Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis

Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR) binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression

The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation

SLC12A3 encodes the thiazide-sensitive sodium chloride cotransporter (NCC), which is primarily expressed in the kidney, but also in intestine and bone. In the kidney, NCC is located in the apical plasma membrane of epithelial cells in the distal convoluted tubule. Although NCC reabsorbs only 5 to 10 % of filtered sodium, it is important for the fine-tuning of renal sodium excretion in response to various hormonal and non-hormonal stimuli. Several new roles for NCC in the regulation of sodium, potassium, and blood pressure have been unraveled recently. For example, the recent discoveries that NCC is activated by angiotensin II but inhibited by dietary potassium shed light on how the kidney handles sodium during hypovolemia (high angiotensin II) and hyperkalemia. The additive effect of angiotensin II and aldosterone maximizes sodium reabsorption during hypovolemia, whereas the inhibitory effect of potassium on NCC increases delivery of sodium to the potassium-secreting portion of the nephron. In addition, great steps have been made in unraveling the molecular machinery that controls NCC. This complex network consists of kinases and ubiquitinases, including WNKs, SGK1, SPAK, Nedd4-2, Cullin-3, and Kelch-like 3. The pathophysiological significance of this network is illustrated by the fact that modification of each individual protein in the network changes NCC activity and results in salt-dependent hypotension or hypertension. This review aims to summarize these new insights in an integrated manner while identifying unanswered questions

Genitourinary Pathology (Including Adrenal Gland)

Our aims in constructing the Genitourinary Pathology chapter are to describe neoplasms of the adrenal gland, urothelial tract, kidney, penis, prostate, and testis in a manner that is both useful for the practicing surgical pathologist and that may be used as a reference for all students of urologic pathology. Whereas the text and figures describe the salient morphologic, immunohistochemical, and molecular attributes for each tumor type and encompass the latest classification schemes, the narrative integrates the clinical and pathological findings that are commonly encountered during surgical pathology sign-out of these cases. Accordingly, it is our hope that this chapter will serve as a guide for both general and subspecialized pathologists in contemporary practice

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Not AvailableSymbiotic (Rhizobia, Frankia, and VAM) or free-living (Azotobacter, and Clostridium) association of plant growth-promoting rhizobacteria (PGPR) and fungi (PGPF) is essential for plant and soil health. Nitrogen (N), phosphorus (P) and potassium (K) as major and iron (Fe) and zinc (Zn) as the minor elements are key to plant health. They are important constituents of plant genetic material (N, P) and chlorophyll content (N, Fe) and important for enzymatic activities (Fe, Zn) and are involved in many biochemical and physiological activities. The ‘microbiome’ around the rhizosphere is specific to plant type and involved in nutrient cycling through various processes such as fixation (N), solubilization, mineralization (P, K) and uptake, with the help of various organic acids (gluconic acid, oxalic acid, and tartaric acid), siderophore activity (Fe uptake) and enzymatic actions (nitrogenase, phytases, and acid phosphatases). Phytohormones essential to plant growth and development are produced by microbes themselves or induce their production via other hormones or communication chemicals, viz., volatile organic compounds (VOCs) like 2-pentylfuran, 2,3-butanediol and acetonin. PGPR (Pseudomonas, Trichoderma and Streptomyces) helps the host plant to fight against various abiotic and biotic stresses by the release of bactericidal and fungicidal enzymes, metabolite accumulation and induced systemic resistance (ISR), systemic acquired resistance (SAR) by phytohormones (jasmonic acid, salicylic acid, and ethylene) and VOCs. Attributing to so many benefits, microbes are increasingly becoming part of sustainable agriculture where PGPR (Rhizobium and Pseudomonas) and fungi (Aspergillus, Trichoderma and VAM) are being used as biofertilizers either single strained or in consortia approach, where the latter is found to be more beneficial for plant and soil health.Not Availabl