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Notch signaling guides vascular development and function by regulating diverse endothelial cell behaviors, including migration, proliferation, vascular density, endothelial junctions, and polarization in response to flow. Notch proteins form transcriptional activation complexes that regulate endothelial gene expression, but few of the downstream effectors that enable these phenotypic changes have been characterized in endothelial cells, limiting our understanding of vascular Notch activities. Using an unbiased screen of translated mRNA rapidly regulated by Notch signaling, we identified novel in vivo targets of Notch signaling in neonatal mouse brain endothelium, including UNC5B, a member of the netrin family of angiogenic-regulatory receptors. Endothelial Notch signaling rapidly upregulates UNC5B in multiple endothelial cell types. Loss or gain of UNC5B recapitulated specific Notch-regulated phenotypes. UNC5B expression inhibited endothelial migration and proliferation and was required for stabilization of endothelial junctions in response to shear stress. Loss of UNC5B partially or wholly blocked the ability of Notch activation to regulate these endothelial cell behaviors. In the developing mouse retina, endothelial-specific loss of UNC5B led to excessive vascularization, including increased vascular outgrowth, density, and branchpoint count. These data indicate that Notch signaling upregulates UNC5B as an effector protein to control specific endothelial cell behaviors and inhibit angiogenic growth., (© 2024. The Author(s).)

In this study, pure nickel oxide (NiO), manganese ferrite (MnFe 2 O 4 or MFO), and binary nickel oxide/manganese ferrite (NiO/MFO1-4) nanocomposites (NCs) were synthesized using the Sol-Gel method. A comprehensive investigation into their photoluminescence, structural, morphological, magnetic, optical, and photocatalytic properties was conducted. Raman analysis, UV-Vis spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction techniques were used to characterize the materials. The synthesized samples exhibited superparamagnetic behavior, as revealed by our analysis of their magnetic properties. A lower recombination rate was shown by the photoluminescence analysis, which is helpful for raising photocatalytic activity. The photocatalytic activity was evaluated for the degradation of Cresol Red (CR) dye. 91.6% of CR dye was degraded by NiO/MFO-4 nanocomposite, and the NC dosage as well as solution pH affected the photocatalytic performance significantly. In four sequential photocatalytic cycles, the magnetically separable NCs were stable and recyclable. The enhanced photocatalytic activity and magnetic separability revealed the potential application of NiO/MFO-4 as an efficient photocatalyst for the removal of dyes from industrial wastewater under solar light irradiation., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background & Objective: Cerebrovascular Accident (CVA) or stroke, Spinal Cord injury can lead to neurological diseases resulting in major loss in motor function causing hemiplegia or tetraplegia. In 2019, according to The Global Burden of Diseases (GBD) CVA/Stroke is the second leading cause of death and the third leading cause of death and disability combined, globally. Its prevalence vary drastically among South Asian countries. The objective of this study was to determine the effectiveness of Functional Electrical Stimulation (FES) machine on neurologically impaired patients at the Physical Therapy department at IHHN, Karachi, Pakistan., Method: In this retrospective study data was extracted from August 2016 to February 2022 on patients with neurological symptoms i.e. hemiplegia or paraplegia with muscle power of two or less on Manual Muscle Testing (MMT). The parameters for evaluating patients progress pre and post treatment were MMT results and their mobility status. The number of sessions ranged between 40 to 100 sessions of Functional Electrical Stimulation (FES) provided on alternate days according to the patient's need., Result: Data of 51 patients who had completed their treatment were extracted and analyzed. The mean age of patients who completed treatment was 49.62 ± 17.26 years. Out of 51(100%), 30 (58.8%) were male and 21 (41.2%) were female. Pre- and post-treatment median (IQR) showed remarkable improvement in MMT of upper limb muscle (from 1.0 to 4.0) and lower limb muscle (from 2.0 to 4.0)., Conclusion: FES cycling is an effective treatment for patients with neurological impairments, as it resulted in improvement in both upper and lower limb muscle strength, along with mobility status., Competing Interests: Conflict of interest: None, (Copyright: © Pakistan Journal of Medical Sciences.)

Objective: This study was aimed at identifying the sources and basic nutrition knowledge among the citizens of Lahore., Methods: This cross-sectional study was conducted in the metropolis city of Lahore, Pakistan. Four hundred and seventy-six adult citizens of Lahore participated. A random sampling method was used to collect data through a food frequency questionnaire consisting of 23 questions. The questionnaire designed for this study contained questions about demographics, sources of nutrition information, the reliability of these sources of nutrition information, and basic nutrition knowledge. The highest possible score of the questionnaire was marked as 15, and a mean value of 7.5 was used to categorize the low and high values for variables like nutrition knowledge., Results: The majority of participants (34.2%) took nutrition information from their families, healthcare professionals (23.9%), and online resources (23.5%). The most reliable source for nutrition information was healthcare professionals (78.6%). Many participants (65.30%) had high nutrition-related basic knowledge, and 34.70% had low knowledge. Although more than 50% of participants reported having high nutrition knowledge, but they were not aware of how to read food labels. Those citizens who referred to online resources for information about nutrition knowledge usually got better results regarding nutrition knowledge., Conclusion: There is a need for more extensive research to identify the quality of sources for nutrition information to form better policies and plans that can be integrated and adopted at the community and national levels to increase the overall nutrition knowledge of people., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Imran et al.)

