Lake surface temperature [in “State of the Climate in 2017”]

Observed lake surface water temperature anomalies in 2017 are placed in the context of the recent warming observed in global surface air temperature by collating long-term in situ lake surface temperature observations from some of the world’s best-studied lakes and a satellite-derived global lake surface water temperature dataset. The period 1996–2015, 20 years for which satellite-derived lake temperatures are available, is used as the base period for all lake temperature anomaly calculations

Localization of a gene for nonsyndromic renal hypodysplasia to chromosome 1p32-33.

Nonsyndromic defects in the urinary tract are the most common cause of end-stage renal failure in children and account for a significant proportion of adult nephropathy. The genetic basis of these disorders is not fully understood. We studied seven multiplex kindreds ascertained via an index case with a nonsyndromic solitary kidney or renal hypodysplasia. Systematic ultrasonographic screening revealed that many family members harbor malformations, such as solitary kidneys, hypodysplasia, or ureteric abnormalities (in a total of 29 affected individuals). A genomewide scan identified significant linkage to a 6.9-Mb segment on chromosome 1p32-33 under an autosomal dominant model with reduced penetrance (peak LOD score 3.5 at D1S2652 in the largest kindred). Altogether, three of the seven families showed positive LOD scores at this interval, demonstrating heterogeneity of the trait (peak HLOD 3.9, with 45% of families linked). The chromosome 1p32-33 interval contains 52 transcription units, and at least 23 of these are expressed at stage E12.5 in the murine ureteric bud and/or metanephric mesenchyme. These data show that autosomal dominant nonsyndromic renal hypodysplasia and associated urinary tract malformations are genetically heterogeneous and identify a locus for this common cause of human kidney failure

Mutations in DSTYK and dominant urinary tract malformations.

ABSTRACT Introduction Congenital abnormalities of the kidney of the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and their etiology is poorly understood. Methods We performed genome-wide linkage analysis and whole-exome sequencing in a family with autosomal dominant congenital abnormalities of the kidney of the urinary tract (7 affected family members). We also performed sequence analysis in 311 unrelated patients, as well as histologic and functional studies. Results Linkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single rare deleterious variant within these linkage intervals, a heterozygous splice-site mutation in dual serine/threonine and tyrosine protein kinase (DSTYK). This variant, which resulted in aberrant gene product splicing, was present in all affected family members. Additional independent DSTYK mutations, including nonsense and splice-site mutations, were detected among 7/311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in multi-organ developmental defects, resembling loss of fibroblast growth factor (FGF) signaling. Consistent with this finding, DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. Finally, DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated ERK-phosphorylation, the principal signal downstream of receptor tyrosine kinases. Conclusions We detected DSTYK mutations in 2.2% of patients with congenital abnormalities of the kidney and urinary tract whom we studied, suggesting that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling

Genetic drivers of kidney defects in the digeorge syndrome

BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P = 4.5×1014). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-Altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver

Phenotypic expansion of DGKE-associated diseases.

Atypical hemolytic uremic syndrome (aHUS) is usually characterized by uncontrolled complement activation. The recent discovery of loss-of-function mutations in DGKE in patients with aHUS and normal complement levels challenged this observation. DGKE, encoding diacylglycerol kinase-ε, has not been implicated in the complement cascade but hypothetically leads to a prothrombotic state. The discovery of this novel mechanism has potential implications for the treatment of infants with aHUS, who are increasingly treated with complement blocking agents. In this study, we used homozygosity mapping and whole-exome sequencing to identify a novel truncating mutation in DGKE (p.K101X) in a consanguineous family with patients affected by thrombotic microangiopathy characterized by significant serum complement activation and consumption of the complement fraction C3. Aggressive plasma infusion therapy controlled systemic symptoms and prevented renal failure, suggesting that this treatment can significantly affect the natural history of this aggressive disease. Our study expands the clinical phenotypes associated with mutations in DGKE and challenges the benefits of complement blockade treatment in such patients. Mechanistic studies of DGKE and aHUS are, therefore, essential to the design of appropriate therapeutic strategies in patients with DGKE mutations

Intoxicação natural de bovinos leiteiros por Cestrum laevigatum (solanaceae) no agreste de Pernambuco – Brasil

The aim of the present study was to report an outbreak of natural poisoning by Cestrum laevigatum in dairy cattle in the “Agreste” region of Pernambuco state, Brazil. Epidemiological and clinical data were collected. Among a lot of 60 cows, eight became ill and four died. Two cows underwent necropsy, during which fragments of the central nervous system, liver, gall bladder, spleen and kidney were collected for histopathlogical analysis. Blood samples were collected for hematological and biochemical tests. The animals exhibited apathy, muscle tremors, reduced appetite, different degrees of dehydration and compromised reticulorumen dynamics as well as a small quantity of dry feces with the presence of mucus and blood. The laboratory exams revealed an increase in serum activity of aspartate aminotransferase and gamma glutamyltransferase as well as hypoalbuminemia. The necropsy revealed an enlarged liver and cutting surface with a nutmeg aspect as well as areas of hemorrhaging in the heart, trachea, abomasum, spleen, intestine and bladder. The microscopic analysis revealed centrilobular hepatic necrosis associated to accentuated hemorrhaging. These findings characterized poisoning by Cestrum laevigatum and led to the adoption of control and prevention measures.KEYWORDS: dairy cattle; hepatotoxic plant; poisoning.Este trabalho teve por objetivo relatar um surto de intoxicação natural por Cestrum laevigatum em um rebanho leiteiro no Agreste do Estado de Pernambuco. Foram resgatadas informações epidemiológicas e clínicas. De um lote de 60 vacas, oito adoeceram e, dessas, quatro vieram a óbito e duas foram necropsiadas onde fragmentos de sistema nervoso central, fígado, vesícula biliar, baço e rim foram coletados para análise histopatológica. Foram colhidas amostras de sangue para realização de provas hematológicas e de bioquímica clínica. Os animais apresentavam apatia, tremores musculares, diminuição do apetite, desidratação em graus variados, comprometimento da dinâmica reticuloruminal, além de fezes em quantidade reduzida, ressecadas com presença de muco e estrias de sangue. Os exames laboratoriais revelaram aumento da atividade sérica da aspartatoaminotransferase e da gamaglutamiltransferase, além de hipoalbuminemia. Na necropsia evidenciou-se fígado aumentado de volume e superfície de corte com aspecto de noz-moscada além de áreas de hemorragias no coração, traqueia, abomaso, baço, intestino e bexiga; na microscopia observou-se necrose hepática centrolobular associada à hemorragia acentuada. Tais achados caracterizaram o quadro de intoxicação por Cestrum laevigatum e deram subsídios para adoção das medidas de controle e prevenção.PALAVRAS-CHAVE: intoxicação; planta hepatotóxica; vacas de leite

Lake surface water temperature [in “State of the Climate in 2019”]

Regional Climates is one chapter from the State of the Climate in 2019 annual report. Compiled by NOAA’s National Centers for Environmental Information, State of the Climate in 2019 is based on contributions from scientists from around the world. It provides a detailed update on global climate indicators, notable weather events, and other data collected by environmental monitoring stations and instruments located on land, water, ice, and in space.Universidad de Costa Rica/[805-B9-454]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI