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In pectin regulation, polygalacturonases (PGs) and pectin methylesterases (PMEs) are critical components in the transformation, disassembly network, and remodeling of plant primary cell walls. In the current study, we identified 36 PG and 47 PME genes using the available genomic resources of grapevine. Herein, we provide a comprehensive overview of PGs and PMEs, including phylogenetic and collinearity relationships, motif and gene structure compositions, gene duplications, principal component analysis, and expression profiling during developmental stages. Phylogenetic analysis of PGs and PMEs revealed similar domain composition patterns with Arabidopsis. The collinearity analysis showed high conservation and gene duplications with purifying selection. The type of duplications also varied in terms of gene numbers in PGs (10 dispersed, 1 proximal, 12 tandem, and 13 segmental, respectively) and PMEs (23 dispersed, 1 proximal, 16 tandem, and 7 segmental, respectively). The tissue-specific response of PG and PME genes based on the reported transcriptomic data exhibited diverged expression patterns in various organs during different developmental stages. Among PGs, VvPG8, VvPG10, VvPG13, VvPG17, VvPG18, VvPG19, VvPG20, VvPG22, and VvPG23 showed tissue- or organ-specific expression in majority of the tissues during development. Similarly, in PMEs, VvPME3, VvPME4, VvPME5, VvPME6, VvPME19, VvPME21, VvPME23, VvPME29, VvPME31, and VvPME32 suggested high tissue-specific response. The gene ontology (GO), Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment, and cis-elements prediction analysis also suggested the putative functions of PGs and PMEs in plant development, such as pectin and carbohydrate metabolism, and stress activities. Moreover, qRT-PCR validation of 32 PG and PME genes revealed their role in various organs of grapevines (i.e., root, stem, tendril, inflorescence, flesh, skins, and leaves). Therefore, these findings will lead to novel insights and encourage cutting-edge research on functional characterization of PGs and PMEs in fruit crop species.

Catherynne M. Valente breaks up and remakes the Orientalist map of Anglo-American fantasy through a process of aggressive revision that she calls \"mythpunk.\" Like her predecessors, Valente borrows images from Middle Eastern folklore, but her mixing and re-remixing of global cultural traditions is value neutral. She does not use images from any one region of the world to represent cultural superiority or inferiority, or to demarcate opposing sides in a battle between good and evil. Her mythpunk approach to fantasy rejects the binary thinking that structures much of C.S. Lewis' influential Chronicles of Narnia—but it at the same time, it engages deeply with the element of cultural syncretism that Lewis himself also includes.

Human history is full of evidence showing a larger number of human and animal populations got affected by infectious diseases, viruses, and bacteria. Like previous life-threatening pandemics, coronavirus appeared to be a deadly virus in 2019 and declared as pandemic in 2020 by WHO. As per Global Reports, senior citizens have been most vulnerable to the corona virus attacks. This paper explores the experiences of family members dealing with elderly at home in the midst of the Covid-19 outbreak and how they managed them keeping in view their mindset on disease and socio-cultural constraints. For this purpose, qualitative research methods were adopted. 20 participants were selected for the in-depth interviews through purposive sampling. Following themes generated as a result of the data analysis: stubborn and rigid behavior of elderly, emotionally complex reactions, socio-cultural barriers, and traditional approach to the disease. Findings depicted the most common social cultural barriers in dealing with the difficult nature of elderly people are family ties, religious norms, respect, and empathy towards elderly people. Further, research findings highlighted major sentiments of older adults comprise attachment towards their grandchildren, feeling of insecurity, feeling of getting stigmatized, considering themselves as a virus spreader and feeling of being left out. It was found that older adults felt stigmatized, lonely, left out and considered SOPs (Standard Operating Procedures) as imposed remedial steps. Overall, it was found that at older age people express more anxiety and fear towards loneliness. Findings will help in sensitizing policy makers to design awareness sessions, religious and other home-based social activities for elderly people to combat stress related to loneliness in older age.

Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old. Estimated buccal proportion declined throughout childhood with both increasing chronological and predicted epigenetic age. However, buccal proportion did not associate with age throughout adolescence. Variability in buccal proportion increased with age through the entire developmental range. These trends held inversely true for neutrophil proportions. Correcting for buccal proportion attenuated the weak association with PedBE age acceleration to non-significance during initial estimation. Notably, correcting for buccal proportion attenuated the association of PedBE age acceleration with obsessive-compulsive disorder and strengthened the association with diurnal cortisol slope. Thus, the age-related change in children’s oral cells is a crucial consideration for cell type-sensitive research. Cheek swabs are widely used in pediatric epigenetic studies, but changes in their cellular composition with age are unclear. Here the authors show that buccal epithelial cells decline with age until adolescence, then stabilize, while variability increases with age, impacting the precision of tools like the PedBE clock in pediatric epigenetics.

Leaf rust caused by Puccinia triticina is the most widespread rust disease of wheat. As pathogen populations are constantly evolving, identification of novel sources of resistance is necessary to maintain disease resistance and stay ahead of this plant-pathogen evolutionary arms race. The wild genepool of wheat is a rich source of genetic diversity, accounting for 44% of the Lr genes identified. Here we performed a genome-wide association study (GWAS) on a diverse germplasm of 385 accessions, including 27 different Triticum and Aegilops species. Genetic characterization using the wheat 90 K array and subsequent filtering identified a set of 20,501 single nucleotide polymorphic (SNP) markers. Of those, 9,570 were validated using exome capture and mapped onto the Chinese Spring reference sequence v1.0. Phylogenetic analyses illustrated four major clades, clearly separating the wild species from the T. aestivum and T. turgidum species. GWAS was conducted using eight statistical models for infection types against six leaf rust isolates and leaf rust severity rated in field trials for 3–4 years at 2–3 locations in Canada. Functional annotation of genes containing significant quantitative trait nucleotides (QTNs) identified 96 disease-related loci associated with leaf rust resistance. A total of 21 QTNs were in haplotype blocks or within flanking markers of at least 16 known Lr genes. The remaining significant QTNs were considered loci that putatively harbor new Lr resistance genes. Isolation of these candidate genes will contribute to the elucidation of their role in leaf rust resistance and promote their usefulness in marker-assisted selection and introgression.

Mothers undergo physiological and molecular changes over the course of gestation. These modifications “get under the skin” and may be reflected in the maternal epigenome through processes such as DNA methylation. Such an epigenetic mark may offer insights into maternal responses to prenatal influences and biological cues from the developing fetus, thereby functioning as an indirect indicator of the conditions the fetus experiences in utero. We measured whole blood DNA methylation using the MethylationEPIC BeadChip Infinium microarray v1.0 in 22 pregnant women from Pakistan, a low- and middle-income country (LMIC), at two timepoints during their term pregnancies (early: 10–19 weeks and late-mid: 22–29 weeks). We used DNA methylation profiles to predict immune cell proportions and tested differences in these proportions and DNA methylation patterns between the two timepoints. Further, we evaluated DNA methylation associations with gestational age at each timepoint and examined the contribution of genetic, psychosocial, and biological factors. Our analyses documented changes in immune cell proportions and DNA methylation profiles over the course of gestation, albeit in a small percentage of the measured DNA methylome. We also observed timepoint-specific DNA methylation associations with gestational age, predominantly at early pregnancy, with predicted interleukin-6 level and socioeconomic status contributing to a few of these associations. On comparing to three external cohorts from different sociocultural contexts, we also noted these signatures to be unique to LMIC settings. Overall, these changes measured in term pregnancies may be used to assess both fluctuations in pregnancy and birth outcomes, particular in women from LMIC settings.

ABSTRACT Objective: To compare the diagnostic accuracy of high neutrophil-to-lymphocyte ratio levels versus leukocytosis in detecting acute cholecystitis. Study Design: Cross-sectional validation study. Place and Duration of Study: Department of General Surgery, Combined Military Hospital, Rawalpindi Pakistan, from Dec 2021 to Jun 2022. Methodology: One hundred eighteen patients with the clinical diagnosis of acute cholecystitis were included in the study. Patients with neoplastic or autoimmune disease or ongoing chronic infections were excluded. All patients underwent a test for complete blood counts to document the total leucocyte count and the neutrophil-to-lymphocyte ratio. The diagnosis of acute cholecystitis was confirmed on contrast-enhanced computed tomography abdomen. Results: The study sample had a mean age of 46.56±13.78 years, with 81(68.6%) females. The total leucocyte count had a sensitivity of 67.1%, a specificity of 73.3% and a diagnostic accuracy of 69.5% for predicting the presence of acute cholecystitis. In contrast, the neutrophil to lymphocyte ratio, with a cut-off of 3, had a sensitivity of 73.7%, a specificity of 68.9% and a diagnos-tic accuracy of 71.2% in predicting the presence of acute cholecystitis using contrast-enhanced computed tomography as a gold standard. Conclusion: Both total leucocyte count and the neutrophil to lymphocyte ratio were equally effective for diagnosing acute cholecystitis in clinically diagnosed patients.

