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Introduction: β-Arrestin1 (ARRB1) belongs to the arrestin family originally identified as a multifunctional adaptor protein that negatively regulates the desensitization and internalization of G-protein-coupled receptors. Recent studies have indicated that ARRB1 can form multiprotein complexes with transcription regulators, thereby indirectly inhibiting the function of some transcription factors, e.g., NF-kB, and promoting the activity of others, e.g., p53. Further, arrestins function as multifunctional adaptors in many signalling pathways, such as the Hedgehog (Hh), Wingless, Notch, and transforming growth factor-β (TGF-β) pathways. Expression of ARRB1 is downregulated in TNBC patients and ARRB1 expression level is inversely correlated with the histological grade of the breast cancer and positively associated with TNBC patient survival, suggestive of a tumour-suppressive function of ARRB1 in breast cancer. Loss of ARRB1 expression is associated with a poor prognosis for non-small cell lung cancer patients. However, the mechanisms regulating the expression of ARRB1 in human cancers remain unclear. We hypothesized that metabolic endoplasmic reticulum (EnR) stressors including low glucose and hypoxia that activate an unfolded protein response (UPR) in tumour cells might regulate the expression of ARRB1 in human cancers. Methods: Expression of ARRB1 was determined by a combination of real-time RT-PCR, western blotting along with promoter reporter assays. Computational target prediction analysis was done to identify miRNAs targeting ARRB1 as well as transcription factors regulating ARRB1 expression. ARRB1overexpressing breast cancer clones were generated by lentiviral transduction to investigate its functional role in tumour progression and drug sensitivity. Results: We observed that ARRB1 expression was significantly reduced in several cancers including breast tumours as compared to normal tissue and decreased expression of ARRB1 was associated with poor prognosis in Luminal A subtype. We found significant downregulation of ARRB1 mRNA and protein during conditions of EnR stress in multiple ER-positive breast cancer cell lines. Using PERK, ATF6 and XBP1 knockdown sub-clones of MCF7 we observed that PERK signalling was required for the downregulation of ARRB1. ATF4 and miR-204/211 downstream of PERK were identified as key regulators of ARRB1 expression. Conclusion: Our results show that ATF4 and miR-204/211 downstream of the PERK signalling pathway repress ARRB1 expression in breast cancer cells. Our results suggest that the downregulation of ARRB1 by EnR stressors in the tumour microenvironment may contribute to breast cancer progression. Citation Format: Afrin Sultana, Ananya Gupta, Sanjeev Gupta. β-arrestin1, a potential tumour suppressor in breast cancer is downregulated in PERK/ATF4-dependent manner [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-25-03.

Background: Autonomic Diabetic Neuropathy, the most frequent diabetic consequence, is commonly treated with medicines without success. Diabetes is a chronic disease due to insulin resistance or reduced insulin secretion, India is known as the "diabetic world capital," with a projected growth of 63 %, exceeding 98 million by 2030. The latest diabetes mellitus statistics are worrying, stating that around 150 million individuals globally have diabetes mellitus, with this number expected to doubling by 2025 Objective: The purpose of the study was to conduct a review on role of Yoga in the management of Autonomic Diabetic Neuropathy. Method: A review was conducted using search terms Autonomic Diabetic Neuropathy and Yoga, Autonomic Diabetic Neuropathy and Alternative Therapy, Diabetic Autonomic Neuropathy and Yoga, Diabetic Autonomic Neuropathy and Alternative Therapy, Diabetic Neuropathy and Yoga, Diabetic Neuropathy and Alternative therapy and all the probable term in national and international data repositories such as PubMed, google scholar, in English language. Only 5 studies are selected out of 1493. For this Review article Literature Searched from starting to till April 2022. Conclusion: Studies showing clinical significance of Yoga in the management of Diabetic Neuropathy, but studies are less available and also lack of quality study. New Researchers should create more original evidences by conducting Randomized Controlled Trials in the large sample size.

