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Background: Understanding how heterogeneous β-cell function impacts diabetes is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some factors driving heterogeneity, but new strategies are required to enhance information capture., Results: We integrate pancreatic islet single-cell and bulk RNA sequencing data to identify β-cell subpopulations based on gene expression and characterize genetic networks associated with β-cell function in obese SM/J mice. We identify β-cell subpopulations associated with basal insulin secretion, hypoxia response, cell polarity, and stress response. Network analysis associates fatty acid metabolism and basal insulin secretion with hyperglycemic-obesity, while expression of Pdyn and hypoxia response is associated with normoglycemic-obesity., Conclusions: By integrating single-cell and bulk islet transcriptomes, our study explores β-cell heterogeneity and identifies novel subpopulations and genetic pathways associated with β-cell function in obesity., (© 2023. The Author(s).)

Background: Iron is a critical component of metabolic homeostasis, but consumption of dietary iron has increased dramatically in the last 30 years, corresponding with the rise of metabolic disease. While the link between iron metabolism and metabolic health is well established, the extent to which dietary iron contributes to metabolic disease risk is unexplored. Further, it is unknown how dietary iron interacts with genetic background to modify metabolic disease risk., Methods: LG/J and SM/J inbred mouse strains were used to investigate the relationship between genetic background and metabolic function during an 8-week high iron diet. Glucose tolerance and adiposity were assessed, colorimetric assays determined levels of circulating metabolic markers, and hepatic iron content was measured. RNA sequencing was performed on white adipose tissue to identify genes differentially expressed across strain, diet, and strain X diet cohorts. Hepatic Hamp expression and circulating hepcidin was measured, and small nucleotide variants were identified in the Hamp genic region., Results: LG/J mice experienced elevated fasting glucose and glucose intolerance during the high iron diet, corresponding with increased hepatic iron load, increased circulating ferritin, and signs of liver injury. Adipose function was also altered in high iron-fed LG/J mice, including decreased adiposity and leptin production and differential expression of genes involved in iron and glucose homeostasis. LG/J mice failed to upregulate hepatic Hamp expression during the high iron diet, resulting in low circulating hepcidin levels compared to SM/J mice., Conclusions: This study highlights the importance of accounting for genetic variation when assessing the effects of diet on metabolic health, and suggests dietary iron's impact on liver and adipose tissue is an underappreciated component of metabolic disease risk., Competing Interests: All experiments were approved by the Institutional Animal Care and Use Committee at the Washington University School of Medicine (WUSM) in accordance with the National Institutes of Health (NIH) guidelines for the care and use of laboratory animals.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: The laboratory mouse is the most commonly used model for studying variation in complex traits relevant to human disease. Here we present the whole-genome sequences of two inbred strains, LG/J and SM/J, which are frequently used to study variation in complex traits as diverse as aging, bone-growth, adiposity, maternal behavior, and methamphetamine sensitivity., Results: We identified small nucleotide variants (SNVs) and structural variants (SVs) in the LG/J and SM/J strains relative to the reference genome and discovered novel variants in these two strains by comparing their sequences to other mouse genomes. We find that 39% of the LG/J and SM/J genomes are identical-by-descent (IBD). We characterized amino-acid changing mutations using three algorithms: LRT, PolyPhen-2 and SIFT. We also identified polymorphisms between LG/J and SM/J that fall in regulatory regions and highly informative transcription factor binding sites (TFBS). We intersected these functional predictions with quantitative trait loci (QTL) mapped in advanced intercrosses of these two strains. We find that QTL are both over-represented in non-IBD regions and highly enriched for variants predicted to have a functional impact. Variants in QTL associated with metabolic (231 QTL identified in an F16 generation) and developmental (41 QTL identified in an F34 generation) traits were interrogated and we highlight candidate quantitative trait genes (QTG) and nucleotides (QTN) in a QTL on chr13 associated with variation in basal glucose levels and in a QTL on chr6 associated with variation in tibia length., Conclusions: We show how integrating genomic sequence with QTL reduces the QTL search space and helps researchers prioritize candidate genes and nucleotides for experimental follow-up. Additionally, given the LG/J and SM/J phylogenetic context among inbred strains, these data contribute important information to the genomic landscape of the laboratory mouse.

Background: Percocypris pingi (Tchang) was classified as Endangered on the Red List of China′s Vertebrates in 2015 and is widely distributed in the Upper Yangtze River. Although breeding and release into wild habitats have been performed for this commercially important fish in recent years, low genetic diversity has been found in wild populations. Genomic resources are strongly recommended before formulating and carrying out conservation strategies for P. pingi. Thus, there is an urgent need to conserve germplasm resources and improve the population diversity of P. pingi. To date, the whole genome of P. pingi has not been reported. Results: In our study, we constructed the first chromosome-level genome of P. pingi by high-throughput chromosome conformation capture (Hi-C) technology and PacBio long-read sequencing. The assembled genome was 1.7 Gb in size, with an N50 of 17,692 bp and a GC content from circular consensus sequencing of 37.67%. The Hi-C results again demonstrated that P. pingi was tetraploid (n = 98), with the genome consisting of 24-type and 25-type chromosomes. Chr.19 of the 24-type chromosomes in P. pingi resulted from the fusion of chr.19 and chr.22 in zebrafish. The divergence times between 24-type and 25-type chromosomes was around 6.1 million years ago. A total of 25,198 and 25,291 protein-coding genes were obtained from the 24-type and 25-type chromosomes, respectively. The ploidy of P. pingi is an allotetraploid. A total of 8,741 genes of P. pingi were clustered into 4,378 gene families that were shared with 14 other species, and the P. pingi genome had 68 unique gene families. Phylogenetic analyses indicated that P. pingi was most closely related to Schizothorax oconnori, and the genes were clustered on one branch. We identified 166 significantly expanded gene families and 173 significantly contracted gene families in P. pingi. The most enriched positive protein-coding genes, such as Bmp-4, Etfdh, homeobox protein HB9, and ATG3, were screened. Conclusion: Our study provides a high-quality chromosome-anchored reference genome for P. pingi and provides sufficient information on the chromosomes, which will lead to valuable resources for genetic, genomic, and biological studies of P. pingi and for improving the genetic diversity, population size, and scientific conservation of endangered fish and other key cyprinid species in aquaculture. [ABSTRACT FROM AUTHOR]

