Low Incidence of Androgen Receptor Mutation Among Egyptian Children with Androgen Resistance

Introduction: In Egypt, disorders of sex development (DSD) constitute a significant entity among the birth defect list. Previous studies have reported that end organ androgen unresponsiveness, i.e. Androgen resistance, was the most prevalent underlying mechanism among Egyptian 46,XY DSD cases. Based on cytogenetic and hormonal diagnostic criteria as well as few sporadic case reports, it was proposed that androgen receptor (AR) defects [i.e. Androgen insensitivity syndrome (AIS), OMIM#300068] might constitute a major etiology within this category. However, this has never been systematically ascertained through an AR molecular diagnostic approach. Aim of the Work: The current study aimed to assess the role of AR mutations as an underlying etiology among a sample of Egyptian 46,XY DSD pediatric patients presenting with androgen end organ unresponsiveness. Patients and Method: In the current study, 21 children [ag

Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma.

Follicular lymphoma (FL) is a common indolent B-cell lymphoma that can transform into the more aggressive transformed FL (tFL). However, the molecular process driving this transformation is uncertain. In this work, we aimed to identify microRNA (miRNA)-binding sites recurrently mutated in follicular lymphoma patients, as well as in transformed FL patients. Using whole-genome sequencing data from FL tumors, we discovered 544 mutations located in bioinformatically predicted microRNA-binding sites. We then studied these specific regions using targeted sequencing in a cohort of 55 FL patients, found 16 recurrent mutations, and identified a further 69 variants. After filtering for QC, we identified 21 genes with mutated miRNA-binding sites that were also enriched for B-cell-associated genes by Gene Ontology. Over 40% of mutations identified in these genes were present exclusively in tFL patients. We validated the predicted miRNA-binding sites of five of the genes by luciferase assay and demonstrated that the identified mutations in BCL2 and EZH2 genes impaired the binding efficiency of miR-5008 and miR-144 and regulated the endogenous levels of messenger RNA (mRNA)

Effect of replacement of berseem (Trifolium alexandrinum L.) hay by berseem silage on performance of growing rabbits

SUMMARY Two experiments were done to study the effect of partial replacement of berseem hay by berseem silage on the performance of growing rabbits. In the first one, 8 mature eight-months-old male NZW rabbits with an average body weight of 2.5 kg were used to determine digestibility coefficients and nutritive values of berseem hay (BH) and berseem silage (BS). In the second one, 30 NZW growing rabbits of 60 days of age were used in a complete randomized design experiment with three treatments. The first group was fed commercial rabbit diet including 40% BH (control diet), while in the other two groups 50 or 100% of BH was replaced by BS throughout the 70 days of the experiment. Results of the first experiment indicated that the contents of crude protein (CP) and ash tended to be higher, but the contents of organic matter (OM), crude fiber (CF), ether extract (EE) and nitrogen free extract (NFE) tended to be lower in BS compared with BH. The digestibility coefficients of DM, OM, CP, CF and NFE and the contents of TDN, DCP and DE were significantly higher (P<0.05) for BS than BH. In the second experiment, the contents of CP and ash tended to increase, but the contents of OM, CF and NFE tended to be decreased with increasing the level of replacing BH by BS. The digestibilities of DM, OM CP, EE and NFE and TDN, DCP and DE values and caecal values (TVFA's and NH 3 -N concentrations) increased significantly (P<0.05), however pH value decreased significantly (P<0.05) with increasing the level of replacing BH by BS. The final body weight, total and daily weight gain, the total and net revenue and net revenue improvement increased significantly (P<0.05), however, the average daily and total DM intake, the amount of DM required per kg weight gain and also the feed cost and feed cost/kg gain decreased significantly (P<0.05) with increasing the level of replacing BH by BS. The slaughter weight, carcass weight, dressing percentage, meat weight and percentage increased significantly (P<0.05), but the DM content of the meat decreased significantly † Corresponding author email: [email protected] H.M.A. Gaafar et al. 60 (P<0.05) with increasing the level of replacing BH by BS. Protein content in meat of rabbits fed 50 and 100% BS diets was significantly higher (P<0.05) than that of those fed commercial diet, while the contents of ether extract and ash were nearly similar for different groups

SOX9 Triggers Different Epithelial to Mesenchymal Transition States to Promote Pancreatic Cancer Progression.

