420 research outputs found
Joint actions with large partners and small-firm ambidexterity in asymmetric alliances:The mediating role of relational identification
This study investigates the role of relational identification in the relation between joint actions and small-firm ambidexterity in asymmetric alliances. Using survey data on Chinese high-technology firms, we find that joint problem-solving and joint sensemaking are both positively associated with small firm's relational identification. We also find a positive relationship between small firm's relational identification and knowledge exploration and exploitation. More importantly, we show that relational identification mediates the relationships between joint actions (i.e., joint problem-solving and joint sensemaking) and small-firm ambidexterity, except for the relationship between joint sensemaking and small-firm knowledge exploitation. This study advances our understanding of the association between joint actions and ambidexterity by providing a social identification explanation
Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study
Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p>
Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p>
Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p>
Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p>
Aldosterone status associates with insulin resistance in patients with heart failure-data from the ALOFT study
ABSTRACT Background: Aldosterone plays a key role in the pathophysiology of heart failure. In around 50% of such patients, aldosterone 'escapes' from inhibition by drugs that interrupt the renin-angiotensin axis; such patients have a worse clinical outcome. Insulin resistance is a risk factor in heart failure and cardiovascular disease. The relationship between aldosterone status and insulin sensitivity was investigated in a cohort of heart failure patients. Methods: 302 patients with New York Heart Association (NYHA) class II-IV heart failure on conventional therapy were randomized in ALiskiren Observation of heart Failure Treatment study (ALOFT), designed to test the safety of a directly acting renin inhibitor. Plasma aldosterone and 24-hour urinary aldosterone excretion as well as fasting insulin and Homeostasis model assessment of insulin resistance (HOMA-IR) were measured. Subjects with aldosterone escape and high urinary aldosterone were identified according to previously accepted definitions. Results: Twenty per-cent of subjects demonstrated aldosterone escape and 34% had high urinary aldosterone levels. At baseline, there was a positive correlation between fasting insulin and plasma(r=0.22 p<0.01) and urinary aldosterone(r=0.19 p<0.03). Aldosterone escape and high urinary aldosterone subjects both demonstrated higher levels of fasting insulin (p<0.008, p<0.03), HOMA-IR (p<0.06, p<0.03) and insulin-glucose ratios (p<0.006, p<0.06) when compared to low aldosterone counterparts. All associations remained significant when adjusted for potential confounders. Conclusions: This study demonstrates a novel direct relationship between aldosterone status and insulin resistance in heart failure. This observation merits further study and may identify an additional mechanism that contributes to the adverse clinical outcome associated with aldosterone escape
Ethanol and acetaldehyde mediate folic acid and human papillomavirus-induced proliferation of oral squamous cell carcinoma cells in vitro
Population genomic analysis reveals highly conserved mitochondrial genomes in the yeast species Lachancea thermotolerans
The increasing availability of mitochondrial (mt) sequence data from various yeasts provides a tool to study genomic evolution within and between different species. While the genomes from a range of lineages are available, there is a lack of information concerning intraspecific mtDNA diversity. Here, we analyzed the mt genomes of 50 strains from Lachancea thermotolerans, a protoploid yeast species that has been isolated from several locations (Europe, Asia, Australia, South Africa, and North / South America) and ecological sources (fruit, tree exudate, plant material, and grape and agave fermentations). Protein-coding genes from the mtDNA were used to construct a phylogeny, which reflected a similar, yet less resolved topology than the phylogenetic tree of 50 nuclear genes. In comparison to its sister species Lachancea kluyveri, L. thermotolerans has a smaller mt genome. This is due to shorter intergenic regions and fewer introns, of which the latter are only found in COX1. We revealed that L. kluyveri and L. thermotolerans share similar levels of intraspecific divergence concerning the nuclear genomes. However, L. thermotolerans has a more highly conserved mt genome with the coding regions characterized by low rates of nonsynonymous substitution. Thus, in the mt genomes of L. thermotolerans, stronger purifying selection and lower mutation rates potentially shape genome diversity in contract to what was found for L. kluyveri, demonstrating that the factors driving mt genome evolution are different even between closely related species
Common Polymorphisms at the <i>CYP17A1 </i>Locus Associate With Steroid Phenotype:Support for Blood Pressure Genome-Wide Association Study Signals at This Locus
