associations with T2D-related pathways. Furthermore, comparison between single- and multi-trait BLR analyses highlights the superior performance of the multi-trait approach in identifying associated pathways, showcasing increased statistical power when analyzing multiple traits jointly. Additionally, enrichment analysis with integrated data from various public resources supports our results, confirming significant enrichment of diabetes-related genes within the top T2D pathways resulting from the multi-trait analysis. The BLR model's ability to handle diverse genomic features, perform regularization, conduct variable selection, and integrate information from multiple traits, genders, and ancestries demonstrates its utility in understanding the genetic architecture of complex traits. Our study provides insights into the potential of the BLR model to prioritize gene sets, offering a flexible framework applicable to various datasets. This model presents opportunities for advancing personalized medicine by exploring the genetic underpinnings of multifactorial traits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gholipourshahraki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Patient-derived organoids provide a unique model system to explore disease-causing mutations ex vivo. By using organoids from duodenal or colonic biopsies of pediatric patients with intestinal epithelial disorders, we can directly assay the patient cells to tailor treatment to their unique disease state. The advent of organoid technology from patients with severe intestinal disorders such as Congenital Diarrhea Enteropathies (CoDE) and Very-Early-Onset Inflammatory Bowel Disease (VEO-IBD) has allowed for rapid advances in the understanding of and the treatment of these monogenic disorders. Still, the expansion of these lines for scalable studies is not trivial, and success rates of expansion are variable between groups, and even lab members within the same group. These protocols have been validated on patients with CoDE or VEO-IBD and age-matched control patients. Here, we present our recommended protocols for the cultivation of organoids from pediatric patients with CoDE and VEO-IBD. These protocols have been validated on organoids generated from the duodenum (duodenoids), ileum (ileoids), colon (colonoids) and iPSC-derived intestinal colonoids from pediatric healthy donors or donors with CoDE or VEO-IBD (Gwilt et al., 2023). Using our modified culture media, extended culture times from biopsy preparation and thawing frozen lines, gentle passaging techniques with the incomplete removal of the organoids from the matrigel, and modified monolayer protocols (Maeda et al., 2023; Maeda et al., 2022), we have been able to successfully culture and expand several lines for more than 5 years. The conditions and protocols used here provide a basis for reproducible phenotypes, scaling for larger functional studies on patient lines, and for reproducibility of results between several investigators. We provide a useful starting point and troubleshooting guidelines for the optimization of culturing organoids from any patient with novel disease pathology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bugda Gwilt, Thiagarajah. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The increasing availability of enzyme turnover number measurements from experiments and of turnover number predictions from deep learning models prompts the use of these enzyme parameters in precise metabolic engineering. Yet, there is no computational approach that allows the prediction of metabolic engineering strategies that rely on the modification of turnover numbers. It is also unclear if modifications of turnover numbers without alterations in the host's transcriptional regulatory machinery suffice to increase the production of chemicals of interest. Here, we present a constraint-based modeling approach, termed Overcoming Kinetic rate Obstacles (OKO), that uses enzyme-constrained metabolic models to predict in silico strategies to increase the production of a given chemical, while ensuring specified cell growth. We demonstrate that the application of OKO to enzyme-constrained metabolic models of Escherichia coli and Saccharomyces cerevisiae results in strategies that can at least double the production of over 40 compounds with little penalty to growth. Interestingly, we show that the overproduction of compounds of interest does not entail only an increase in the values of turnover numbers. Lastly, we demonstrate that a refinement of OKO, allowing also for manipulation of enzyme abundance, facilitates the usage of the available compendia and deep learning models of turnover numbers in the design of precise metabolic engineering strategies. Our results expand the usage of genome-scale metabolic models toward the identification of targets for protein engineering, allowing their direct usage in the generation of innovative metabolic engineering designs for various biotechnological applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Razaghi-Moghadam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Aedes albopictus (Skuse 1894) mosquitoes can transmit deadly arboviruses and are globally invasive due to their ability to survive in both tropical and temperate climates. Although adults cannot survive harsh winters, females are capable of anticipating seasonal change and producing overwintering diapause (DP) eggs that remain in a state of arrested development over the winter and hatch when favorable conditions return in the spring. While low temperatures can facilitate DP entry under short photoperiods, temperature signals alone are not sufficient to induce DP., Methodology/principal Findings: To identify maternal phenotypes predictive of DP egg production in laboratory conditions, we characterized aspects of maternal physiology and behavior to identify those that correlate with DP egg production and changes in photoperiod, versus changes in temperature. Neither changes in temperature nor photoperiod impacted protein preference, blood meal consumption, or total number of eggs produced per female. Egg retention and oviposition timing were influenced by temperature, independent of DP egg production. However, females housed under short photoperiod conditions showed increased starvation resistance, despite showing similar levels of locomotor activity and internal stores of triacylglycerols, glucose, glycogen, and trehalose compared to females housed in long photoperiods., Conclusions/significance: These results suggest that temperature and photoperiod differentially affect maternal phenotypes and identify starvation resistance as a maternal phenotype that is influenced by photoperiod and correlates with DP egg status., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plasmodium falciparum infections elicit strong humoral immune responses to two main groups of antigens expressed by blood-stage parasites: merozoite antigens that are involved in the erythrocyte invasion process and variant surface antigens that mediate endothelial sequestration of infected erythrocytes. Long-lived B cells against both antigen classes can be detected in the circulation for years after exposure, but have not been directly compared. Here, we studied the phenotype of long-lived memory and atypical B cells to merozoite antigens (MSP1 and AMA1) and variant surface antigens (the CIDRα1 domain of PfEMP1) in ten Ugandan adults before and after local reduction of P. falciparum transmission. After a median of 1.7 years without P. falciparum infections, the percentage of antigen-specific activated B cells declined, but long-lived antigen-specific B cells were still detectable in all individuals. The majority of MSP1/AMA1-specific B cells were CD95+CD11c+ memory B cells, which are primed for rapid differentiation into antibody-secreting cells, and FcRL5-T-bet- atypical B cells. On the other hand, most CIDRα1-specific B cells were CD95-CD11c- memory B cells. CIDRα1-specific B cells were also enriched among a subset of atypical B cells that seem poised for antigen presentation. These results point to differences in how these antigens are recognized or processed by the immune system and how P. falciparum-specific B cells will respond upon re-infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Reyes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clonorchis sinensis infection is an important risk factor for cholangiocarcinoma (CCA). It has been reported that extracellular vesicles (EVs) are involved in the parasite-host interaction, and EVs of C. sinensis (CsEVs) can contribute to biliary injuries and inflammation. However, uncertainty surrounds the function of CsEVs in the progression of CCA. In this study, differential ultracentrifugation was used to separate CsEVs from the culture supernatant of C. sinensis adult worms, and they were then identified by transmission electron microscopy, nanoparticle tracking analysis and proteome assays. CCK8, EdU-488 and colony formation assays were used to explore the effect of CsEVs on the proliferation of CCA cells in vitro. Wound healing assays, transwell assays and in vivo lung metastasis model were conducted to evaluate the migration and invasion abilities. Moreover, the involvement of EMT process, as well as NF-κB and ERK signaling pathway was assessed. Results showed that CsEVs were successfully isolated and could be taken up by CCA cells, which promoted proliferation by accelerating cell cycle progression. In addition, CsEVs could facilitate cell metastasis by triggering the epithelial-mesenchymal transition (EMT). Mechanistically, activation of NF-κB signaling pathway was involved in the CsEVs-mediated EMT, which could be reversed partly by BAY 11-7082 (an inhibitor of NF-κB). In conclusion, these findings suggested that CsEVs could induce the aberrant proliferation and metastasis of CCA cells by stimulating the NF-κB/EMT axis, providing a novel theoretical explanation for liver fluke-associated CCA., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although the Djungarian hamster (Phodopus sungorus) is a seasonality model, it presents substantial variability in winter acclimation. In response to short photoperiod, some individuals express a suite of winter traits such as low body mass, regressed gonads, white fur, and daily torpor, while others develop only some adjustments or maintain a summer phenotype. Despite comprehensive research, the mechanisms underlying polymorphism of winter phenotype are still unknown. We compared key elements of the hypothalamic thyroid hormone system, as well as the tanycyte architecture in hamsters of both sexes. Individuals presented different responses to short photoperiod characterized either as phenotypes (non-responder, partial-responder and full-responder) or photoresponsive index. We measured the