Actin-related protein 6 facilitates proneural protein-induced gene activation for rapid neural differentiation.

Neurogenesis is initiated by basic helix-loop-helix proneural proteins. Here, we show that Actin-related protein 6 (Arp6), a core component of the H2A.Z exchange complex SWR1, interacts with proneural proteins and is crucial for efficient onset of proneural protein target gene expression. Arp6 mutants exhibit reduced transcription in sensory organ precursors (SOPs) downstream of the proneural protein patterning event. This leads to retarded differentiation and division of SOPs and smaller sensory organs. These phenotypes are also observed in proneural gene hypomorphic mutants. Proneural protein expression is not reduced in Arp6 mutants. Enhanced proneural gene expression fails to rescue retarded differentiation in Arp6 mutants, suggesting that Arp6 acts downstream of or in parallel with proneural proteins. H2A.Z mutants display Arp6-like retardation in SOPs. Transcriptomic analyses demonstrate that loss of Arp6 and H2A.Z preferentially decreases expression of proneural protein-activated genes. H2A.Z enrichment in nucleosomes around the transcription start site before neurogenesis correlates highly with greater activation of proneural protein target genes by H2A.Z. We propose that upon proneural protein binding to E-box sites, H2A.Z incorporation around the transcription start site allows rapid and efficient activation of target genes, promoting rapid neural differentiation.

Corneal nerve loss in patients with TIA and acute ischemic stroke in relation to circulating markers of inflammation and vascular integrity.

Vascular and inflammatory mechanisms are implicated in the development of cerebrovascular disease and corneal nerve loss occurs in patients with transient ischemic attack (TIA) and acute ischemic stroke (AIS). We have assessed whether serum markers of inflammation and vascular integrity are associated with the severity of corneal nerve loss in patients with TIA and AIS. Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) in 105 patients with TIA (n = 24) or AIS (n = 81) and age matched control subjects (n = 56). Circulating levels of IL-6, MMP-2, MMP-9, E-Selectin, P-Selectin and VEGF were quantified in patients within 48 h of presentation with a TIA or AIS. CNFL (P = 0.000, P = 0.000), CNFD (P = 0.122, P = 0.000) and CNBD (P = 0.002, P = 0.000) were reduced in patients with TIA and AIS compared to controls, respectively with no difference between patients with AIS and TIA. The NIHSS Score (P = 0.000), IL-6 (P = 0.011) and E-Selectin (P = 0.032) were higher in patients with AIS compared to TIA with no difference in MMP-2 (P = 0.636), MMP-9 (P = 0.098), P-Selectin (P = 0.395) and VEGF (P = 0.831). CNFL (r = 0.218, P = 0.026) and CNFD (r = 0.230, P = 0.019) correlated with IL-6 and multiple regression analysis showed a positive association of CNFL and CNFD with IL-6 (P = 0.041, P = 0.043). Patients with TIA and AIS have evidence of corneal nerve loss and elevated IL6 and E-selectin levels. Larger longitudinal studies are required to determine the association between inflammatory and vascular markers and corneal nerve fiber loss in patients with cerebrovascular disease.

The efficacy and effectiveness of the COVID-19 vaccines in reducing infection, severity, hospitalization, and mortality: a systematic review.

With the relatively rapid development of the COVID-19 pandemic, vaccine development has become crucial for limiting disease transmission. The accelerated growth in the approved COVID-19 vaccines has sparked concerns about their efficacies which have been assessed by many studies. This systematic review compares the efficacy and effectiveness of seven COVID-19 vaccines. A comprehensive systematic literature search was performed using several databases to identify studies reporting the effectiveness or the efficacy of the vaccines. Only 42 studies met our inclusion criteria, which revealed that the COVID-19 vaccines have successfully reduced the rates of infections, severity, hospitalization, and mortality among the different populations. The full-dose regimen of the Pfizer/BioNTech vaccine is the most effective against infections with the B.1.1.7 and B.1.351 variants. Despite of the high effectiveness of some of the COVID-19 vaccines, more efforts are required to test their effectiveness against the other newly emerging variants.

Coronary Microvascular Dysfunction in Patients with Non-Obstructive Coronary Arteries: Current Gaps and Future Directions.

There has been increasing interest in open artery syndrome, also known as ischemia with non-obstructive coronary arteries (INOCA). INOCA has been increasingly recognized as a heterogeneous clinical entity. Diagnostic evaluation of this heterogeneous entity, including invasive assessment, remains key to diagnose this clinical condition and provide the appropriate treatment. Importantly, medical stratification based on the type of INOCA has shown benefit in improving the symptoms in these patients, as illustrated in the CorMicA trial. The Women's IschemiA Trial to Reduce Events in Non-ObstRuctIve CORonary Artery Disease (WARRIOR) is another promising landmark trial that is currently enrolling patients and will address some of the unanswered questions for management of women with INOCA. In this review, we discuss the pathophysiology, management options, knowledge gaps, and future directions while highlighting the rationale and design of the ongoing WARRIOR trial.

ßPS-Integrin acts downstream of Innexin 2 in modulating stretched cell morphogenesis in the Drosophila ovary.

During oogenesis, a group of specialized follicle cells, known as stretched cells (StCs), flatten drastically from cuboidal to squamous shape. While morphogenesis of epithelia is critical for organogenesis, genes and signaling pathways involved in this process remain to be revealed. In addition to formation of gap junctions for intercellular exchange of small molecules, gap junction proteins form channels or act as adaptor proteins to regulate various cellular behaviors. In invertebrates, gap junction proteins are Innexins. Knockdown of Innexin 2 but not other Innexins expressed in follicle cells attenuates StC morphogenesis. Interestingly, blocking of gap junctions with an inhibitor carbenoxolone does not affect StC morphogenesis, suggesting that Innexin 2 might control StCs flattening in a gap-junction-independent manner. An excessive level of ßPS-Integrin encoded by myospheroid is detected in Innexin 2 mutant cells specifically during StC morphogenesis. Simultaneous knockdown of Innexin 2 and myospheroid partially rescues the morphogenetic defect resulted from Innexin 2 knockdown. Furthermore, reduction of ßPS-Integrin is sufficient to induce early StCs flattening. Taken together, our data suggest that ßPS-Integrin acts downstream of Innexin 2 in modulating StCs morphogenesis.

Colorimetric and Fluorometric Paper-Based Assay for Cu2+ Detection Based on Green Synthesis of 2-Aminoterephthalic Acid-Derived Pigments.

In this study, we developed a simple and economical method for the green synthesis of Cu2+ sensors based on betaxanthin pigments. Aminoisophthalic acid-betaxanthin was synthesized by coupling 2-aminoisophthalic acid and betalamic acid produced from DOPA-extradiol-4,5-dioxygenase in situ and in vitro. The resulting 2-aminoterephthalic acid-betaxanthin (2-AIPA-BX) presented a satisfying fluorescence quantum yield in water and a high degree of selectivity for Cu2+ over interfering metal ions. The bioproduction process of 2-AIPA-BX was scaled up from test tubes to 1 L-flasks, indicating the robustness and reproducibility of this method. Additionally, we successfully incorporated 2-AIPA-BX into paper-based analytical devices to facilitate simple, inexpensive, and portable setup with lower sample consumption for onsite monitoring of environmental and biological samples.