The role of bicarbonate in proximal tubular sodium chloride transport

The role of bicarbonate in proximal tubular sodium chloride transport. Microperfusion studies of single proximal tubules in rat kidney cortex slices show a progressive increase in the rate of reabsorption of isosmotic fluid and NaCl as the bathing medium bicarbonate concentration is raised from 0 to 12 mEq/liter while the pH is maintained at 7.3 to 7.4. When bathing medium bicarbonate was 25 mEq/liter, tubules maintained a significantly lower intraluminal NaHCO3 concentration: 15 mEq/liter. At the same time luminal NaCl concentration was equivalently elevated above that of the bathing medium. Reabsorptive rates were decreased when acetazolamide was added either to the bathing medium or to the tubular perfusate. Intratubular carbonic anhydrase reversed the effects of acetazolamide. Active transport of NaHCO3 stimulates NaCl reabsorption by generating and maintaining concentration gradients favoring passive reabsorption of this salt. The proximal tubule also possesses mechanisms for active NaCl reabsorption

Aménagements de gestion de l'eau sur la propriété privée : analyse multicritère pour une implantation citoyenne

La surconsommation de la ressource par le peuple québécois combinée à l’imperméabilisation du territoire mène à de sérieux problèmes de gestion de l’eau. Des interventions politiques ont été mises en place, pour améliorer la gestion de l’eau. Sachant que 55 % des eaux collectées par les municipalités proviennent des résidences, le citoyen se positionne alors judicieusement comme agent de changement. D’ailleurs dans sa Politique nationale de l’eau, le Québec souhaite impliquer davantage les citoyens dans la gestion de la ressource. L'objectif de cet essai est d’évaluer différents aménagements et pratiques réalisables à l’extérieur d’une propriété privée de réduction de la consommation, de captation ainsi que de rétention et d’infiltration de l’eau pour en faire ressortir les plus intéressants et ainsi guider les gestionnaires municipaux dans leur choix des mesures à conseiller pour une application citoyenne. L’essai met en lumière les réels impacts des pratiques et aménagements de gestion de l’eau dans le secteur résidentiel. Pour ce faire, dix-huit aménagements et pratiques de gestion de l’eau sont évalués au moyen d’une analyse multicritère de type boussole bernoise en tenant compte de quatre dimensions, soit les dimensions : environnement, économie, sociale et technique. Des recommandations sont formulées aux gestionnaires municipaux pour inviter ces derniers à promouvoir l'application d'une gestion adéquate de la ressource sachant qu’ils possèdent le cadre légal et les outils nécessaires. De plus, à partir des meilleurs aménagements déterminés, des recommandations sont effectuées en fonction de la densité du secteur résidentiel. Les principaux aménagements retenus sont : l’aménagement paysager, le jardin de pluie, la bande filtrante, le baril de pluie, le réservoir souterrain ainsi que la toiture verte extensive

CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a genetically heterogeneous subtype of B-cell ALL characterized by chromosomal rearrangements and mutations that result in aberrant cytokine receptor and kinase signaling. In particular, chromosomal rearrangements resulting in the overexpression of cytokine receptor-like factor 2 (CRLF2) occur in 50% of Ph-like ALL cases. CRLF2 overexpression is associated with particularly poor clinical outcomes, though the molecular basis for this is currently unknown. Glucocorticoids (GCs) are integral to the treatment of ALL and GC resistance at diagnosis is an important negative prognostic factor. Given the importance of GCs in ALL therapy and the poor outcomes for patients with CRLF2 overexpression, we hypothesized that the aberrant signal transduction associated with CRLF2 overexpression might mediate intrinsic GC insensitivity. To test this hypothesis, we exposed Ph-like ALL cells from patient-derived xenografts to GCs and found that CRLF2 rearranged (CRLF2R) leukemias uniformly demonstrated reduced GC sensitivity in vitro. Furthermore, targeted inhibition of signal transduction with the MEK inhibitor trametinib and the Akt inhibitor MK2206, but not the JAK inhibitor ruxolitinib, was sufficient to augment GC sensitivity. These data suggest that suboptimal GC responses may in part underlie the poor clinical outcomes for patients with CRLF2 overexpression and provide rationale for combination therapy involving GCs and signal transduction inhibitors as a means of enhancing GC efficacy

Can we accelerate autism discoveries through crowdsourcing?

