OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis.

Purpose: Nephrolithiasis (NL) affects 1 in 11 individuals worldwide, leading to significant patient morbidity. NL is associated with nephrocalcinosis (NC), a risk factor for chronic kidney disease. Causative genetic variants are detected in 11% to 28% of NL and/or NC, suggesting that additional NL/NC-associated genetic loci await discovery.

Portable NMR for quantification of breast density in vivo: Proof-of-concept measurements and comparison with quantitative MRI.

Mammographic Density (MD) is the degree of radio-opacity of the breast in an X-ray mammogram. It is determined by the Fibroglandular: Adipose tissue ratio. MD has major implications in breast cancer risk and breast cancer chemoprevention.

Usefulness of Electoral Models for COVID-19 Vaccine Distribution.

Purpose Of Review: In response to the COVID-19 pandemic, there has been a remarkably accelerated development of vaccines worldwide. However, an effective distribution system is crucial for vaccination at a national level. Ecuador was one of the first Latin American countries to be most severely affected by the pandemic.

Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?

Regions of high mammographic density (MD) in the breast are characterised by a proteoglycan (PG)-rich fibrous stroma, where PGs mediate aligned collagen fibrils to control tissue stiffness and hence the response to mechanical forces. Literature is accumulating to support the notion that mechanical stiffness may drive PG synthesis in the breast contributing to MD. We review emerging patterns in MD and other biological settings, of a positive feedback cycle of force promoting PG synthesis, such as in articular cartilage, due to increased pressure on weight bearing joints.

RASSF1A Suppression as a Potential Regulator of Mechano-Pathobiology Associated with Mammographic Density in BRCA Mutation Carriers.

High mammographic density (MD) increases breast cancer (BC) risk and creates a stiff tissue environment. BC risk is also increased in gene mutation carriers, which may be in part due to genetic disruption of the tumour suppressor gene Ras association domain family member 1 (), a gene that is also directly regulated by tissue stiffness. High MD combined with mutations further increase breast cancer risk, yet mutations alone or in combination do not increase MD.

Corrigendum: Heparanase Promotes Syndecan-1 Expression to Mediate Fibrillar Collagen and Mammographic Density in Human Breast Tissue Cultured .

[This corrects the article DOI: 10.3389/fcell.2020.

The role of mechanical interactions in EMT.

The detachment of cells from the boundary of an epithelial tissue and the subsequent invasion of these cells into surrounding tissues is important for cancer development and wound healing, and is strongly associated with the epithelial-mesenchymal transition (EMT). Chemical signals, such as TGF-, produced by surrounding tissue can be uptaken by cells and induce EMT. In this work, we present a novel cell-based discrete mathematical model of mechanical cellular relaxation, cell proliferation, and cell detachment driven by chemically-dependent EMT in an epithelial tissue.

Generation of Monogenic Candidate Genes for Human Nephrotic Syndrome Using 3 Independent Approaches.

Introduction: Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease during childhood. Identification of 63 monogenic human genes has delineated 12 distinct pathogenic pathways.

Methods: Here, we generated 2 independent sets of nephrotic syndrome (NS) candidate genes to augment the discovery of additional monogenic causes based on whole-exome sequencing (WES) data from 1382 families with NS.

First evidence of wasp brood development inside active nests of a termite with the description of a previously unknown potter wasp species.

Potter wasps (Vespidae: Eumeninae) are known to exhibit not only sophisticated preying strategies but also a remarkable ability to manipulate clay during nest building. Due to a mixture of plasticity in building behavior and flexibility in substrate preferences during nest building, the group has been reported nesting in a variety of places, including decaying nests abandoned by termite species. Yet, evidence of wasps nesting inside senescent termite mounds is poorly reported, and to date, accounts confirming their presence inside active colonies of termites are absent.

Integrin alpha-2 and beta-1 expression increases through multiple generations of the EDW01 patient-derived xenograft model of breast cancer-insight into their role in epithelial mesenchymal transition in vivo gained from an in vitro model system.

Background: Breast cancers acquire aggressive capabilities via epithelial to mesenchymal transition (EMT), in which various integrins/integrin-linked kinase signalling are upregulated.

Methods: We investigated this in two patient-derived xenografts (PDXs) developed from breast-to-bone metastases, and its functional significance in a breast cancer cell line system. ED03 and EDW01 PDXs were grown subcutaneously in immunocompromised SCID mice through 11 passages and 7 passages, respectively.

Nonaggressive behavior: A strategy employed by an obligate nest invader to avoid conflict with its host species.

In addition to its builders, termite nests are known to house a variety of secondary opportunistic termite species so-called inquilines, but little is known about the mechanisms governing the maintenance of these symbioses. In a single nest, host and inquiline colonies are likely to engage in conflict due to nestmate discrimination, and an intriguing question is how both species cope with each other in the long term. Evasive behaviour has been suggested as one of the mechanisms reducing the frequency of host-inquiline encounters, yet, the confinement imposed by the nests' physical boundaries suggests that cohabiting species would eventually come across each other.

Heparanase Promotes Syndecan-1 Expression to Mediate Fibrillar Collagen and Mammographic Density in Human Breast Tissue Cultured .