Chronic disease rates are increasing globally, this is partially attributable to the global epidemic of physical inactivity. Physical activity promotion in primary care is regarded as the best approach for combating chronic disease. This study investigated the common beliefs and opinions among general practitioners and nurses on promoting physical activity to patients in Ireland. This research took a mixed-methods approach consisting of an online questionnaire (n=79) and semi-structured interviews (n=8). Lack of time, expertise, cohesiveness, referral pathways, and exercise professionals were the main barriers to physical activity promotion experienced. A small minority (7.6%) of participants were trained in exercise prescription, and 40.5% had knowledge of a local exercise professional. Furthermore, the research indicated that 70.2% of GPs and 86.4% of GP nurses did not provide an exercise referral. Physical activity promotion in primary care needs a cohesive approach. Involving an exercise professional is crucial to help facilitate to aid physical activity promotion.

Chronic disease rates are increasing globally, this is partially attributable to the global epidemic of physical inactivity. Physical activity promotion in primary care is regarded as the best approach for combating chronic disease. This study investigated the common beliefs and opinions among general practitioners and nurses on promoting physical activity to patients in Ireland. This research took a mixed-methods approach consisting of an online questionnaire (n=79) and semi-structured interviews (n=8). Lack of time, expertise, cohesiveness, referral pathways, and exercise professionals were the main barriers to physical activity promotion experienced. A small minority (7.6%) of participants were trained in exercise prescription, and 40.5% had knowledge of a local exercise professional. Furthermore, the research indicated that 70.2% of GPs and 86.4% of GP nurses did not provide an exercise referral. Physical activity promotion in primary care needs a cohesive approach. Involving an exercise professional is crucial to help facilitate to aid physical activity promotion.

Purpose: This review will provide an overview of the current state of knowledge by 1) evaluating the feasibility and safety of exercise as a treatment for patients with breast cancer-related lymphedema (BCRL), and 2) exploring the effects of different exercises on patients with BCRL. Method: A systematic literature review of relevant studies published before 30 June 2022 was performed using three scientific databases PubMed, Embase, and Scopus. Result: A total of 611 articles were found. Eventually, 15 articles fulfilled the inclusion criteria and were used for this literature review. A total of 5 different exercises, consisting of yoga, Pilates, resistance exercise, aquatic-based exercise, and complex exercise of aerobic and resistance training are included. Conclusion: The review shows that these exercises are safe for patients with BCRL. Some measurable effects of exercises on lymphedema and some possible reasons/theories are shown. Implications for Cancer Survivors: Although only yoga, Pilates, and resistance exercise may improve the severity of lymphedema based on the measurement of limb volume, all 5 exercise modes can help improve lymphedema symptoms to some extent. The improvement of symptoms may cause the increased quality of life (QoL) in symptom and physical functioning domains, leading to increased emotional and social function.

Neuropathy is a common diabetes complication that can't be treated. Diabetes mellitus causes insulin resistance or decreased insulin production. India is considered as the "diabetes world capital," with 98 million patients expected by 2030. 150 million people worldwide have diabetes mellitus, and this number could double by 2025. Aim of this study: To see effect of 1 month of Yoga module practice on depression and quality of life in patients of Diabetic Neuropathy. Materials and Methods: This study used n=10 type 2 diabetes mellitus patients from AIIMS Rishikesh's OPD. This study aims to determine the effect of 30 days of Yoga asanas on diabetic neuropathy patients' depression and quality of life. WHO-5 well-being index was used to measure life quality. 0-10 years of diabetes. DAN patient. Participants were asked to do daily yoga online with a yoga pro using Zoom. 30-45 minutes of yoga 6 days a week for 1 month. Subjects were given medications and food. After 30 days of Yogic practice, the PHQ-9 and WHO-5 Well-being index scores were repeated. Results: Total 10 patients were included for this pilot study, mean age 59.4 and average BMI was 26.76 We found that yoga practice is beneficial for diabetic neuropathy patients in managing the symptoms of depression (p< 0.005) and improving quality of life (p< .005) Conclusion: Yoga is a recognized non pharmacotherapy. Yoga in addition to Pharmacotherapy is to be beneficial in managing symptoms of depression and to improving Quality of Life of Diabetic neuropathy patients.

