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2%, respectively. The results showed that the residual efficacy of Actellic 300CS was up to 9 mo with the first 6 mo exhibiting mortalities of greater than 99% while the next 3 mo showed mortalities exceeding 85%. Actellic 300CS was effective against fully susceptible laboratory-reared Anopheles arabiensis on all four surface types (rough, smooth, dung, and painted surfaces) tested in this study and could be used as one of the chemical insecticides of choice for the ongoing IRS programs in Ethiopia.The literature on the relation between adiposity and the onset of puberty is extensive, both in size and in the length of time this question has been alive in the biomedical literature. It is easy to wonder, then, whether there is anything new to be learned in this crowded field. In this issue of the American Journal of Epidemiology, Deardorff and colleagues (Am J Epidemiol XXXX; XXXX) show that it is still possible to innovate in this area. The authors report on the relation between body mass index (BMI) at age 5 with a variety of markers of the onset of puberty. Consistent with the current literature they show no association between BMI at age 5 and pubertal onset in boys. They also show an association between obesity at age 5 years with earlier onset of secondary sexual characteristics in girls, making an important subject-matter contribution that addresses many of the concerns of the existing literature in assigning causality. At the same time, the authors make an important, although less evident contribution to the practice of epidemiology for studies where the assessment of pubertal status is of interest.Although adequate periconceptional folic acid (FA) supplementation has reduced the occurrence of pregnancies affected by neural tube defects (NTDs), the mechanisms underlying FA-resistant NTDs are poorly understood, and thus NTDs still remain a global public health concern. A high level of Krüppel-like factor 12 (KLF12) exerts deleterious effects on heath in most cases, but evidence for its roles in development has not been published. We observed KLF12-overexpressing mice showed disturbed neural tube development. KLF12-overexpressing foetuses died in utero at approximately 10.5 days post coitus, with 100% presenting cranial NTDs. Neither FA nor formate promoted normal neural tube closure in mutant foetuses. The RNA-seq results showed that a high level of KLF12 caused NTDs in mice via overactivating the sonic hedgehog (Shh) signalling pathway, leading to the upregulation of patched 1, GLI-Krüppel family member GLI1, hedgehog-interacting protein, etc., while FA metabolism-related enzymes did not express differently. PF-5274857, an antagonist of the Shh signalling pathway, significantly promoted dorsolateral hinge point formation and partially rescued the NTDs. The regulatory hierarchy between a high level of KLF12 and FA-resistant NTDs might provide new insights into the diagnosis and treatment of unexplained NTDs in the future.
To assess aortic flow and stiffness in patients with Loeys-Dietz syndrome (LDS) by 4D flow and cine cardiovascular magnetic resonance (CMR) and compare the results with those of healthy volunteers (HV) and Marfan syndrome (MFS) patients.
Twenty-one LDS and 44 MFS patients with no previous aortic dissection or surgery and 35 HV underwent non-contrast-enhanced 4D flow CMR. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), and aortic diameters were obtained at 20 planes from the ascending (AAo) to the proximal descending aorta (DAo). IRF and SFRR were also quantified for aortic regions (proximal and distal AAo, arch and proximal DAo). find more Peak-systolic wall shear stress (WSS) maps were also estimated. Aortic stiffness was quantified using pulse wave velocity (PWV) and proximal AAo longitudinal strain. Compared to HV, LDS patients had lower rotational flow at the distal AAo (P = 0.002), arch (P = 0.002), and proximal DAo (P < 0.001) even after adjustment for age, stroke volume, and local diameter. LDS patients had higher SFRR in the proximal DAo compared to both HV (P = 0.024) and MFS patients (P = 0.015), even after adjustment for age and local diameter. Axial and circumferential WSS in LDS patients were lower than in HV. AAo circumferential WSS was lower in LDS compared to MFS patients. AAo and DAo PWV and proximal AAo longitudinal strain revealed stiffer aortas in LDS patients compared to HV (P = 0.007, 0.005, and 0.029, respectively) but no differences vs. MFS patients.
Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys-Dietz and Marfan patients.
Greater aortic stiffness as well as impaired IRF and WSS were present in LDS patients compared to HV. Conversely, similar aortic stiffness and overlapping aortic flow features were found in Loeys-Dietz and Marfan patients.
Increased shedding of extracellular vesicles (EVs)-small, lipid bilayer-delimited particles with a role in paracrine signalling-has been associated with human pathologies, e.g. atherosclerosis, but whether this is true for cardiac diseases is unknown.
Here, we used the surface antigen CD172a as a specific marker of cardiomyocyte (CM)-derived EVs; the CM origin of CD172a+ EVs was supported by their content of cardiac-specific proteins and heart-enriched microRNAs. We found that patients with aortic stenosis, ischaemic heart disease, or cardiomyopathy had higher circulating CD172a+ cardiac EV counts than did healthy subjects. Cellular stress was a major determinant of EV release from CMs, with hypoxia increasing shedding in in vitro and in vivo experiments. At the functional level, EVs isolated from the supernatant of CMs derived from human-induced pluripotent stem cells and cultured in a hypoxic atmosphere elicited a positive inotropic response in unstressed CMs, an effect we found to be dependent on an increase in the number of EVs expressing ceramide on their surface. Of potential clinical relevance, aortic stenosis patients with the highest counts of circulating cardiac CD172a+ EVs had a more favourable prognosis for transcatheter aortic valve replacement than those with lower counts.
