Nisin probiotic prevents inflammatory bone loss while promoting reparative proliferation and a healthy microbiome.

Dysbiosis of the oral microbiome mediates chronic periodontal disease. Realignment of microbial dysbiosis towards health may prevent disease. Treatment with antibiotics and probiotics can modulate the microbial, immunological, and clinical landscape of periodontal disease with some success.

Deep longitudinal multiomics profiling reveals two biological seasonal patterns in California.

The influence of seasons on biological processes is poorly understood. In order to identify biological seasonal patterns based on diverse molecular data, rather than calendar dates, we performed a deep longitudinal multiomics profiling of 105 individuals over 4 years. Here, we report more than 1000 seasonal variations in omics analytes and clinical measures.

Candidate variants in TUB are associated with familial tremor.

Essential tremor (ET) is the most common adult-onset movement disorder. In the present study, we performed whole exome sequencing of a large ET-affected family (10 affected and 6 un-affected family members) and identified a TUB p.V431I variant (rs75594955) segregating in a manner consistent with autosomal-dominant inheritance.

Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma.

Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome.

Personal aging markers and ageotypes revealed by deep longitudinal profiling.

The molecular changes that occur with aging are not well understood. Here, we performed longitudinal and deep multiomics profiling of 106 healthy individuals from 29 to 75 years of age and examined how different types of 'omic' measurements, including transcripts, proteins, metabolites, cytokines, microbes and clinical laboratory values, correlate with age. We identified both known and new markers that associated with age, as well as distinct molecular patterns of aging in insulin-resistant as compared to insulin-sensitive individuals.

Longitudinal multi-omics of host-microbe dynamics in prediabetes.

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability.

A longitudinal big data approach for precision health.

Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus.

Lifelong physical activity is associated with promoter hypomethylation of genes involved in metabolism, myogenesis, contractile properties and oxidative stress resistance in aged human skeletal muscle.

Lifelong regular physical activity is associated with reduced risk of type 2 diabetes (T2D), maintenance of muscle mass and increased metabolic capacity. However, little is known about epigenetic mechanisms that might contribute to these beneficial effects in aged individuals. We investigated the effect of lifelong physical activity on global DNA methylation patterns in skeletal muscle of healthy aged men, who had either performed regular exercise or remained sedentary their entire lives (average age 62 years).

High-frequency actionable pathogenic exome variants in an average-risk cohort.

Exome sequencing is increasingly utilized in both clinical and nonclinical settings, but little is known about its utility in healthy individuals. Most previous studies on this topic have examined a small subset of genes known to be implicated in human disease and/or have used automated pipelines to assess pathogenicity of known variants. To determine the frequency of both medically actionable and nonactionable but medically relevant exome findings in the general population we assessed the exomes of 70 participants who have been extensively characterized over the past several years as part of a longitudinal integrated multiomics profiling study.

Circular DNA elements of chromosomal origin are common in healthy human somatic tissue.

The human genome is generally organized into stable chromosomes, and only tumor cells are known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccDNAs). However, it must be expected that kb eccDNAs exist in normal cells as a result of mutations. Here, we purify and sequence eccDNAs from muscle and blood samples from 16 healthy men, detecting ~100,000 unique eccDNA types from 16 million nuclei.

Integrative Personal Omics Profiles during Periods of Weight Gain and Loss.

Advances in omics technologies now allow an unprecedented level of phenotyping for human diseases, including obesity, in which individual responses to excess weight are heterogeneous and unpredictable. To aid the development of better understanding of these phenotypes, we performed a controlled longitudinal weight perturbation study combining multiple omics strategies (genomics, transcriptomics, multiple proteomics assays, metabolomics, and microbiomics) during periods of weight gain and loss in humans. Results demonstrated that: (1) weight gain is associated with the activation of strong inflammatory and hypertrophic cardiomyopathy signatures in blood; (2) although weight loss reverses some changes, a number of signatures persist, indicative of long-term physiologic changes; (3) we observed omics signatures associated with insulin resistance that may serve as novel diagnostics; (4) specific biomolecules were highly individualized and stable in response to perturbations, potentially representing stable personalized markers.

Slightly deleterious genomic variants and transcriptome perturbations in Down syndrome embryonic selection.