At present an astonishing awareness of health and natural remedies by Yoga and Pranayama has been observed in the population of the whole world, which has proved to be an effective way of improving health apart from prevention and management of diseases.Along with the increasing scientific researches of yoga, the search for its medical aspects is also continuing.On the basis of important studies related to the balancing of Vata doshas, management of Vata diseases and its effects on physical health of Pranayama, it was found that the practice Pranayama, besides being an efficient practice in the treatment of Vata diseases, has proved to be very beneficial for the physical health of the person besides maintaining the Vata dosha in a balanced state.Currently, among the alternative therapies for treating Vata diseases, yoga management is the most popular way to treat Vata diseases naturally and balance Vata dosha. Pranayama has been exclusively discussed in the yogic methods of management of Vata diseases in the major yogic scriptures such as Hatha Yoga Pradipika, Hath Ratnavali, Asan Pranayama Mudra Bandha, and Gherand Samhita. Under which the place of Bhastrika Pranayama and Suryabhedi Pranayama is prominent due to the Vata balancing benefits obtained from them. Hence the importance of Pranayama has been clarified under the Yoga Shastras to emerge from these conditions naturally and to balance the Vata Dosha (Mallinson, 2004; Muktibodhananda, 2012; (Gharote, Devnath, & Jha, 2002). Suryabhedi and Bhastrika Pranayama are considered to be the best for the management of Vata doshas among the different types of Pranayama described under the major Hatha Yogic texts.Therefore, in the present research study, a descriptive study of the role of Pranayama in the management of Vata diseases has been done on the basis of major Yoga texts.

The security of women is of prime concern around the world. Women feel insecure while traveling out of the home due to the fear of violence. The fear of violence restricts women's participating in different social activities. So instead of becoming a victim of a violent crime such as domestic violence, robbery, or rape, women should call on resources to help her out of that situation. In this paper, the authors develop a women safety device, namely SafeWomen, which helps in reducing the crimes held against women. This is a new approach for providing security to women in any unsafe situation by sending an alert having geographical location along with emergency message to the registered contact numbers so that the incident could be prevented. Also, it can track the current location of the victim just by knowing the IP address of the device she is using. One can also use this system for the safety and security of kids and elderly people just by making some changes in the functionality of the system.

There was an average of 45,753 cancer diagnoses each year in Ireland from 2018 to 2020. Estimates state that by the year 2045, this average could increase by 50-100%. There are over 170,000 cancer survivors living in Ireland. Cancer-related fatigue (CRF) is a prevalent and debilitating side effect of cancer and cancer treatment. Research has demonstrated that exercise is an effective intervention to combat CRF. This review will examine the scope of CRF and critically analyse exercise interventions to combat CRF in cancer patients undergoing treatment. Aerobic exercise interventions and multimodal exercise (aerobic exercise, resistance exercise and flexibility exercise) interventions have been shown to improve symptoms of fatigue in cancer patients undergoing treatment. The effect of resistance training on CRF in cancer patients during treatment is not well understood. Aerobic exercise and multimodal exercise appear to combat CRF by improving one or more of the following health-related fitness parameters; aerobic capacity, muscular strength and endurance, flexibility, and body composition. A standardized process of recording the intensity and volume of aerobic, resistance and flexibility exercise should be developed. Future studies should investigate in greater detail the role of resistance training in reducing CRF among cancer patients. Qualitative methods should be developed to investigate the role the group dynamic has on cancer patients during group-based interventions. These qualitative methods may be able to determine the importance the delivery of exercise plays in reducing CRF. Biomarkers of CRF should be investigated and examined in relation to the specific dose of exercise that patients perform.

The security of women is of prime concern around the world. Women feel insecure while traveling out of the home due to the fear of violence. The fear of violence restricts women's participating in different social activities. So instead of becoming a victim of a violent crime such as domestic violence, robbery, or rape, women should call on resources to help her out of that situation. In this paper, the authors develop a women safety device, namely SafeWomen, which helps in reducing the crimes held against women. This is a new approach for providing security to women in any unsafe situation by sending an alert having geographical location along with emergency message to the registered contact numbers so that the incident could be prevented. Also, it can track the current location of the victim just by knowing the IP address of the device she is using. One can also use this system for the safety and security of kids and elderly people just by making some changes in the functionality of the system.