We identified circulating CD172a+ EVs as cardiac derived, showing their release and function and providing evidence for their prognostic potential in aortic stenosis patients.
We identified circulating CD172a+ EVs as cardiac derived, showing their release and function and providing evidence for their prognostic potential in aortic stenosis patients.A cue for long-range vision allows mosquitoes to identify hosts and differentiate the ecological niches (e.g., habitats). However, the visual factors involved in attracting mosquitoes to a host are complex and have not been fully understood. Therefore, we assessed color preference to Aedes albopictus (Skuse) and Culex pipiens (Conquillett) as diurnal and nocturnal species, respectively, using seven fundamental colors including black, white, red, yellow, green, blue, and purple with each trap at 100 lux in a laboratory. We used a binary behavioral assay using the Mosquito Preference Index (MPI) as a preference ratio with a range of 0-1. Our analyses showed that Ae. albopictus had a greater response to black (MPIs, 0.7), followed closely by red, blue, and purple (MPIs, 0.6). We also found that red, blue, and purple were significantly higher (P less then 0.05) than those of green (MPI, 0.5), white (MPI, 0.3), and yellow (MPI, 0.2). Similarly, the MPIs for Cx. pipiens were significantly higher at black and red (MPIs, 0.7; P less then 0.05) compare to those of white and yellow (MPIs, 0.3; P less then 0.05). The color preference of Ae. albopictus showed significant correlation to luminous intensities (L-value) (r = -0.640; P = 0.000) and blue intensities (b-value) (r = -0.372; P = 0.000) for all seven colors. In addition, Cx. pipiens negatively correlated (r = -0.703; P = 0.000) between color preference and L-value. Our analyses provide a greater understanding of how color plays a role in visual sensory stimuli, and how that could potentially affect mosquito host-seeking behavior.Epithelial cilia, whether motile or primary, often display an off-center planar localization within the apical cell surface. This form of planar cell polarity (PCP) involves the asymmetric positioning of the ciliary basal body (BB). Using the monociliated epithelium of the embryonic zebrafish floor-plate, we investigated the dynamics and mechanisms of BB polarization by live imaging. BBs were highly motile, making back-and-forth movements along the antero-posterior (AP) axis and contacting both the anterior and posterior membranes. Contacts exclusively occurred at junctional Par3 patches and were often preceded by membrane digitations extending towards the BB, suggesting focused cortical pulling forces. Accordingly, BBs and Par3 patches were linked by dynamic microtubules. Later, BBs became less motile and eventually settled at posterior apical junctions enriched in Par3. BB posterior positioning followed Par3 posterior enrichment and was impaired upon Par3 depletion or disorganization of Par3 patches. In the PCP mutant vangl2, BBs were still motile but displayed poorly oriented membrane contacts that correlated with Par3 patch fragmentation and lateral spreading. Thus, we propose an unexpected function for posterior Par3 enrichment in controlling BB positioning downstream of the PCP pathway.Zygotic genomic activation (ZGA) is a landmark event in the maternal-to-zygotic transition (MZT), and the regulation of ZGA by maternal factors remains to be elucidated. In this study, the depletion of maternal ring finger protein 114 (RNF114), a ubiquitin E3 ligase, led to developmental arrest of two-cell mouse embryos. Using immunofluorescence and transcriptome analysis, RNF114 was proven to play a crucial role in major ZGA. To study the underlying mechanism, we performed protein profiling in mature oocytes and found a potential substrate for RNF114, chromobox 5 (CBX5), ubiquitylation and degradation of which was regulated by RNF114. The overexpression of CBX5 prevented embryonic development and impeded major ZGA. Furthermore, TAB1 was abnormally accumulated in mutant two-cell embryos, which was consistent with the result of in vitro knockdown of Rnf114. Knockdown of Cbx5 or Tab1 in maternal RNF114-depleted embryos partially rescued developmental arrest and the defect of major ZGA. In summary, our study reveals that maternal RNF114 plays a precise role in degrading some important substrates during the MZT, the misregulation of which may impede the appropriate activation of major ZGA in mouse embryos.Over 80% of all children living with HIV reside in Africa and are at risk of developing HIV-associated nephropathy (HIVAN). Once HIVAN is established in children, it is difficult to revert its progression to chronic kidney failure even using antiretroviral drugs. Therefore, new therapeutic strategies are needed. Previous studies showed that the risk of developing HIVAN increases in children with high circulating levels of FGF-2, but it is unclear whether FGF-2 per se precipitates HIVAN. To unravel the role of circulating FGF-2 in childhood HIVAN, we used the HIV-Tg26 mouse model of HIVAN. Briefly, we demonstrated that circulating FGF-2 was preferentially recruited in the kidney of HIV-Tg26 mice with renal disease, and precipitated HIVAN in young mice without pre-existing kidney disease by activating the pERK pathway in renal epithelial cells without previously inducing the expression of HIV-1 genes. Wild type mice injected with recombinant adenoviral FGF-2 vectors (rAd-FGF-2) carrying a secreted form of human FGF-2 developed transient and reversible HIVAN-like lesions, including proteinuria and glomerular enlargement.