Polyglutamine Expanded Huntingtin Dramatically Alters the Genome-Wide Binding of HSF1

In Huntington's disease (HD), polyglutamine expansions in the huntingtin (Htt) protein cause subtle changes in cellular functions that, over-time, lead to neurodegeneration and death. Studies have indicated that activation of the heat shock response can reduce many of the effects of mutant Htt in disease models, suggesting that the heat shock response is impaired in the disease. To understand the basis for this impairment, we have used genome-wide chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) to examine the effects of mutant Htt on the master regulator of the heat shock response, HSF1. We find that, under normal conditions, HSF1 function is highly similar in cells carrying either wild-type or mutant Htt. However, polyQ-expanded Htt severely blunts the HSF1-mediated stress response. Surprisingly, we find that the HSF1 targets most affected upon stress are not directly associated with proteostasis, but with cytoskeletal binding, focal adhesion and GTPase activity. Our data raise the intriguing hypothesis that the accumulated damage from life-long impairment in these stress responses may contribute significantly to the etiology of Huntington's disease.National Institutes of Health (U.S.) (Grant R24 DK-090963)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (Grant P30-ES002109)National Science Foundation (U.S.) (Award DB1-0821391

Effect of hot and cooled carbohydrate diet on glycemic response in healthy individuals: a cross over study

Background: Cooling of starch after cooking is known to cause starch retrogradation which increases resistant starch content. Resistant starch cannot be digested in the gut and acts as dietary fiber. The study aimsed to determine the effect of cooling of carbohydrate rich diet on glycemic response on healthy adults.Methods: The present study was a randomized, single blind, crossover study where 20 healthy subjects were selected. Two rice preparations were used, one freshly prepared hot, second, cooked and cooled at 4°C for 12 hours. All subjects were evaluated after giving both rice preparations separately with a crossover period of 7 days.  Glycemic response was checked over a period of 2 hours at various time intervals using ACCU-CHEK® Active glucometer.Results: Glycemic response with cooled white rice was better in comparison to freshly prepared hot white rice at all time points (mean±SD, 121.9±17.4 vs 128.0± 22.1 mg/dl). However, the difference in means at 30 mins was maximum and statistically significant (p<0.001).Conclusions: Cooled white rice yields better glycemic response when consumed by healthy individuals possibly due to formation of resistant starch

Development of Advanced Bioinformatics Tools for Integrating Genomic Data and Enhancing Diagnosis of Rare Diseases

Rare diseases pose significant challenges in diagnosis and treatment due to their genetic complexity and the limited availability of comprehensive genomic data. Current bioinformatics tools often struggle with accurately detecting rare mutations and integrating diverse genomic and clinical data, leading to delays in diagnosis and suboptimal patient care. This research proposes the development of an advanced bioinformatics pipeline aimed at enhancing the accuracy of mutation detection, integrating genomic, phenotypic, and clinical data, and providing a user-friendly interface for clinicians. The pipeline uses machine learning algorithms for improved mutation calling and data integration techniques to correlate genetic variants with clinical outcomes. The tool was evaluated on multiple rare disease datasets, demonstrating significant improvements in diagnostic accuracy and efficiency. With precision and recall rates of 92% and 88%, respectively, and a 40% reduction in diagnostic time, this approach promises to revolutionize rare disease diagnostics by facilitating faster, more accurate diagnoses and personalized treatment options

Role Based Secure Data Access Control for Cost Optimized Cloud Storage Using Data Fragmentation While Maintaining Data Confidentiality

The paper proposes a role-based secure data access control framework for cost-optimized cloud storage, addressing the challenge of maintaining data security, privacy, integrity, and availability at lower cost. The proposed framework incorporates a secure authenticity scheme to protect data during storage or transfer over the cloud. The framework leverages storage cost optimization by compressing high-resolution images and fragmenting them into multiple encrypted chunks using the owner's private key. The proposed approach offers two layers of security, ensuring that only authorized users can decrypt and reconstruct data into its original format. The implementation results depicts that the proposed scheme outperforms existing systems in various aspects, making it a reliable solution for cloud service providers to enhance data security while reducing storage costs

Expanding Bioenergy: A Comparison of Waste-to-Energy Techniques

The paper explores the ability of biomass as a renewable energy source globally and analysis of waste generation and bioenergy abilities. It highlights the significance of sustainable waste control and the performance of numerous biomass conversion technology in producing bioenergy, biofuels, and bio-chemical compounds. The study highlights worldwide initiatives and challenges confronted in maximizing biomass capability, specially inside the bioenergy sector. It emphasizes the need for improved waste management strategies, technological improvements, and political guidance to enhance the contribution of bioenergy to worldwide energy demands

Functional disruption of α4 integrin mobilizes bone marrow–derived endothelial progenitors and augments ischemic neovascularization

The cell surface receptor α4 integrin plays a critical role in the homing, engraftment, and maintenance of hematopoietic progenitor cells (HPCs) in the bone marrow (BM). Down-regulation or functional blockade of α4 integrin or its ligand vascular cell adhesion molecule-1 mobilizes long-term HPCs. We investigated the role of α4 integrin in the mobilization and homing of BM endothelial progenitor cells (EPCs). EPCs with endothelial colony-forming activity in the BM are exclusively α4 integrin–expressing cells. In vivo, a single dose of anti–α4 integrin antibody resulted in increased circulating EPC counts for 3 d. In hindlimb ischemia and myocardial infarction, systemically administered anti–α4 integrin antibody increased recruitment and incorporation of BM EPCs in newly formed vasculature and improved functional blood flow recovery and tissue preservation. Interestingly, BM EPCs that had been preblocked with anti–α4 integrin ex vivo or collected from α4 integrin–deficient mice incorporated as well as control cells into the neovasculature in ischemic sites, suggesting that α4 integrin may be dispensable or play a redundant role in EPC homing to ischemic tissue. These data indicate that functional disruption of α4 integrin may represent a potential angiogenic therapy for ischemic disease by increasing the available circulating supply of EPCs

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusion: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown