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Primary congenital glaucoma (PCG) occurs in children due to developmental abnormalities in the trabecular meshwork and anterior chamber angle. Previous studies have implicated rare variants in CYP1B1, LTBP2, and TEK and their interactions with MYOC, FOXC1, and PRSS56 in the genetic complexity and clinical heterogeneity of PCG. Given that some of the gene-encoded proteins are localized in the centrosomes (MYOC) and perform ciliary functions (TEK), we explored the involvement of a core centrosomal protein, CEP164, which is responsible for ocular development and regulation of intraocular pressure. Deep sequencing of CEP164 in a PCG cohort devoid of homozygous mutations in candidate genes (n = 298) and controls (n = 1757) revealed CEP164 rare pathogenic variants in 16 cases (5.36%). Co-occurrences of heterozygous alleles of CEP164 with other genes were seen in four cases (1.34%), and a physical interaction was noted for CEP164 and CYP1B1 in HEK293 cells. Cases of co-harboring alleles of the CEP164 and other genes had a poor prognosis compared with those with a single copy of the CEP164 allele. We also screened INPP5E, which synergistically interacts with CEP164, and observed a lower frequency of pathogenic variants (0.67%). Our data suggest the potential involvements of CEP164 and INPP5E and the yet unexplored cilia-centrosomal functions in PCG pathogenesis. [ABSTRACT FROM AUTHOR]

Work-life balance is now a major factor for employees and employers for so many reasons. Every employee in any industry; sector; role; level, etc. needs to balance their life between work and family so that they can give their best to the organization and their family. For employers also it is very important to have fair WLB initiatives or practices so that the potential employee can retain in the organization and contribute their best for the organization's success. Work-life balance was part of this review to understand the importance and need of WLB initiatives/Policies in an organization. So the objective of this review is to know in detail about the WLB initiatives\practices or policies of any type of organization, the research work taken in this review from 2001 to 2020, which includes the supported studies of WLB, the significance of WLB, theoretical base for WLBI/WLBP studies, WLBI/WLBP benefits, different type of WLBI/WLBP along with critical review of WLBI/WLBP literature work, and at the end a model was proposed based on research gap found after this critical review. [ABSTRACT FROM AUTHOR]

This article explores the challenges and benefits associated with implementing flexitime and dependent care facilities as work-life balance programs within organizations. Employing a qualitative research design with an exploratory methodology, data was gathered through a self-organized direct approach with non-probability purposive sampling, covering 25 organizations in NCR Uttar Pradesh. Findings were categorized into personnel challenges, employer challenges, shared advantages, and requirements for successful implementation of flexitime and dependent care as work-life balance practices/initiatives. The study underscores the importance for human specialists to ensure effective utilization of these facilities, facilitating organizational growth and individual development. It offers practical insights to help organizations address workforce challenges, ultimately fostering a more balanced and productive workplace. The originality of the study lies in its pioneering examination of specific work-life balance initiatives/practices, highlighting the necessity of such research for fostering a forwardlooking approach to workplace enhancement. [ABSTRACT FROM AUTHOR]

The present study mainly focused on synthesizing novel triazolo[1,5‐a]pyrimidine‐6‐carboxamide derivatives using multicomponent reaction. Synthesized derivatives were duly characterized using spectroscopic methods of analysis FT‐IR and mass spectroscopy, and 1H NMR and 13C NMR confirmed the structure of compounds. Further, the potential of the synthesized compounds against Plasmodium falciparum dihydrofolate reductase (Pf‐DHFR) inhibitors was evaluated by in vitro antimalarial activity, and the results of the study showed moderate to good antimalarial profile of synthesized entities. In silico study of all the synthesized compounds was carried out using Schrödinger LLC‐2020‐3 Software to explain the binding mode and interactions between molecules and pf DHFR enzyme. To study the drug likeliness of molecules, 3D QSAR and Pharmacokinetic studies have been carried out, and the results obtained showed a good pharmacokinetics profile of two compounds, namely AMP‐24 and AMP‐28, having good IC50 values concerning standard drugs. Further, the in vitro enzyme inhibition assay results suggested that the synthesized compound interacts nicely with the enzyme and might be used as a potent antimalarial agent. [ABSTRACT FROM AUTHOR]

