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

Statistical Static Timing Analysis for Digital Circuitry

This paper proposed the impact of variations on delay in CMOS technology of 32 nm. The magnitude of process variations have grown, there has been an increasing realization that traditional design methodologies both for analysis and optimization are no longer acceptable. The main objective of the project is that Statistical Static Timing Analysis method has the result closer to best method and less time consuming which is far more acceptable. So we consider Statistical Static timing Analysis is the best and acceptable method for timing analysis of digital Circuits. The variation in propagation delay is big concern. The proposed system considers the variations in the designing process and finds the propagation delay. This is compared with another method called as Monte Carlo method. Also the simulation time required for both the methods are considered

Statistical Static Timing Analysis for Performance of Logic Gates

In the recent nanotechnology, the variation in the gate propagation delay is the big concern. This paper proposes the new model for gate delay propagation using the Statistical Static Timing Analysis and the results of it are compared with another modelling called as Monte-Carlo analysis. The proposed model uses Statistical analysis to find accurate propagation delay of the logic gates with reduced simulation time for 16nm technology. DOI: 10.17762/ijritcc2321-8169.15057

Age-dependent decline in beta-cell proliferation restricts the capacity of beta-cell regeneration in mice.

ObjectiveThe aim of this study was to elucidate whether age plays a role in the expansion or regeneration of beta-cell mass.Research design and methodsWe analyzed the capacity of beta-cell expansion in 1.5- and 8-month-old mice in response to a high-fat diet, after short-term treatment with the glucagon-like peptide 1 (GLP-1) analog exendin-4, or after streptozotocin (STZ) administration.ResultsYoung mice responded to high-fat diet by increasing beta-cell mass and beta-cell proliferation and maintaining normoglycemia. Old mice, by contrast, did not display any increases in beta-cell mass or beta-cell proliferation in response to high-fat diet and became diabetic. To further assess the plasticity of beta-cell mass with respect to age, young and old mice were injected with a single dose of STZ, and beta-cell proliferation was analyzed to assess the regeneration of beta-cells. We observed a fourfold increase in beta-cell proliferation in young mice after STZ administration, whereas no changes in beta-cell proliferation were observed in older mice. The capacity to expand beta-cell mass in response to short-term treatment with the GLP-1 analog exendin-4 also declined with age. The ability of beta-cell mass to expand was correlated with higher levels of Bmi1, a polycomb group protein that is known to regulate the Ink4a locus, and decreased levels of p16(Ink4a)expression in the beta-cells. Young Bmi1(-/-) mice that prematurely upregulate p16(Ink4a)failed to expand beta-cell mass in response to exendin-4, indicating that p16(Ink4a)levels are a critical determinant of beta-cell mass expansion.Conclusionsbeta-Cell proliferation and the capacity of beta-cells to regenerate declines with age and is regulated by the Bmi1/p16(Ink4a)pathway

Smad7 Inhibits Mesoderm Formation and Promotes Neural Cell Fate inXenopusEmbryos

AbstractWe report the isolation and characterization of a new inhibitory Smad inXenopus,which we have designated asXenopusSmad7. Smad7 is present at fairly constant levels throughout early development and at blastula stages enriched in the ventral side of the animal hemisphere. The induction of mesoderm by TGF-β-like signals is mediated by receptor ALK-4 and we show that Smad7 blocks signaling of ALK-4 in a graded fashion: lower levels of Smad7 block activation of dorsal mesoderm genes and higher levels block all mesoderm genes expression. Smad7 is able to directly activate neural markers in explants in the absence of mesoderm or endoderm. This neural-inducing activity of Smad7 may be due to inhibition of BMP-4 signaling because Smad7 can also block BMP-4-mediated mesoderm induction. Thus, Smad7 acts as a potent inhibitor of mesoderm formation and also activates the default neural induction pathway

ETIOLOGICAL FACTORS, CLINICAL PRESENTATIONS AND TREATMENT OUTCOME OF CERVICAL LYMPHADENOPATHY: AN OBSERVATIONAL DESCRIPTIVE STUDY

