Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication.

Diabetes is associated with loss of functional pancreatic β-cells, and restoration of β-cells is a major goal for regenerative therapies. Endogenous regeneration of β-cells via β-cell replication has the potential to restore cellular mass; however, pharmacological agents that promote regeneration or expansion of endogenous β-cells have been elusive. The regenerative capacity of β-cells declines rapidly with age, due to accumulation of p16(INK4a), resulting in limited capacity for adult endocrine pancreas regeneration. Here, we show that transforming growth factor-β (TGF-β) signaling via Smad3 integrates with the trithorax complex to activate and maintain Ink4a expression to prevent β-cell replication. Importantly, inhibition of TGF-β signaling can result in repression of the Ink4a/Arf locus, resulting in increased β-cell replication in adult mice. Furthermore, small molecule inhibitors of the TGF-β pathway promote β-cell replication in human islets transplanted into NOD-scid IL-2Rg(null) mice. These data reveal a novel role for TGF-β signaling in the regulation of the Ink4a/Arf locus and highlight the potential of using small molecule inhibitors of TGF-β signaling to promote human β-cell replication

Analysis of Tertiary Control for PV based Microgrid System

With the rising demand in electricity, increasing fuel cost, global climatic changes and concern on greenhouse gas emission the use of renewable energy resources is becoming a necessity. Microgrid is a systematic integration of various Distributed Energy Resources (DERs) and connected loads to operate as single entity which can either be connected to the grid or can operate as a separate independent island. Power electronic converters are employed to provide flexibility for the integration of various distributed energy sources in the grid. Microgrid draws power from utility grid or supplies to the grid depending upon load demand and generationin grid connected mode. In case of power interruption or load shedding microgrid can be switchedto island mode of operation. One of the important issues of microgrid is to achieve the bump less transition between the grid and islanded mode of operation. In this paper Photo voltaic (PV) sources based microgrid system has been considered and a coordinated control scheme for the control of a microgrid system is implemented in Matlab / Simulink environment. This paper investigates the bump less transition between the grid and islanded mode of operation with reduced harmonic distortion and frequency variation

Nanotechnology: emerging tools for biology and medicine

Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology-based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicineDamon Runyon Cancer Research Foundation (Merck Fellow, DRG-2065-10)Howard Hughes Medical Institute (Investigator)Lustgarten FoundationNational Institutes of Health (U.S.) (U54CA151884, , Massachusetts Institute of Technology-Harvard Center of Cancer Nanotechnology Excellence)National Institutes of Health (U.S.) (P41- EB002503, BIoMEMS Resource Center

Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems

Hepatitis B virus (HBV) chronically infects 400 million people worldwide and is a leading driver of end-stage liver disease and liver cancer. Research into the biology and treatment of HBV requires an in vitro cell-culture system that supports the infection of human hepatocytes, and accurately recapitulates virus–host interactions. Here, we report that micropatterned cocultures of primary human hepatocytes with stromal cells (MPCCs) reliably support productive HBV infection, and infection can be enhanced by blocking elements of the hepatocyte innate immune response associated with the induction of IFN-stimulated genes. MPCCs maintain prolonged, productive infection and represent a facile platform for studying virus–host interactions and for developing antiviral interventions. Hepatocytes obtained from different human donors vary dramatically in their permissiveness to HBV infection, suggesting that factors—such as divergence in genetic susceptibility to infection—may influence infection in vitro. To establish a complementary, renewable system on an isogenic background in which candidate genetics can be interrogated, we show that inducible pluripotent stem cells differentiated into hepatocyte-like cells (iHeps) support HBV infection that can also be enhanced by blocking interferon-stimulated gene induction. Notably, the emergence of the capacity to support HBV transcriptional activity and initial permissiveness for infection are marked by distinct stages of iHep differentiation, suggesting that infection of iHeps can be used both to study HBV, and conversely to assess the degree of iHep differentiation. Our work demonstrates the utility of these infectious systems for studying HBV biology and the virus’ interactions with host hepatocyte genetics and physiology.Skolkovo Institute of Science and Technology (Grant 022423-003)National Institutes of Health (U.S.) (Grant UH2 EB017103)National Institutes of Health (U.S.) (Grant DK085713)National Cancer Institute (U.S.) (Koch Institute Support. Grant P30-CA14051)American Gastroenterological Association (Research Scholar Award)National Institutes of Health (U.S.) (Grant 1K08DK101754)Hertz Foundation (Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship Progra