Mammographic density (MD) is a strong and independent factor for breast cancer (BC) risk and is increasingly associated with BC progression. We have previously shown in mice that high MD, which is characterized by the preponderance of a fibrous stroma, facilitates BC xenograft growth and metastasis. This stroma is rich in extracellular matrix (ECM) factors, including heparan sulfate proteoglycans (HSPGs), such as the BC-associated syndecan-1 (SDC1).

ADCK4 Deficiency Destabilizes the Coenzyme Q Complex, Which Is Rescued by 2,4-Dihydroxybenzoic Acid Treatment.

Background: Mutations in (aarF domain containing kinase 4) generally manifest as steroid-resistant nephrotic syndrome and induce coenzyme Q (CoQ) deficiency. However, the molecular mechanisms underlying steroid-resistant nephrotic syndrome resulting from mutations are not well understood, largely because the function of ADCK4 remains unknown.

Methods: To elucidate the ADCK4's function in podocytes, we generated a podocyte-specific, -knockout mouse model and a human podocyte cell line featuring knockout of .

Mutations in KIRREL1, a slit diaphragm component, cause steroid-resistant nephrotic syndrome.

Steroid-resistant nephrotic syndrome is a frequent cause of chronic kidney disease almost inevitably progressing to end-stage renal disease. More than 58 monogenic causes of SRNS have been discovered and majority of known steroid-resistant nephrotic syndrome causing genes are predominantly expressed in glomerular podocytes, placing them at the center of disease pathogenesis. Herein, we describe two unrelated families with steroid-resistant nephrotic syndrome with homozygous mutations in the KIRREL1 gene.

Quantification of breast tissue density: Correlation between single-sided portable NMR and micro-CT measurements.

Mammographic density (MD) is a strong independent risk factor for breast cancer. Traditional screening for MD using X-ray mammography involves ionising radiation, which is not suitable for young women, those with previous radiation exposure, or those having undergone a partial mastectomy. Therefore, alternative approaches for MD screening that do not involve ionising radiation will be important as the clinical use of MD increases, and as more frequent MD testing becomes desirable for research purposes.

Transverse relaxation-based assessment of mammographic density and breast tissue composition by single-sided portable NMR.

Purpose: Elevated mammographic density (MD) is an independent risk factor for breast cancer (BC) as well as a source of masking in X-ray mammography. High-frequency longitudinal monitoring of MD could also be beneficial in hormonal BC prevention, where early MD changes herald the treatment's success. We present a novel approach to quantification of MD in breast tissue using single-sided portable NMR.

Treatment with 2,4-Dihydroxybenzoic Acid Prevents FSGS Progression and Renal Fibrosis in Podocyte-Specific Knockout Mice.

Background: Although studies have identified >55 genes as causing steroid-resistant nephrotic syndrome (SRNS) and localized its pathogenesis to glomerular podocytes, the disease mechanisms of SRNS remain largely enigmatic. We recently reported that individuals with mutations in COQ6, a coenzyme Q (also called CoQ, CoQ, or ubiquinone) biosynthesis pathway enzyme, develop SRNS with sensorineural deafness, and demonstrated the beneficial effect of CoQ for maintenace of kidney function.

Methods: To study function in podocytes, we generated a podocyte-specific knockout mouse ( ) model and a transient siRNA-based knockdown in a human podocyte cell line.

Whole-Exome Sequencing Enables a Precision Medicine Approach for Kidney Transplant Recipients.

Background: Whole-exome sequencing (WES) finds a CKD-related mutation in approximately 20% of patients presenting with CKD before 25 years of age. Although provision of a molecular diagnosis could have important implications for clinical management, evidence is lacking on the diagnostic yield and clinical utility of WES for pediatric renal transplant recipients.

Methods: To determine the diagnostic yield of WES in pediatric kidney transplant recipients, we recruited 104 patients who had received a transplant at Boston Children's Hospital from 2007 through 2017, performed WES, and analyzed results for likely deleterious variants in approximately 400 genes known to cause CKD.

Mutations in multiple components of the nuclear pore complex cause nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) almost invariably progresses to end-stage renal disease. Although more than 50 monogenic causes of SRNS have been described, a large proportion of SRNS remains unexplained. Recently, it was discovered that mutations of NUP93 and NUP205, encoding 2 proteins of the inner ring subunit of the nuclear pore complex (NPC), cause SRNS.

Whole-Exome Sequencing Identifies Causative Mutations in Families with Congenital Anomalies of the Kidney and Urinary Tract.

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most prevalent cause of kidney disease in the first three decades of life. Previous gene panel studies showed monogenic causation in up to 12% of patients with CAKUT.

Methods: We applied whole-exome sequencing to analyze the genotypes of individuals from 232 families with CAKUT, evaluating for mutations in single genes known to cause human CAKUT and genes known to cause CAKUT in mice.

Mutations in WDR4 as a new cause of Galloway-Mowat syndrome.

Galloway-Mowat syndrome (GAMOS) is a phenotypically heterogeneous disorder characterized by neurodevelopmental defects combined with renal-glomerular disease, manifesting with proteinuria. To identify additional monogenic disease causes, we here performed whole exome sequencing (WES), linkage analysis, and homozygosity mapping in three affected siblings of an Indian family with GAMOS. Applying established criteria for variant filtering, we identify a novel homozygous splice site mutation in the gene WDR4 as the likely disease-causing mutation in this family.