The majority of aneuploid fetuses are spontaneously miscarried. Nevertheless, some aneuploid individuals survive despite the strong genetic insult. Here, we investigate if the survival probability of aneuploid fetuses is affected by the genome-wide burden of slightly deleterious variants.

mutation associated with pseudorheumatoid dysplasia.

Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness. Here we report genetic characterization of a consanguineous family segregating an uncharacterized from of skeletal dysplasia. Whole-exome sequencing of four affected siblings and their parents identified a loss-of-function homozygous mutation in the gene, leading to diagnosis of PPD in the affected individuals.

Identification of a novel mutation in the gene associated with ataxia-oculomotor apraxia.

Hereditary ataxias are a clinically and genetically heterogeneous family of disorders defined by the inability to control gait and muscle coordination. Given the nonspecific symptoms of many hereditary ataxias, precise diagnosis relies on molecular genetic testing. To this end, we conducted whole-exome sequencing (WES) on a large consanguineous Iranian family with hereditary ataxia and oculomotor apraxia.

Isolated Congenital Anosmia and CNGA2 Mutation.

Isolated congenital anosmia (ICA) is a rare condition that is associated with life-long inability to smell. Here we report a genetic characterization of a large Iranian family segregating ICA. Whole exome sequencing in five affected family members and five healthy members revealed a stop gain mutation in CNGA2 (OMIM 300338) (chrX:150,911,102; CNGA2.

DNA-Methylation Patterns in Trisomy 21 Using Cells from Monozygotic Twins.

DNA methylation is essential in mammalian development. We have hypothesized that methylation differences induced by trisomy 21 (T21) contribute to the phenotypic characteristics and heterogeneity in Down syndrome (DS). In order to determine the methylation differences in T21 without interference of the interindividual genomic variation, we have used fetal skin fibroblasts from monozygotic (MZ) twins discordant for T21.

Domains of genome-wide gene expression dysregulation in Down's syndrome.

Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated.

Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21.

Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome.

The complex SNP and CNV genetic architecture of the increased risk of congenital heart defects in Down syndrome.

Congenital heart defect (CHD) occurs in 40% of Down syndrome (DS) cases. While carrying three copies of chromosome 21 increases the risk for CHD, trisomy 21 itself is not sufficient to cause CHD. Thus, additional genetic variation and/or environmental factors could contribute to the CHD risk.

Tandem repeat sequence variation as causative cis-eQTLs for protein-coding gene expression variation: the case of CSTB.

Association studies have revealed expression quantitative trait loci (eQTLs) for a large number of genes. However, the causative variants that regulate gene expression levels are generally unknown. We hypothesized that copy-number variation of sequence repeats contribute to the expression variation of some genes.

NANOG priming before full reprogramming may generate germ cell tumours.

Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC) lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression.

Methylation profiling in individuals with uniparental disomy identifies novel differentially methylated regions on chromosome 15.

The maternal and paternal genomes possess distinct epigenetic marks that distinguish them at imprinted loci. In order to identify imprinted loci, we used a novel method, taking advantage of the fact that uniparental disomy (UPD) provides a system that allows the two parental chromosomes to be studied independently. We profiled the paternal and maternal methylation on chromosome 15 using immunoprecipitation of methylated DNA and hybridization to tiling oligonucleotide arrays.

Effect of Ruta graveolens and Cannabis sativa alcoholic extract on spermatogenesis in the adult wistar male rats.

Objective: The present study was undertaken to evaluate the effects of alcohol extracts of Ruta graveolens and Cannabis sativa that were used traditionally in medieval Persian medicine as male contraceptive drugs, on spermatogenesis in the adult male rats.

Materials And Methods: Ethanol extracts of these plants were obtained by the maceration method. The male rats were injected intraperitionaly with C.

Effect of static electric field treatment on multiple antibiotic-resistant pathogenic strains of Escherichia coli and Staphylococcus aureus.

This study evaluated the effect of a (4.5 kV/cm, 50 Hz) static electric field (SEF) on pathogenic strains of Escherichia coli and Staphylococcus aureus with multiple antibiotic resistance. The bacteria were grown overnight at 37 degrees C in a nutrient broth medium, then inoculated in 5 mL fresh nutrient broth medium and incubated for 2 h at 25 degrees C with continuous shaking at 190 rpm.