expression of genes coding iodothyronine deiodinase 2 and 3, monocarboxylate transporter 8, thyrotropin-releasing hormone, and somatostatin in 40 individuals and counted the number of immunolabeled tanycyte processes in standardized regions of interest around the third ventricle in 30 individuals. Animals acclimated to short photoperiod presented a downregulation of diodinase 2 and somatostatin and an upregulation of deiodinase 3, as well as a decreased number of tanycyte processes, compared to long photoperiod-exposed individuals. Although phenotypes did not differ in gene expression, the higher the photoresponsive index, the lower was the deiodinase 2 expression and the higher the deiodinase 3 expression. Partial-responders and full-responders had less tanycyte processes than non-responders, and the number of tanycyte processes correlated with the photoresponsive index. Sexes differed neither in their seasonal response, nor hypothalamic gene expression, but females had more tanycyte processes. Our results are in accordance with studies emphasizing the pivotal role of thyroid hormones in seasonal response. We suggest that the whole spectrum of winter phenotypes exists within the population of Djungarian hamsters and that it is reflected also at the level of neuroendocrine regulation. However, the neuroendocrine underpinnings of winter phenotype polymorphism require further investigation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Przybylska-Piech et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To summarize and meta-analyze uveitis characteristics and multiple sclerosis (MS) phenotype of patients with multiple sclerosis-associated uveitis (MSAU) within a systematic review and meta-analysis., Methods: A comprehensive literature search was performed on January 25, 2023, utilizing PubMed, Embase, and Virtual Health Library (VHL) databases. We included studies involving patients with MSAU, such as case series with over 10 patients, cross-sectional, case-control, and cohort studies. Quality and risk of bias were assessed using CLARITY tools and validated metrics like the Hoy et al. and Hassan Murad et al. tools. The pooled analysis focused on 1) uveitis characteristics, 2) ocular complications, 3) MS phenotype, and 3) administered treatments for uveitis and MS. Gender-based subgroup analysis was conducted across continents; heterogeneity was measured using the I2 statistic. Statistical analysis was performed using R software version 4.3.1. The study was registered in PROSPERO with CRD42023453495 number., Results: Thirty-six studies were analyzed (24 with a low risk of bias, 8 with some concerns, and 4 with a high risk of bias), including 1,257 patients and 2,034 eyes with MSAU. The pooled analysis showed a mean age of 38.2 ± 12.1 years with a notable female predominance (67%, 95% CI [59%-73%]). MS before uveitis was seen in 59% of the cases (95% CI [48%-69%]), while uveitis was present before MS in 38% (95% CI [30%-48%]). The mean age for the first uveitis episode was 35.7 ± 8.3 years, predominantly affecting both eyes (77%, 95% CI [69%-83%], from 23 studies involving 452 patients). Intermediate uveitis was the most frequent anatomical location (68%, 95% CI [49%-82%], from 22 studies involving 530 patients), often following a recurrent course (63%, 95% CI [38%-83%]). Key complications included vision reduction (42%, 95% CI [19%-70%], from five articles involving 90 eyes), macular compromise (45%, 95% CI [20%-73%], from 4 studies involving 95 eyes), and cataracts (46%, 95% CI [32%-61%], from eight articles involving 230 eyes). Concerning MS phenotype, relapsing-remitting MS (RRMS) was the most common subtype (74%, 95% CI [64%-82%], from eight articles involving 134 patients), followed by secondary progressive MS (24%, 95% CI [18%-33%], from eight articles involving 125 patients). The most frequently occurring central nervous lesions were supratentorial (95%, 95% CI [70%-99%], from two articles involving 17 patients) and spinal cord (39%, 95% CI [16%-68%], from two articles involving 29 patients). The mean Expanded Disability Status Scale (EDSS) score and annual recurrence rates were 2.9 ± 0.6 and 1.07 ± 0.56, respectively. Treatment trends showed the prevalent use of Fingolimod (96%, 95% CI [17%-100%], from two articles involving 196 patients), Mycophenolate (48%, 95% CI [11%-87%], from four articles involving 51 patients), and Interferon-beta (43%, 95% CI [24%-65%], from 11 articles involving 325 patients)., Conclusion: MSAU primarily affects young adult females, typically presenting as bilateral intermediate uveitis with vision-related complications. The most common MS phenotype is RRMS, often associated with supratentorial and spinal cord lesions on imaging. These findings give ophthalmologists and neurologists a comprehensive clinical picture of MSAU, facilitating prompt diagnosis., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Saboya-Galindo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The amylose content can significantly impact the diverse industrial applications of cassava starch. This study aimed to assess the variability of cassava germplasm concerning amylose content and other attributes pertinent to root quality, alongside its correlation with paste properties. Starch extracted from 281 genotypes, obtained in germplasm evaluation trials, was evaluated for amylose content, with additional analysis of parameters such as pasting temperature, time to peak viscosity (TPV), viscosity breakdown (BrD), retrogradation tendency, and maximum, minimum, and final viscosities. The genotypes exhibited considerable variation in dry matter content (ranging from 27.06% to 41.02%), starch content (from 14.61% to 25.67%), cyanogenic compounds (1.77 to 7.81), and amylose content (0.05% to 33.23%). High phenotypic variability in paste properties was observed, alongside a low residual effect for most traits, resulting in high broad-sense heritabilities (>0.95). Strong correlations of significant magnitude (>0.80) were found between parameters such as peak viscosity × viscosity breakdown, minimum viscosity × final viscosity, and final viscosity × retrogradation tendency. Moderate correlations were also identified, such as between dry matter content × starch content (0.56). While positive, correlations between amylose content and paste properties were of low magnitude (ranging from 0.13 to 0.35), except for TPV and BrD. Principal component discriminant analysis clustered the germplasm into six distinct groups based on root quality and paste properties, with most improved genotypes falling into two clusters characterized by high starch and dry matter contents. This study underscores the necessity of simultaneous evaluation of amylose content and paste properties in the breeding pipeline. Additionally, clustering cassava genotypes proves beneficial in identifying those that fulfill specific requirements in industrial and breeding applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ribeiro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Isolating microorganisms from natural environments for cultivation under optimized laboratory settings has markedly improved our understanding of microbial ecology. Artificial growth conditions often diverge from those in natural ecosystems, forcing wild isolates into distinct selective pressures, resulting in diverse eco-physiological adaptations mediated by modification of key phenotypic traits. For motile microorganisms we still lack a biophysical understanding of the relevant traits emerging during domestication and their mechanistic interplay driving short-to-long-term microbial adaptation under laboratory conditions. Using microfluidics, atomic force microscopy, quantitative imaging, and mathematical modeling, we study phenotypic adaptation of Chromatium okenii, a motile phototrophic purple sulfur bacterium from meromictic Lake Cadagno, grown under laboratory conditions over multiple generations. Our results indicate that naturally planktonic C. okenii leverage shifts in cell-surface adhesive interactions, synergistically with changes in cell morphology, mass density, and distribution of intracellular sulfur globules, to suppress their swimming traits, ultimately switching to a sessile lifeform. A computational model of cell mechanics confirms the role of such phenotypic shifts in suppressing the planktonic lifeform. By investigating key phenotypic traits across different physiological stages of lab-grown C. okenii, we uncover a progressive loss of motility during the early stages of domestication, followed by concomitant deflagellation and enhanced surface attachment, ultimately driving the transition of motile sulfur bacteria to a sessile state. Our results establish a mechanistic link between suppression of motility and surface attachment via phenotypic changes, underscoring the emergence of adaptive fitness under laboratory conditions at the expense of traits tailored for natural environments., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Di Nezio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The audiological features of hearing loss (HL) in patients with autosomal recessive deafness type 1A (DFNB1A) caused by splice site variants of the GJB2 gene are less studied than those of patients with other variants of this gene. In this study, we present the audiological features of DFNB1A in a large cohort of 134 patients with the homozygous splice site variant c.-23+1G>A and 34 patients with other biallelic GJB2 genotypes (n = 168 patients with DFNB1A). We found that the preservation of hearing thresholds in the speech frequency range (PTA0.5,1.0,2.0,4.0 kHz) in patients with the c.[-23+1G>A];[-23+1G>A] genotype is significantly better than in patients with the "severe" c.[35delG];[35delG] genotype (p = 0.005) and significantly worse than in patients with the "mild" c.[109G>A];[109G>A] genotype (p = 0.041). This finding indicates a "medium" pathological effect of this splice site variant on hearing function. A detailed clinical and audiological analysis showed that in patients with the c.[-23+1G>A];[-23+1G>A] genotype, HL is characterized as congenital or early onset (57.5% onset before 12 months), sensorineural (97.8%), bilateral, symmetrical (82.8%), variable in severity (from mild to profound HL, median hearing threshold in PTA0.5,1.0,2.0,4.0 kHz is 86.73±21.98 dB), with an extremely "flat" audioprofile, and with a tendency toward slow progression (a positive correlation of hearing thresholds with age, r = 0.144, p = 0.041). In addition, we found that the hearing thresholds in PTA0.5,1.0,2.0,4.0 kHz were significantly better preserved in females (82.34 dB) than in males (90.62 dB) (p = 0.001). We can conclude that in patients with DFNB1A caused by the c.