Genome-wide association studies implicate the CYP17A1 gene in human blood pressure regulation although the causative polymorphisms are as yet unknown. We sought to identify common polymorphisms likely to explain this association. We sequenced the CYP17A1 locus in 60 normotensive individuals and observed 24 previously identified single-nucleotide polymorphisms with minor allele frequency >0.05. From these, we selected, for further studies, 7 polymorphisms located ≤2 kb upstream of the CYP17A1 transcription start site. In vitro reporter gene assays identified 3 of these (rs138009835, rs2150927, and rs2486758) as having significant functional effects. We then analyzed the association between the 7 polymorphisms and the urinary steroid metabolites in a hypertensive cohort (n=232). Significant associations included that of rs138009835 with aldosterone metabolite excretion; rs2150927 associated with the ratio of tetrahydrodeoxycorticosterone to tetrahydrodeoxycortisol, which we used as an index of 17α-hydroxylation. Linkage analysis showed rs138009835 to be the only 1 of the 7 polymorphisms in strong linkage disequilibrium with the blood pressure–associated polymorphisms identified in the previous studies. In conclusion, we have identified, characterized, and investigated common polymorphisms at the CYP17A1 locus that have functional effects on gene transcription in vitro and associate with corticosteroid phenotype in vivo. Of these, rs138009835—which we associate with changes in aldosterone level—is in strong linkage disequilibrium with polymorphisms linked by genome-wide association studies to blood pressure regulation. This finding clearly has implications for the development of high blood pressure in a large proportion of the population and justifies further investigation of rs138009835 and its effects
Differential susceptibility of S and M phase cyclin/CDK complexes to inhibitory tyrosine phosphorylation in yeast
Several checkpoint pathways employ Wee1-mediated inhibitory tyrosine phosphorylation of cyclin-dependent kinases (CDKs) to restrain cell-cycle progression. Whereas in vertebrates this strategy can delay both DNA replication and mitosis, in yeast cells only mitosis is delayed. This is particularly surprising because yeasts, unlike vertebrates, employ a single family of cyclins (B-type) and the same CDK to promote both S phase and mitosis. The G2-specific arrest could be explained in two fundamentally different ways: tyrosine phosphorylation of cyclin/CDK complexes could leave sufficient residual activity to promote S phase, or S phase-promoting cyclin/CDK complexes could somehow be protected from checkpoint-induced tyrosine phosphorylation
Whole-Genome Sequencing and Intraspecific Analysis of the Yeast Species Lachancea quebecensis
The gold standard in yeast population genomics has been the model organism Saccharomyces cerevisiae. However, the exploration of yeast species outside the Saccharomyces genus is essential to broaden the understanding of genome evolution. Here, we report the analyses of whole-genome sequences of nineisolates from the recently described yeast species Lachancea quebecensis. The genome of one isolate was assembled and annotated, and the intraspecific variability within L. quebecensis was surveyed by comparing the sequences from the eight other isolates to this reference sequence. Our study revealed that these strains harbor genomes with an average nucleotide diversity of pi = 2 x 10(-3) which is slightly lower, although on the same order of magnitude, as that previously determined for S. cerevisiae (pi = 4 x 10(-3)). Our results show that even though these isolates were all obtained from a relatively isolated geographic location, the same ecological source, and represent a smaller sample size than is available for S. cerevisiae, the levels of divergence are similar to those observed in this model species. This divergence is essentially linked to the presence of two distinct clusters delineated according to geographic location. However, even with relatively similar ranges of genome divergence, L. quebecensis has an extremely low global phenotypic variance of 0.062 compared with 0.59 previously determined in S. cerevisiae
The contrasting effects of active and passive cooperation on innovation and productivity: Evidence from British local innovation networks
This paper studies the contrasting effects on innovations and productivity arising from active cooperation in innovation activities among competitors and from passive cooperation induced by these activities’ spillovers. A three-stage productivity function is estimated showing that firms’ innovations are supported by their active cooperation within their local innovation network of suppliers and customers and by passive cooperation through sectors’ spillovers. Contrary to this, active cooperation in innovation activities among competitors reduces their innovation rates and, indirectly, productivity. Hence, innovation policies and strategies aimed at restraining active cooperation among competitors, while encouraging it within a firm's local innovation network, may contribute to the system-wide introduction of process and product innovations and ultimately productivity
Mitochondrial fusion is regulated by Reaper to modulate Drosophila programmed cell death
In most multicellular organisms, the decision to undergo programmed cell death in response to cellular damage or developmental cues is typically transmitted through mitochondria. It has been suggested that an exception is the apoptotic pathway of Drosophila melanogaster, in which the role of mitochondria remains unclear. Although IAP antagonists in Drosophila such as Reaper, Hid and Grim may induce cell death without mitochondrial membrane permeabilization, it is surprising that all three localize to mitochondria. Moreover, induction of Reaper and Hid appears to result in mitochondrial fragmentation during Drosophila cell death. Most importantly, disruption of mitochondrial fission can inhibit Reaper and Hid-induced cell death, suggesting that alterations in mitochondrial dynamics can modulate cell death in fly cells. We report here that Drosophila Reaper can induce mitochondrial fragmentation by binding to and inhibiting the pro-fusion protein MFN2 and its Drosophila counterpart dMFN/Marf. Our in vitro and in vivo analyses reveal that dMFN overexpression can inhibit cell death induced by Reaper or Îł-irradiation. In addition, knockdown of dMFN causes a striking loss of adult wing tissue and significant apoptosis in the developing wing discs. Our findings are consistent with a growing body of work describing a role for mitochondrial fission and fusion machinery in the decision of cells to die
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