Background: Indigenous buffaloes, as the important livestock species contributing to economy of the country, are the lifeline of livelihood in Nepal. They are distributed across diverse geographical regions of the country and have adapted to various feeding, breeding, and management conditions. The larger group of these native buffalo breeds are present in narrow and stiff hilly terrains. Their dispersal indicates a possible environmental adaptation mechanism, which is crucial for the conservation of these breeds. Results: We utilized whole-genome sequencing (WGS) to investigate the genetic diversity, population structure, and selection signatures of Nepalese indigenous buffaloes. We compared 66 whole-genome sequences with 118 publicly available sequences from six river and five swamp buffalo breeds. Genomic diversity parameters indicated genetic variability level in the Nepalese buffaloes comparable to those of Indian breeds, and population genetic structure revealed distinct geography-mediated genetic differentiation among these breeds. We used locus-specific branch length analysis (LSBL) for genome-wide scan, which revealed a list of potentially selected genes in Lime and Parkote breeds that inhabit the hilly region. A gene ontology (GO) analysis discovered that many GO terms were associated with cardiac function regulation. Furthermore, complementary analyses of local selection signatures, tissue expression profiles, and haplotype differences identified candidate genes, including KCNE1, CSF1R, and PDGFRB, related to the regulation of cardiac and pulmonary functions. Conclusions: This study is a comprehensive WGS-based genetic analysis of the native Nepalese buffalo breeds. Our study suggested that the Nepalese "hilly" buffaloes, especially the Lime and Parkote breeds, have undergone some characteristic genetic changes and evolved increased cardiac and pulmonary function for their adaptation to the steep hilly terrains of the country. [ABSTRACT FROM AUTHOR]

Background: Ineffective family interventions for the prevention of childhood obesity have, in part, been attributed to the challenges of reaching and engaging parents. With a particular focus on parent engagement, this study utilized community-based participatory research to develop and pilot test a family-centered intervention for low-income families with preschool-aged children enrolled in Head Start., Methods: During year 1 (2009-2010), parents played an active and equal role with the research team in planning and conducting a community assessment and using the results to design a family-centered childhood obesity intervention. During year 2 (2010-2011), parents played a leading role in implementing the intervention and worked with the research team to evaluate its results using a pre-post cohort design. Intervention components included: (1) revisions to letters sent home to families reporting child body mass index (BMI); (2) a communication campaign to raise parents' awareness of their child's weight status; (3) the integration of nutrition counseling into Head Start family engagement activities; and (4) a 6-week parent-led program to strengthen parents' communication skills, conflict resolution, resource-related empowerment for healthy lifestyles, social networks, and media literacy. A total of 423 children ages 2-5 years, from five Head Start centers in upstate New York, and their families were exposed to the intervention and 154 families participated in its evaluation. Child outcome measures included BMI z-score, accelerometer-assessed physical activity, and dietary intake assessed using 24-hour recall. Parent outcomes included food-, physical activity- and media-related parenting practices and attitudes., Results: Compared with pre intervention, children at post intervention exhibited significant improvements in their rate of obesity, light physical activity, daily TV viewing, and dietary intake (energy and macronutrient intake). Trends were observed for BMI z-score, sedentary activity and moderate activity. Parents at post intervention reported significantly greater self-efficacy to promote healthy eating in children and increased support for children's physical activity. Dose effects were observed for most outcomes., Conclusions: Empowering parents to play an equal role in intervention design and implementation is a promising approach to family-centered obesity prevention and merits further testing in a larger trial with a rigorous research design.

Objective: To characterise lifestyle patterns (comprising dietary and movement behaviour aspects) of children in Singapore and examine the correlates of these patterns. Design: An observational study approach was used. Children recorded their diet and activities over two weekdays and two weekend days on a validated web-based assessment, My E-Diary for Activities and Lifestyle (MEDAL). Lifestyle patterns were derived using principal component analysis, and the correlations of these with multiple known determinants organised by distal, intermediate, and proximal levels of influence were studied. Setting: Children of the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Participants: Ten-year-old children (n = 397). Results: Three lifestyle patterns, "high snacks and processed food", "balanced" and "mixed", were identified. We focused on the more health-promoting "balanced" pattern, characterised by lower screen-viewing and higher consumption of fruits, vegetables, wholegrains, and dairy. Among the distal factors, girls were more adherent to the "balanced" pattern compared to boys, and children of parents with lower education levels were less adherent to this pattern. Among intermediate factors, children of mothers with higher diet quality were more adherent to the "balanced" pattern. Among the proximal factors, engagement in active transport, leisure sports, and educational activities outside of school were positively associated with the "balanced" pattern, whereas screen-viewing while travelling was negatively associated with this pattern. Having siblings, pet ownership, mother's physical activity, parenting style, parental bonding, child's outdoor time, and breakfast consumption were not associated with children's lifestyle patterns. Conclusions: These findings provide direction for future interventions by identifying vulnerable groups and contexts that should be prioritised. [ABSTRACT FROM AUTHOR]

Understanding the nature of evolutionary relationships among persons and populations is important for the efficient application of genome science to biomedical research. We have analysed 8,525 autosomal single nucleotide polymorphisms (SNPs) in 84 individuals from four populations: African-American, European-American, Chinese and Japanese. Individual relationships were reconstructed using the allele sharing distance and the neighbour-joining tree making method. Trees show clear clustering according to population, with the root branching from the African-American clade. The African-American cluster is much less star-like than European-American and East Asian clusters, primarily because of admixture. Furthermore, on the East Asian branch, all ten Chinese individuals cluster together and all ten Japanese individuals cluster together. Using positional information, we demonstrate strong correlations between inter-marker distance and both locus-specific FST (the proportion of total variation due to differentiation) levels and branch lengths. Chromosomal maps of the distribution of locus-specific branch lengths were constructed by combining these data with other published SNP markers (total of 33,704 SNPs). These maps clearly illustrate a non-uniform distribution of human genetic substructure, an instructional and useful paradigm for education and research.