Background Endocrine-resistant breast cancers have elevated expression of XBP1, where it drives endocrine resistance by controlling the expression of its target genes. Despite the in-depth understanding of the biological functions of XBP1 in ER-positive breast cancer, effectors of endocrine resistance downstream of XBP1 are poorly understood. The aim of this study was to identify the XBP1-regulated genes contributing to endocrine resistance in breast cancer. Methods XBP1 deficient sub-clones in MCF7 cells were generated using the CRISPR-Cas9 gene knockout strategy and were validated using western blot and RT-PCR. Cell viability and cell proliferation were evaluated using the MTS assay and colony formation assay, respectively. Cell death and cell cycle analysis were determined using flow cytometry. Transcriptomic data was analysed to identify XBP1-regulated targets and differential expression of target genes was evaluated using western blot and qRT-PCR. Lentivirus and retrovirus transfection were used to generate RRM2 and CDC6 overexpressing clones, respectively. The prognostic value of the XBP1-gene signature was analysed using Kaplan–Meier survival analysis. Results Deletion of XBP1 compromised the upregulation of UPR-target genes during conditions of endoplasmic reticulum (EnR) stress and sensitized cells to EnR stress-induced cell death. Loss of XBP1 in MCF7 cells decreased cell growth, attenuated the induction of estrogen-responsive genes and sensitized them to anti-estrogen agents. The expression of cell cycle associated genes RRM2, CDC6, and TOP2A was significantly reduced upon XBP1 deletion/inhibition in several ER-positive breast cancer cells. Expression of RRM2, CDC6, and TOP2A was increased upon estrogen stimulation and in cells harbouring point-mutants (Y537S, D538G) of ESR1 in steroid free conditions. Ectopic expression of RRM2 and CDC6 increased cell growth and reversed the hypersensitivity of XBP1 KO cells towards tamoxifen conferring endocrine resistance. Importantly, increased expression of XBP1-gene signature was associated with poor outcome and reduced efficacy of tamoxifen treatment in ER-positive breast cancer. Conclusions Our results suggest that RRM2 and CDC6 downstream of XBP1 contribute to endocrine resistance in ER-positive breast cancer. XBP1-gene signature is associated with poor outcome and response to tamoxifen in ER-positive breast cancer.

Introduction MicroRNAs (miRNAs) have been shown to be altered in both CVD and T2DM and can have an application as diagnostic and prognostic biomarkers. miRNAs are released into circulation when the cardiomyocyte is subjected to injury and damage. Objectives Measuring circulating miRNA levels in human plasma may be of great potential use for measuring the extent of damage to cardiomyocytes and response to exercise. This review is aimed to highlight the potential application of miRNAs as biomarkers of CVD progression in T2DM, and the impact of exercise on recovery. Methods The review aims to examine whether the health improvements following exercise in T2DM patients are reflective of changes in expression of plasma miRNAs. For this purpose, studies were identified from the literature that have established a correlation between diabetes, disease progression and plasma miRNA levels. We also reviewed studies which looked at the effect of exercise on plasma miRNA levels. Results The review identified miRNA signatures that are affected by T2DM and DHD and a subset of these miRNAs that are also affected by different types of exercise. This approach helped us to identify those miRNAs whose expression and function can be altered by regular bouts of exercise. Conclusions miRNAs identified as part of this review can serve as tools to monitor the cardio-protective, anti-inflammatory and metabolic effects of exercise in people suffering from T2DM. Future research should focus on regulation of these miRNAs in T2DM and how they can be altered by appropriate exercise interventions.

BackgroundThere are few data to support accurate interpretation of spirometry data in South Asia, a major global region with a high reported burden of chronic respiratory disease.MethodWe measured lung function in 7453 healthy men and women aged ≥18 years, from Bangladesh, North India, South India, Pakistan and Sri Lanka, as part of the South Asia Biobank study. First, we assessed the accuracy of existing equations for predicting normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC ratio. Then, we used our data to derive (n=5589) and internally validate (n=1864) new prediction equations among South Asians, with further external validation among 339 healthy South Asians living in Singapore.ResultsThe Global Lung Initiative (GLI) and National Health and Nutrition Examination Survey consistently overestimated expiratory volumes (best fit GLI-African American, mean±sdz-score: FEV1−0.94±1.05, FVC −0.91±1.10; n=7453). Age, height and weight were strong predictors of lung function in our participants (p10.03±0.99, FVC 0.04±0.97, FEV1/FVC −0.03±0.99) and external validation (z-scores: FEV10.31±0.99, FVC 0.24±0.97, FEV1/FVC 0.16±0.91). Further adjustment for study regions improves the model fit, with highest accuracy for estimation of region-specific lung function in South Asia.ConclusionWe present improved equations for predicting lung function in South Asians. These offer the opportunity to enhance diagnosis and management of acute and chronic lung diseases in this major global population.

Soft artificial skin capable of sensing touch, pressure and bending similar to soft human skin is important in many modern-day applications including socially interactive robotics, modern healthcare, augmented reality, etc. However, most of the research effort on soft artificial skin are confined to the lab-scale demonstration. We have demonstrated how a fundamental understanding of the contact mechanics of soft material and a specially constructed soft optical waveguide let us develop a highly efficient, resilient, and large-area soft artificial skin for futuristic applications. The soft artificial skin capable of detect touch, load and bending shows extreme sensitivity (up to \({150 \text{k}\text{P}\text{a}}^{-1}\)) to touch, and load, which is 750 times higher than earlier work. The soft-a-skin shows excellent long-term stability i.e. it shows consistent performance up to almost a year. In addition, we describe a 3D printing process capable of producing large areas, large numbers yet cost-effective soft artificial skin. We have shown the functioning of the soft-a-skin in various means.

Funder: Singapore Ministry of Health's National Medical Research Council, Funder: National Institute for Health Research, Funder: Wellcome Trust or the Department of Health, Funder: NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme; Grant(s): IS-BRC-1215-20014

An important event in the unfolded protein response (UPR) is activation of the endoplasmic reticulum (ER) kinase PERK. The PERK signalling branch initially mediates a prosurvival response, which progresses to a proapoptotic response upon prolonged ER stress. However, the molecular mechanisms of PERK-mediated cell death are not well understood. Here we show that expression of the primary miR-17-92 transcript and mature miRNAs belonging to the miR-17-92 cluster are decreased during UPR. We found that miR-17-92 promoter reporter activity was reduced during UPR in a PERK-dependent manner. Furthermore, we show that activity of the miR-17-92 promoter is repressed by ectopic expression of ATF4 and NRF2. Promoter deletion analysis mapped the region responding to UPR-mediated repression to a site in the proximal region of the miR-17-92 promoter. Hypericin-mediated photo-oxidative ER damage reduced the expression of miRNAs belonging to the miR-17-92 cluster in wild-type but not in PERK-deficient cells. Importantly, ER stress-induced apoptosis was inhibited upon miR-17-92 overexpression in SH-SY5Y and H9c2 cells. Our results reveal a novel function for ATF4 and NRF2, where repression of the miR-17-92 cluster plays an important role in ER stress-mediated apoptosis. Mechanistic details are provided for the potentiation of cell death via sustained PERK signalling mediated repression of the miR-17-92 cluster. ispartof: LIFE-BASEL vol:11 issue:1 ispartof: location:Switzerland status: published