Background: Plant aquaporins are critical genetic players performing multiple biological functions, especially climate resilience and water-use efficiency. Their genomic diversity across genus Oryza is yet to be explored., Results: This study identified 369 aquaporin-encoding genes from 11 cultivated and wild rice species and further categorized these into four major subfamilies, among which small basic intrinsic proteins are speculated to be ancestral to all land plant aquaporins. Evolutionarily conserved motifs in peptides of aquaporins participate in transmembrane transport of materials and their relatively complex gene structures provide an evolutionary playground for regulation of genome structure and transcription. Duplication and evolution analyses revealed higher genetic conservation among Oryza aquaporins and strong purifying selections are assisting in conserving the climate resilience associated functions. Promoter analysis highlighted enrichment of gene upstream regions with cis-acting regulatory elements involved in diverse biological processes, whereas miRNA target site prediction analysis unveiled substantial involvement of osa-miR2102-3p, osa-miR2927 and osa-miR5075 in post-transcriptional regulation of gene expression patterns. Moreover, expression patterns of japonica aquaporins were significantly perturbed in response to different treatment levels of six phytohormones and four abiotic stresses, suggesting their multifarious roles in plants survival under stressed environments. Furthermore, superior haplotypes of seven conserved orthologous aquaporins for higher thousand-grain weight are reported from a gold mine of 3,010 sequenced rice pangenomes., Conclusions: This study unveils the complete genomic atlas of aquaporins across genus Oryza and provides a comprehensive genetic resource for genomics-assisted development of climate-resilient rice cultivars., (© 2023. The Author(s).)

Very long-chain fatty acids (VLCFAs) possess more than twenty carbon atoms and are the major components of seed storage oil, wax, and lipids. FAE (Fatty Acid Elongation) like genes take part in the biosynthesis of VLCFAs, growth regulation, and stress responses, and are further comprised of KCS (Ketoacyl-CoA synthase) and ELO (Elongation Defective Elongase) sub-gene families. The comparative genome-wide analysis and mode of evolution of KCS and ELO gene families have not been investigated in tetraploid Brassica carinata and its diploid progenitors. In this study, 53 KCS genes were identified in B. carinata compared to 32 and 33 KCS genes in B. nigra and B. oleracea respectively, which suggests that polyploidization might has impacted the fatty acid elongation process during Brassica evolution. Polyploidization has also increased the number of ELO genes in B. carinata (17) over its progenitors B. nigra (7) and B. oleracea (6). Based on comparative phylogenetics, KCS, and ELO proteins can be classified into eight and four major groups, respectively. The approximate date of divergence for duplicated KCS and ELO genes varied from 0.03 to 3.20 million years ago (MYA). Gene structure analysis indicated that the maximum number of genes were intron-less and remained conserved during evolution. The neutral type of selection seemed to be predominant in both KCS and ELO genes evolution. String-based protein-protein interaction analysis suggested that bZIP53, a transcription factor might be involved in the activation of transcription of ELO/KCS genes. The presence of biotic and abiotic stress-related cis-regulatory elements in the promoter region suggests that both KCS and ELO genes might also play their role in stress tolerance. The expression analysis of both gene family members reflect their preferential seed-specific expression, especially during the mature embryo development stage. Furthermore, some KCS and ELO genes were found to be specifically expressed under heat stress, phosphorus starvation, and Xanthomonas campestris infection. The current study provides a basis to understand the evolution of both KCS and ELO genes in fatty acid elongation and their role in stress tolerance., (© 2023. The Author(s).)

DNA-binding with one finger (Dof) transcription factors have been demonstrated to regulate various stresses and developmental processes in plants. Their identification and comparative evolutionary analyses in cultivated and wild species of genus oryza were yet to be explored. In this context, we report a comprehensive genomics atlas of DNA-binding with one finger (Dof) family genes in 13 diverse rice genomes (five cultivated and eight rice wild-relatives) through a genome-wide scanning approach. A galore of 238 Dof genes, identified across the genus Oryza , are categorized into seven distinct subgroups by comparative phylogenetic analysis with the model plant Arabidopsis . Conserved motifs and gene structure analyses unveiled the prevalence of species- and subgroups-specific structural and functional diversity that is expediating with the evolutionary period. Our results indicate that Dof genes might have undergone strong purifying selections and segmental duplications to expand their gene family members in corresponding Oryza genomes. We speculate that miR2927 potentially targets the Dof domain to regulate gene expression under different climatic conditions, which are supported by in-silico and wet-lab experiments-based expression profiles. In a nutshell, we report several superior haplotypes significantly associated with early flowering in a treasure trove of 3,010 sequenced rice accessions and have validated these haplotypes with two years of field evaluation-based flowering data of a representative subpanel. Finally, we have provided some insights on the resolution of Oryza species phylogeny discordance and divergence highlighting the mosaic evolutionary history of the genus Oryza . Overall, this study reports a complete genomic landscape of the Dof family in cultivated and wild Oryza species that could greatly facilitate in fast-track development of early maturing and climate-resilient rice cultivars through modern haplotype-led breeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tabassum, Raza, Riaz, Ahmad, Rashid, Javed, Ali, Kang, Khan, Atif and Luo.)

The gaps between the complex nature of cancer and therapeutics have been narrowed down due to extensive research in molecular oncology. Despite gathering massive insight into the mysteries of tumor heterogeneity and the molecular framework of tumor cells, therapy resistance and adverse side effects of current therapeutic remain the major challenge. This has shifted the attention towards therapeutics with less toxicity and high efficacy. Myricetin a natural flavonoid has been under the spotlight for its anti-cancer, anti-oxidant, and anti-inflammatory properties. The cutting-edge molecular techniques have shed light on the interplay between myricetin and dysregulated signaling cascades in cancer progression, invasion, and metastasis. However, there are limited data available regarding the nano-delivery platforms composed of myricetin in cancer. In this review, we have provided a comprehensive detail of myricetin-mediated regulation of different cellular pathways, its implications in cancer prevention, preclinical and clinical trials, and its current available nano-formulations for the treatment of various cancers., (© 2022. The Author(s).)