Background: Consumer involvement in health research is when patients, their families and caregivers work with researchers on research projects. Despite the growing expectation for health services to facilitate the involvement of consumers in research, the practical integration of this approach is an ongoing process, with limited research conducted into how Australian health services can support this practice. This study explored consumer perspectives on the barriers and solutions to enabling consumer involvement in research within an Australian tertiary hospital and health service, and staff perspectives on the solutions to facilitating consumer involvement. A prior survey had identified barriers to consumer involvement from the staff perspective. The broad aim was to inform the development of a framework to help promote consumer involvement in research within the health service. Methods: A Nominal Group Technique (NGT) was utilised with groups comprised of health service consumers and staff. Three health consumers were co-researchers in the full life-cycle of this study and are included as authors. Results: Ten consumers and 14 staff participated across three sessions ranging from one to three hours. For consumers, barriers to their involvement were grouped into seven domains: (1) lack of connection with researchers/research projects, (2) low research literacy, (3) structural barriers, (4) lack of acknowledgement, (5) implementation challenges, (6) inadequate information provision, and (7) representation concerns. Solutions to enabling involvement were grouped into five domains: (1) support to connect with researchers/research projects, (2) adequate information provision, (3) incentive for involvement, (4) acknowledgement, and (5) balanced representation. Staff ideas for solutions were grouped into five domains: (1) support to connect with consumers, (2) support to involve consumers, (3) access to funds to remunerate consumers, (4) more time to involve consumers, and (5) staff training. Conclusion: Through an NGT methodology, this study delivered a nuanced comprehension of perspectives on involving consumers in research from both health service consumers and staff. These findings serve as a foundation for identifying strategies that foster enhanced and refined relationships between consumers and researchers, advancing the collaborative landscape in health research. The findings from this project offer valuable strategies for researchers to better engage consumers in research and for consumer groups to enhance their involvement. Additionally, these insights could be used by other health services to advocate for essential resources. Plain English Summary: Consumer involvement in health research is when patients, their families, and caregivers work with researchers on research projects. While there is a growing expectation for health services to promote the involvement of consumers in health service research, it is still a work in progress, especially in Australia, where there hasn't been much research done on this topic. This study looked at what consumers and staff at an Australian hospital thought would hinder or help consumers to become involved in health research. The study used a method called the Nominal Group Technique (NGT), where groups of staff and consumers met for sessions ranging from one to three hours to share and prioritise their ideas. Consumers thought that barriers to their involvement included difficulty connecting with researchers or projects, not knowing much about research, and personal barriers to involvement (such as lack of childcare). They believed that better connection with researchers, information, incentives for involvement, and ensuring everyone's voices are heard were possible solutions. Staff also had ideas for solutions, like providing support to connect with consumers and more time for research activities. Overall, this study describes what consumers and staff think about working together on research. These findings can help develop strategies for building relationships between consumers and researchers, advancing collaborative efforts in health research. [ABSTRACT FROM AUTHOR]

Background: The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse. Results: We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes. Conclusions: Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs. [ABSTRACT FROM AUTHOR]

Background: The honey bee reference genome, HAv3.1, was produced from a commercial line sample that was thought to have a largely dominant Apis mellifera ligustica genetic background. Apis mellifera mellifera, often referred to as the black bee, has a separate evolutionary history and is the original type in western and northern Europe. Growing interest in this subspecies for conservation and non-professional apicultural practices, together with the necessity of deciphering genome backgrounds in hybrids, triggered the necessity for a specific genome assembly. Moreover, having several high-quality genomes is becoming key for taking structural variations into account in pangenome analyses. Results: Pacific Bioscience technology long reads were produced from a single haploid black bee drone. Scaffolding contigs into chromosomes was done using a high-density genetic map. This allowed for re-estimation of the recombination rate, which was over-estimated in some previous studies due to mis-assemblies, which resulted in spurious inversions in the older reference genomes. The sequence continuity obtained was very high and the only limit towards continuous chromosome-wide sequences seemed to be due to tandem repeat arrays that were usually longer than 10 kb and that belonged to two main families, the 371 and 91 bp repeats, causing problems in the assembly process due to high internal sequence similarity. Our assembly was used together with the reference genome to genotype two structural variants by a pangenome graph approach with Graphtyper2. Genotypes obtained were either correct or missing, when compared to an approach based on sequencing depth analysis, and genotyping rates were 89 and 76% for the two variants. Conclusions: Our new assembly for the Apis mellifera mellifera honey bee subspecies demonstrates the utility of multiple high-quality genomes for the genotyping of structural variants, with a test case on two insertions and deletions. It will therefore be an invaluable resource for future studies, for instance by including structural variants in GWAS. Having used a single haploid drone for sequencing allowed a refined analysis of very large tandem repeat arrays, raising the question of their function in the genome. High quality genome assemblies for multiple subspecies such as presented here, are crucial for emerging projects using pangenomes. [ABSTRACT FROM AUTHOR]

The interface between science and policy is a complex space, in theory and practice, that sees the interaction of various actors and perspectives coming together to enable policy-relevant evidence to support decision-making. Early Career Researchers (ECRs) are increasingly interested in working at the science-policy interface to support evidence-informed policy, with the number of opportunities to do so increasing at national and international levels. However, there are still many challenges limiting ECRs participation, not least how such a complex space can be accessed and navigated. While recommendations for engaging at the science-policy interface already exist, a practical 'map' of the science-policy interface landscape which would allow for ECR participation in evidence co-production and synthesis in science-policy is missing. With the purpose of facilitating the engagement of ECRs producing biodiversity and ecosystem services policy-relevant evidence at the interface between science and policy, the authors have co-created a 'mind-map'—a tool to review the landscape of and leverage access to the science-policy interface. This tool was developed through reviewing published literature, collating personal experiences of the ECR authors, and validating against wider peer perspectives in an ECR workshop during the 7th Plenary of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). This co-created tool sees ECR engagement in (co-)producing evidence at the science-policy interface as an interaction of three main factors: the environment of the ECR, which mediates their acts of engagement at the science-policy interface leading to outcomes that will ultimately have a reciprocal impact on the ECR's environment. [ABSTRACT FROM AUTHOR]

Telomeres are regions of repetitive DNA at the ends of linear chromosomes which protect chromosome ends from degradation. Telomere lengths have been extensively studied in the context of aging and disease, though most studies use average telomere lengths which are of limited utility. We present a method for identifying all 92 telomere alleles from long read sequencing data. Individual telomeres are identified using variant repeats proximal to telomere regions, which are unique across alleles. This high-throughput and high-resolution characterization of telomeres could be foundational to future studies investigating the roles of specific telomeres in aging and disease. [ABSTRACT FROM AUTHOR]