Somatic mutations of the estrogen receptor 1 gene (ESR1) is an emerging mechanism of acquired resistance to endocrine therapy in hormonal breast cancers. Hotspot point mutations in the ligand- binding domain of estrogen receptor α (ER) and genomic rearrangements producing ESR1 fusion genes are the two major types of mutations that are associated with endocrine resistance. The crosstalk between X-box binding protein 1 (XBP1), a key transcription factor of the unfolded protein response (UPR) and ER signalling creates a positive feedback loop that results in increased expression of XBP1 in ER-positive breast cancer. Here we report that XBP1 co-operated with point mutants (Y537S, D538G) and fusion mutants (ESR1-YAP1, ESR1-DAB2) of ESR1 to increase their transcriptional activity. XBP1 was required for optimal expression of estrogen-regulated genes, and up to 40% of XBP1-dependent genes were estrogen-responsive genes. Knockdown of XBP1 in genome-edited MCF7 cells expressing Y537S mutant reduced their growth, re-sensitized them to anti-estrogens and attenuated the constitutive and estrogen-stimulated expression of estrogen-regulated genes. Our study provides a rationale for overcoming endocrine resistance in breast cancers expressing ESR1 mutation by combining the XBP1 targeting agents with anti-estrogen agents., Cell biology; Transcriptomics; Biochemistry; Molecular biology; Cancer research; ESR1 mutations, Endocrine resistance, XBP1, ER-Positive breast cancer

Background and aimsThis paper describes the data resource profile of South Asia Biobank (SAB), which was set up in South Asia from November 2018 to March 2020, to identify the risk factors and their complex interactions underlying the development of type-2 diabetes mellitus, cardiovascular disease and other chronic diseases in South Asians.Data resource basicsThis cross-sectional population-based study has recruited 52713 South Asian adults from 118 surveillance sites at five centres of excellence in South Asia (Bangladesh, North India, South India, Pakistan and Sri Lanka). Structured assessments of participants included six complementary domains: i). Registration and consent; ii). Questionnaire (information on behavioural risk factors, personal and family medical history, medications, socioeconomic status); iii). Physical measurements (height, weight, waist and hip circumference and bio-impedance for body fat composition, blood pressure, cardiac evaluation, retinal photography, respiratory evaluation); iv). Biological samples (blood and urine); v). Physical activity monitoring and vi). Dietary intake by a 24-hour recall. Aliquots of whole blood, serum, plasma, and urine were put into storage at −80°C for further analysis.Key resultsThe prevalence of obesity is 6.6% in Bangladesh, 19.7% in India, 33.9% in Pakistan and 15.7% in Sri Lanka. The prevalence of diabetes is 11.5%, 27.7%, 25.3%, and 24.8%, and the prevalence of hypertension is 26.7%, 36.9%, 44.5%, 35.0% in Bangladesh, India, Pakistan and Sri Lanka respectively.Collaboration and data accessSAB is the first comprehensive biobank of South Asian individuals. Collected data are available to the global scientific community upon request.

LiDAR provides highly accurate 3-D point clouds. However, data need to be manually labeled in order to provide subsequent useful information. Manual annotation of such data is time-consuming, tedious, and error prone, and hence, in this article, we present three automatic methods for annotating trees in LiDAR data. The first method requires high-density point clouds and uses certain LiDAR data attributes for the purpose of tree identification, achieving almost 90% accuracy. The second method uses a voxel-based 3-D convolutional neural network on low-density LiDAR data sets and is able to identify most large trees accurately but struggles with smaller ones due to the voxelization process. The third method is a scaled version of the PointNet++ method and works directly on outdoor point clouds and achieves an $F_{\mathrm{ score}}$ of 82.1% on the ISPRS benchmark data set, comparable to the state-of-the-art methods but with increased efficiency.

Satellite images are an extremely valuable resource in the aftermath of natural disasters such as hurricanes and tsunamis where they can be used for risk assessment and disaster management. In order to provide timely and actionable information for disaster response, in this paper a framework utilising segmentation neural networks is proposed to identify impacted areas and accessible roads in post-disaster scenarios. The effectiveness of pretraining with ImageNet on the task of aerial image segmentation has been analysed and performances of popular segmentation models compared. Experimental results show that pretraining on ImageNet usually improves the segmentation performance for a number of models. Open data available from OpenStreetMap (OSM) is used for training, forgoing the need for time-consuming manual annotation. The method also makes use of graph theory to update road network data available from OSM and to detect the changes caused by a natural disaster. Extensive experiments on data from the 2018 tsunami that struck Palu, Indonesia show the effectiveness of the proposed framework. ENetSeparable, with 30% fewer parameters compared to ENet, achieved comparable segmentation results to that of the state-of-the-art networks., Comment: Accepted in Neurocomputing, 2020