MADS-box gene family members play multifarious roles in regulating the growth and development of crop plants and hold enormous promise for bolstering grain yield potential under changing global environments. Bread wheat ( Triticum aestivum L . ) is a key stable food crop around the globe. Until now, the available information concerning MADS-box genes in the wheat genome has been insufficient. Here, a comprehensive genome-wide analysis identified 300 high confidence MADS-box genes from the publicly available reference genome of wheat. Comparative phylogenetic analyses with Arabidopsis and rice MADS-box genes classified the wheat genes into 16 distinct subfamilies. Gene duplications were mainly identified in subfamilies containing unbalanced homeologs, pointing towards a potential mechanism for gene family expansion. Moreover, a more rapid evolution was inferred for M-type genes, as compared with MIKC-type genes, indicating their significance in understanding the evolutionary history of the wheat genome. We speculate that subfamily-specific distal telomeric duplications in unbalanced homeologs facilitate the rapid adaptation of wheat to changing environments. Furthermore, our in-silico expression data strongly proposed MADS-box genes as active guardians of plants against pathogen insurgency and harsh environmental conditions. In conclusion, we provide an entire complement of MADS-box genes identified in the wheat genome that could accelerate functional genomics efforts and possibly facilitate bridging gaps between genotype-to-phenotype relationships through fine-tuning of agronomically important traits., Competing Interests: Author HB is employed by Montana BioAgriculture Incorporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Raza, Riaz, Atif, Hussain, Rana, Ali, Budak and Alaraidh.)

Class III peroxidases (PODs) are plant-specific glycoproteins, that play essential roles in various plant physiological processes and defence responses. To date, scarce information is available about the POD gene family in soybean. Hence, the present study is the first comprehensive report about the genome-wide characterization of GmPOD gene family in soybean (Glycine max L.). Here, we identified a total of 124 GmPOD genes in soybean, that are unevenly distributed across the genome. Phylogenetic analysis classified them into six distinct sub-groups (A-F), with one soybean specific subgroup. Exon-intron and motif analysis suggested the existence of structural and functional diversity among the sub-groups. Duplication analysis identified 58 paralogous gene pairs; segmental duplication and positive/Darwinian selection were observed as the major factors involved in the evolution of GmPODs. Furthermore, RNA-seq analysis revealed that 23 out of a total 124 GmPODs showed differential expression between drought-tolerant and drought-sensitive genotypes under stress conditions; however, two of them (GmPOD40 and GmPOD42) revealed the maximum deregulation in all contrasting genotypes. Overexpression (OE) lines of GsPOD40 showed considerably higher drought tolerance compared to wild type (WT) plants under stress treatment. Moreover, the OE lines showed enhanced photosynthesis and enzymatic antioxidant activities under drought stress, resulting in alleviation of ROS induced oxidative damage. Hence, the GsPOD40 enhanced drought tolerance in soybean by regulating the key physiological and biochemical pathways involved in the defence response. Lastly, the results of our study will greatly assist in further functional characterization of GsPODs in plant growth and stress tolerance in soybean., (Copyright © 2021. Published by Elsevier Inc.)

Collagen type IV (Col IV) is a basement membrane protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. Defects in vascular Col IV deposition are the basis of heritable disorders, such as small vessel disease, marked by cerebral hemorrhage and drastically shorten lifespan. To date, little is known about how endothelial cells regulate the intracellular transport and selective secretion of Col IV in response to angiogenic cues, leaving a void in our understanding of this critical process. Our aim was to identify trafficking pathways that regulate Col IV deposition during angiogenic blood vessel development. We have identified the GTPase Rab10 as a major regulator of Col IV vesicular trafficking during vascular development using both in vitro imaging and biochemistry as well as in vivo models. Knockdown of Rab10 reduced de novo Col IV secretion in vivo and in vitro. Mechanistically, we determined that Rab10 is an indirect mediator of Col IV secretion, partnering with atypical Rab25 to deliver the enzyme lysyl hydroxylase 3 (LH3) to Col IV-containing vesicles staged for secretion. Loss of Rab10 or Rab25 results in depletion of LH3 from Col IV-containing vesicles and rapid lysosomal degradation of Col IV. Furthermore, we demonstrate that Rab10 is Notch responsive, indicating a novel connection between permissive Notch-based vessel maturation programs and vesicle trafficking. Our results illustrate both a new trafficking-based component in the regulated secretion of Col IV and how this vesicle trafficking program interfaces with Notch signaling to fine-tune basement membrane secretion during blood vessel development., (© 2021. The Author(s).)

The prevalence of overweight and obesity is on the rise around the world, not only in the West, but also in Asian countries. South Asian countries in particular are experiencing a rapid increase in overweight and obesity, that coexists with the rapid increase in non-communicable diseases linked to obesity such as diabetes and cardiovascular disease than any other country in Asia. The phenomena observed in South Asian countries are due to the size of the population, the ageing of the population, the high degree of urbanization and the lifestyle changes in favor of increased energy consumption and reduced physical activity. The imbalance between energy consumption and energy expenditure results in the development of a positive energy balance that, over time, accumulates in higher body fat. South Asians were reported to have a more unfavorable body composition with a higher percentage of body fat than Caucasians with an equivalent BMI. Body composition is a major determinant of resting energy expenditure. It has been reported that South Asians have a lower resting energy expenditure than Caucasians with the same BMI. Resting energy expenditure accounts for the majority of total daily energy expenditure and, therefore, plays a crucial role in achieving the balance between energy intake and expenditure.

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.