Boolean modelling of biological networks is a well-established technique for abstracting dynamical biomolecular regulation in cells. Specifically, decoding linkages between salient regulatory network states and corresponding cell fate outcomes can help uncover pathological foundations of diseases such as cancer. Attractor landscape analysis is one such methodology which converts complex network behavior into a landscape of network states wherein each state is represented by propensity of its occurrence. Towards undertaking attractor landscape analysis of Boolean networks, we propose an Attractor Landscape Analysis Toolbox (ATLANTIS) for cell fate discovery, from biomolecular networks, and reprogramming upon network perturbation. ATLANTIS can be employed to perform both deterministic and probabilistic analyses. It has been validated by successfully reconstructing attractor landscapes from several published case studies followed by reprogramming of cell fates upon therapeutic treatment of network. Additionally, the biomolecular network of HCT-116 colorectal cancer cell line has been screened for therapeutic evaluation of drug-targets. Our results show agreement between therapeutic efficacies reported by ATLANTIS and the published literature. These case studies sufficiently highlight the in silico cell fate prediction and therapeutic screening potential of the toolbox. Lastly, ATLANTIS can also help guide single or combinatorial therapy responses towards reprogramming biomolecular networks to recover cell fates.

ABSTRACT Objective: To compare the outcomes of three-port versus four-port laparoscopic cholecystectomy(LC) and assess the safety and efficacy of three-port LC as routine procedure. Study Design: Retrospective comparative study. Place and Duration of Study: Combined Military Hospital Kohat/CMH Multan, from Oct 2013 to Dec 2016. Methodology: Total of 403 patients were selected and were divided into two groups based on the principles of non-randomized clinical trial; group A having three-port laparoscopic cholecystectomy(LC) and group B having four-port laparoscopic cholecystectomy(LC). Fourth port in right axillary line at umbilicus level was not established in group A. Outcomes were recorded in terms of operating time, complications, pain assessment/ analgesic requirement and hospital stay. Results: A total of 218(54.09%) patients in group A and 185(45.91%) patients in group B were assessed. The difference in terms of verbal pain score, analgesic requirement and duration of hospital stay/return to activity were significant statistically, all being less in group A. Cosmetic outcome as perceived by patients was also better in the group A because of less numbers of scars. Operative time(minutes) was less in group A in our study(35.59 ± 10.75) as compared to group B(50.17 ± 10.14). Results of other variables including intra-operative/post-operative complications were comparable among the two groups. Conclusion: Three-port LC has advantages of being less painful, with less analgesics requirement and reduced hospital stay without compromising the safety and efficacy. It is more acceptable to patients due to less numbers of scars and better cosmesis.

Tuberculosis (TB) and diabetes mellitus (DM) are both highly prevalent in Pakistan. Latent Mycobacterium tuberculosis  (Mtb) infection is common however the effect of DM and latent TB infection (LTBI) is less understood. We used RNA arrays to study host transcriptional responses to investigate this. Participants were controls (EC) and with DM, sub-classified to LTBI and DM-LTBI. Host blood transcriptomes were studied using microarrays followed by GO, WikiPathway and reactome pathway analyses. Gene expression compared with EC revealed 187 differentially expressed genes (DEGs) associated with LTBI; 182 DEGs with DM and 13 DEGs with DM-LTBI. In LTBI and DM, downregulation of antigen presentation and upregulation of inflammatory genes was evident whilst in DM, mostly immune related genes were downregulated. Comparison between LTBI-DM and LTBI revealed 321 up- and 12 downregulated DEGs, with upregulated immune response and inflammatory genes whilst a downregulation of genes associated with insulin metabolism and oxidative stress were observed. The impact of uncontrolled hyperglycemia was seen as downregulation in protein synthesis and oxidative phosphorylation in the host. This effect was further enhanced in those with hyperglycemia within the LTBI-DM group. Importantly, our observations of dysregulated pathways observed in diabetic individuals fit with earlier reports. We show that LTBI and DM synergistically increase host inflammatory and metabolic processes whilst reducing innate immunity. Such dysregulation by uncontrolled hyperglyemia highlights increased risk of progression of Mtb infection in this cohort and emphasizes the need for diabetes control in a TB endemic population.