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Insect Hox3/zen genes represent an evolutionary hotspot for changes in function and copy number. Single orthologues are required either for early specification or late morphogenesis of the extraembryonic tissues, which protect the embryo. The tandemly duplicated zen paralogues of the beetle Tribolium castaneum present a unique opportunity to investigate both functions in a single species. We dissect the paralogues' expression dynamics (transcript and protein) and transcriptional targets (RNA-seq after RNAi) throughout embryogenesis. selleck kinase inhibitor We identify an unexpected role of Tc-Zen2 in repression of Tc-zen1, generating a negative feedback loop that promotes developmental progression. Tc-Zen2 regulation is dynamic, including within co-expressed multigene loci. We also show that extraembryonic development is the major event within the transcriptional landscape of late embryogenesis and provide a global molecular characterization of the extraembryonic serosal tissue. Altogether, we propose that paralogue mutual regulation arose through multiple instances of zen subfunctionalization, leading to their complementary extant roles.New clinical trials for diabetic macular oedema (DMO) are being designed to prove superiority over aflibercept when this agent is already very effective in improving visual acuity (VA) and DMO. The aim of this study was to determine the optimal inclusion-exclusion criteria for trials to aim for superiority in visual outcomes with newer agents. As Phase 1 studies are short duration, we aimed to evaluate the early response of aflibercept in a real-world cohort initiated on monthly aflibercept for 3 consecutive injections and observed the effects at 4 months. The sub-optimal responders were pre-defined based on different cut-offs for VA and central sub-field thickness (CST). 200 patients with treatment naïve DMO treated with 3 loading doses of aflibercept were included in the study. We found that those presenting with baseline VA of 35-54 ETDRS letters (n = 43) had higher proportion of sub-optimal responders compared to other categories (p  less then  0.001). Patients with baseline CST of less than 400 µm (n = 96) responded less well functionally and anatomically to loading dose than eyes with baseline CST of 400 µm or more (n = 104, p = 0.02), indicating that eyes with CST ≥ 400 µm is another inclusion criteria. There was minimal correlation between change in CST and change in VA at 4 months (r = - 0.27), suggesting that both these inclusion criteria are non-exclusive. However, for maximal efficacy, patients that meet both these inclusion criteria are more likely to show benefit from an alternative intervention. New trials should aim to include patients with treatment naïve DMO with VA between 35-54 letters and CST of 400 µm or more when aflibercept is used as the comparator.Like pro-inflammatory cytokines, the role of anti-inflammatory cytokines in both learning and memory has been investigated, revealing beneficial effects for both interleukin-4 and interleukin-13 via the common interleukin-4 receptor alpha chain complex. In this study, using the Morris water maze spatial task for cognition, we compared interleukin-4 receptor alpha- deficient mice and their ligands interleukin-4/ interleukin-13 double deficient mice, on a Balb/c background. We demonstrate that while interleukin-4/ interleukin-13 double deficient mice are significantly impaired in both learning and reference memory, interleukin-4 receptor alpha-deficiency impairs only reference memory, compared to the wild-type control mice. In order to better understand how interleukin-4 receptor alpha- deficient mice are able to learn but not remember, we investigated the BDNF/TrkB- and the ARC-signaling pathways. We show that interleukin-4 receptor alpha-deficiency disrupts activation of BDNF/TrkB- and ARC-signaling pathways during reference memory, while the pathway for spatial learning is spared.To describe patterns of reperfusion in the superficial vascular plexus (SVP), deep capillary plexus (DCP) and choriocapillaris (CC) as detected on optical coherence tomography (OCTA) in cynomogulus macaque monkey model following increase in intraocular pressure by an intravitreal injection. Animal imaging study. Two cynomogulus macaque monkeys. A 100 µL intravitreal injection (IVI) of saline was given in one eye of each monkey. Serial OCTA using a Zeiss Plex Elite 9000 was used to evaluate reperfusion patterns within the SCP, DCP, and CC. OCTA evidence of perfusion. Pulsation of the central retinal artery was detected after the intraocular pressure was elevated to 98 and ≥ 99 mmHg from IVI. Episodic flow within the SVP arterioles and venules and poor visualization of flow in capillaries was noted during the initial phase of elevated pressure. As the pressure declined, the flow signal within the DCP appeared initially as dots, which progressed laterally to loops which form capillary vortex configuration. Recovery of flow within the SVP and CC appeared sooner than in the DCP. At 40 min after the injection, well after the intraocular pressure normalized, the retinal and choriocapillaris vascular perfusion showed focal defects in every layer. Compared with pre-injection images, vessel density in the DCP was 68.8% and 78.6% of baseline in monkey 1 and monkey 2, respectively. In contrast vessel density in the SVP recovered to 84.2% and 88.9% of baseline. Increases in intraocular pressure from IVI have the potential to affect every layer of blood flow in the fundus. After nominal return of intraocular pressure, focal defects in flow persisted, which may result in longer term damage to the retina.After the COVID-19 worldwide spread, evidence suggested a vast diffusion of negative consequences on people's mental health. Together with depression and sleep difficulties, anxiety symptoms seem to be the most diffused clinical outcome. The current contribution aimed to examine attentional bias for virus-related stimuli in people varying in their degree of health anxiety (HA). Consistent with previous literature, it was hypothesized that higher HA would predict attentional bias, tested using a visual dot-probe task, to virus-related stimuli. Participants were 132 Italian individuals that participated in the study during the lockdown phase in Italy. Results indicated that the HA level predicts attentional bias toward virus-related objects. This relationship is double mediated by the belief of contagion and by the consequences of contagion as assessed through a recent questionnaire developed to measure the fear for COVID-19. These findings are discussed in the context of cognitive-behavioral conceptualizations of anxiety suggesting a risk for a loop effect.
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