Background: Heterosis has successfully enhanced maize productivity and quality. Although significant progress has been made in delineating the genetic basis of heterosis, the molecular mechanisms underlying its genetic components remain less explored. Allele-specific expression (ASE), the imbalanced expression between two parental alleles in hybrids, is increasingly being recognized as a factor contributing to heterosis. ASE is a complex process regulated by both epigenetic and genetic variations in response to developmental and environmental conditions. Results: In this study, we explored the differential characteristics of ASE by analyzing the transcriptome data of two maize hybrids and their parents under four light conditions. On the basis of allele expression patterns in different hybrids under various conditions, ASE genes were divided into three categories: bias-consistent genes involved in basal metabolic processes in a functionally complementary manner, bias-reversal genes adapting to the light environment, and bias-specific genes maintaining cell homeostasis. We observed that 758 ASE genes (ASEGs) were significantly overlapped with heterosis quantitative trait loci (QTLs), and high-frequency variations in the promoter regions of heterosis-related ASEGs were identified between parents. In addition, 10 heterosis-related ASEGs participating in yield heterosis were selected during domestication. Conclusions: The comprehensive analysis of ASEGs offers a distinctive perspective on how light quality influences gene expression patterns and gene-environment interactions, with implications for the identification of heterosis-related ASEGs to enhance maize yield. [ABSTRACT FROM AUTHOR]

Background: Gene expression divergence between populations and between individuals can emerge from genetic variations within the genes and/or in the cis regulatory elements. Since epigenetic modifications regulate gene expression, it is conceivable that epigenetic variations in cis regulatory elements can also be a source of gene expression divergence. Results: In this study, we compared histone acetylation (namely, H3K9ac) profiles in two mouse strains of different subspecies origin, C57BL/6 J (B6) and MSM/Ms (MSM), as well as their F1 hybrids. This identified 319 regions of strain-specific acetylation, about half of which were observed between the alleles of F1 hybrids. While the allele-specific presence of the interferon regulatory factor 3 (IRF3) binding sequence was associated with allele-specific histone acetylation, we also revealed that B6-specific insertions of a short 3′ fragment of LINE-1 (L1) retrotransposon occur within or proximal to MSM-specific acetylated regions. Furthermore, even in hyperacetylated domains, flanking regions of non-polymorphic 3′ L1 fragments were hypoacetylated, suggesting a general activity of the 3′ L1 fragment to induce hypoacetylation. Indeed, we confirmed the binding of the 3′ region of L1 by three Krüppel-associated box domain-containing zinc finger proteins (KZFPs), which interact with histone deacetylases. These results suggest that even a short insertion of L1 would be excluded from gene- and acetylation-rich regions by natural selection. Finally, mRNA-seq analysis for F1 hybrids was carried out, which disclosed a link between allele-specific promoter/enhancer acetylation and gene expression. Conclusions: This study disclosed a number of genetic changes that have changed the histone acetylation levels during the evolution of mouse subspecies, a part of which is associated with gene expression changes. Insertions of even a very short L1 fragment can decrease the acetylation level in their neighboring regions and thereby have been counter-selected in gene-rich regions, which may explain a long-standing mystery of discrete genomic distribution of LINEs and SINEs. [ABSTRACT FROM AUTHOR]

Background: Gene flow is crucial for enhancing economic traits of livestock. In China, breeders have used hybridization strategies for decades to improve livestock performance. Here, we performed whole-genome sequencing of a native Chinese Lijiang pig (LJP) breed. By integrating previously published data, we explored the genetic structure and introgression of genetic components from commercial European pigs (EP) into the LJP, and examined the impact of this introgression on phenotypic traits. Results: Our analysis revealed significant introgression of EP breeds into the LJP and other domestic pig breeds in China. Using a haplotype-based approach, we quantified introgression levels and compared EP to LJP and other Chinese domestic pigs. The results show that EP introgression is widely prevalent in Chinese domestic pigs, although there are significant differences between breeds. We propose that LJP could potentially act as a mediator for the transmission of EP haplotypes. We also examined the correlation between EP introgression and the number of thoracic vertebrae in LJP and identified VRTN and STUM as candidate genes for this trait. Conclusions: Our study provides evidence of introgressed European haplotypes in the LJP breed and describes the potential role of EP introgression on phenotypic changes of this indigenous breed. [ABSTRACT FROM AUTHOR]

Polyploidy is typically described as the condition wherein a cell or organism has more than two complete sets of chromosomes. Occurrence of polyploidy is a naturally occurring phenomenon in the body's development and differentiation processes under normal physiological conditions. However, in pathological conditions, the occurrence of polyploidy is documented in numerous disorders, including cancer, aging and diabetes. Due to the frequent association that the polyploidy has with these pathologies and physiological process, understanding the cause and consequences of polyploidy would be beneficial to develop potential therapeutic applications. Many of the genetic and epigenetic alterations leading to cancer, diabetes and aging are linked to signaling pathways. Nonetheless, the specific signaling pathway associated with the cause and consequences of polyploidy still remains largely unknown. Mammalian/mechanistic target of rapamycin (mTOR) plays a key role in the coordination between eukaryotic cell growth and metabolism, thereby simultaneously respond to various environmental inputs including nutrients and growth factors. Extensive research over the past two decades has established a central role for mTOR in the regulation of many fundamental cellular processes that range from protein synthesis to autophagy. Dysregulated mTOR signaling has been found to be implicated in various disease progressions. Importantly, there is a strong correlation between the hallmarks of polyploidy and dysregulated mTOR signaling. In this review, we explore and discuss the molecular connection between mTOR signaling and polyploidy along with its association with cancer, diabetes and aging. Additionally, we address some unanswered questions and provide recommendations to further advance our understanding of the intricate relationship between mTOR signaling and polyploidy. [ABSTRACT FROM AUTHOR]

Background: The development of children's gender roles in single-parent families is worthy of attention. It may be affected by family members' gender roles and parental child-rearing gender-role attitudes (PCGA). PCGA will form a consistent or inconsistent intergenerational relationship between parents and children. Objective: This study examined the intergenerational similarities in gender roles and PCGA. Also, the intergenerational transmission of parental child-rearing gender-role attitudes (ITPCGA) in single-parent families, and the impact of various family factors on children's gender roles were comprehensively considered. Method: Participants were 550 single-parent parent-adolescent dyads. The Gender-role Scale and the Parental Child-rearing Gender-role Attitude Scale were used to evaluate participants' gender-role and PCGA. Chi-square tests and logistic regression analyses were used to examine the intergenerational similarities in gender roles and PCGA, and the influencing family factors of ITPCGA and children's gender roles. Results: The intergenerational similarities of gender role types and PCGA types existed. Both parents' gender roles and family gender pairs affected ITPCGA, father-daughter families and parents' undifferentiated and sex-typed gender roles significantly predicted undesirable ITPCGA. Family gender pair, parent's gender roles and ITPCGA types affected children's gender roles. Undesirable ITPCGA significantly predicted children's undifferentiated gender roles; father-daughter families and mother-son families, parents' undifferentiated and sex-typed gender roles significantly predicted children's sex-typed gender roles, and mother-son families and parents' reversed gender roles significantly predicted children's reversed gender role. Conclusions: This study highlights the effects of single-parent family gender pairs and parents' gender roles on ITPCGA, which influences the development of children's gender roles. [ABSTRACT FROM AUTHOR]