Matrix nanocomposites are high performance materials possessing unusual features along with unique design possibilities. Due to extraordinary thermophysical characteristic contained by these matrix nanocomposites materials they are useful in several areas ranging from packaging to biomedical applications. Being an environment friendly, utilization of nanocomposites offer new technological opportunities for several sectors of aerospace, automotive, electronics and biotechnology. In this regards, current pagination is devoted to analyze thermal features of viscous fluid flow between orthogonally rotating disks with inclusion of metallic matrix nanocomposite (MMNC) and ceramic matrix nanocomposites (CMNC) materials. Morphological aspects of these nanomaterials on flow and heat transfer characteristics has been investigated on hybrid viscous fluid flow. Mathematical structuring of problem along with empirical relations for nanocomposites materials are formulated in the form of partial differential equations and later on converted into ordinary differential expressions by using suitable variables. Solution of constructed coupled differential system is found by collaboration of Runge-Kutta and shooting methods. Variation in skin friction coefficient at lower and upper walls of disks along with measurement about heat transfer rate are calculated against governing physical parameters. Impact of flow concerning variables on axial, radial components of velocity and temperature distribution are also evaluated. Contour plots are also drawn to explore heat and thermal profiles. Comparison and critical analysis of MMNc and CMNc have been presented at lower and upper porous disks. Our computed analysis indicates that hybrid nanofluids show significant influence as compared to simple nanofluids with the permutation of the different shape factors.

Adenosine plays a significant role in neurotransmission process by controlling the blood pressure, while adenosine triphosphate (ATP) acts as a neuromodulator and neurotransmitter and by activation of P2 receptors, regulates the contractility of the heart. Adenosine signaling is essential in the process of regeneration by regulating proliferation, differentiation, and apoptosis of stem cells. In this review, we have selected neurological disorders (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and epilepsy) with clinical trials using antagonists and epigenetic tools targeting adenosine receptor as a therapeutic approach in the treatment of these disorders. Promising results have been reported from many clinical trials. It has been found that higher expression levels of A2A and P2X7 receptors in neurological disorders further complicate the disease condition. Therefore, modulations of these receptors by using antagonists of these receptors or SAM (S-adenosylmethionine) therapy as an epigenetic tool could be useful in reversing the complications of these disorders. Finally, we suggest that modulation of adenosine receptors in neurological disorders can increase the regenerative phase by increasing the rate of proliferation and differentiation in the damaged tissues.

The objective of this study is to compare game-based digital therapeutic device and other DHI like (smartphone apps, wearable technologies) for ADHD with the current pharmacological and behavior therapy. The FDA has approved a game-based digital therapeutic device - EndeavorRx, for the treatment of ADHD in pediatric patients belonging to the age group of 8-12 years old. This has been primarily recommended for the treatment of inattentive or combined-type ADHD who have demonstrated an attention issue. This is the first game-based therapeutic device to be approved by the FDA for any type of condition. According to the FDA, this has been shown to improve attention which is measured by computer-based testing. Objective: The objective of this study is to compare a game-based digital therapeutic device and other DHI (smartphone apps, wearable technologies) with the current pharmacological and behavior therapy used in the treatment of ADHD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To explore the current intake/changed dietary habits being associated with risk of cardiovascular disease after migration from Pakistan to the Netherlands., Methods: Data collection started in March 2012 and ended in July 2013. Self-administered survey with respect to cardiovascular disease and dietary intake was filled by 154 adult Pakistanis. Participants were approached through festivals and community centres. Descriptive statistics was used to analyse the data., Results: There were 41 (61%) participants who reported drinking fruit juice every day, while 13 (18.6%) participants reported drinking soft drinks 5-7 days a week. In addition, 20 (30%) participants reported decreased intake of high fat/fried foods, deserts/candy/sweets and red meat, while 23 (35%) reported an increased intake of soft drinks and convenience foods, as far as high calorie and refined food items were considered, after migration., Conclusions: The study showed significant changes in dietary habits, both favourable and unfavourable, being associated with risk of cardiovascular diseases among immigrant Pakistanis living in The Netherlands.

Gliomas are one of the most annihilating types of brain tumours having a high rate of annual incidence worldwide. Notch signaling is an evolutionary conserved pathway that regulates differentiation and development. Aberrations in Notch signalling pathways lead to severe pathological state such as the Gliomas. MicroRNAs (miRNAs) are the tiny molecules less than 200 bps in length and regulate a myriad of cellular processes. Categorically, miRNAs are divided in to oncogenic and tumours suppressor miRNAs. Accumulating data have identified miRNAs, which positively or negatively regulate Notch signaling in Gliomas. Here, we have assessed status of our understanding of the interplay between miRNA-base regulation of Notch signaling in gliomas, interaction between Notch signaling and other signaling cascades and have also discussed use of natural compounds that will help us get closer to personalized medicine for gliomas.

Competing Interests: There are no conflicts of interest.

Breast cancer is a complex disease posing a serious threat to the female population worldwide. A complex molecular landscape and tumor heterogeneity render breast cancer cells resistant to drugs and able to promote metastasis and invasiveness. Despite the recent advancements in diagnostics and drug discovery, finding an effective cure for breast cancer is still a major challenge. Positive and negative regulation of apoptosis has been a subject of extensive study over the years. Numerous studies have shed light on the mechanisms that impede the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling cascade. Long non-coding RNAs (lncRNAs) have been implicated in the orchestration, development, proliferation, differentiation and metastasis of breast cancer. However, the roles of lncRNAs in fine-tuning apoptosis regulating machinery in breast cancer remain to be elucidated. The present review illuminates the roles of these molecules in the regulation of breast cancer and the interplay between lncRNA and TRAIL in breast cancer. The present review also attempts to reveal their role in the regulation of apoptosis in breast cancer appears a promising approach for the development of new diagnostic and therapeutic regimens., (Copyright: © Javed et al.)

