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We also show that treatment with short- (N-hexanoyl-l-homoserine lactone) and medium-chain (N-3-oxo-decanoyl-l-homoserine lactone) AHLs promoted primary root elongation and modified root architecture, respectively, resulting in enhanced plant growth.Connexins (Cxs) oligomerise to form hexameric hemichannels in the plasma membrane that can further dock together on adjacent cells to form gap junctions and facilitate intercellular-trafficking of molecules. In this study, we report the expression and function of an 'orphan' connexin, Cx62, in human and mouse (Cx57, mouse homologue) platelets. A novel mimetic peptide (62Gap27) was developed to target the second extracellular loop of Cx62 and 3D structural models predicted its interference with gap junction and hemichannel function. The ability of 62Gap27 to regulate both gap junction and hemichannel-mediated intercellular communication was observed using FRAP analysis and flow cytometry. Cx62 inhibition by 62Gap27 suppressed a range of agonist-stimulated platelet functions and impaired thrombosis and haemostasis. This was associated with elevated PKA-dependent signalling in a cyclic adenosine monophosphate-independent manner, and was not observed in Cx57 deficient mouse platelets (in which the selectivity of 62Gap27 for this connexin was also confirmed). Notably, Cx62 hemichannels were observed to function independently of Cx37 and Cx40 hemichannels. Together, our data reveal a fundamental role for a hitherto uncharacterised connexin in the regulation of the function of circulating cells.

Stress imaging has been the standard for diagnosing functionally significant coronary artery disease. It is unknown whether novel, atherosclerotic plaque measures improve accuracy beyond coronary stenosis for diagnosing invasive fractional flow reserve (FFR) measurement.

To compare the diagnostic accuracy of comprehensive anatomic (obstructive and nonobstructive atherosclerotic plaque) vs functional imaging measures for estimating vessel-specific FFR.

Controlled clinical trial of diagnostic accuracy with a multicenter derivation-validation cohort of patients referred for nonemergent invasive coronary angiography. A total of 612 patients (64 [10] years; 30% women) with signs and symptoms suggestive of myocardial ischemia from 23 sites were included. Patients were recruited from 2014 to 2017. Data analysis began in August 2018.

Patients underwent invasive coronary angiography with measurement of invasive FFR, coronary computed tomographic angiography (CCTA) quantification of atherosclerotic plaque and Fyocardial perfusion imaging predictors were the summed rest and difference scores. In the validation cohort, the areas under the receiver operating characteristic curve were 0.81 for CCTA vs 0.67 for myocardial perfusion imaging (P < .001).

A comprehensive anatomic interpretation with CCTA, including quantification of obstructive and nonobstructive atherosclerotic plaque, was superior to functional imaging in the diagnosis of invasive FFR. Comprehensive CCTA measures improve prediction of vessel-specific coronary physiology more so than stress-induced alterations in myocardial perfusion.

ClinicalTrials.gov Identifier NCT02173275.

ClinicalTrials.gov Identifier NCT02173275.

Malaria is highly heterogeneous; its changing malaria micro-epidemiology needs to be addressed to support malaria elimination efforts at the regional level.

A three-year, population-based cohort study in two settings in the Peruvian Amazon (Lupuna, Cahuide) followed participants by passive and active case detection from January 2013 to December 2015. Incidence and prevalence rates were estimated using microscopy and PCR.

Lupuna registered 1,828 infections (1,708 P. vivax, 120 P. falciparum; incidence was 80.7 infections/100 person-years (95%CI [77.1-84.5]). Cahuide detected 1,046 infections (1,024 P. vivax, 20 P. falciparum, two mixed); incidence was 40.2 infections/100 person-years (95%CI [37.9-42.7]). Recurrent P. vivax infections predominated onwards from 2013. According to PCR data, submicroscopic predominated over microscopic infections, especially in periods of low transmission. SBE-β-CD The integration of parasitological, entomological and environmental observations evidenced an intense and seasonal transmission resilient to standard control measures in Lupuna, and a persistent residual transmission after severe outbreaks were intensively handled in Cahuide.

In two exemplars of complex local malaria transmission, standard control strategies failed to eliminate submicroscopic and hypnozoite reservoirs, enabling persistent transmission.

In two exemplars of complex local malaria transmission, standard control strategies failed to eliminate submicroscopic and hypnozoite reservoirs, enabling persistent transmission.A significant rise of SARS-CoV-2 transmission in Arizona in June 2020 prompted the need to evaluate potential dispersion to other regions in the United States. We evaluate the potential for domestic dissemination of SARS-CoV-2 from Arizona using mobile device-location and scheduled flights data.The canonical Wnt signaling pathway is mediated by interaction of β-catenin with the T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) transcription factors and subsequent transcription activation of Wnt-target genes. In the hematopoietic system, the function of the pathway has been mainly investigated by rather unspecific genetic manipulations of β-catenin that yielded contradictory results. Here, we used a mouse expressing a truncated dominant negative form of the human TCF4 transcription factor (dnTCF4) that specifically abrogates β-catenin-TCF/LEF interaction. Disruption of the β-catenin-TCF/LEF interaction resulted in the accumulation of immature cells and reduced granulocytic differentiation. Mechanistically, dnTCF4 progenitors exhibited downregulation of the Csf3r gene, reduced granulocyte colony-stimulating factor (G-CSF) receptor levels, attenuation of downstream Stat3 phosphorylation after G-CSF treatment, and impaired G-CSF-mediated differentiation. Chromatin immunoprecipitation assays confiof neutrophils.

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