Background: Jianli pig, a renowned indigenous breed in China, has the characteristics of a two-end black (TEB) coat color, excellent meat quality, strong adaptability and increased prolificacy. However, there is limited information available regarding the genetic diversity, population structure and genomic regions under selection of Jianli pig. On the other hand, the genetic mechanism of TEB coat color has remained largely unknown. Results: In this study, the whole genome resequencing of 30 Jianli pigs within a context of 153 individuals representing 13 diverse breeds was performed. The population structure analysis revealed that Jianli pigs have close genetic relationships with the Tongcheng pig breed, their geographical neighbors. Three methods (observed heterozygosity, expected heterozygosity, and runs of homozygosity) implied a relatively high level of genetic diversity and, a low inbreeding coefficient in Jianli compared with other pigs. We used Fst and XP-EHH to detect the selection signatures in Jianli pigs compared with Asian wild boar. A total of 451 candidate genes influencing meat quality (CREBBP, ADCY9, EEPD1 and HDAC9), reproduction (ESR1 and FANCA), and coat color (EDNRB, MITF and MC1R), were detected by gene annotation analysis. Finally, to fine-map the genomic region for the two-end black (TEB) coat color phenotype in Jianli pigs, we performed three signature selection methods between the TEB coat color and no-TEB coat color pig breeds. The current study, further confirmed that the EDNRB gene is a candidate gene for TEB color phenotype found in Chinese pigs, including Jinhua pigs, and the haplotype harboring 25 SNPs in the EDNRB gene may promote the formation of TEB coat color. Further ATAC-seq and luciferase reporter assays of these regions suggest that the 25-SNPs region was a strong candidate causative mutation that regulates the TEB coat color phenotype by altering enhancer function. Conclusion: Our results advanced the understanding of the genetic mechanism behind artificial selection, and provided further resources for the protection and breeding improvement of Jianli pigs. [ABSTRACT FROM AUTHOR]

Background and aim: "Inflammatory bowel disease" (IBD) is a chronic, relapsing inflammatory disease of the intestinal tract that typically begins at a young age and might transit to colorectal cancer (CRC). In this manuscript, we discussed the epigenetic and metabolic change to present a extensive view of IBDs transition to CRC. This study discusses the possible biomarkers for evaluating the condition of IBDs patients, especially before the transition to CRC. Research approach: We searched "PubMed" and "Google Scholar" using the keywords from 2000 to 2022. Discussion: In this manuscript, interesting titles associated with IBD and CRC are discussed to present a broad view regarding the epigenetic and metabolic reprogramming and the biomarkers. Conclusion: Epigenetics can be the main reason in IBD transition to CRC, and Hypermethylation of several genes, such as VIM, OSM4, SEPT9, GATA4 and GATA5, NDRG4, BMP3, ITGA4 and plus hypomethylation of LINE1 can be used in IBD and CRC management. Epigenetic, metabolisms and microbiome-derived biomarkers, such as Linoleic acid and 12 hydroxy 8,10-octadecadienoic acid, Serum M2-pyruvate kinase and Six metabolic genes (NAT2, XDH, GPX3, AKR1C4, SPHK and ADCY5) expression are valuable biomarkers for early detection and transition to CRC condition. Some miRs, such as miR-31, miR-139-5p, miR -155, miR-17, miR-223, miR-370-3p, miR-31, miR -106a, miR -135b and miR-320 can be used as biomarkers to estimate IBD transition to CRC condition. Highlights: Inflammatory signals, cytokines and immune cell interaction lead to epigenetic reprogramming in IBD. The imprinting profile of IGF2, NOD2, ATG16L1 and IRGM is considerable in IBD. Microbiota plays an essential role in IBD transition to CRC via NF-kB and STAT3 signaling pathways. TLR4 activates β-catenin via PI3K then it interacts with Wnt pathway and leads to a metabolic and neoplastic reprograming in IBD. [ABSTRACT FROM AUTHOR]

Background: Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Results: Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. Conclusion: VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function. [ABSTRACT FROM AUTHOR]

Background: Role models have been identified as a potential means to tackle the persisting low levels of physical activity among young girls. The aim of this research was to explore the involvement of community- and peer role models within the CHARMING (CHoosing Active Role Models to INspire Girls) intervention, an intervention which aims to increase and sustain physical activity among 9–10-year-old girls. The research questions were, is it feasible and acceptable to recruit role models? and what are the perceived barriers and facilitators to the inclusion of peer role models within the intervention? Methods: A mixed methods process evaluation was embedded within a larger feasibility study, involving three secondary schools and four adjoining primary schools in South Wales, United Kingdom. One-to-one interviews were conducted with teachers (N = 10) across the seven schools and community role models (N = 10). Focus groups were conducted with 18 peer role models (older girls from adjoining secondary schools) and 18 girls aged 9–10-years who had participated in the intervention. Primary school teachers kept observation logs of each intervention session. A researcher completed observation logs of two random sessions per school. Qualitative data were analysed using thematic analysis with a combined deductive and inductive coding approach. Observation data were analysed using descriptive statistics. Data were triangulated and comparative analyses conducted across schools. Results: Twenty-three peer role models (aged 12–16-years) and 16 community role models participated in intervention delivery. Overall, the inclusion of both types of role models was shown as acceptable and feasible within the CHARMING intervention. Observation data highlighted key areas (i.e., intervention components delivered inconsistently) for further qualitative exploration. Six themes were identified during analyses; reach and access, communication, logistics, existing systems, interpersonal relationships, and perceived impacts. Themes were intertwined across the barriers and facilitators of recruitment and implementation. Areas for future improvement were highlighted. Conclusions: Findings can be used to optimise the CHARMING intervention and inform wider interventions or policies employing several role models across settings to promote physical activity among children. [ABSTRACT FROM AUTHOR]