Rice is critical for sustainable food and nutritional security; however, nominal micronutrient quantities in grains aggravate malnutrition in rice-eating poor populations. In this study, we evaluated genetic diversity in grain iron (Fe) and zinc (Zn) contents using trait-linked simple sequence repeat (SSR) markers in the representative subset of a large collection of local and exotic rice germplasm. Results demonstrated that aromatic fine grain accessions contained relatively higher Fe and Zn contents in brown rice (BR) than coarse grain accessions and a strong positive correlation between both mineral elements. Genotyping with 24 trait-linked SSR markers identified 21 polymorphic markers, among which 17 demonstrated higher gene diversity and polymorphism information content (PIC) values, strongly indicating that markers used in current research were moderate to highly informative for evaluating the genetic diversity. Population structure, principal coordinate and phylogenetic analyses classified studied rice accessions into two fine grain specific and one fine and coarse grain admixture subpopulations. Single marker analysis recognized four ZnBR and single FeBR significant marker-trait associations (MTAs) contributing 15.41-39.72% in total observed phenotypic variance. Furthermore, high grain Fe and Zn contents linked marker alleles from significant MTAs were also identified. Collectively, these results indicate a wide genetic diversity exist in grain Fe and Zn contents of studied rice accessions and reveal perspective for marker-assisted biofortification breeding., Competing Interests: The authors have declared that no competing interests exist.

Key Message: By integrating genetics and genomics data, reproductive tissues-specific and heat stress responsive 35 meta-QTLs and 45 candidate genes were identified, which could be exploited through marker-assisted breeding for fast-track development of heat-tolerant rice cultivars. Rice holds the key to future food security. In rice-growing areas, temperature has already reached an optimum level for growth, hence, any further increase due to global climate change could significantly reduce rice yield. Several mapping studies have identified a plethora of reproductive tissue-specific and heat stress associated inconsistent quantitative trait loci (QTL), which could be exploited for improvement of heat tolerance. In this study, we performed a meta-analysis on previously reported QTLs and identified 35 most consistent meta-QTLs (MQTLs) across diverse genetic backgrounds and environments. Genetic and physical intervals of nearly 66% MQTLs were narrower than 5 cM and 2 Mb respectively, indicating hotspot genomic regions for heat tolerance. Comparative analyses of MQTLs underlying genes with microarray and RNA-seq based transcriptomic data sets revealed a core set of 45 heat-responsive genes, among which 24 were reproductive tissue-specific and have not been studied in detail before. Remarkably, all these genes corresponded to various stress associated functions, ranging from abiotic stress sensing to regulating plant stress responses, and included heat-shock genes (OsBiP2, OsMed37_1), transcription factors (OsNAS3, OsTEF1, OsWRKY10, OsWRKY21), transmembrane transporters (OsAAP7A, OsAMT2;1), sugar metabolizing (OsSUS4, α-Gal III) and abiotic stress (OsRCI2-7, SRWD1) genes. Functional data evidences from Arabidopsis heat-shock genes also suggest that OsBIP2 may be associated with thermotolerance of pollen tubes under heat stress conditions. Furthermore, promoters of identified genes were enriched with heat, dehydration, pollen and sugar responsive cis-acting regulatory elements, proposing a common regulatory mechanism might exist in rice for mitigating reproductive stage heat stress. These findings strongly support our results and provide new candidate genes for fast-track development of heat-tolerant rice cultivars.

Thyroid cancer (TC) is the most common cancer of endocrine system. TC can be subdivided into 4 different entities, papillary, follicular, medullary and anaplastic thyroid cancer. Among them, anaplastic thyroid cancer has the poorest prognosis. Exploring new therapeutic approach may entail favorable prediction as well as increasing overall survival rate of patients. Long non-coding RNAs (lncRNAs), have vast implications in different cancer types. Although they are not transcribed into proteins, they can act as a harness in regulating a plethora of biological functions. They have been implicated in a decisive role in gene expression via modulation of both coding and non-coding RNAs. This article discuss the multi-facet role of lncRNA in thyroid cancer biology., .

Biofortification of staple crops with essential micronutrients is the sustainable way to overcome the hidden hunger. A large number of quantitative trait loci (QTL) linked with grain micronutrient contents have been reported in different mapping studies. Identification of consistent QTLs across diverse genetic backgrounds is useful for candidate gene analysis and marker assisted selection of target traits. In this study, an up to date meta-analysis of grain iron and zinc associated QTLs was performed and 48 meta-QTLs (MQTLs) distributed across 12 rice chromosomes were identified. The 95% confidence intervals of identified genomic regions were significantly narrower than the average of their corresponding original QTLs. A total of 9308 genes/transcripts physically located within or near MQTL regions were retrieved and through prioritization of candidate genes (CGs) 663 non-redundant iron and zinc CGs were selected and studied in detailed. Several functionally characterized iron and zinc homoeostasis related genes e.g OsATM3, OsDMAS1, OsFRO2, OsNAS1-3, OsVIT2, OsYSL16, OsZIP3 and OsZIP7 were also included in our MQTL analysis. More than 64% genes were enriched with zinc and iron binding gene ontology terms and were involved in oxidation reduction process, carbohydrate metabolic process, regulation of transcription, trans-membrane transport, response to oxidative stress, cell redox homeostasis and proteolysis etc. In-silico transcriptomic analysis of rice identified 260 CGs which were regulated in response to iron and zinc stresses. We also identified at least 37 genes which were differentially expressed under both stress conditions and majority of these have not been studied in detailed before. Our results strongly indicate that majority of the MQTLs identified in this study are hotspots for grain iron and zinc concentration and are worth of intensive functional studies in near future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The adherens junction (AJ) couples the actin cytoskeletons of neighboring cells to allow mechanical integration and tissue organization. The physiological demands of intercellular adhesion require that the AJ be responsive to dynamic changes in force while maintaining mechanical load. These demands are tested in the heart, where cardiomyocyte AJs must withstand repeated cycles of actomyosin-mediated contractile force. Here we show that force-responsive cardiomyocyte AJs recruit actin-binding ligands to selectively couple actin networks. We employed a panel of N-cadherin-αE-catenin fusion proteins to rebuild AJs with specific actin linkages in N-cadherin-null cardiomyocytes. In this system, vinculin recruitment was required to rescue myofibril integration at nascent contacts. In contrast, loss of vinculin from the AJ disrupted junction morphology and blocked myofibril integration at cell-cell contacts. Our results identify vinculin as a critical link to contractile actomyosin and offer insight to how actin integration at the AJ is regulated to provide stability under mechanical load.