AbstractAutism is a dramatically expanding public health challenge. The search for genomic variants underlying the disease concomitantly accelerated over the last 5 years, leading to a general consensus that genetics can explain between 40% and 60% of the symptomatic variability seen in autism. This stresses both an urgent need to continue devoting resources to the search for genetic etiologies that define the forms of autism, and an equal need for attention to the interactive roles of the environment. While some environmental factors have been investigated, few studies have attempted to elucidate the combination and interplay between gene and environment to gain clear understanding of the mechanisms by which environmental factors interact with genetic susceptibilities in Autism Spectrum Disorder. Due to financial constraints as well as recruitment protocols limited by geography, such studies have been challenging to implement. We discuss here how crowdsourcing approaches can overcome these limitations

Comparing different types of patagial tags for use on vultures

Raptor research often requires identifying individuals. Researchers place patagial tags on raptors to facilitate such identification. Researchers in southern African use two main types of patagial tags: hard plastic ear tags originally designed for cattle and soft vinyl tags. We deployed both types of tags on vultures in Botswana.  Based on our observations, we recommend using soft vinyl tags as they appear to be more aerodynamic and  can be read from below when a raptor is soaring, as well as when the bird is perched. Cattle ear tags  sometimes flutter when raptors fly and can only be read when the dorsal surface of the wing is visible

Identification of active oxalotrophic bacteria by Bromodeoxyuridine DNA labeling in a microcosm soil experiments

The oxalate-carbonate pathway (OCP) leads to a potential carbon sink in terrestrial environments. This process is linked to the activity of oxalotrophic bacteria. Although isolation and molecular characterizations are used to study oxalotrophic bacteria, these approaches do not give information on the active oxalotrophs present in soil undergoing the OCP. The aim of this study was to assess the diversity of active oxalotrophic bacteria in soil microcosms using the Bromodeoxyuridine (BrdU) DNA labeling technique. Soil was collected near an oxalogenic tree (Milicia excelsa). Different concentrations of calcium oxalate (0.5%, 1%, and 4% w/w) were added to the soil microcosms and compared with an untreated control. After 12 days of incubation, a maximal pH of 7.7 was measured for microcosms with oxalate (initial pH 6.4). At this time point, a DGGE profile of the frc gene was performed from BrdU-labeled soil DNA and unlabeled soil DNA. Actinobacteria (Streptomyces- and Kribbella-like sequences), Gammaproteobacteria and Betaproteobacteria were found as the main active oxalotrophic bacterial groups. This study highlights the relevance of Actinobacteria as members of the active bacterial community and the identification of novel uncultured oxalotrophic groups (i.e. Kribbella) active in soil

FOAM (functional ontology assignments for metagenomes):a hidden markov model (HMM) database with environmental focus

A new functional gene database, FOAM (Functional Ontology Assignments for Metagenomes), was developed to screen environmental metagenomic sequence datasets. FOAM provides a new functional ontology dedicated to classify gene functions relevant to environmental microorganisms based on Hidden Markov Models (HMMs). Sets of aligned protein sequences (i.e. ‘profiles’) were tailored to a large group of target KEGG Orthologs (KOs) from which HMMs were trained. The alignments were checked and curated to make them specific to the targeted KO. Within this process, sequence profiles were enriched with the most abundant sequences available to maximize the yield of accurate classifier models. An associated functional ontology was built to describe the functional groups and hierarchy. FOAM allows the user to select the target search space before HMM-based comparison steps and to easily organize the results into different functional categories and subcategories. FOAM is publicly available at http://portal.nersc.gov/project/m1317/FOAM/

Klf4 protects thymus integrity during late pregnancy

Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a Psmb11-iCre : Klf4lox/lox mouse model to study the impact of TEC-specific Klf4 deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, Klf4 deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking Klf4 expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of Klf4-/- TECs revealed that Klf4 maintains cTEC numbers by supporting cell survival and preventing epithelial-to-mesenchymal plasticity during late pregnancy. We conclude that Klf4 is essential for preserving TEC’s integrity and mitigating thymic involution during late pregnancy