Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1

Both tyrosine-phosphorylated caveolin-1 (pY14Cav1) and GlcNAc-transferase V (Mgat5) are linked with focal adhesions (FAs); however, their function in this context is unknown. Here, we show that galectin-3 binding to Mgat5-modified N-glycans functions together with pY14Cav1 to stabilize focal adhesion kinase (FAK) within FAs, and thereby promotes FA disassembly and turnover. Expression of the Mgat5/galectin lattice alone induces FAs and cell spreading. However, FAK stabilization in FAs also requires expression of pY14Cav1. In cells lacking the Mgat5/galectin lattice, pY14Cav1 is not sufficient to promote FAK stabilization, FA disassembly, and turnover. In human MDA-435 cancer cells, Cav1 expression, but not mutant Y14FCav1, stabilizes FAK exchange and stimulates de novo FA formation in protrusive cellular regions. Thus, transmembrane crosstalk between the galectin lattice and pY14Cav1 promotes FA turnover by stabilizing FAK within FAs defining previously unknown, interdependent roles for galectin-3 and pY14Cav1 in tumor cell migration

Phosphocaveolin-1 is a mechanotransducer that induces caveola biogenesis via Egr1 transcriptional regulation

Caveolin-1 (Cav1) is an essential component of caveolae whose Src kinase-dependent phosphorylation on tyrosine 14 (Y14) is associated with regulation of focal adhesion dynamics. However, the relationship between these disparate functions remains to be elucidated. Caveola biogenesis requires expression of both Cav1 and cavin-1, but Cav1Y14 phosphorylation is dispensable. In this paper, we show that Cav1 tyrosine phosphorylation induces caveola biogenesis via actin-dependent mechanotransduction and inactivation of the Egr1 (early growth response-1) transcription factor, relieving inhibition of endogenous Cav1 and cavin-1 genes. Cav1 phosphorylation reduces Egr1 binding to Cav1 and cavin-1 promoters and stimulates their activity. In MDA-231 breast carcinoma cells that express elevated levels of Cav1 and caveolae, Egr1 regulated Cav1, and cavin-1 promoter activity was dependent on actin, Cav1, Src, and Rho-associated kinase as well as downstream protein kinase C (PKC) signaling. pCav1 is therefore a mechanotransducer that acts via PKC to relieve Egr1 transcriptional inhibition of Cav1 and cavin-1, defining a novel feedback regulatory loop to regulate caveola biogenesis

A case report of Mycoplasma wenyonii associated immune-mediated haemolytic anaemia in a dairy cow

Background and case presentation: A three year old, second lactation Holstein dairy cow presented to the Scottish Centre for Production Animal Health and Food Safety, Glasgow University Veterinary School in November 2014 with a history of post-calving vulval/vaginal bleeding nine days prior to presentation, followed by a sudden reduction in milk yield. Subsequent investigations resulted in a diagnosis of immune-mediated haemolytic anaemia secondary to infection with Mycoplasma wenyonii. Conclusion: This report of a novel presentation of Mycoplasma wenyonii in a dairy cow illustrates the need to consider M.wenyonii as a potential differential diagnosis when a cow presents with anaemia and will discuss the potential implications of the condition at herd-level

Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1

Klebsiella pneumoniae is a major threat to public health with the emergence of isolates resistant to most, if not all, useful antibiotics. We present an in-depth analysis of 178 extended-spectrum beta-lactamase (ESBL)-producing K. pneumoniae collected from patients resident in a region of Pakistan, during the period 2010-2012, when the now globally-distributed carbapenemase bla-NDM-1 was being acquired by Klebsiella. We observed two dominant lineages, but neither the overall resistance profile nor virulence-associated factors, explain their evolutionary success. Phenotypic analysis of resistance shows few differences between the acquisition of resistance genes and the phenotypic resistance profile, including beta-lactam antibiotics that were used to treat ESBL-positive strains. Resistance against these drugs could be explained by inhibitor-resistant beta-lactamase enzymes, carbapenemases or ampC type beta-lactamases, at least one of which was detected in most, but not all relevant strains analysed. Complete genomes for six selected strains are reported, these provide detailed insights into the mobile elements present in these isolates during the initial spread of NDM-1. The unexplained success of some lineages within this pool of highly resistant strains, and the discontinuity between phenotypic resistance and genotype at the macro level, indicate that intrinsic mechanisms contribute to competitive advantage and/or resistance