-23+1G>A variant, male sex is associated with deteriorating auditory function; in contrast, female sex is a protective factor., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Teryutin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Developing lettuce varieties with salt tolerance at the seed germination stage is essential since lettuce seeds are planted half an inch deep in soil where salt levels are often highest in the salinity-affected growing regions. Greater knowledge of genetics and genomics of salt tolerance in lettuce will facilitate breeding of improved lettuce varieties with salt tolerance. Accordingly, we conducted a genome-wide association study (GWAS) in lettuce to identify marker-trait association for salt tolerance at the seed germination stage. The study involved 445 diverse lettuce accessions and 56,820 single nucleotide polymorphism (SNP) markers obtained through genotype-by-sequencing technology using lettuce reference genome version v8. GWAS using two single-locus and three multi-locus models for germination rate (GR) under salinity stress, 5 days post seeding (GR5d_S) and a salinity susceptibility index (SSI) based on GR under salinity stress and control conditions, 5 days post seeding (SSI_GR5d) revealed 10 significant SNPs on lettuce chromosomes 2, 4, and 7. The 10 SNPs were associated with five novel QTLs for salt tolerance in lettuce, explaining phenotyping variations of 5.85%, 4.38%, 4.26%, 3.77%, and 1.80%, indicating the quantitative nature of these two salt tolerance-related traits. Using the basic local alignment search tool (BLAST) within 100 Kb upstream and downstream of each of the 10 SNPs, we identified 25 salt tolerance-related putative candidate genes including four genes encoding for major transcription factors. The 10 significant salt tolerance-related SNPs and the 25 candidate genes identified in the current study will be a valuable resource for molecular marker development and marker-assisted selection for breeding lettuce varieties with improved salt tolerance at the seed germination stage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Breast cancer remains a significant global health challenge. Understanding its etiological factors, particularly the role of immune system components, is crucial. This study leverages Mendelian randomization (MR) to investigate the causal relationship between various immune cell features and the risk of developing breast cancer., Methods: Utilizing two-sample MR analysis, we examined 731 immune cell features across 7 groups for their potential causal links to breast cancer. We analyzed genome-wide association studies (GWAS) data of 257,730 Europeans, comprising 17,389 cases and 240,341 controls, focusing on 24,133,589 single nucleotide polymorphisms (SNPs). Instrumental variables (IVs) were selected based on genetic associations, with rigorous statistical methods employed, including inverse variance weighting (IVW) and weighted median-based estimation., Results: Our analysis identified 20 immunophenotypes with significant causal associations with breast cancer risk. Notably, contain B cell, mature T cell, T + B + NK (TBNK) cells, regulatory T (Treg) cell, Classic dendritic cells (cDCs), Monocyte, and Myeloid cell group features displayed positive or negative correlations with breast cancer. For instance, specific B cell phenotypes were found to have both positive and negative causal relationships with breast cancer. Additionally, reverse MR analysis revealed no significant causal effects of breast cancer on these immune characteristics., Conclusions: This study underscores the complex interplay between various immune cell phenotypes and breast cancer risk. The identified immunophenotypes could be potential biomarkers or targets for future therapeutic interventions. Our findings contribute to a deeper understanding of the immunological dimensions of breast cancer etiology., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Recognizing the influence of pathogen diversity on infection dynamics is crucial for mitigating emerging infectious diseases. Characterising such diversity is often complex, for instance when multiple pathogen variants exist that interact differently with the environment and host. Here, we explore genotypic and phenotypic variation of Batrachochytrium salamandrivorans (Bsal), an emerging fungal pathogen that is driving declines among an increasing number of European amphibian species. For thirteen isolates, spanning most of the known temporal and geographical Bsal range in Europe, we mapped phenotypic diversity through numerous measurements that describe varying reproductive rates in vitro across a range of temperatures. Bsal isolates are revealed to have different thermal optima and tolerances, with phenotypic variation correlating with genomic diversity. Using a mechanistic niche model of the fire salamander (Salamandra salamandra) as an example, we illustrate how host steady-state body temperature and Bsal thermal range variation may influence pathogen growth through space and time across Europe. Our combined findings show how the identity of emergent pathogen variants may strongly influence when and which host populations are most at risk., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kelly et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The relationship between dysregulation of the immune system and reproductive health, particularly in the context of abortion, is an area of critical research. Identifying the immunological factors that contribute to abortion could provide valuable insights into its prevention and management., Methods: This study used bidirectional two-sample Mendelian Randomization (MR) approach to evaluate the causal link between 731 immune cell features and the risk of abortion. The study analyzed GWAS data from 257,561 Europeans, including 7,069 cases and 250,492 controls, by utilizing genetic variation as instrumental variables. The immune phenotypes included several cell types, including B cells, T cells, TBNK cells, Treg cells, and monocytes. These were analyzed using the 'TwoSampleMR' package in R software., Results: The study identified 34 immune phenotypes that have a significant causal relationship with abortion risk. Notably, Results from the B cell group showed a positive correlation between abortion and certain phenotypes, including Unsw mem %B cell, PB/PC %B cell, IgD+ CD24+ %B cell and Naive-mature B cell %lymphocyte. In the T cell group, certain maturation stages such as Naive CD8br %T cell and CD4 on CD45RA+ CD4+ exhibited negative causal links, whereas CCR7 on naive CD8br showed a positive association. The group of Treg cells showed both positive and negative causal relationships with abortion, highlighting the complexity of immune regulation in reproductive health., Conclusions: This study reflects the causal relationship between different subtypes of different immune cells and abortion. The results underscore the importance of the immune system in reproductive health and suggest potential therapeutic interventions targeting these immunological pathways., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In both statistical genetics and phylogenetics, a major goal is to identify correlations between genetic loci or other aspects of the phenotype or environment and a focal trait. In these 2 fields, there are sophisticated but disparate statistical traditions aimed at these tasks. The disconnect between their respective approaches is becoming untenable as questions in medicine, conservation biology, and evolutionary biology increasingly rely on integrating data from within and among species, and once-clear conceptual divisions are becoming increasingly blurred. To help bridge this divide, we lay out a general model describing the covariance between the genetic contributions to the quantitative phenotypes of different individuals. Taking this approach shows that standard models in both statistical genetics (e.g., genome-wide association studies; GWAS) and phylogenetic comparative biology (e.g., phylogenetic regression) can be interpreted as special cases of this more general quantitative-genetic model. The fact that these models share the same core architecture means that we can build a unified understanding of the strengths and limitations of different methods for controlling for genetic structure when testing for associations. We develop intuition for why and when spurious correlations may occur analytically and conduct population-genetic and phylogenetic simulations of quantitative traits. The structural similarity of problems in statistical genetics and phylogenetics enables us to take methodological advances from one field and apply them in the other. We demonstrate by showing how a standard GWAS technique-including both the genetic relatedness matrix (GRM) as well as its leading eigenvectors, corresponding to the principal components of the genotype matrix, in a regression model-can mitigate spurious correlations in phylogenetic analyses. As a case study, we re-examine an analysis testing for coevolution of expression levels between genes across a fungal phylogeny and show that including eigenvectors of the covariance matrix as covariates decreases the false positive rate while simultaneously increasing the true positive rate. More generally, this work provides a foundation for more integrative approaches for understanding the genetic architecture of phenotypes and how evolutionary processes shape it., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Schraiber et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Analysis of existing mutations of Angiotensin-I-Converting Enzyme (ACE) led us to hypothesize that the carriers of damaging ACE mutations (accompanied by low ACE levels) could be at risk for the development of late-onset Alzheimer's disease (AD)., Methodology/principal Findings: We quantified blood ACE levels in EDTA-containing plasma from 15 patients with 11 different heterozygous ACE mutations and estimated the effects of these mutations on ACE phenotypes, using a set of mAbs to ACE and two ACE substrates. We confirmed prior observations that the relatively frequent Y215C mutation in the N domain of ACE (present in ~1% of the population) is associated with both Alzheimer's disease (AD) and reduced plasma levels of ACE (~50% of controls), indicating that it likely results in a transport-deficient protein. In addition, we identified another 4 mutations in both ACE domains (M118T, C734Y, V992M and V997M) which are also associated with decreased ACE levels in the blood, and, thus, could be putative risk factors for late-onset AD. One of these mutations, C734Y, is likely transport-deficient, while the other mutations appear to influence ACE catalytic properties. The precipitation of mutant M118T by mAb 2D1 and ACE mutant C734Y by mAb 3F10 increased 2-3-fold compared to native ACE, and therefore, these mAbs could be