Grasses represent a major family of monocots comprising mostly cereals. When compared to their eudicot counterparts, cereals show a remarkable morphological diversity. Understanding the molecular basis of floral organ identity and inflorescence development is crucial to gain insight into the grain development for yield improvement purposes in cereals, however, the exact genetic mechanism of floral organogenesis remains elusive due to their complex inflorescence architecture. Extensive molecular analyses of Arabidopsis and other plant genera and species have established the ABCDE floral organ identity model. According to this model, hierarchical combinatorial activities of A, B, C, D, and E classes of homeotic genes regulate the identity of different floral organs with partial conservation and partial diversification between eudicots and cereals. Here, we review the developmental role of A, B, C, D, and E gene classes and explore the recent advances in understanding the floral development and subsequent organ specification in major cereals with reference to model plants. Furthermore, we discuss the evolutionary relationships among known floral organ identity genes. This comparative overview of floral developmental genes and associated regulatory factors, within and between species, will provide a thorough understanding of underlying complex genetic and molecular control of flower development and floral organ identity, which can be helpful to devise innovative strategies for grain yield improvement in cereals.

Cellular maintenance and development are two fundamental mechanisms regulated by the canonical Wnt signaling pathway. Wnt/beta-catenin signaling pathway controls a myriad of cellular processes that are essential for normal cell functioning. Cell cycle progression, differentiation, fate determination, and migration are generally orchestrated by canonical Wnt signaling. Altered Wnt/beta-catenin signaling has been considered a promoting event for different types of cancers and the oncogenic potential of Wnt signaling have been discussed in many cancer types, including breast, colon, pancreatic as well as head and neck. Furthermore, Wnt signaling is critical for the maintenance and stemness of both the normal as well as cancer stem cells. This review sheds new light on Wnt signaling and explains how it can regulate normal physiological processes and curtail the development of cancer. It depicts the vital functions of Wnt signaling in the stem cell growth and differentiation by focusing on current druggable targets that have been ascribed by recent studies. Thus, Wnt signaling pathway retains a tremendous potential in eradicating head and neck squamous cell carcinoma., (Creative Commons Attribution License)

The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Evolutionary rate covariation (ERC) identifies proteins with correlated fluctuations in evolutionary rate that can reflect shared selective pressures and functions. Here we use ERC to identify proteins with evolutionary histories similar to the Drosophila E-cadherin (DE-cad) ortholog. Core adherens junction components α-catenin and p120-catenin displayed positive ERC correlations with DE-cad, indicating that they evolved under similar selective pressures during evolution between Drosophila species. Further analysis of the DE-cad ERC profile revealed a collection of proteins not previously associated with DE-cad function or cadherin-mediated adhesion. We then analyzed the function of a subset of ERC-identified candidates by RNAi during border cell (BC) migration and identified novel genes that function to regulate DE-cad. Among these, we found that the gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates BC migration and adhesion. We named CG42684 raskol ("to split" in Russian) and show that it regulates DE-cad levels and actin protrusions in BCs. We propose that Raskol functions with DE-cad to restrict Ras/Rho signaling and help guide BC migration. Our results demonstrate that a coordinated selective pressure has shaped the adherens junction and this can be leveraged to identify novel components of the complexes and signaling pathways that regulate cadherin-mediated adhesion., Competing Interests: The authors have declared that no competing interests exist.

Plant WRKY transcription factors (TFs) are active guardians against pathogens' insurgency, key components in developmental processes, contributors in signal transduction pathways, and regulators of diverse biotic and abiotic stress responses. In this research, we isolated, cloned, and functionally characterized a new WRKY TF GmWRKY49 from soybean. GmWRKY49 is a nuclear protein which contains two highly conserved WRKY domains and a C 2 H 2 -type zinc-finger structure. The normalized expression (log 2 ratio) of GmWRKY49 was 2.75- and 1.90-fold in salt-tolerant and salt-susceptible soybean genotypes, respectively. The transcripts of GmWRKY49 could be detected in roots, stems, leaves, flowers, and almost no expression in pod tissues. The salinity-tolerance response of this gene was studied through overexpression in soybean composite seedlings and transgenic Arabidopsis . The effect of GmWRKY49 overexpression on root length of transgenic Arabidopsis was also investigated. Under salt stress, several parameters including germination rate, survival rate, root length, rosette diameter, relative electrolyte leakage, and proline content were significantly higher in composite seedlings and transgenic Arabidopsis than those in wild-type. Moreover, GmWRKY49 enhanced salinity tolerance in soybean mosaic seedlings and transgenic Arabidopsis . These results suggest that GmWRKY49 is a positive regulator of salinity tolerance in soybean and has high potential utilization for crop improvement.

