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Marek's disease (MD) is a neoplastic disease of chickens caused by Marek's disease virus (MDV), a member of the subfamily Alphaherpesvirinae Like other alphaherpesviruses, MDV encodes a serine/threonine protein kinase, US3. The functions of US3 have been extensively studied in other alphaherpesviruses; however, the biological functions of MDV US3 and its substrates have not been studied in detail. In this study, we investigated potential cellular pathways that are regulated by MDV US3 and identified chicken CREB (chCREB) as a substrate of MDV US3. We show that wild-type MDV US3, but not kinase-dead US3 (US3-K220A), increases CREB phosphorylation, leading to recruitment of phospho-CREB (pCREB) to the promoter of the CREB-responsive gene and activation of CREB target gene expression. Using US3 deletion and US3 kinase-dead recombinant MDV, we identified US3-responsive MDV genes during infection and found that the majority of US3-responsive genes were located in the MDV repeat regions. Chromatin immunoprecipitation sequencing (ChIP-seq) studies determined that some US3-regulated genes colocalized with Meq (an MDV-encoded oncoprotein) recruitment sites. Chromatin immunoprecipitation-PCR (ChIP-PCR) further confirmed Meq binding to the ICP4/LAT region, which is also regulated by US3. Furthermore, biochemical studies demonstrated that MDV US3 interacts with Meq in transfected cells and MDV-infected chicken embryonic fibroblasts in a phosphorylation-dependent manner. Finally, in vitro kinase studies revealed that Meq is a US3 substrate. MDV US3 thus acts as an upstream kinase of the CREB signaling pathway to regulate the transcription function of the CREB/Meq heterodimer, which targets cellular and viral gene expression.IMPORTANCE MDV is a potent oncogenic herpesvirus that induces T-cell lymphoma in infected chickens. Marek's disease continues to have a significant economic impact on the poultry industry worldwide. US3 encoded by alphaherpesviruses is a multifunctional kinase involved in the regulation of various cellular pathways. Using an MDV genome quantitative reverse transcriptase PCR (qRT-PCR) array and chromatin immunoprecipitation, we elucidated the role of MDV US3 in viral and cellular gene regulation. Our results provide insights into how viral kinase regulates host cell signaling pathways to activate both viral and host gene expression. This is an important step toward understanding host-pathogen interaction through activation of signaling cascades.

Background: Glaucoma stands as a prominent contributor to irreversible vision impairment on a global scale. For decades, the Baerveldt Glaucoma Implant (BGI) has been used to treat refractory glaucoma. Yet, the cost‐effective Aurolab Aqueous Drainage Implant (AADI) has gained clinical attention as a viable alternative for managing glaucoma. Objective: The purpose of this study was to evaluate and compare the efficacy and safety of AADI and BGI in the treatment of refractory glaucoma. Methods: Following PRISMA guidelines, we conducted a systematic search of multiple databases, identifying relevant comparative studies assessing AADI versus BGI in patients with refractory glaucoma. Key outcomes included postoperative IOP, surgical success rates, antiglaucoma medication reduction (AGMR), and complication rates. Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Results: Three studies comprised a total of 176 individuals with refractory glaucoma, with 107 patients receiving the AADI and 69 patients receiving the BGI. The meta‐analysis revealed a statistically borderline significant reduction in postoperative IOP favoring the AADI at 3 months (mean difference [MD] = −2.74, p = 0.05). There was no significant difference in the MD of AGMR between the AADI and BGI groups. The rates of total complications and surgical success did not differ significantly between the AADI and BGI groups. Conclusion: AADI demonstrates promising results in reducing IOP at 3 months compared to BGI, with comparable surgical outcomes and complication rates over the long term. Further studies with larger samples are warranted to validate these findings and assess cost‐effectiveness, particularly in developing countries. [ABSTRACT FROM AUTHOR]

The objective of this paper is to explore certain properties involving the generalized hypergeometric function ..., as introduced by Khan et al. [27]. Several fractional derivatives and integral formulas involving the generalized hypergeometric function are computed. Further, we derive the solution of generalized fractional kinetic equations involving generalized hypergeometric function. The respective solution is given in terms of Mittag-Leffler function. [ABSTRACT FROM AUTHOR]

Children with cerebral palsy (CP) exhibit impaired motor control and significant muscle weakness due to a brain lesion. However, studies that assess the relationship between brain activity and performance on dynamic functional muscle strength assessments in CP are needed. The aim of this study was to determine the effect of a progressive lateral step‐up test on prefrontal cortex (PFC) hemodynamic activity in children with CP. Fourteen ambulatory children with spastic CP (Gross Motor Function Classification System level I; 5–11 y) and 14 age‐ and sex‐matched typically developing control children completed a progressive lateral step‐up test at incremental step heights (0, 10, 15 and 20 cm) using their non‐dominant lower limb. Hemodynamic activity in the PFC was assessed using non‐invasive, portable functional neuroimaging (functional near‐infrared spectroscopy). Children with CP completed fewer repetitions at each step height and exhibited lower PFC hemodynamic activity across step heights compared to controls. Lower PFC activation in CP was maintained after statistically controlling for the number of repetitions completed at each step height. PFC hemodynamic activity was not associated with LSUT task performance in children with CP, but a positive relationship was observed in controls at the most challenging 20 cm step height. The results suggest there is an altered PFC recruitment pattern in children with CP during a highly dynamic test of functional strength. Further studies are needed to explore the mechanisms underlying the suppressed PFC activation observed in children with CP compared to typically developing children. [ABSTRACT FROM AUTHOR]