markers of these mutations. Also, we identified a mutation I989T, which is associated with increased ACE levels in the blood., Conclusions/significance: Conducting a systematic analysis of blood ACE levels in patients with ACE mutations holds promise for identifying individuals with low blood ACE levels. Such individuals may be at increased risk for late-onset AD. The patients with transport-deficient ACE mutations may benefit from therapeutic treatment with a combination of chemical and pharmacological chaperones and proteasome inhibitors, as was demonstrated previously using a cell model of the transport-deficient ACE mutation, Q1069R [Danilov et al, PLoS One, 2010]., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kryukova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Maize is one of the main food crops in the world, and cultivating high-yield and high-quality maize varieties is of great significance in addressing food security issues. Leaves are crucial photosynthetic organs in maize, and leaf senescence can result in the degradation of chlorophyll. This, in turn, impacts photosynthetic activity and the accumulation of photosynthetic products. Delaying leaf senescence and increasing carbon assimilation can enhance grain yield and biomass production. The stay green of maize is an important trait closely related to yield, feed quality and resistance. Therefore, this study employed multi-generation joint analysis of major genes and a polygene model to investigate the genetic inheritance of stay green-related traits. Four populations (P1, P2, F1 and F2) were obtained by crossing T01 (stay green) × Xin3 (non-stay green) and T01 (stay green) × Mo17 (non-stay green) under two environments. Six stay green-related traits, including visual stay green (VSG), number of green leaves (GLNM), SPAD value of ear leaf at anthesis (SPADS), SPAD value of ear leaf at maturity (SPADM), absolute green leaf area (GLAD), grain yield per plant (GYP), displayed continuous variations with kurtosis and skewness values of absolute value less than 1 and distribution close to normal. They were characterized by typical inheritance of quantitative traits, with these traits demonstrating the transgressive segregation. The correlation analysis among the traits revealed that five stay green traits have a positive impact on yield. VSG, GLNM and SPADM in the two populations were regulated by the two major genes of additive effects plus additive-dominance polygene model with a major gene heritability varying from 89.03 to 95.95% in the F2 generation. GLAD in TMF2 was controlled by two major genes of equal-additive dominance effects with high heritability (93.47%). However, in TXF2, GLAD was regulated by two major genes of additive-dominance interaction effects plus additive-dominance polygene model. These results provide important genetic information for breeding, which could guide the improvement of stay green-related traits. They also lay a foundation for quantitative trait loci mapping of the stay stay-green traits in maize., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Persons with germline variants in the tumor suppressor gene phosphatase and tensin homolog, PTEN, are molecularly diagnosed with PTEN hamartoma tumor syndrome (PHTS). PHTS confers high risks of specific malignancies, and up to 23% of the patients are diagnosed with autism spectrum disorder (ASD) and/or developmental delay (DD). The accurate prediction of these two seemingly disparate phenotypes (cancer vs. ASD/DD) for PHTS at the individual level remains elusive despite the available statistical prevalence of specific phenotypes of the syndrome at the population level. The pleiotropy of the syndrome may, in part, be due to the alterations of the key multi-functions of PTEN. Maintenance of genome integrity is one of the key biological functions of PTEN, but no integrative studies have been conducted to quantify the DNA damage response (DDR) in individuals with PHTS and to relate to phenotypes and genotypes. In this study, we used 43 PHTS patient-derived lymphoblastoid cell lines (LCLs) to investigate the associations between DDR and PTEN genotypes and/or clinical phenotypes ASD/DD vs. cancer. The dynamics of DDR of γ-irradiated LCLs were analyzed using the exponential decay mathematical model to fit temporal changes in γH2AX levels which report the degree of DNA damage. We found that PTEN nonsense variants are associated with less efficient DNA damage repair ability resulting in higher DNA damage levels at 24 hours after irradiation compared to PTEN missense variants. Regarding PHTS phenotypes, LCLs from PHTS individuals with ASD/DD showed faster DNA damage repairing rate than those from patients without ASD/DD or cancer. We also applied the reaction-diffusion partial differential equation (PDE) mathematical model, a cell growth model with a DNA damage term, to accurately describe the DDR process in the LCLs. For each LCL, we can derive parameters of the PDE. Then we averaged the numerical results by PHTS phenotypes. By performing simple subtraction of two subgroup average results, we found that PHTS-ASD/DD is associated with higher live cell density at lower DNA damage level but lower cell density level at higher DNA damage level compared to LCLs from individuals with PHTS-cancer and PHTS-neither., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The evolution of convergent phenotypes is of major interest in biology because of their omnipresence and ability to inform the study of evolutionary novelty and constraint. Convergent phenotypes can be combinations of traits that evolve concertedly, called syndromes, and these can be shaped by a common environmental pressure. Parasitoid wasps which use a wide variety of arthropod hosts have also repeatedly and convergently switched host use across their evolutionary history. They thus represent a natural laboratory for the evolution of trait syndromes that are associated with parasitism of specific hosts and host substrates. In this study, we tested the evolution of co-evolving characters in the highly diverse family Ichneumonidae associated with ovipositing in a specific and well-defined substrate: wood. Using a newly constructed phylogeny and an existing morphological dataset, we identified six traits correlated with the wood-boring lifestyle that demonstrate convergent evolution. At least one trait, the presence of teeth on the ovipositor, typically preceded the evolution of other traits and possibly the switch to parasitism of wood-boring hosts. For each trait, we provide a historical review of their associations with wood-boring parasitoids, reevaluate the function of some characters, and suggest future coding improvements. Overall, we demonstrate the convergent evolution of multiple traits associated with parasitism of woodboring hosts and propose a syndrome in a hyper diverse lineage of parasitoid wasps., Competing Interests: The authors have declared that no competing interests exist, (Copyright: © 2024 Dal Pos, Sharanowski. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tuberculosis has posed a serious threat to human health. It is imperative to investigate the geographic prevalence of tuberculosis and medication resistance, as this information is essential for informing strategies for its prevention and treatment. Drug resistance was identified using a proportion method. Drug-resistant genes and pathways were predicted using whole genome sequencing. The drug resistance range of bedaquiline was identified using the microporous plate two-fold dilution method, and drug resistance genes were studied using sequencing. The study revealed that 19.99% of the tuberculosis cases had multidrug resistance. The genes of M. tuberculosis are predominantly involved in the synthesis of ABC transporters, two-component systems, and bacterial secretion systems, as well as in energy production and conversion, and lipid transport and metabolism. The genes encode for 82.45% of carbohydrate-related enzymes such as glycoside hydrolases, glycosyl transferases, and carbohydrate esterases. The minimum inhibitory concentration (MIC) of bedaquiline against clinical strains was approximately 0.06 μg/mL, with identified mutations in drug-resistant genes Rv0678, atpE, and pepQ, specifically V152A, P62A, and T222N, respectively. The multidrug resistance tuberculosis development was attributed to the strong medication resistance exhibited. It was concluded that tuberculosis had presented a high level of drug resistance. Phenotypic resistance was related to genes, existing potential genetic resistance in M. tuberculosis. Bedaquiline was found to possess effective antibacterial properties against M. tuberculosis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright: © 2024 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

New mutations provide the source of all genetic variation but their impact on trait variation remains poorly understood. A new study published in PLOS Biology addresses this question, finding that new mutations exert only weak effects on some traits in mice., Competing Interests: The author has declared that no competing interests exist., (Copyright: © 2024 Beth L. Dumont. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Understanding perturbations in circulating lipid levels that often occur years or decades before clinical symptoms may enhance our understanding of disease mechanisms and provide novel intervention opportunities. Here, we assessed if polygenic scores (PGSs) for complex traits could detect lipid dysfunctions related to the traits and provide new biological insights. We constructed genome-wide PGSs (approximately 1 million genetic variants) for 50 complex traits in 7,169 Finnish individuals with routine clinical lipid profiles and lipidomics measurements (179 lipid species). We identified 678 associations (P < 9.0 × 10-5) involving 26 traits and 142 lipids. Most of these associations were also validated with the actual phenotype measurements where available (89.5% of 181 associations where the trait was available), suggesting that these associations represent early signs of physiological changes of the traits. We detected many known relationships (e.g., PGS for body mass index (BMI) and lysophospholipids, PGS for type 2 diabetes and triacyglycerols) and those that suggested potential target for prevention strategies (e.g., PGS for venous thromboembolism and arachidonic acid). We also found association of PGS for favorable adiposity with increased sphingomyelins levels, suggesting a probable role of sphingomyelins in increased risk for certain disease, e.g., venous thromboembolism as reported previously, in favorable adiposity despite its favorable metabolic effect. Altogether, our study provides a comprehensive characterization of lipidomic alterations in genetic predisposition for a wide