Homologous recombination between the maternal and paternal copies of a chromosome is a key mechanism for human inheritance and shapes population genetic properties of our species. However, a similar mechanism can also act between different copies of the same sequence, then called non-allelic homologous recombination (NAHR). This process can result in genomic rearrangements—including deletion, duplication, and inversion—and is underlying many genomic disorders. Despite its importance for genome evolution and disease, there is a lack of computational models to study genomic loci prone to NAHR. In this work, we propose such a computational model, providing a unified framework for both (allelic) homologous recombination and NAHR. Our model represents a set of genomes as a graph, where haplotypes correspond to walks through this graph. We formulate two founder set problems under our recombination model, provide flow-based algorithms for their solution, describe exact methods to characterize the number of recombinations, and demonstrate scalability to problem instances arising in practice. [ABSTRACT FROM AUTHOR]

Interspersed repetitions called transposable elements (TEs), commonly referred to as mobile elements, make up a significant portion of the genomes of higher animals. TEs contribute in controlling the expression of genes locally and even far away at the transcriptional and post-transcriptional levels, which is one of their significant functional effects on gene function and genome evolution. There are different mechanisms through which TEs control the expression of genes. First, TEs offer cis-regulatory regions in the genome with their inherent regulatory features for their own expression, making them potential factors for controlling the expression of the host genes. Promoter and enhancer elements contain cis-regulatory sites generated from TE, which function as binding sites for a variety of trans-acting factors. Second, a significant portion of miRNAs and long non-coding RNAs (lncRNAs) have been shown to have TEs that encode for regulatory RNAs, revealing the TE origin of these RNAs. Furthermore, it was shown that TE sequences are essential for these RNAs' regulatory actions, which include binding to the target mRNA. By being a member of cis-regulatory and regulatory RNA sequences, TEs therefore play essential regulatory roles. Additionally, it has been suggested that TE-derived regulatory RNAs and cis-regulatory regions both contribute to the evolutionary novelty of gene regulation. Additionally, these regulatory systems arising from TE frequently have tissue-specific functions. The objective of this review is to discuss TE-mediated gene regulation, with a particular emphasis on the processes, contributions of various TE types, differential roles of various tissue types, based mostly on recent studies on humans. [ABSTRACT FROM AUTHOR]

Background: With the continuous advances in third-generation sequencing technology and the increasing affordability of next-generation sequencing technology, sequencing data from different sequencing technology platforms is becoming more common. While numerous benchmarking studies have been conducted to compare variant-calling performance across different platforms and approaches, little attention has been paid to the potential of leveraging the strengths of different platforms to optimize overall performance, especially integrating Oxford Nanopore and Illumina sequencing data. Results: We investigated the impact of multi-platform data on the performance of variant calling through carefully designed experiments with a deep learning-based variant caller named Clair3-MP (Multi-Platform). Through our research, we not only demonstrated the capability of ONT-Illumina data for improved variant calling, but also identified the optimal scenarios for utilizing ONT-Illumina data. In addition, we revealed that the improvement in variant calling using ONT-Illumina data comes from an improvement in difficult genomic regions, such as the large low-complexity regions and segmental and collapse duplication regions. Moreover, Clair3-MP can incorporate reference genome stratification information to achieve a small but measurable improvement in variant calling. Clair3-MP is accessible as an open-source project at: https://github.com/HKU-BAL/Clair3-MP. Conclusions: These insights have important implications for researchers and practitioners alike, providing valuable guidance for improving the reliability and efficiency of genomic analysis in diverse applications. [ABSTRACT FROM AUTHOR]

Background: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance—in particular, parent of origin effects—may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. Methods: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N = 407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (σ2P) between sons that could uniquely be attributed to their shared genetics (σ2g), expressed as σ2g/σ2P (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h2). Results: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. Limitations: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. Conclusions: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability. [ABSTRACT FROM AUTHOR]

Background: Syndecan-4 (SDC4) is a member of the heparan sulfate proteoglycan family of cell-surface receptors. We and others previously reported that variation in the SDC4 gene was associated with several components of the metabolic syndrome, including intra-abdominal fat, fasting glucose and triglyceride levels, and hypertension, in human cohorts. Additionally, we demonstrated that high fat diet (HFD)-induced obese female mice with a Sdc4 genetic deletion had higher visceral adiposity and a worse metabolic profile than control mice. Here, we aimed to first investigate whether the mouse Sdc4 null mutation impacts metabolic phenotypes in a sex- and diet-dependent manner. We then tested whether SDC4 polymorphisms are related to the metabolic syndrome (MetS) in humans. Methods: For the mouse experiment, Sdc4-deficient (Sdc4−/−) and wild-type (WT) mice were treated with 14-weeks of low-fat diet (LFD). Body composition, energy balance, and selected metabolic phenotypes were assessed. For the human genetic study, we used logistic regression models to test 11 SDC4 SNPs for association with the MetS and its components in a cohort of 274 (113 with MetS) elderly subjects from southern Italy. Results: Following the dietary intervention in mice, we observed that the effects of the Sdc4 null mutation on several phenotypes were different from those previously reported in the mice kept on an HFD. Nonetheless, LFD-fed female Sdc4−/− mice, but not males, displayed higher levels of triglycerides and lower insulin sensitivity at fasting than WT mice, as seen earlier in the HFD conditions. In the parallel human study, we found that carriers of SDC4 rs2228384 allele C and rs2072785 allele T had reduced risk of MetS. The opposite was true for carriers of the SDC4 rs1981429 allele G. Additionally, the SNPs were found related to fasting triglyceride levels and triglyceride glucose (TyG) index, a reliable indicator of insulin resistance, with sex-stratified analysis detecting the association of rs1981429 with these phenotypes only in females. Conclusions: Altogether, our results suggest that SDC4 is an evolutionary conserved genetic determinant of MetS and that its genetic variation is associated with fasting triglyceride levels in a female-specific manner. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing survival rates, liver transplant patients experience numerous postoperative complications and encounter significant challenges in long-term self-management. This study aims to examine the effectiveness of empowerment education in enhancing self-management skills and self-efficacy among liver transplant recipients. Methods: A randomized, single-blind, single-center trial was conducted in China between August 2019 and September 2020, involving liver transplant recipients. The intervention group received 12 weeks of empowerment education, while the control group received 12 weeks of routine education..The study assessed the patients' self-management and self-efficacy using the Liver Transplant Recipient Self-Management Questionnaire and the Self-efficacy for Managing Chronic Disease 6-Item Scale. Follow-up assessments were conducted at 1, 3, and 6 months after the intervention. Results: Eighty-four patients were initially randomized to either the intervention group (n1 = 42) or the routine education group (n2 = 42). Twelve patients were excluded from the analysis due to loss of follow-up or discontinuation of the intervention, leaving 72 patients (n1 = 35, n2 = 37) for the final analysis. The scores for exercise and lifestyle management were significantly higher in the intervention group than in the control group at 1, 3, and 6 months after the intervention (t = 3.047, 5.875, 8.356, and t = 5.759, 4.681, 11.759, respectively; P < 0.05). At 3 and 6 months after the intervention, the scores for cognitive symptom management, communication with physicians, and self-efficacy were significantly higher in the intervention group than in the control group (t = 5.609, 6.416, and t = 5.576, 11.601, and t = 6.867, 15.071, respectively; P < 0.001). Within the intervention group, self-management scores increased significantly over time, while within the control group, the scores for communication with physicians, lifestyle, and self-efficacy showed a significant decline from 3 to 6 months after routine health education. Conclusions: The results of this study suggest that empowerment education is an effective means of improving the self-management and self-efficacy of liver transplant patients, with better outcomes compared to routine health education. These findings have important implications for nursing practice and provide valuable guidance for clinical education of liver transplant patients. Trial registration: ChiCTR2200061561. [ABSTRACT FROM AUTHOR]