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers mainly due to spatial obstacles to complete resection, early metastasis and therapy resistance. The molecular events accompanying PDAC progression remain poorly understood. SOX9 is required for maintaining the pancreatic ductal identity and it is involved in the initiation of pancreatic cancer. In addition, SOX9 is a transcription factor linked to stem cell activity and is commonly overexpressed in solid cancers. It cooperates with Snail/Slug to induce epithelial-mesenchymal transition (EMT) during neural development and in diseases such as organ fibrosis or different types of cancer. METHODS We investigated the roles of SOX9 in pancreatic tumor cell plasticity, metastatic dissemination and chemoresistance using pancreatic cancer cell lines as well as mouse embryo fibroblasts. In addition, we characterized the clinical relevance of SOX9 in pancreatic cancer using human biopsies. RESULTS Gain- and loss-of-function of SOX9 in PDAC cells revealed that high levels of SOX9 increased migration and invasion, and promoted EMT and metastatic dissemination, whilst SOX9 silencing resulted in metastasis inhibition, along with a phenotypic reversion to epithelial features and loss of stemness potential. In both contexts, EMT factors were not altered. Moreover, high levels of SOX9 promoted resistance to gemcitabine. In contrast, overexpression of SOX9 was sufficient to promote metastatic potential in K-Ras transformed MEFs, triggering EMT associated with Snail/Slug activity. In clinical samples, SOX9 expression was analyzed in 198 PDAC cases by immunohistochemistry and in 53 patient derived xenografts (PDXs). SOX9 was overexpressed in primary adenocarcinomas and particularly in metastases. Notably, SOX9 expression correlated with high vimentin and low E-cadherin expression. CONCLUSIONS Our results indicate that SOX9 facilitates PDAC progression and metastasis by triggering stemness and EMT

A distributed architecture of parallel buck-boost converters and cascaded control of DC microgrids-real time implementation

To enhance the stability and reliability of the system, the converters’ parallel operation can be cascaded to address the constraints posed by the substantial integration of renewable resources. Buck-boost DC-DC converters are often controlled via a cascaded control approach to allow parallel operation. The converter’s output current and its voltage will be controlled by nested loop control. This study proposes adaptive droop control parameters that are updated and verified online using the principal current sharing loops to minimize the fluctuation in load current sharing. When the converters in the microgrid are paralleled, load sharing will be accomplished using the droop control approach in addition to nested proportional-integral-based voltage and current control loops. To restore the correct voltage across the DC microgrid, an outer addition voltage secondary loop will be used, rectifying any voltage disparities caused by the droop management strategy. Several common load resistances and input voltage variations are used to test the suggested method. Using a linearized model, this work assesses the stability and performance of the proposed method. It then confirms the findings with an adequate model created in MATLAB/SIMULINK, Real-Time Simulation Fundamentals, and hardware-based experiments

Guidelines for the establishment and functioning of Animal Ethics Commitees (Institutional Animal Care and Use Committees) in Africa.

Animals are used for scientific purposes across Africa to benefit humans, animals or the environment. Nonetheless, ethical and regulatory oversight remains limited in many parts of the continent. To strengthen this governance framework, the Pan-African Network for Laboratory Animal Science and Ethics brought together experts from 12 African countries to create an Africa-centric practical guide to facilitate the establishment and appropriate functioning of Institutional Animal Ethics Committees across Africa. The Guidelines are based on universal principles for the care and use of sentient animals for scientific purposes, with consideration of the cultural, religious, political and socio-economic diversity in Africa. They focus on 11 key elements, including responsibilities of institutions and of the Institutional Official; composition of the Committee; its responsibilities, functioning and authority; ethical application and review processes; oversight and monitoring of animal care and use and of training and competence; quality assurance; and the roles of other responsible parties. The intent is for African institutions to adopt and adapt the guidelines, aligning with existing national legislation and standards where relevant, thus ensuring incorporation into practice. More broadly, the Guidelines form an essential component of the growing discourse in Africa regarding moral considerations of, and appropriate standards for, the care and use of animals for scientific purposes. The increased establishment of appropriately functioning animal ethics committees and robust ethical review procedures across Africa will enhance research quality and culture, strengthen societal awareness of animals as sentient beings, improve animal well-being, bolster standards of animal care and use, and contribute to sustainable socio-economic development

Dystocia in Friesian cows and its effects on postpartum reproductive performance and milk production

A total of 1,243 records for 585 dairy Friesian cows from 1997–2004 were used to study the factors affecting dystocia and its effects on reproductive performance and milk production. The overall incidence of dystocia was 6.9%. The percentage of dystocia decreased with increasing live body weight, age, and parity of cows (P < 0.05); however, it increased with increasing birth weight of calves (P < 0.05). The highest percentage of dystocia was detected in winter season, but the least percentage was in summer season (P < 0.05). The percentage of incidence of dystocia was significantly (P < 0.05) higher with winter feeding compared to summer ration (8.2% vs. 5.1%). The percentage of incidence of dystocia was significantly (P < 0.05) higher with twinning than single calving (15.5% vs. 6.5%), while not significantly affected by the sex of born calves. Incidence of dystocia had adverse effects on reproductive performance and milk yield. The service interval, service period, days open, and calving interval were significantly (P < 0.05) longer in cows afflicted with dystocia compared to normal cows. The conception rate was lower (P < 0.05), but the number of service per conception was higher (P < 0.05) in cows afflicted with dystocia compared to normal cows (60.5% vs. 73.0% and 3.4 vs. 2.7, respectively). Average daily milk yield was lower (P < 0.05) by 1 kg for cows with incidence of dystocia compared to normal cows