range of complex traits. The study also demonstrates potential of PGSs for complex traits to capture early, presymptomatic lipid alterations, highlighting its utility in understanding disease mechanisms and early disease detection., Competing Interests: MJG is an employee of Lipotype GmbH. KS is CEO of Lipotype GmbH. KS and CK are shareholders of Lipotype GmbH. The remaining authors have no relevant competing interests., (Copyright: © 2024 Tabassum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Each generation, spontaneous mutations introduce heritable changes that tend to reduce fitness in populations of highly adapted living organisms. This erosion of fitness is countered by natural selection, which keeps deleterious mutations at low frequencies and ultimately removes most of them from the population. The classical way of studying the impact of spontaneous mutations is via mutation accumulation (MA) experiments, where lines of small effective population size are bred for many generations in conditions where natural selection is largely removed. Such experiments in microbes, invertebrates, and plants have generally demonstrated that fitness decays as a result of MA. However, the phenotypic consequences of MA in vertebrates are largely unknown, because no replicated MA experiment has previously been carried out. This gap in our knowledge is relevant for human populations, where societal changes have reduced the strength of natural selection, potentially allowing deleterious mutations to accumulate. Here, we study the impact of spontaneous MA on the mean and genetic variation for quantitative and fitness-related traits in the house mouse using the MA experimental design, with a cryopreserved control to account for environmental influences. We show that variation for morphological and life history traits accumulates at a sufficiently high rate to maintain genetic variation and selection response. Weight and tail length measures decrease significantly between 0.04% and 0.3% per generation with narrow confidence intervals. Fitness proxy measures (litter size and surviving offspring) decrease on average by about 0.2% per generation, but with confidence intervals overlapping zero. When extrapolated to humans, our results imply that the rate of fitness loss should not be of concern in the foreseeable future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chebib et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many distantly related organisms have convergently evolved traits and lifestyles that enable them to live in similar ecological environments. However, the extent of phenotypic convergence evolving through the same or distinct genetic trajectories remains an open question. Here, we leverage a comprehensive dataset of genomic and phenotypic data from 1,049 yeast species in the subphylum Saccharomycotina (Kingdom Fungi, Phylum Ascomycota) to explore signatures of convergent evolution in cactophilic yeasts, ecological specialists associated with cacti. We inferred that the ecological association of yeasts with cacti arose independently approximately 17 times. Using a machine learning-based approach, we further found that cactophily can be predicted with 76% accuracy from both functional genomic and phenotypic data. The most informative feature for predicting cactophily was thermotolerance, which we found to be likely associated with altered evolutionary rates of genes impacting the cell envelope in several cactophilic lineages. We also identified horizontal gene transfer and duplication events of plant cell wall-degrading enzymes in distantly related cactophilic clades, suggesting that putatively adaptive traits evolved independently through disparate molecular mechanisms. Notably, we found that multiple cactophilic species and their close relatives have been reported as emerging human opportunistic pathogens, suggesting that the cactophilic lifestyle-and perhaps more generally lifestyles favoring thermotolerance-might preadapt yeasts to cause human disease. This work underscores the potential of a multifaceted approach involving high-throughput genomic and phenotypic data to shed light onto ecological adaptation and highlights how convergent evolution to wild environments could facilitate the transition to human pathogenicity., Competing Interests: JLS is a scientific advisor for WittGen Biotechnologies. JLS is an advisor for ForensisGroup Inc. AR is a scientific consultant for LifeMine Therapeutics, Inc. All other authors have declared that no competing interests exist., (Copyright: © 2024 Gonçalves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Transgenic lines engineered through wild type Rhizobium rhizogenes display an altered phenotype known as the Ri phenotype. This phenotype includes a more compact plant habit, which has proved useful to obtain more compact varieties that require less chemical growth regulation. Here, we develop a method for the molecular and cytogenetic characterization of Cape daisy (Osteospermum fruticosum Norl.) Ri lines in order to predict segregation of pRi T-DNA genes. Analysis of copy number variation (CNV) by means of digital PCR indicated large variation in the copy number of the inserted root oncogenic loci (rol) genes, ranging from 1 to more than 15 copies. In addition, up to 9 copies of the auxin biosynthesis genes (aux) were present in a single Ri line. Visualization of pRiA4 and pRi1724 rol and aux insertion in 4 Ri lines was performed through Fluorescence In Situ Hybridization. The number of rol integrated loci varied from 1 to 3 loci. In contrast, the different TR-gene copies were confined to a single locus which consistently co-localized with a TL locus, this was demonstrated for the first time. Based on CNV and FISH a single Ri line, harboring 7 pRi1724 rol gene copies dispersed over 3 integration loci, was selected for breeding. Copy number segregation in R1 progeny of 2, 3, 4 and 5 pRi1724 copies was confirmed, indicating that the evaluation of the breeding value of first generation Ri lines is possible through CNV and FISH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Desmet et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The pathology in Duchenne muscular dystrophy (DMD) is characterized by degenerating muscle fibers, inflammation, fibro-fatty infiltrate, and edema, and these pathological processes replace normal healthy muscle tissue. The mdx mouse model is one of the most commonly used preclinical models to study DMD. Mounting evidence has emerged illustrating that muscle disease progression varies considerably in mdx mice, with inter-animal differences as well as intra-muscular differences in pathology in individual mdx mice. This variation is important to consider when conducting assessments of drug efficacy and in longitudinal studies. We developed a magnetic resonance imaging (MRI) segmentation and analysis pipeline to rapidly and non-invasively measure the severity of muscle disease in mdx mice., Methods: Wildtype and mdx mice were imaged with MRI and T2 maps were obtained axially across the hindlimbs. A neural network was trained to rapidly and semi-automatically segment the muscle tissue, and the distribution of resulting T2 values was analyzed. Interdecile range and Pearson Skew were identified as biomarkers to quickly and accurately estimate muscle disease severity in mice., Results: The semiautomated segmentation tool reduced image processing time approximately tenfold. Measures of Pearson skew and interdecile range based on that segmentation were repeatable and reflected muscle disease severity in healthy wildtype and diseased mdx mice based on both qualitative observation of images and correlation with Evans blue dye uptake., Conclusion: Use of this rapid, non-invasive, semi-automated MR image segmentation and analysis pipeline has the potential to transform preclinical studies, allowing for pre-screening of dystrophic mice prior to study enrollment to ensure more uniform muscle disease pathology across treatment groups, improving study outcomes., Competing Interests: EMM has consulted for Amgen, AstraZeneca, Cytokinetics, Pfizer, Tenaya Therapeutics and is the founder of Ikaika Therapeutics. ARD is the Chief Scientific Officer at Ikaika Therapeutics. These activities are unrelated to the content of this manuscript. The other authors have no conflicts of interest to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Waters et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Epidemiological profiles and the rundown crisis of antimicrobial resistance from bacterial isolates in neonatal sepsis compel regular surveillance to enhance data-driven decision-making. Accordingly, this study aimed to assess the phenotypic epidemiology and antimicrobial resistance profiles of bacteria isolated from clinically suspected neonatal sepsis in Ethiopia., Methods: A total of 342 neonates suspected of clinical sepsis were randomly included in a prospective observational study conducted at the neonatal intensive care unit (NICU) of Jimma medical center (JMC) from May 2022 to July 2023. Blood samples were collected from each neonate and subjected to a culture test for identification of bacterial isolates and their antibiotic resistance profiles following the standardized guidelines. The laboratory results, along with relevant clinical data, were recorded using WHONET and analyzed using STATA software., Results: Out of the 342 blood samples that were analyzed, 138 samples (40.4%, 95% CI: 35.1-45.6, P<0.01) exhibited proven bacterial infection. The infection rates were notably higher in males with 85/138 (61.6%, 95% CI: 53.4-69.8, P<0.01) and neonates aged 0-3 days with 81/138 (58.7%, 95% CI: 50.5-66.9, P<0.01). The majority of the infections were attributed to Gram-negative bacteria, accounting for 101/138(73.2%, 95% CI: 65.6-80.7) cases, with 69/101(68.3%, 95% CI: 63.8-72.8) cases involving ESBL-producing strains, while Gram-positive bacteria were responsible for 26.8% (95% CI: 19.3-34.4) of the infections. The predominant isolates included Klebsiella pneumoniae (37.7%, 95% CI: 29.6-45.8), Coagulase-negative Staphylococci (CoNs) (20.3%, 95% CI: 13.6-27.0), and Acinetobacter species (11.6%, 95% CI: 6.0-17.1). Of the total cases, 43/72 (59.7%, 95% CI: 48.4-71.1, P<0.01) resulted in mortality, with 28/72 (38.9%, 95% CI: 27.70-50.1, P<0.03) deaths linked to Extended-Spectrum Beta-Lactamase (ESBL)-producing strains. Klebsiella pneumoniae displayed high resistance rates to trimethoprim-sulfamethoxazole (100%), ceftriaxone (100%), cefotaxime (98.1%), ceftazidime (90.4%), and gentamicin (84.6%). Acinetobacter species showed resistance to ampicillin (100%), cefotaxime (100%), trimethoprim-sulfamethoxazole (75%), ceftazidime (68.8%), chloramphenicol (68.8%), and ceftriaxone (68.8%). Likewise, CoNs displayed resistance to ampicillin (100%), penicillin (100%), cefotaxime (86.0%), gentamicin (57.2%), and oxacillin (32.2%). Multidrug resistance was observed in 88.4% (95% CI: 81.8-93.0) of isolates, with ESBL-producers significantly contributing (49.3%, 95% CI: 45.1-53.5). Furthermore, 23.0% (95% CI: 15.8-31.6) exhibited a prevalent resistance pattern to seven distinct antibiotic classes., Conclusion: The prevalence and mortality rates of neonatal sepsis were significantly high at JMC, with a notable surge in antibiotic and multidrug resistance among bacterial strains isolated from infected neonates, specifically ESBL-producers. These resistant strains have a significant impact on infection rates and resistance profiles, highlighting the requisite for enhanced diagnostic and antimicrobial stewardship, stringent infection control, and further molecular characterization of isolates to enhance neonatal survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Geleta et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An understanding of human brain individuality requires the integration of data on brain organization across people and brain regions, molecular and systems scales, as well as healthy and clinical states. Here, we help advance this understanding by leveraging methods from computational genomics to integrate large-scale genomic, transcriptomic, neuroimaging, and electronic-health record data sets. We estimated genetically regulated gene expression (gr-expression) of 18,647 genes, across 10 cortical and subcortical regions of 45,549 people from the UK Biobank. First, we showed that patterns of estimated gr-expression reflect known genetic-ancestry relationships, regional identities, as well as inter-regional correlation structure of directly assayed gene expression. Second, we performed transcriptome-wide association studies (TWAS) to discover 1,065 associations between individual variation in gr-expression and gray-matter volumes across people and brain regions. We benchmarked these associations against results from genome-wide association studies (GWAS) of the same sample and found hundreds of novel associations relative to these GWAS. Third, we integrated our results with clinical associations of gr-expression from the Vanderbilt Biobank. This integration allowed us to link genes, via gr-expression, to neuroimaging and clinical phenotypes. Fourth, we identified associations of polygenic gr-expression with structural and functional MRI phenotypes in the Human Connectome Project (HCP), a small neuroimaging-genomic data set with high-quality functional imaging data. Finally, we showed that estimates of gr-expression and magnitudes of TWAS were generally replicable and that the p-values of TWAS were replicable in large samples. Collectively, our results provide a powerful new resource for integrating gr-expression with population genetics of brain organization and disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hoang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mutations in glycosylation pathways, such as N-linked glycosylation, O-linked glycosylation, and GPI anchor synthesis, lead to Congenital Disorders of Glycosylation (CDG). CDG typically present with seizures, hypotonia, and developmental delay but display large clinical variability with symptoms affecting every system in the body. This variability suggests modifier genes might influence the phenotypes. Because of the similar physiology and clinical symptoms, there are likely common genetic modifiers between CDG. Here, we use evolution as a tool to identify common modifiers between CDG and glycosylation genes. Protein glycosylation is evolutionarily conserved from yeast to mammals. Evolutionary rate covariation (ERC) identifies proteins with similar evolutionary rates that indicate shared biological functions and pathways. Using ERC, we identified strong evolutionary rate signatures between proteins in the same and different glycosylation pathways. Genome-wide analysis of proteins showing significant ERC with GPI anchor synthesis proteins revealed strong signatures with ncRNA modification proteins and DNA repair proteins. We also identified strong patterns of ERC based on cellular sub-localization of the GPI anchor synthesis enzymes. Functional testing of the highest scoring candidates validated genetic interactions and identified novel genetic modifiers of CDG genes. ERC analysis of disease genes and biological pathways allows for rapid prioritization of potential genetic modifiers, which can provide a better understanding of disease pathophysiology and novel therapeutic targets., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thorpe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The information contained in population genomic data can tell us much about the past ecology and evolution of species. We leveraged detailed phenotypic and genomic data of nearly all living kākāpō to understand the evolution of its feather color polymorphism. The kākāpō is an endangered and culturally significant parrot endemic to Aotearoa New Zealand, and the green and olive feather colorations are present at similar frequencies in the population. The presence of such a neatly balanced color polymorphism is remarkable because the entire population currently numbers less than 250 birds, which means it has been exposed to severe genetic drift. We dissected the color phenotype, demonstrating that the two colors differ in their light reflectance patterns due to differential feather structure. We used quantitative genomics methods to identify two genetic variants whose epistatic interaction can fully explain the species' color phenotype. Our genomic forward simulations show that balancing selection might have been pivotal to establish the polymorphism in the ancestrally large population, and to maintain it during population declines that involved a severe bottleneck. We hypothesize that an extinct apex predator was the likely agent of balancing selection, making the color polymorphism in the kākāpō a "ghost of selection past.", Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Urban et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome., Methods: We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently., Results: We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts., Conclusion: S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mertelsmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

How can inter-individual variability be quantified? Measuring many features per experiment raises the question of choosing them to recapitulate high-dimensional data. Tackling this challenge on spindle elongation phenotypes, we showed that only three typical elongation patterns describe spindle elongation in C. elegans one-cell embryo. These archetypes, automatically extracted from the experimental data using principal component analysis (PCA), accounted for more than 95% of inter-individual variability of more than 1600 experiments across more than 100 different conditions. The two first archetypes were related to spindle average length and anaphasic elongation rate. The third archetype, accounting for 6% of the variability, was novel and corresponded to a transient spindle shortening in late metaphase, reminiscent of kinetochore function-defect phenotypes. Importantly, these three archetypes were robust to the choice of the dataset and were found even considering only non-treated conditions. Thus, the inter-individual differences between genetically perturbed embryos have the same underlying nature as natural inter-individual differences between wild-type embryos, independently of the temperatures. We thus propose that beyond the apparent complexity of the spindle, only three independent mechanisms account for spindle elongation, weighted differently in the various conditions. Interestingly, the spindle-length archetypes covered both metaphase and anaphase, suggesting that spindle elongation in late metaphase is sufficient to predict the late anaphase length. We validated this idea using a machine-learning approach. Finally, given amounts of these three archetypes could represent a quantitative phenotype. To take advantage of this, we set out to predict interacting genes from a seed based on the PCA coefficients. We exemplified this firstly on the role of tpxl-1 whose homolog tpx2 is involved in spindle microtubule branching, secondly the mechanism regulating metaphase length, and thirdly the central spindle players which set the length at anaphase. We found novel interactors not in public databases but supported by recent experimental publications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Le Cunff et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs)., Methods: Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO+N group), sildenafil positive control group (GO+S group), and PI3K inhibitor group (GO+N+E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group., Results: (1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue., Conclusions: Nesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We present a comparison of machine learning methods for the prediction of four quantitative traits in Arabidopsis thaliana. High prediction accuracies were achieved on individuals grown under standardized laboratory conditions from the 1001 Arabidopsis Genomes Project. An existing body of evidence suggests that linear models may be impeded by their inability to make use of non-additive effects to explain phenotypic variation at the population level. The results presented here use a nested cross-validation approach to confirm that some machine learning methods have the ability to statistically outperform linear prediction models, with the optimal model dependent on availability of training data and genetic architecture of the trait in question. Linear models were competitive in their performance as per previous work, though the neural network class of predictors was observed to be the most accurate and robust for traits with high heritability. The extent to which non-linear models exploit interaction effects will require further investigation of the causal pathways that lay behind their predictions. Future work utilizing more traits and larger sample sizes, combined with an improved understanding of their respective genetic architectures, may lead to improvements in prediction accuracy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kelly, McLaughlin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Epidemiological studies suggest that poor nutrition during pregnancy predisposes offspring to the development of lifestyle-related noncommunicable diseases and psychiatric disorders later in life. However, the molecular mechanisms underlying this predisposition are not well understood. In our previous study, using rats as model animals, we showed that behavioral impairments