Aim: To study various etiological factors, clinical presentations of cervical lymphadenopathy. To study the management and outcome of cervical lymphadenopathy Method: Proper clinical history was first noted, local and systemic examination was performed and a clinical diagnosis was made. Gender wise distribution, presenting symptoms, site distribution, and treatment outcome were noted. Result: Gender wise distribution of male and female was 52%, and 48%, commonest site of primary in cases of metastatic Secondaries was tongue followed by oesophagus and thyroid. After proper diagnosis confirmed by Histopathology (biopsy), treatment constituted properly- Cases of Tubercular Lymphadenitis (49 cases) were Started on Anti-tubercular treatment, all were showed improvement in symptoms. Cases of Reactive lymphadenitis (26 cases) started on antibiotics, all recovered well. Among 14 Cases of Metastatic secondaries, 5 cases were given Chemotherapy/Radiotherapy after expert oncologist opinion out of which 3 showed improved symptoms and 2 were expired, 6 cases were operated out of which 5 showed improved symptoms and 1 expired post operatively, 3 cases were referred to specialized oncological and oncosurgical center for further management. All 6 Lymphoma cases were started on chemotherapy after expert oncologist opinion showed improvement in symptoms. Conclusion: Commonest site of primary in cases of metastatic Secondaries was tongue followed by oesophagus and thyroid. Anti-tubercular treatment for tubercular lymphadenitis was highly satisfactory with improvement in almost all patients. Surgery was restricted as an adjuvant to chemotherapy, as diagnostic biopsy, for treatment of abscess/sinuses and for a lymph nodes that do not resolve with chemotherapy. Non-tuberculous non-neoplastic lesions can be best managed by conservatively. Keywords: Cervical lymphadenopathy; Clinical presentations; Treatment outcome

Cyclin D2 is sufficient to drive β cell self-renewal and regeneration

Diabetes results from an inadequate mass of functional β cells, due to either β cell loss caused by autoimmune destruction (type I diabetes) or β cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate β cell mass may be key to developing new techniques that foster β cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal β cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive β cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in β cells, we show that cyclin D2 overexpression increases β cell self-renewal post-weaning and results in increased β cell mass. β cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. β cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive β cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in β cells of cyclin D2−/− mice. Transgenic overexpression of cyclin D2 in cyclin D2−/− β cells was sufficient to restore β cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2−/− littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate β cell self-renewal and that manipulation of its expression could be used to enhance β cell regeneration

Combining ability and heterosis analysis for fibre yield and quality parameters in roselle (Hibiscus sabdariffa L.)

Roselle (Hibiscus sabdariffa L.) is second important bast fibre crop after jute in India. With an aim to ex-ploit non-additive genetic variance present experiment was designed to identify good general combining parents and specific cross combination for fibre yield and fibre quality parameters (fibre fineness, fibre tenacity) in roselle. A total of 11 parents were crossed in complete diallel fashion which resulted 55 F1, 55 RF1 (reciprocal F1). Parents, F1s and RF1s were grown in randomized block design. Analysis of variance revealed significant differences (P< 0.01, P<0.05) among the parents and their hybrids. The parents AMV 1, AMV 5, GR 27 and AHS 160 were identified as good combiners since they recorded significant general combining ability (GCA) effects for fibre yield and quality parameters. Further, For fibre yield only three crosses (AMV 1 × AMV 4, AMV 1 × GR 27, HS 4288 × JRR 07) showed significant specific combining ability (SCA) effects from them hybrid AMV 1 × GR 27 (fibre yield=27.37g/ plant) exhibited positively significant best parent (Non bris 4, Mean fibre yield=21.16g/plant) heterosis (29.35%). Similarly, for fibre tenacity, hybrid GR 27 × JRR 07 (fibre tenacity=23.47g/tex) exhibited positively significant best parent (HS 4288; fibre tenacity=20.35g/tex) heterosis (15.30%)

Verrucous Hyperplasia : Case report and differential diagnosis

Verrucous hyperplasia (VH) is a rare exophytic oral mucosal lesion which can transform into verrucous carcinoma (VC), its malignant but clinically similar counterpart. These entities can be distinguished by the lack of invasive growth in VH cases; as such, it is essential to include a margin with adequate depth whenperforming a biopsy of the epithelium of the lesion. We report an 80-year-old male patient who presented to the Bapuji Dental College & Hospital, Davangere, Karanataka, India, in 2011 with a warty whitish-pink growth on the inside of his cheek. The patient was treated with wide surgical excision of the lesion and a diagnosis of VH was made based on histopathological features. There was no evidence of recurrence at a five-year follow-up. This report highlights the histological variations, pathogenesis and differential diagnosis of VH