Explainability is an important factor to drive user trust in the use of neural networks for tasks with material impact. However, most of the work done in this area focuses on image analysis and does not take into account 3D data. We extend the saliency methods that have been shown to work on image data to deal with 3D data. We analyse the features in point clouds and voxel spaces and show that edges and corners in 3D data are deemed as important features while planar surfaces are deemed less important. The approach is model-agnostic and can provide useful information about learnt features. Driven by the insight that 3D data is inherently sparse, we visualise the features learnt by a voxel-based classification network and show that these features are also sparse and can be pruned relatively easily, leading to more efficient neural networks. Our results show that the Voxception-ResNet model can be pruned down to 5\% of its parameters with negligible loss in accuracy., Comment: Accepted for IJCNN 2020

Recent evidence has shown that the miR-17-92 cluster can function either as oncogene or tumor suppressor in human cancers. The function of miR-17-92 in subtypes of breast cancer remains largely unknown. The expression of miR-17-92 is elevated in triple negative breast cancer (TNBC) but reduced in estrogen receptor (ER)-positive breast cancer (ERPBC). We show that increased expression of miRNAs belonging to the miR-17-92 cluster is associated with poor outcome in TNBC, whereas the expression of miR-17-92 miRNAs is with good outcome in ERPBC. We show that ectopic expression of miR-17-92 inhibited cell growth and invasion of ER-positive and HER2-enriched cells. On the contrary, miR-17-92 expression enhanced cell growth and invasion of TNBC cells. Further, we found that miR-17-92 expression sensitized MCF7 cells to chemotherapeutic compounds, whereas it rendered SKBR3 cells resistant to them. We found that expression of ADORA1 was reduced by miR-17-92-expressing breast cancer cells, specifically in ERPBC. We observed an inverse correlation between the expression of ADORA1 and miR-17-92 in human breast cancer. Treatment with DPCPX, a selective ADORA1 antagonist, abolished the difference in the growth of control and miR-17-92 overexpressing MCF7 cells and identified ADORA1 as a key functional target of miR-17-92 in ERPBC. Furthermore, increased expression of ADORA1 in ERPBC is associated with a poor outcome. Our observations underscore the context-dependent role of miR-17-92 in breast cancer subtypes and suggest that miR-17-92 could serve as novel prognostic markers in breast cancer.

Antibiotic-resistant bacteria in the genus Enterococcus are a major cause of nosocomial infections and are an emergent public health concern. Similar to a number of bacterial species, resistance to the antibiotic rifampicin (Rif