are induced by prenatal undernutrition. In this study, we identified solute carrier 22 family member 23 (Slc22a23) as a gene that is irreversibly upregulated in the rat brain by undernutrition during fetal development. Because the substrate of the SLC22A23 transporter has not yet been identified and the biological role of the Slc22a23 gene in vivo is not fully understood, we generated pan-Slc22a23 knockout rats and examined their phenotype in detail. The Slc22a23 knockout rats showed a lean phenotype, an increase in spontaneous locomotion, and improved endurance, indicating that they are not overweight and are even healthier in an ad libitum feeding environment. However, the knockout rats had reduced hippocampal volume, and the behavioral analysis suggested that they may have impaired cognitive function regarding novel objects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Uchimura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chemical mutagenesis-driven forward genetic screens are pivotal in unveiling gene functions, yet identifying causal mutations behind phenotypes remains laborious, hindering their high-throughput application. Here, we reveal a non-uniform mutation rate caused by Ethyl Methane Sulfonate (EMS) mutagenesis in the C. elegans genome, indicating that mutation frequency is influenced by proximate sequence context and chromatin status. Leveraging these factors, we developed a machine learning enhanced pipeline to create a comprehensive EMS mutagenesis probability map for the C. elegans genome. This map operates on the principle that causative mutations are enriched in genetic screens targeting specific phenotypes among random mutations. Applying this map to Whole Genome Sequencing (WGS) data of genetic suppressors that rescue a C. elegans ciliary kinesin mutant, we successfully pinpointed causal mutations without generating recombinant inbred lines. This method can be adapted in other species, offering a scalable approach for identifying causal genes and revitalizing the effectiveness of forward genetic screens., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dioscorea bulbifera is an edible yam specie with aerial bulbils. Assessing the genetic diversity of D. bulbifera accession for cultivation and breeding purposes is essential for it genetic improvement, especially where the crop faces minimal attention. The aims of this study was to assess the genetic diversity of Dioscorea bulbifera accessions collected from Nigeria and accessions maintained at the genebank of International Institute of Tropical Agriculture (IITA) Ibadan. Accessions were profiled using quatitative and qualitative phenotypic traits and Diversity Array Technology SNP-markers. Multivariate analysis based phenotypic traits revealed high variability among the evaluated accessions and all phenotypic traits assessed were useful in discriminating the aerial yam accessions. Clustering analysis based phenotypic traits revealed the presence of two well defined clusters. Using DArT-Seq marker, the 94 accessions were classified into three genetic group through the admixture and the phylogeny analysis. The comparision of phenotypic and genotypic clustering revealed inconsistency membership across the two clustering methods. The study established a baseline for the selection of parental lines from the genetic groups for genetic improvement of the D. bulbifera., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ekaette et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Helicobacter pylori (H. pylori) is frequently associated with non-cardia type gastric cancer, and it is designated as a group I carcinogen. This study aimed to systematically review and meta-analyze the evidence on the prevalence of CagA status in people with gastric disorders in the Indo-Pacific region, and to examine the association of CagA positive in the risk of gastric disorders. This study focused on the Indo-Pacific region owing to the high disability adjusted life-years related to these disorders, the accessibility of efficient treatments for this common bacterial infection, and the varying standard of care for these disorders, particularly among the elderly population in the region., Methods: Relevant studies were identified in the health-related electronic databases including PubMed, Ovid, Medline, Ovid Embase, Index Medicus, and Google Scholar that were published in English between 1 January 2000, and 18 November 2023. For pooled prevalence, meta-analysis of proportional studies was done, after Freeman-Tukey double arcsine transformation of data. A random-effect model was used to compute the pooled odds ratio (OR) and 95% confidence interval (CI) to investigate the relationship between CagA positivity and gastric disorders., Results: Twenty-four studies from eight Indo-Pacific countries (Bhutan, India, Indonesia, Malaysia, Myanmar, Singapore, Thailand, Vietnam) were included. Overall pooled prevalence of CagA positivity in H. pylori-infected gastric disorders was 83% (95%CI = 73-91%). Following stratification, the pooled prevalence of CagA positivity was 78% (95%CI = 67-90%) in H. pylori-infected gastritis, 86% (95%CI = 73-96%) in peptic ulcer disease, and 83% (95%CI = 51-100%) in gastric cancer. Geographic locations encountered variations in CagA prevalence. There was a greater risk of developing gastric cancer in those with CagA positivity compared with gastritis (OR = 2.53,95%CI = 1.15-5.55)., Conclusion: Findings suggest that the distribution of CagA in H. pylori-infected gastric disorders varies among different type of gastric disorders in the study countries, and CagA may play a role in the development of gastric cancer. It is important to provide a high standard of care for the management of gastric diseases, particularly in a region where the prevalence of these disorders is high. Better strategies for effective treatment for high-risk groups are required for health programs to revisit this often-neglected infectious disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Naing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over half of the world's arable land is acidic, which constrains cereal production. In South America, different rice-growing regions (Cerrado in Brazil and Llanos in Colombia and Venezuela) are particularly affected due to high aluminum toxicity levels. For this reason, efforts have been made to breed for tolerance to aluminum toxicity using synthetic populations. The breeding program of CIAT-CIRAD is a good example of the use of recurrent selection to increase productivity for the Llanos in Colombia. In this study, we evaluated the performance of genomic prediction models to optimize the breeding scheme by hastening the development of an improved synthetic population and elite lines. We characterized 334 families at the S0:4 generation in two conditions. One condition was the control, managed with liming, while the other had high aluminum toxicity. Four traits were considered: days to flowering (FL), plant height (PH), grain yield (YLD), and zinc concentration in the polished grain (ZN). The population presented a high tolerance to aluminum toxicity, with more than 72% of the families showing a higher yield under aluminum conditions. The performance of the families under the aluminum toxicity condition was predicted using four different models: a single-environment model and three multi-environment models. The multi-environment models differed in the way they integrated genotype-by-environment interactions. The best predictive abilities were achieved using multi-environment models: 0.67 for FL, 0.60 for PH, 0.53 for YLD, and 0.65 for ZN. The gain of multi-environment over single-environment models ranged from 71% for YLD to 430% for FL. The selection of the best-performing families based on multi-trait indices, including the four traits mentioned above, facilitated the identification of suitable families for recombination. This information will be used to develop a new cycle of recurrent selection through genomic selection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bartholomé et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cucurbita moschata varieties grown in Africa have very low yield. They have been neglected, and totally ignored in agricultural research programs. However, interest in their fruits, seeds, flowers and leaves is growing nowadays due to their nutritional and medicinal potentials. That growing interest has prompted plant breeders and agronomists to develop research programs for their improvement. A complete diallel cross analysis of four parental lines, Long, Zouan-H, Oval, and Soubre and their twelve F1 hybrids, was carried out in a farming environment at the University Nangui Abrogoua, Abidjan, Côte d'Ivoire. The four parental lines and the F1 hybrids were evaluated for their general performances, combining abilities, potency ratio and heterosis effects. The investigated traits included plant height, and eleven fruit- and seed-related characters. The analysis of variance showed significant differences for all traits studied. In addition, the diallel model yielded highly significant gca effects of the female parents. The gca effects of the male parents were significant for all traits except plant height, length of the fruit, width of the fruit and length of the seed. Highly significant sca effects were observed in the crosses for all the traits. Strong maternal effects were observed for the weight and diameter of the fruit, weight of the pulp, number of seeds per fruit, weight of the fresh seeds and 100-seed weight. The general predictive ratio approached the value 1 for all the traits except weight of the fresh seed and width of the dry seed. Most of the characters under this study are predominantly determined by the effects of additive genes. But, weight of the fresh seed and width of the dry seed may be controlled by non-additive genes. Mid-parent heterosis was significant for all measured traits in the crosses, except the length of the fruit. And better-parent heterosis was significant for all traits except plant height, number of fruits per plant and length of the fruit. Gene expression is described by a super-dominance for many traits, and partial dominance for some other traits in all twelve F1 hybrids. Classification of the parental lines based on the effects of their general combining ability grouped the Soubre lines as promising contributors to fruit yield. The parental lines Long and Oval formed another group likely on the basis of the small size of their fruits, the small pulps, the smaller number of fruits per plant and the large number of seeds per fruit. However, Long would be a candidate parent for the development of cultivars with longer vegetative growth. The parental line Zouan-H formed the third group and it was mostly characterized by its large