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Bertha C. Elias Sijo Mathew Manakan B. Srichai Riya Palamuttam Nada Bulus Glenda Mernaugh Amar B. Singh Charles R. Sanders Raymond C. Harris Ambra Pozzi Roy Zent 《The Journal of biological chemistry》2014,289(12):8532-8544
Epithelial cells lining the gastrointestinal tract and kidney have different abilities to facilitate paracellular and transcellular transport of water and solutes. In the kidney, the proximal tubule allows both transcellular and paracellular transport, while the collecting duct primarily facilitates transcellular transport. The claudins and E-cadherin are major structural and functional components regulating paracellular transport. In this study we present the novel finding that the transmembrane matrix receptors, integrins, play a role in regulating paracellular transport of renal proximal tubule cells. Deleting the integrin β1 subunit in these cells converts them from a “loose” epithelium, characterized by low expression of E-cadherin and claudin-7 and high expression of claudin-2, to a “tight” epithelium with increased E-cadherin and claudin-7 expression and decreased claudin-2 expression. This effect is mediated by the integrin β1 cytoplasmic tail and does not entail β1 heterodimerization with an α-subunit or its localization to the cell surface. In addition, we demonstrate that deleting the β1 subunit in the proximal tubule of the kidney results in a major urine-concentrating defect. Thus, the integrin β1 tail plays a key role in regulating the composition and function of tight and adherens junctions that define paracellular transport properties of terminally differentiated renal proximal tubule epithelial cells. 相似文献
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Bortezomib is a chemotherapeutic agent used to treat several cancers; however, it exhibits severe side effects in testicular tissue. We investigated the use of agomelatine to prevent testicular tissue damage caused by bortezomib. We used 36 male Sprague-Dawley rats divided randomly into six equal groups: group 1, no treatment control; group 2, agomelatine treatment only; group 3, bortezomib treatment only for 48 h; group 4, bortezomib + agomelatine treatment for 48 h; group 5, bortezomib treatment only for 72 h; and group 6, bortezomib + agomelatine treatment for 72 h. After treatments, the rats were sacrificed and testicular tissue was harvested. Lipid oxidation (LPO) and superoxide dismutase (SOD) levels in the tissues were determined using biochemical methods. Tissue samples also were examined using histopathological and immunohistochemical techniques. The LPO level was increased, while the SOD level was decreased in the bortezomib treated groups. We found that agomelatine treatment normalized LPO and SOD activities in the bortezomib treated groups. In the spermatogonia and Sertoli cells, the staining density of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and caspase 3 were decreased in the bortezomib + agomelatine groups at both 48 and 72 h compared to bortezomib only treated groups. We observed maturation arrest, basal membrane thickening, increase in inflammatory cells and connective tissue, and edema between germ cells in the bortezomib only treated groups. By contrast, normal basal membrane, less edema and more normal maturation were observed in the bortezomib + agomelatine groups at 48 and 72 h. We found that agomelatine reduced the damaging effects of bortezomib. The use of agomelatine to prevent bortezomib induced testicular tissue damage in human patients should be investigated further. 相似文献
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Bianca V Gapp Tomasz Konopka Thomas Penz Vineet Dalal Tilmann Bürckstümmer Christoph Bock Sebastian MB Nijman 《Molecular systems biology》2016,12(8)
Reverse genetic screens have driven gene annotation and target discovery in model organisms. However, many disease‐relevant genotypes and phenotypes cannot be studied in lower organisms. It is therefore essential to overcome technical hurdles associated with large‐scale reverse genetics in human cells. Here, we establish a reverse genetic approach based on highly robust and sensitive multiplexed RNA sequencing of mutant human cells. We conduct 10 parallel screens using a collection of engineered haploid isogenic cell lines with knockouts covering tyrosine kinases and identify known and unexpected effects on signaling pathways. Our study provides proof of concept for a scalable approach to link genotype to phenotype in human cells, which has broad applications. In particular, it clears the way for systematic phenotyping of still poorly characterized human genes and for systematic study of uncharacterized genomic features associated with human disease. 相似文献
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Most estrous cycles in cows consist of 2 or 3 waves of follicular activity. Waves of ovarian follicular development comprise
the growth of dominant follicles some of which become ovulatory and the others are anovulatory. Ovarian follicular activity
in cows during estrous cycle was studied with a special reference to follicular waves and the circulating concentrations of
estradiol and progesterone. Transrectal ultrasound examination was carried out during 14 interovulatory intervals in 7 cows.
Ovarian follicular activity was recorded together with assessment of serum estradiol and progesterone concentrations. Three-wave
versus two-wave interovulatory intervals was observed in 71.4% of cows. The 3-wave interovulatory intervals differed from
2-wave intervals in: 1) earlier emergence of the dominant follicles, 2) longer in length, and 3) shorter interval from emergence
to ovulation. There was a progressive increase in follicular size and estradiol production during growth phase of each wave.
A drop in estradiol concentration was observed during the static phase of dominant anovulatory follicles. The size of the
ovulatory follicle was always greater and produced higher estradiol compared with the anovulatory follicle. In conclusion,
there was a predominance of 3-wave follicular activity that was associated with an increase in length of interovulatory intervals.
A dominant anovulatory follicle during its static phase may initiate the emergence of a subsequent wave. Follicular size and
estradiol concentration may have an important role in controlling follicular development and in determining whether an estrous
cycle will have 2 or 3-waves. 相似文献
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The O-antigen chain from the lipopolysaccharide of Helicobacter pylori
strain UA861 was determined to be composed of an elongated type 2 N -
acetyllactosamine backbone,
-[-->3)-beta-D-Gal-(1-->4)-beta-D-GlcNAc-(1- ]n-->, with
approximately half of the GlcNAc units carrying a terminal alpha-d-Glc
residue at the O -6 position. The O-chain of H.pylori UA861 was terminated
by a N -acetyllactosamine [beta-D-Gal-(1-->4)-beta-D- GlcNAc] (LacNAc)
epitope and did not express terminal Lewis X or Lewis Y blood-group
determinants as previously found in other H.pylori strains. The absence of
terminal Lewis X and Lewis Y blood-group epitopes and the replacement of
Fuc by Glc as a side chain in the O- chain of H.pylori UA861 represents yet
another type of lipopolysaccharide structure from H.pylori species. These
structural differences in H.pylori lipopolysaccharide molecules carry
implications with regard to possible different pathogenic events between
strains and respective hosts.
相似文献