The Kidney Health Score: A Practical Guide to Early Detection of Kidney Disease Risk for Optimal Kidney Health.

Chronic kidney disease (CKD) affects 10% of the global population, with increasing prevalence driven by diabetes, hypertension, and aging populations. CKD often progresses asymptomatically, frequently undetected until advanced stages, and may require costly treatments, such as dialysis or transplantation. CKD imposes a substantial financial burden on health care systems, with management costs rising sharply as the disease progresses, underscoring the need for early, cost-effective interventions.

Disrupted rest-activity circadian rhythms are associated with all-cause mortality in patients with chronic kidney diseases.

Circadian rhythms are important biological contributors to health. Rest activity rhythms (RAR) are emerging as biomarkers of circadian behavior that are associated with chronic disease when abnormal. RAR have not yet been characterized in chronic kidney diseases (CKD).

A Variant-Centric Analysis of Allele Sharing in Dogs and Wolves.

Canines are an important model system for genetics and evolution. Recent advances in sequencing technologies have enabled the creation of large databases of genetic variation in canines, but analyses of allele sharing among canine groups have been limited. We applied GeoVar, an approach originally developed to study the sharing of single nucleotide polymorphisms across human populations, to assess the sharing of genetic variation among groups of wolves, village dogs, and breed dogs.

A map of canine sequence variation relative to a Greenland wolf outgroup.

For over 15 years, canine genetics research relied on a reference assembly from a Boxer breed dog named Tasha (i.e., canFam3.

Duplications and Retrogenes Are Numerous and Widespread in Modern Canine Genomic Assemblies.

Recent years have seen a dramatic increase in the number of canine genome assemblies available. Duplications are an important source of evolutionary novelty and are also prone to misassembly. We explored the duplication content of nine canine genome assemblies using both genome self-alignment and read-depth approaches.

Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes.

Alu elements are non-autonomous Short INterspersed Elements (SINEs) derived from the 7SL RNA gene that are present at over one million copies in human genomic DNA. Alu mobilizes by a mechanism known as retrotransposition, which requires the Long INterspersed Element-1 (LINE-1) ORF2-encoded protein (ORF2p). Here, we demonstrate that HeLa strains differ in their capacity to support Alu retrotransposition.

Mapping recurrent mosaic copy number variation in human neurons.

When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers.

Variable patterns of retrotransposition in different HeLa strains provide mechanistic insights into SINE RNA mobilization processes.

elements are non-autonomous Short INterspersed Elements (SINEs) derived from the gene that are present at over one million copies in human genomic DNA. mobilizes by a mechanism known as retrotransposition, which requires the Long INterspersed Element-1 (LINE-1 or L1) -encoded protein (ORF2p). Here, we demonstrate that HeLa strains differ in their capacity to support retrotransposition.

Podocyte-specific silencing of acid sphingomyelinase gene to abrogate hyperhomocysteinemia-induced NLRP3 inflammasome activation and glomerular inflammation.

Acid sphingomyelinase (ASM) has been reported to increase tissue ceramide and thereby mediate hyperhomocysteinemia (hHcy)-induced glomerular nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation, inflammation, and sclerosis. In the present study, we tested whether somatic podocyte-specific silencing of gene (mouse ASM gene code) attenuates hHcy-induced NLRP3 inflammasome activation and associated extracellular vesicle (EV) release in podocytes and thereby suppresses glomerular inflammatory response and injury. In vivo, somatic podocyte-specific Smpd1 gene silencing almost blocked hHcy-induced glomerular NLRP3 inflammasome activation in Podo (podocyte-specific expression of cre recombinase) mice compared with control littermates.

Genomic data resources of the Brain Somatic Mosaicism Network for neuropsychiatric diseases.

Somatic mosaicism is defined as an occurrence of two or more populations of cells having genomic sequences differing at given loci in an individual who is derived from a single zygote. It is a characteristic of multicellular organisms that plays a crucial role in normal development and disease. To study the nature and extent of somatic mosaicism in autism spectrum disorder, bipolar disorder, focal cortical dysplasia, schizophrenia, and Tourette syndrome, a multi-institutional consortium called the Brain Somatic Mosaicism Network (BSMN) was formed through the National Institute of Mental Health (NIMH).

Regulation of NLRP3 Inflammasome Activation and Inflammatory Exosome Release in Podocytes by Acid Sphingomyelinase During Obesity.

The activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome has been reported to importantly contribute to glomerular inflammation and injury under different pathological conditions such as obesity. However, the mechanism mediating NLRP3 inflammasome activation in podocytes and subsequent glomerular injury remains poorly understood. Given that the ceramide signaling pathway has been reported to be implicated in obesity-related glomerulopathy (ORG), the present study was designed to test whether the ceramide-producing enzyme, acid sphingomyelinase (ASM), determines NLRP3 inflammasome activation and inflammatory exosome release in podocytes leading to glomerular inflammation and injury during ORG.

A first-in-class inhibitor of Hsp110 molecular chaperones of pathogenic fungi.

Proteins of the Hsp110 family are molecular chaperones that play important roles in protein homeostasis in eukaryotes. The pathogenic fungus Candida albicans, which causes infections in humans, has a single Hsp110, termed Msi3. Here, we provide proof-of-principle evidence supporting fungal Hsp110s as targets for the development of new antifungal drugs.

Mapping the Complex Genetic Landscape of Human Neurons.

When somatic cells acquire complex karyotypes, they are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers.

Recent, full-length gene retrocopies are common in canids.

Gene retrocopies arise from the reverse transcription and insertion into the genome of processed mRNA transcripts. Although many retrocopies have acquired mutations that render them functionally inactive, most mammals retain active LINE-1 sequences capable of producing new retrocopies. New retrocopies, referred to as retro copy number variants (retroCNVs), may not be identified by standard variant calling techniques in high-throughput sequencing data.