NKX2‐5, a master cardiac regulatory transcription factor was the first known genetic cause of congenital heart diseases (CHDs). To further investigate its role in CHD pathogenesis, we performed mutational screening of 285 CHD probands and 200 healthy controls. Five coding sequence variants were identified in six CHD cases (2.1%), including three in the N‐terminal region (p.A61G, p.R95L, and p.E131K) and one each in homeodomain (HD) (p.A148E) and tyrosine‐rich domain (p.P247A). Variant‐p.A148E showed tertiary structure changes and differential DNA binding affinity of mutant compared to wild type. Two N‐terminal variants—p.A61G and p.E131K along with HD variant p.A148E demonstrated significantly reduced transcriptional activity of Nppa and Actc1 promoters in dual luciferase promoter assay supported by their reduced expression in qRT‐PCR. Nonetheless, variant p.R95L affected the synergy of NKX2‐5 with serum response factor and TBX5 leading to significantly decreased Actc1 promoter activity depicting a distinctive role of this region. The aberrant expression of other target genes—Irx4, Mef2c, Bmp10, Myh6, Myh7, and Myocd is also observed in response to NKX2‐5 variants, possibly due to the defective gene regulatory network. Severely impaired downstream promoter activities and abnormal expression of target genes due to N‐terminal variants supports the emerging role of this region during cardiac‐developmental pathways. [ABSTRACT FROM AUTHOR]

Transcription factor GATA4 is known to play crucial role during heart development, regulating expression of several other key cardiogenic factors. Various GATA4 mutations are reported in familial as well as sporadic cases of congenital heart defects (CHDs). To estimate the prevalence and pathogenic potential of GATA4 variants in our CHD cohort, we have screened 285 CHD cases along with 200 controls by Sanger sequencing and identified 9 genetic variants (c.23C>A; p.Ala8Asp, c.25G>A; p.Ala9Thr, c.223G>T; p.Ala75Ser, c.383A>T; p.Glu128Val, c.397A>T; p.Ser133Cys, c.682T>A; p.Trp228Arg, c.1064C>G; p.Thr355Ser, c.1073G>C; p.Ser358Thr, and c.1220C>A; p.Pro407Gln) in 22 unrelated CHD probands (frequency:7.72%). Five of these are novel and located in the N‐terminal transactivation domain (TAD) and first zinc finger domain. Majority C‐terminal domain variants are polymorphic. Two of the TAD variants p.Glu128Val, p.Ser133Cys, and a first zinc finger variant p.Trp228Arg, impair combinatorial synergy of NKX2‐5, SRF, and TBX5, suggesting potential role of these domains in GATA4 interactions with these factors. Decreased DNA‐binding affinity with EMSA also supports this observation. Homology modeling and tertiary structure comparison show conformational changes in these variants. Interestingly, GATA4 variants are more frequently associated with ToF (45%; P = 0.0046) and PS (22.7%; P < 0.0001) in spite of abundance of septal defects in our study cohort. The genetic etiology of congenital heart disease (CHD) is poorly understood. In order to evaluate the frequency of GATA4 variations, direct sequencing of GATA4 was performed in 285 CHD cases. We identified 9 variations in 22 unrelated probands with a relatively higher frequency (7.22%). TOF and PS were more significantly associated with GATA4 variations compared to septal defects. Here we also demonstrate functional deficit in mutant proteins through in vitro and in silico studies implicating GATA4 haploinsufficiency as a causative mechanism of CHD. [ABSTRACT FROM AUTHOR]

Abstract During biotic stress, plants use several mechanisms to protect themselves that include the production of reactive oxygen species (ROS), induction of pathogenesis-related proteins and cell death. Some plant growth promoting rhizobacteria (PGPR) are known to act as bio-control agents that protect crops against pathogens. The biocontrol activity of PGPR Paenibacillus lentimorbus (B-30488) against Sclerotium rolfsii showed previously where several defense-related genes were upregulated with ROS induction in tomato. We further evaluate the other possibility, i.e. role of autophagy in enhancing defense in tomato using PGPR. Confocal microscopy revealed the presence of an acidotropic dye Mono Dansyl Cadaverine (MDC) stained autophagosomes in B-30488 treated healthy and infected plants. These autophagosomes almost disappeared in plants treated with an autophagy inhibitor chloroquine. The results were also confirmed by ultrastructural analysis of leaf tissues using transmission electron microscopy. Enhanced expression of autophagy-related genes was also monitored in B-30488 primed fungal infected tissues as compared to control by qRT-PCR. Results of ROS accumulation, fluorescence, confocal and transmission electron microscopy and gene expression analysis revealed induction of autophagy using B-30488 as a biocontrol agent suggesting a role in enhancing disease resistance in tomato. Overall, the present study indicated a role of B-30488 as a biocontrol in enhancing disease resistance in tomato and also assists a better understanding of fungal pathogenesis that is expected to be useful in developing new strategies for disease control. [ABSTRACT FROM AUTHOR]