Objective: South Asians living in Western countries have shown higher prevalence of cardiovascular disease and related non-communicable diseases as compared to the local populations. The aim of this study was to compare the general health status and prevalence of myocardial infarction (MI), diabetes, high blood pressure, overweight, obesity, and fruit and vegetable intake between Pakistani immigrants in the Netherlands and local Amsterdam population., Design: A health survey was conducted in 2012-2013 among Pakistanis in the Netherlands. Results were compared with a health survey conducted among inhabitants of Amsterdam in 2012. One hundred and fifty-four Pakistanis from four big cities of the Netherlands and 7218 inhabitants of Amsterdam participated. The data for Amsterdam population were weighed on the basis of age, gender, city district, marital status, ethnicity and income level while the data for Pakistanis were weighed on the basis of age and gender to make both data-sets representative of their general population., Results: Pakistanis reported a high prevalence of MI (3.3%), diabetes (11.4%), high blood pressure (14.4%), overweight (35.5%) and obesity (18.5%) while Amsterdam population reported the prevalence as 2.5% for MI, 6.8% for diabetes, 15.3% for high blood pressure, 28.1% for overweight and 11.1% for obesity. Pakistanis had a significantly higher level of MI (OR = 2.71; 95% CI: 1.19-6.14), diabetes (OR = 4.41; 95% CI: 2.66-7.33) and obesity (OR = 2.51; 95% CI: 1.53-4.12) after controlling for age, sex and educational level with Amsterdam population as the reference group. Pakistanis showed a higher intake of fruit and fruit juice as compared to Amsterdam population though the latter showed a higher intake of cooked vegetables., Conclusion: Higher prevalence of MI, diabetes and obesity among Pakistanis than Amsterdam population indicates the need for health scientists and policy-makers to develop interventions for tackling non-communicable diseases and its determinants among Pakistanis living in the Netherlands.

Microinjection is an established and reliable method to deliver biological reagents such as transgenic constructs and drugs, to specific locations inside organisms such as the Drosophila embryo and C. elegans worm. In this paper, a simple compliant mechanism based PDMS-microinjection system has been demonstrated. Unlike conventional microinjectors, this unique system could allow one to precisely insert a long taper microneedle laterally and at various positions inside the length of the Drosophila embryo (up to 250 μm) with the resolution of 5 μm. Volumes as low as 30 pL with accuracy of ±10 pL were delivered inside the embryo via pressure pulses. The device has been used to study the effect of toxins on cardiogenesis in Drosophila embryos. Using this device, we demonstrate that the cardioblast (CB) migration velocity is modified in a dose sensitive manner to varying doses of injected sodium azide (NaN 3 ) and, for the first time, quantify the effect of the toxin on heart assembly. Injection with 40 pL of NaN 3 was shown to decrease CB migration velocity and filopodia number at concentrations above 10 mM, while embryos injected with the tracer Rhodamine B (0 mM NaN 3 ) displayed no significant difference when compared to uninjected embryos. This device can be potentially used for other embryonic assays, which require accurate delivery of the reagents to a specific location within the embryo.

Objective: To test Koctürk's model of dietary change among South-Asian Surinamese in the Netherlands. The model categorizes foods into staple, complementary and accessory foods and postulates that dietary change after migration begins with accessory foods while foods associated with ethnic identity (staple foods) change at a slower rate., Design: Cross-sectional data from the HELIUS study. Dietary intake was assessed with an FFQ. Acculturation was based on social contacts and sense of belonging and was translated into four strategies of acculturation: assimilation, integration, separation and marginalization. Other indicators of acculturation included residence duration, age at migration and migration generation status., Setting: Amsterdam, the Netherlands., Subjects: Participants of Dutch (n 1456) and South-Asian Surinamese origin (n 968)., Results: Across all acculturation strategies, South-Asian Surinamese participants reported significantly higher intakes of rice (staple food) and chicken (complementary food) and significantly lower intakes of red meat and vegetables (complementary foods) and cookies and sweets (accessory food) than Dutch participants. Men, second-generation and assimilated South-Asian Surinamese were inclined towards Dutch foods such as potato, pasta and red meat. Accessory foods like fruits showed variation across acculturation strategies., Conclusions: Consistent with the Koctürk model, the intake of staple foods was stable among South-Asian Surinamese irrespective of acculturation strategy while the intake of accessory foods like fruit varied. Contrary to expectations, South-Asian Surinamese showed consistently high intakes of complementary foods like chicken and fish irrespective of acculturation strategy. Public health practitioners should take into consideration the complex and dynamic nature of dietary acculturation.

Background: Ethnic differences regarding the percent of non-communicable diseases have been shown in Asia but the studies on Asian subgroups living in the western countries regarding percent of cardiovascular risk factors and dietary intakes have been scarce. Therefore we compared the percent of cardiovascular risk factors and dietary intakes between Javanese Surinamese who are originally from Indonesia and South-Asian Surinamese who are originally from India., Methods: Cross-sectional baseline data of the HELIUS (Healthy Life in an Urban Setting) study were used, including data of 2935 Surinamese participants (197 of Javanese and 2738 of South-Asian origin) out of which 1160 participants (78 Javanese and 1082 South-Asian) additionally reported dietary intake data. Descriptive statistics were used to compare the two ethnic groups regarding cardiovascular disease, diabetes, obesity, hypertension and hypercholesterolemia; in addition, dietary intake of foods like vegetables, red meat, fruit, high fibre foods, low fibre foods, high fat and low fat dairy products, chicken and sugar sweetened beverages were also compared between the two groups. Binary logistic regression analyses were used to adjust for age and sex when comparing the two groups., Results: South-Asian Surinamese had a significantly higher percent of abdominal obesity (OR 2.44; CI 1.66-3.57), cardiovascular disease (OR 2.55; CI 1.48-4.35) and diabetes (OR 2.77; CI 1.67-4.60) as compared with Javanese Surinamese after adjustment for age and sex. The percent of obesity (BMI), hypertension, and lipids was not significantly different between the ethnic groups. Javanese Surinamese had a significantly higher intake of red meat and a significantly lower intake of dairy products as compared with South-Asian Surinamese. Intakes of vegetables, grains, fish, fruits, tea and coffee did not significantly differ between the ethnic groups. Both groups showed intake of considerable amount of sugar sweetened beverages., Conclusions: Public health practitioners in the Netherlands and elsewhere in the world should take into account the ethnic subgroup differences within the broader groups like Asians when developing interventions related to health among ethnic minorities.