Background: The miR-17-92 is an oncogenic miRNA cluster that generate six mature miRNAs: miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92-1. Accumulating evidences indicate the oncogenic role of the miR-17-92 cluster in human cancers. Amplification of 13q31-q32, which is the locus of the miR-17-92 cluster, have been reported in haematopoietic malignancies, such as B cell lymphoma. In contrast, MIR17HG was deleted in 21.9% of breast cancers and loss of heterozygosity at 13q12-q13 was associated with poor prognosis in breast cancer. This oncogenic miRNA cluster is deferentially expressed in various cancer. Since, miR-17-92 cluster shows differential expression among the cancers types, it is hypothesized that biological function may also vary depending on the context. Indeed, this cluster has been shown to act a tumour suppressor in some cancers. However, the functional role of this cluster in the subtypes of breast cancer remains largely unknown. Methods: The oncomine datasets were analysed for expression of MIR17HG in breast cancer at parameters p-value threshold of 0.01 with minimum 2-fold change. We generated stable sub-clones of MCF7, T47D, SKBR3 and MDA-MB231 cells overexpressing miR-17-92 cluster by transducing with lentivirus expressing miR-17-92. Proliferation was assessed by MTS assay and colony forming assay. Cell migration was tested using scratch method. Invasion potentiality was monitored by using matrigel Boyden chamber invasion assay. For drug response analysis, control and microRNA overexpressing sub-clones were exposed to different chemotherapeutic agents at different concentrations followed by MTS assay at different time intervals. Association of miRNAs belonging to miR-17-92 with outcome in breast cancer was determined by Kaplan-Meier analysis on METABRIC dataset. Results: We observed that expression of MIR17HG was increased in tissues and cell lines from triple negative breast cancer (TNBC) but decreased in the tissues and cell lines from the estrogen receptor (ER)-positive breast cancer. Our results showed that ectopic expression of miR-17-92 cluster significantly suppressed cell proliferation, colony formation, migration and invasion of ER-positive (MCF7, T47D) and HER2-enriched (SKBR3) cells whereas it enhanced cell proliferation, colony formation, migration and invasion in (TNBC) MDA-MB 231 cells. Further, we found that expression of miR-17-92 cluster sensitized MCF7 cells whereas it rendered SKBR3 cells resistant to chemotherapeutic compounds. Higher expression of five miRNAs of this cluster was associated with better relapse free survival (RFS) in (miR-17, miR-19a, miR-20a, miR-19b and miR-92) Luminal A subtype whereas three miRNAs of this cluster were associated with poor RFS in (miR-17, miR-18a and miR-92) HER2-enriched and (miR-17, miR-19b and miR-92) TNBC subtypes. Conclusions: Taken together our results suggest that miR-17-92 cluster acts as a tumour suppressor in ER-positive and HER2-enriched breast cancer cells but shows oncogenic role in TNBC. Our observations underscore the functional complexity of miR-17-92 in a context-dependent and cell type-dependent manner, and more investigations are warranted to fully explore the functional complexity of miR-17-92 in subtypes of breast cancer. Citation Format: Hossain MM, Arabkari V, Barua D, Gupta A, Islam MN, Gupta S. miR-17-92 cluster, an oncogenic microRNA cluster acts as a context dependent tumour suppressor in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-14.

Current methods for building tissues usually start with a non-biological blueprint, or rely on self-organization, which does not extend to organ-scales. This has limited the construction of large tissues that simultaneously encode fine-scale cell organization. Here we bridge scales by mimicking developmental dynamics using “kinomorphs”, tissue scaffolds that undergo globally programmed shape and density changes to trigger local self-organization of cells in many locations at once. In this first report, we focus on mimicking the extracellular matrix (ECM) compaction and division into leaflets that occurs in kidney collecting duct development. We start by creating single-cell resolution cell patterns in ECM-mimetic hydrogels that are >10x larger than previously described, by leveraging photo-lithographic technology. These patterns are designed to mimic the branch geometry of the embryonic kidney collecting duct tree. We then predict the shape dynamics of kinomorphs driven by cell contractility-based compaction of the ECM using kinematic origami simulations. We show that these dynamics spur centimeter-scale assembly of structurally mature ~50 μm-diameter epithelial tubules that are locally self-organized, but globally programmed. Our approach prescribes tubule network geometry at ~5x smaller length-scales than currently possible using 3D printing, and at local cell densities comparable to in vivo tissues. Kinomorphs could be used to scaffold and “plumb” arrays of organoids in the future, by guiding the morphogenesis of epithelial networks. Such hybrid globally programmed/locally self-organized tissues address a major gap in our ability to recapitulate organ-scale tissue structure.Significance StatementEngineers are attempting to build tissues that mimic human diseases outside of the body. Although stem cells can be coaxed to form small organoids with a diversity of cell types, they do not properly organize over large distances by themselves. We report a strategy to mimic developmental processes using dynamic materials that attempt to guide a cellular “blueprint” towards a more complex tissue endpoint. We call these materials kinomorphs, combining the Greek kinó (propel, drive) and morfí (form, shape), since they seek to shepherd both the shape and developmental trajectory of cell collectives within them. Kinomorphs could pave the way towards organ-scale synthetic tissues built through a hybrid of engineering and self-organization strategies.

Accurate road maps are important for timely disaster relief efforts and risk management. Current disaster mapping is done manually by volunteers following a disaster and the process is slow and error prone. We propose a framework for identifying accessible roads in post-disaster satellite imagery by detecting changes from pre-disaster imagery, in conjunction with OpenStreetMap data. We validate our results with data from Indonesia 2018 tsunami, obtained from DigitalGlobe.