number of seeds per fruit and relatively large fruits., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 KOUAGO et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The fruit fly Drosophila is a major discovery platform in the biology of ageing due to its balance of relatively short lifespan and relatively complex physiology and behaviour. Previous studies have suggested that some important phenotypes of ageing, for instance increasingly fragmented sleep, are shared from humans to Drosophila and can be useful measures of behavioural change with age: these phenotypes therefore hold potential as readouts of healthy ageing for genetic or pharmacological interventions aimed at the underpinning biology of ageing. However, some age-related phenotypes in Drosophila show differing results among studies, leading to questions regarding the source of discrepancies among experiments. In this study, I have tested females and males from three common laboratory strains of Drosophila to determine the extent to which sex and background strain influence age-related behavioural changes in sleep and activity patterns. Surprisingly, I find that some phenotypes-including age-related changes in total activity, total sleep, and sleep fragmentation-depend strongly on sex and strain, to the extent that some phenotypes show opposing age-related changes in different sexes or strains. Conversely, I identify other phenotypes, including age-related decreases in morning and evening anticipation, that are more uniform across sexes and strains. These results reinforce the importance of controlling for background strain in both behavioural and ageing experiments, and they imply that caution should be used when drawing conclusions from studies on a single sex or strain of Drosophila. At the same time, these findings also offer suggestions for behavioural measures that merit further investigation as potentially more consistent phenotypes of ageing., Competing Interests: The author has declared that no competing interests exist., (Copyright: © 2024 Nathan Woodling. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Pleurotus ostreatus is a global mushroom crop with nutritional and medicinal benefits. However, the genetic basis of several commercial traits remains unknown. To address this, we analyzed the quantitative trait loci (QTLs) for two representative cultivars, "Heuktari" and "Miso," with apparently distinct alleles. A genetic map with 11 linkage groups was constructed, in which 27 QTLs were assigned to 14 traits. The explained phenotypic variations in QTLs ranged from 7.8% to 22.0%. Relatively high LOD values of 6.190 and 5.485 were estimated for the pinheading period and the number of valid stipes, respectively. Some QTL-derived molecular markers showed potential enhancement rates of selection precision in inbred lines, especially for cap shape (50%) and cap thickness (30%). Candidate genes were inferred from the QTL regions and validated using qRT-PCR, particularly for the cysteine and glutathione pathway, in relation to cap yellowness. The molecular markers in this study are expected to facilitate the breeding of the Heuktari and Miso lines and provide probes to identify related genes in P. ostreatus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ryu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cancer is a significant global health issue, with treatment challenges arising from intratumor heterogeneity. This heterogeneity stems mainly from somatic evolution, causing genetic diversity within the tumor, and phenotypic plasticity of tumor cells leading to reversible phenotypic changes. However, the interplay of both factors has not been rigorously investigated. Here, we examine the complex relationship between somatic evolution and phenotypic plasticity, explicitly focusing on the interplay between cell migration and proliferation. This type of phenotypic plasticity is essential in glioblastoma, the most aggressive form of brain tumor. We propose that somatic evolution alters the regulation of phenotypic plasticity in tumor cells, specifically the reaction to changes in the microenvironment. We study this hypothesis using a novel, spatially explicit model that tracks individual cells' phenotypic and genetic states. We assume cells change between migratory and proliferative states controlled by inherited and mutation-driven genotypes and the cells' microenvironment. We observe that cells at the tumor edge evolve to favor migration over proliferation and vice versa in the tumor bulk. Notably, different genetic configurations can result in this pattern of phenotypic heterogeneity. We analytically predict the outcome of the evolutionary process, showing that it depends on the tumor microenvironment. Synthetic tumors display varying levels of genetic and phenotypic heterogeneity, which we show are predictors of tumor recurrence time after treatment. Interestingly, higher phenotypic heterogeneity predicts poor treatment outcomes, unlike genetic heterogeneity. Our research offers a novel explanation for heterogeneous patterns of tumor recurrence in glioblastoma patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Syga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Ten SSR markers based on transcriptome sequencing were employed to genotype 231 samples of G. littoralis subsp. littoralis (Apiaceae) from nine cultivated populations and seven wild populations, aiming to assess the genetic diversity and genetic structure, and elucidate the origin of the cultivated populations. Cultivated populations exhibited relatively high genetic diversity (h = 0.441, I = 0.877), slightly lower than that of their wild counterparts (h = 0.491, I = 0.930), likely due to recent domestication and ongoing gene flow between wild and cultivated germplasm. The primary cultivated population in Shandong have the crucial genetic status. A single origin of domestication was inferred through multiple analysis, and wild populations from Liaoning and Shandong are inferred to be potentially the ancestor source for the present cultivated populations. Phenotypic analysis revealed a relatively high heritability of root length across three growth periods (0.683, 0.284, 0.402), with significant correlations observed between root length and petiole length (Pearson correlation coefficient = 0.30, P<0.05), as well as between root diameter and leaf area (Pearson correlation coefficient = 0.36, P<0.01). These parameters can serve as valuable indicators for monitoring the developmental progress of medicinal plants during field management. In summary, this study can shed light on the intricate genetic landscape of G. littoralis subsp. littoralis, providing foundational insights crucial for conservation strategies, targeted breeding initiatives, and sustainable management practices in both agricultural and natural habitats., Competing Interests: The authors declare no competing interests., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to characterise three Ghanaian local chicken ecotypes, namely, Interior Savannah, Forest, and Coastal Savannah, based on morphological data and single nucleotide polymorphism (SNP) genotypes. Morphological data including body weight, shank length, body girth, back length, thigh length, beak length, comb length, and wattle length were collected from 250 local chickens. DNA isolated from blood of 1,440 local chickens was used for SNP genotyping with the Affymetrix chicken 600k SNP chip. Principal component analysis showed that Forest and Coastal Savannah birds were closely related. Generally, all three ecotypes exhibited high genetic diversity, especially birds from the Interior Savannah zone. Morphological characterisation showed that ecotype (p = 0.016) and sex (p = 0.000) had significant effects on body weight. Birds of the Interior Savannah ecotype were the heaviest (p = 0.004), with mean weights of 1.23 kg for females and 1.40 kg for males. Sex also had a strong significant effect on most of the morphological measurements, but the sex * ecotype interaction effect was not significant. Very few of the feather phenotypes previously reported to be associated with heat resistance-frizzle (2%) and naked neck (1.6%)-were found in the studied populations. It is concluded that the three local ecotypes are genetically diverse but with similar morphological features and the information provided would be useful for future selection decisions., Competing Interests: The authors have declared no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Silybum marianum (L.) Gaertn. is a multipurpose crop native to the Mediterranean and middle east regions and mainly known for the hepatoprotective properties of fruit-derived silymarin. Despite growing interest in milk thistle as a versatile crop with medicinal value, its potential in agroindustry is hindered by incomplete domestication and limited genomic knowledge, impeding the development of competitive breeding programs. The present study aimed to evaluate genetic diversity in a panel of S. marianum accessions (n = 31), previously characterized for morphological and phytochemical traits, using 5,178 polymorphic DArTseq SNP markers. The genetic structure investigated using both parametric and non-parametric approaches (e.g. PCA, AWclust, Admixture), revealed three distinctive groups reflecting geographical origins. Indeed, Pop1 grouped accessions from Central Europe and UK, Pop3 consisted mainly of accessions of Italian origin, and Pop2 included accessions from different geographical areas. Interestingly, Italian genotypes showed a divergent phenotypic distribution, particularly in fruit oleic and linoleic acid content, compared to the other two groups. Genetic differentiation among the three groups, investigated by computing pairwise fixation index (FST), confirmed a greater differentiation of Pop3 compared to other subpopulations, also based on other diversity indices (e.g. private alleles, heterozygosity). Finally, 22 markers were declared as putatively under natural selection, of which seven significantly affected some important phenotypic traits such as oleic, arachidonic, behenic and linoleic acid content. These findings suggest that these markers, and overall, the seven SNP markers identified within Pop3, could be exploited in specific breeding programs, potentially aimed at diversifying the use of milk thistle. Indeed, incorporating genetic material from Pop3 haplotypes carrying the selected loci into milk thistle breeding populations might be the basis for developing milk thistle lines with higher levels of oleic, arachidonic, and behenic acids, and lower levels of linoleic acid, paving new avenues for enhancing the nutritional and agronomic characteristics of milk thistle., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Puglisi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)