Collective cell migration is the coordinated movement of cells, which organize tissues during morphogenesis, repair and some cancers. The motile cell membrane of the advancing front in collective cell migration is termed the Leading Edge. The embryonic development of the vertebrate and Drosophila hearts are both characterized by the coordinated medial migration of a bilateral cluster of mesodermal cells. In Drosophila, the cardioblasts form cohesive bilateral rows that migrate collectively as a unit towards the dorsal midline to form the dorsal vessel. We have characterized the collective cell migration of cardioblasts as an in vivo quantitative model to study the behaviour of the Leading Edge. We investigated whether guidance signalling through Slit and Netrin pathways plays a role in cell migration during heart development. Through time-lapse imaging and quantitative assessment of migratory behaviour of the cardioblasts in loss-of-function mutants, we demonstrate that both Slit and Netrin mediated signals are autonomously and concomitantly required to maximize migration velocity, filopodial and lamellipodial activities. Additionally, we show that another Slit and Netrin receptor, Dscam1, the role of which during heart development was previously unknown, is required for both normal migration of cardioblasts and luminal expansion. Leading edge behaviour analysis revealed a dosage dependent genetic interaction between Slit and Netrin receptors suggesting that downstream signalling through these receptors converge on a common output that increases leading edge activity of the cardioblasts. Finally, we found that guidance signalling maintains the balance between epithelial and mesenchymal characteristics of the migrating cardioblasts., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: A training physician has his first interaction with a pharmaceutical representative during medical school. Medical students are often provided with small gifts such as pens, calendars and books, as well as free lunches as part of drug promotion offers. Ethical impact of these transactions as perceived by young medical students has not been investigated in Pakistan before. This study aimed to assess the association of socio-demographic variables with the attitudes of medical students towards pharmaceutical companies and their incentives., Methods: As part of a cross-sectional survey, a validated questionnaire previously used for assessing attitude of medical students towards pharmaceutical industry, was modified, pre-tested and distributed among consenting clinical year students at DUHS and AKU. Questions included acceptability of pharmaceutically sponsored gifts, events and tuition fee, and their impact on future prescription. Responses were graded as agree, disagree or neutral which were then scored according to the AMSA guidelines of ethical conduct., Results: Out of a total of 353 targeted students 303 responded, corresponding to a response rate of 85.8%. Responses indicated that 42.7% students believed in no interaction with drug companies during medical school. However, 81% of students favored pharmaceutical sponsorship of student-body events/seminars at medical colleges. More than one-third of the students were comfortable receiving gifts from drug companies. Overall, the results of this study offer an interesting comparison between the students of a private medical school (AKU) and a public medical school (DUHS); AKU students exhibited a greater degree of mistrust towards drug information provided by pharmaceutical companies compared to DUHS students (p = 0.040). Furthermore, when asked if there was a need to incorporate guidelines in the undergraduate curriculum with regard to interaction with drug companies, 84.2% students at AKU agreed, compared to 54.9% at DUHS. Medical student Attitude Scores are more or less similar to each other independent of their various demographical differences., Conclusion: This study highlights that medical students in our population have a high level of acceptability towards incentives offered by pharmaceutical industry and that formal guidance regarding the subject should be incorporated into medical curriculum.

Aim: The aim of this study was to systematically describe the gender and ethnic differences regarding the prevalence of general/central obesity and cardiovascular disease (CVD) risk factors such as diabetes mellitus type 2, hypertension, and hypercholesterolemia among the indigenous and immigrant Pakistani communities., Methods: The search engine used was PubMed, supplemented with regional data from the Medical Institutes of Pakistan. The focus was on the adult Pakistani population (18 years and older)., Results: We found only 7 studies among the immigrant Pakistani community and 24 studies among the indigenous Pakistani community. The studies had limitations such as low participation rates and use of self-reported data. There is a higher prevalence of central obesity among women (42.2%) than among men (14.7%) (National Health Survey of Pakistan). Certain ethnicities such as Muhajir and Baluchis showed a higher prevalence of cardiovascular risk factors when compared to other ethnicities in the indigenous Pakistani population. The results also indicate that the prevalence of obesity is 10-20% higher among the immigrant Pakistanis than in the indigenous Pakistanis., Conclusion: The relatively high prevalence of obesity and associated CVD risk factors (especially in women) among both indigenous and immigrant Pakistani populations require the attention of the healthcare professionals and policy makers, both inside and outside Pakistan., (© 2013 S. Karger GmbH, Freiburg.)

Objective: To compare accuracy and throughput time for the measurement of HDL and LDL cholesterol by manual precipitation and fully automated enzymatic methods., Methods: Fifty, serum samples collected over a 4 months period (February - May 2004) were analyzed for HDL and LDL cholesterol by two different methods i.e. precipitation manual and automatic enzymatic method in the section of chemical pathology, Department of Pathology and Microbiology, Aga Khan University Hospital, Karachi Pakistan., Results: The mean standard deviation for HDL Cholesterol by precipitation method and automated method were 43.12 +/- 8.97mg/dl and 43.86 +/- 10.34mg/dl respectively (p-value = 0.301). The mean standard deviation for LDL cholesterol by precipitation method and automated method were 111.76 +/- 25.57mg/dl and 111.8 +/- 28.41mg/dl respectively (p-value = 0.981). The calculated "t" and "F" value for HDL-C was 0.0172 and 0.75 respectively, and calculated "t" and "F" values for LDL-C were 0.047 and 0.809 respectively. Average time for manual method was 45 minutes and automation 20 minutes., Conclusion: Both the precipitation (manual) method and the automated method provide reliable, precise and accurate results. In both the methods "t" and "F" values were less than critical. Automated method provide high throughput and are less labor intensive. The choice of method can depend on laboratory facilities and workload