Enhancing women's knowledge and awareness of preconception care: promoting optimal reproductive health outcomes

Background: Preconception care (PCC) is crucial to mother and child health. Many women don't realise how PCC might affect pregnancy and labour. Hence, we aimed to assess women's current knowledge and awareness levels regarding PCC, enhance knowledge, and empower women to prioritize proactive healthcare before conception. Methods: This cross-sectional study consisted of 200 reproductive-age women. Infertility therapy (n=50), poor obstetrics history (n=50), and term delivery (n=100) were the three groups. Family, gynaecological, and demographic data were obtained. Preconception care and medical issues that affect pregnancy outcomes were taught to all study participants to identify risk factors. Results: Most participants were aged between 18 and 25 (48%). Primary infertility was present in 52% of women. The main causes of infertility were pelvic inflammatory disease (40%) and genital tuberculosis (20%), treated with antibiotics and anti-tubercular medicines, respectively. Only 1 woman had both preconception and antenatal checkups, while 30 had neither. Maternal morbidity occurred in 52% of normal deliveries, with anaemia being the most prevalent. Caesarean sections were mostly due to prior 1 lower segment caesarean section (LSCS) (32%). Conception and healthy births were achieved in 10% and 6% of BOH patients and 18% and 10% of infertile patients, respectively. Conclusions: There is a need to provide women with accurate and detailed information on PCC and to establish functional clinics with evidence-based guidelines to enhance uptake and pregnancy outcomes

A computational framework for identifying design guidelines to increase the penetration of targeted nanoparticles into tumors

Targeted nanoparticles are increasingly being engineered for the treatment of cancer. By design, they can passively accumulate in tumors, selectively bind to targets in their environment, and deliver localized treatments. However, the penetration of targeted nanoparticles deep into tissue can be hindered by their slow diffusion and a high binding affinity. As a result, they often localize to areas around the vessels from which they extravasate, never reaching the deep-seeded tumor cells, thereby limiting their efficacy. To increase tissue penetration and cellular accumulation, we propose generalizable guidelines for nanoparticle design and validate them using two different computer models that capture the potency, motion, binding kinetics, and cellular internalization of targeted nanoparticles in a section of tumor tissue. One strategy that emerged from the models was delaying nanoparticle binding until after the nanoparticles have had time to diffuse deep into the tissue. Results show that nanoparticles that are designed according to these guidelines do not require fine-tuning of their kinetics or size and can be administered in lower doses than classical targeted nanoparticles for a desired tissue penetration in a large variety of tumor scenarios. In the future, similar models could serve as a testbed to explore engineered tissue-distributions that arise when large numbers of nanoparticles interact in a tumor environment.Human Frontier Science Program (Strasbourg, France)David H. Koch Institute for Integrative Cancer Research at MIT (Marie D. and Pierre Casimir-Lambert Fund)National Institutes of Health (U.S.) (Grant U54 CA151884)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051