Background: Recent advances in long-read sequencing technologies have enabled accurate identification of all genetic variants in individuals or cells; this procedure is known as variant calling. However, benchmarking studies on variant calling using different long-read sequencing technologies are still lacking. Results: We used two Caenorhabditis elegans strains to measure several variant calling metrics. These two strains shared true-positive genetic variants that were introduced during strain generation. In addition, both strains contained common and distinguishable variants induced by DNA damage, possibly leading to false-positive estimation. We obtained accurate and noisy long reads from both strains using high-fidelity (HiFi) and continuous long-read (CLR) sequencing platforms, and compared the variant calling performance of the two platforms. HiFi identified a 1.65-fold higher number of true-positive variants on average, with 60% fewer false-positive variants, than CLR did. We also compared read-based and assembly-based variant calling methods in combination with subsampling of various sequencing depths and demonstrated that variant calling after genome assembly was particularly effective for detection of large insertions, even with 10 × sequencing depth of accurate long-read sequencing data. Conclusions: By directly comparing the two long-read sequencing technologies, we demonstrated that variant calling after genome assembly with 10 × or more depth of accurate long-read sequencing data allowed reliable detection of true-positive variants. Considering the high cost of HiFi sequencing, we herein propose appropriate methodologies for performing cost-effective and high-quality variant calling: 10 × assembly-based variant calling. The results of the present study may facilitate the development of methods for identifying all genetic variants at the population level. [ABSTRACT FROM AUTHOR]

Due to its potential to address low achievement, high dropout rates, and misbehavior among students, school engagement has become an important topic in contemporary developmental psychology and educational research. Although there is a wealth of literature on the causes and effects of student engagement, the current understanding of how student engagement varies in response to different teaching styles is limited. This study examined the engagement and burnout profiles of elementary school pupils (N = 798; 51% females; Mage = 11.54, SDage = 0.72) and the interactions between those profiles, students' characteristics and their perceptions of instructional behaviors (e.g., supporting criticism, suppressing criticism & independent viewpoints, intruding). Latent profile analysis revealed five types of profiles: moderately burned out, slightly burned out, moderately engaged, highly engaged, and highly burned out. Follow-up logistic regression analysis found that students clustered into engagement groups were likely to report higher autonomy support from teachers, especially when teachers permit criticism and independent thinking from students. In contrast, students clustered into burned out profiles were more likely to rate teacher strategies as autonomy suppressive. This became more obvious when instructors imposed meaningless and uninteresting activities. Taken together, this study indicated that autonomy-supportive teaching behaviors are pivotal in understanding student engagement and school burnout. The significance of the findings was addressed, along with implications and limitations. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that structural variants (SV) play a substantial role in the evolution of species and have an impact on Mendelian traits in the genome. However, unlike small variants (< 50 bp), it has been challenging to accurately identify and genotype SV at the population scale using short-read sequencing. Long-read sequencing technologies are becoming competitively priced and can address several of the disadvantages of short-read sequencing for the discovery and genotyping of SV. In livestock species, analysis of SV at the population scale still faces challenges due to the lack of resources, high costs, technological barriers, and computational limitations. In this review, we summarize recent progress in the characterization of SV in the major livestock species, the obstacles that still need to be overcome, as well as the future directions in this growing field. It seems timely that research communities pool resources to build global population-scale long-read sequencing consortiums for the major livestock species for which the application of genomic tools has become cost-effective. [ABSTRACT FROM AUTHOR]

Background: Precision medicine with gene panel testing based on next-generation sequencing for patients with cancer is being used increasingly in clinical practice. HER2, which encodes the human epidermal growth factor receptor 2 (HER2), is a potentially important driver gene. However, therapeutic strategies aimed at mutations in the HER2 extracellular domain have not been clarified. We therefore investigated the effect of EGFR co-targeted therapy with HER2 on patient-derived cancer models with the HER2 extracellular domain mutation E401G, based on our previous findings that this mutation has an epidermal growth factor receptor (EGFR)-mediated activation mechanism. Methods: We generated a xenograft (PDX) and a cancer tissue-originated spheroid (CTOS) from a patient's cancer containing an amplified HER2 E401G mutation. With these platforms, we compared the efficacy of afatinib, a tyrosine kinase inhibitor having anti-HER2 and anti-EGFR activity, with two other therapeutic options: lapatinib, which has similar properties but weaker EGFR inhibition, and trastuzumab plus pertuzumab, for which evidence exists of treatment efficacy against cancers with wild-type HER2 amplification. Similar experiments were also performed with H2170, a cell line with wild-type HER2 amplification, to contrast the characteristics of these drug's efficacies against HER2 E401G. Results: We confirmed that PDX and CTOS retained morphological and immunohistochemical characteristics and HER2 gene profiles of the original tumor. In both PDX and CTOS, afatinib reduced tumor size more than lapatinib or trastuzumab plus pertuzumab. In addition, afatinib treatment resulted in a statistically significant reduction in HER2 copy number at the end of treatment. On the other hand, in H2170 xenografts with wild-type HER2 amplification, trastuzumab plus pertuzumab was most effective. Conclusions: Afatinib, a dual inhibitor of HER2 and EGFR, showed a promising effect on cancers with amplified HER2 E401G, which have an EGFR-mediated activation mechanism. Analysis of the activation mechanisms of mutations and development of therapeutic strategies based on those mechanisms are critical in precision medicine for cancer patients. [ABSTRACT FROM AUTHOR]