Assessment of nitric oxide and uric acid in patients of leprosy

Background: Leprosy is an old, dreaded infectious disease caused by the obligate intracellular bacterium mycobacterium leprae. Leprosy still continues to be a significant public health problem in few countries including India. Oxidative stress caused by derangement in the balance between ROS and natural antioxidants plays a crucial role in the pathogenesis of leprosy. Hence this study attempts to assess the oxidative stress and antioxidant status in terms of Nitric oxide and uric acid.Methods: A case control observational study was carried out in100 untreated leprosy patients and compared with 50 healthy controls.  Leprosy patients were divided as paucibacillary and multibacillary. Serum Nitric oxide and uric acid levels were estimated in both groups to find out correlation of Nitric Oxide with uric acid.Results: There was a significant rise in serum NO in both PB and MB leprosy as compared to controls. The uric acid level was significantly decreased in both PB and MB leprosy patients as compared to controls.Conclusions: Elevated NO levels indicate oxidative stress in leprosy patients, denoting its crucial involvement in the pathogenesis and nerve damage in leprosy. Low uric acid indicates decrease defence of antioxidants in leprosy

Oxidative stress and antioxidant vitamins in leprosy

Background: Leprosy is a disease of great antiquity and it still continues to be a significant public health problem in few countries including India .Of the various mechanisms that influence the pathogenesis of leprosy, oxidative stress is important which occurs due to derangement in the balance between ROS and natural antioxidants. Hence this study attempted to assess the oxidative stress and antioxidant status in terms of MDA and vitamin E, vitamin C respectively in leprosy.Methods: Hundred untreated leprosy patients (50 PB and 50 MB) were studied and compared with 50 healthy controls. Serum Malondialdehyde (MDA) and vitamin E, vitamin C was measured by spectrophotometric method. Serum malondialdehyde (MDA) was measured as an indicator of lipid peroxidation and antioxidant status was assessed by estimating serum vitamin E and vitamin C levels.Results: Significant rise in serum MDA (P <0.001) in both PB and MB leprosy was seen when compared with controls. The vitamin E level was significantly decreased in both PB and MB leprosy patients as compared to controls. The vitamin C level was significantly decrease (P<0.001) in MB leprosy patients as compared to controls.Conclusions: Elevated MDA levels indicate oxidative stress in leprosy patients, denoting its crucial involvement in the pathogenesis and tissue damage in leprosy. Hence MDA levels can be used to monitor prognosis, treatment and control of leprosy. Decreased vitamin E, C levels in leprosy can be improved by oral vitamin E, C supplementation

An osteological study of morphometry of hard palate and its importance

Background: The hard palate is an essential part of human skull, the detailed knowledge of which plays an important role in the passive articulation of speech.Methods: The present study was conducted on 65 dry skulls from the department of anatomy, MVJMC & RH, Bangalore. With vernier caliper, palatine length, palatine breadth and heights were measured. Palatine index and palatine height index were calculated.Results: Mean palatine length was 48.47 ± 4.66 mm. Mean palatine breadth was 36 ± 4.41 mm and height was 8.62 ± 2.76 mm. According to the palatine index range, 66% of the hard palate belongs to leptostaphyline, 18.5% belongs to mesostaphyline and 15. 5% was brachystaphyline. As per palatine height index, 72.3% of hard palate showed chamestaphyline followed by 26.1% orthostaphyline and 1.6% hypistaphyline.Conclusions: These observations can be utilised for ethnic and racial classification of crania, anthropological studies, fabricating complete maxillary dentures for edentulous patients and performing certain surgical procedures in hard palate & soft palate

Macro-to-Micro Interface for the Control of Cellular Organization

The spatial organization of cellular communities plays a fundamental role in determining intercellular communication and emergent behavior. Few tools, however, exist to modulate tissue organization at the scale of individual cells, particularly in the case of dynamic manipulation. Micromechanical reconfigurable culture achieves dynamic control of tissue organization by culturing adherent cells on microfabricated plates that can be shifted to reorganize the arrangement of the cells. Although biological studies using this approach have been previously reported, this paper focuses on the engineering of the device, including the mechanism for translating manual manipulation to precise microscale position control, fault-tolerant design for manufacture, and the synthetic-to-living interface.National Science Foundation (U.S.) (Faculty Early Career Development Program)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)David & Lucile Packard FoundationNational Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Awar