Background: This study reports the outcomes of Communities for Healthy Living (CHL), a cluster randomized obesity prevention trial implemented in partnership with Head Start, a federally-funded preschool program for low-income families. Methods: Using a stepped wedge design, Head Start programs (n = 16; Boston, MA, USA) were randomly assigned to one of three intervention start times. CHL involved a media campaign and enhanced nutrition support. Parents were invited to join Parents Connect for Healthy Living (PConnect), a 10-week wellness program. At the beginning and end of each school year (2017-2019), data were collected on the primary outcome of child Body Mass Index z-score (BMIz) and modified BMIz, and secondary outcomes of child weight-related behaviors (diet, physical activity, sleep, media use) and parents' weight-related parenting practices and empowerment. Data from 2 years, rather than three, were utilized to evaluate CHL due to the COVID-19 pandemic. We used mixed effects linear regression to compare relative differences during intervention vs. control periods (n = 1274 vs. 2476 children) in (1) mean change in child BMIz and modified BMIz, (2) the odds of meeting child health behavior recommendations, (3) mean change in parenting practices, and (4) mean change in parent empowerment. We also compared outcomes among parents who chose post-randomization to participate in PConnect vs. not (n = 55 vs. 443). Results: During intervention periods (vs. control), children experienced greater increases in BMIz and modified BMIz (b = 0.06, 95% CI = 0.02,0.10; b = 0.07, 95% CI = 0.03, 0.12), yet were more likely to meet recommendations related to three of eight measured behaviors: sugar-sweetened beverage consumption (i.e., rarely consume; Odds Ratio (OR) = 1.5, 95% CI = 1.2,2.3), water consumption (i.e., multiple times per day; OR = 1.6, 95% CI = 1.2,2.3), and screen time (i.e., ≤1 hour/day; OR = 1.4, 95% CI = 1.0,1.8). No statistically significant differences for intervention (vs. control) periods were observed in parent empowerment or parenting practices. However, parents who enrolled in PConnect (vs. not) demonstrated greater increases in empowerment (b = 0.17, 95% CI = 0.04,0.31). Conclusions: Interventions that emphasize parent engagement may increase parental empowerment. Intervention exposure was associated with statistically, but not clinically, significant increases in BMIz and increased odds of meeting recommendations for three child behaviors; premature trial suspension may explain mixed results. Trial registration: ClinicalTrials.gov, NCT03334669, Registered October 2017. [ABSTRACT FROM AUTHOR]

Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case–control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene → endophenotype → disorder pathways. [ABSTRACT FROM AUTHOR]

Given the global increase in air pollution and its crucial role in human health, as well as the steep rise in prevalence of metabolic syndrome (MetS), a better understanding of the underlying mechanisms by which environmental pollution may influence MetS is imperative. Exposure to air pollution is known to impact DNA methylation, which in turn may affect human health. This paper comprehensively reviews the evidence for the hypothesis that the effect of air pollution on the MetS is mediated by DNA methylation in blood. First, we present a summary of the impact of air pollution on metabolic dysregulation, including the components of MetS, i.e., disorders in blood glucose, lipid profile, blood pressure, and obesity. Then, we provide evidence on the relation between air pollution and endothelial dysfunction as one possible mechanism underlying the relation between air pollution and MetS. Subsequently, we review the evidence that air pollution (PM, ozone, NO2 and PAHs) influences DNA methylation. Finally, we summarize association studies between DNA methylation and MetS. Integration of current evidence supports our hypothesis that methylation may partly mediate the effect of air pollution on MetS. [ABSTRACT FROM AUTHOR]

Background: Peer support work for substance use disorders is widely implemented in high-income countries. More research is still needed to understand its applicability in settings which have proportionately low budgets allocated to mental health. Peer Support Workers are individuals who managed to achieve recovery from substance use disorders and help people remain engaged in their recovery and prevent relapse through shared understanding.Aim: To investigate the experience of peer support workers providing recovery support to people with substance use disorders in Egypt.Methods: A qualitative phenomenological design was used in which 17 adults working as peer support workers for substance use disorders were recruited by means of purposive and snowball sampling. A semi-structured interview with participants was conducted by phone or video-call. Interviews were transcribed and thematically analysed based on descriptive phenomenology.Results: Three superordinate themes were identified: role responsibility, Peer Support Workers' need for organizational and stakeholders' support, and challenges to the role integrity.Conclusion and Recommendations: The findings indicate the need for national and governmental support to peer support workers engaged with people with substance use disorders in Egypt and educating families and the public about the role of peer support workers in substance use disorders. [ABSTRACT FROM AUTHOR]

Background: The Covid-19 pandemic has changed children's eating and physical activity behaviours. These changes have been positive for some households and negative for others, revealing health inequalities that have ramifications for childhood obesity. This study investigates the pandemic's impact on families of children aged 2–6 years with overweight or obesity. Methods: Drawing on interviews conducted as part of a randomised controlled trial (RCT) for childhood obesity, thematic analysis was used to examine how parents of pre-schoolers perceived changes in their eating, screentime and physical activity behaviours between the first and second waves of Covid-19. Parents (n = 70, representing 68 families) were interviewed twice during a period of 6 months in three countries with markedly different pandemic policies – Sweden, Romania, and Spain. The analysis is informed by Bronfenbrenner's ecological systems theory, which embeds home- and school-based influences within societal and policy contexts. Results: The findings show that, although all participants were recruited from an RCT for families of children with excess weight, they reported different responses to the pandemic's second wave, with some children engaging in healthier eating and physical activity, and others engaging in comfort eating and a more sedentary lifestyle. Differences in children's obesity-related behaviours were closely related to differences in parents' practices, which were, in turn, linked to their emotional and social wellbeing. Notably, across all sites, parents' feeding and physical activity facilitation practices, as well as their emotional and social wellbeing, were embedded in household resilience. In resilient households, where parents had secure housing and employment, they were better able to adapt to the challenges posed by the pandemic, whereas parents who experienced household insecurity found it more difficult to cope. Conclusions: As the Covid-19 pandemic is turning into a long-term public health challenge, studies that address household resilience are crucial for developing effective prevention and treatment responses to childhood obesity. [ABSTRACT FROM AUTHOR]

Background: Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose: Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods: Ten behavioural variables related to child's diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5–6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. Results: Three broadly similar lifestyle patterns were identified in both cohorts: "discretionary consumption and high screen time", "fruit, vegetables, and low screen time" and "high outdoor playtime and walking". The latter two patterns showed small differences between cohorts and sexes. The "discretionary consumption and high screen time" pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. Conclusions: Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health. [ABSTRACT FROM AUTHOR]