Proline, catalase and root traits as indices of drought resistance in bold grained rice (Oryza sativa) genotypes

The present experiment was carried out with 39 bold grained rice genotypes to study the genetic variability of the traits conferring drought resistance and to screen the drought tolerant rice genotypeswith a view to formulate an efficient breeding programme for time bound genetic enhancement. The field experiment was grown during Sali season of 2007 to estimate the genetic variability of eight quantitative traits; root weight (g), number of primary roots, number of tillers/plant, root length (cm),shoot weight (g), root:shoot ratio by length and root:shoot ratio by weight. The data for the quantitative traits were recorded after 60 days of transplanting. The analysis of variance of eight quantitative traitsrevealed that there was significant genetic variation among the genotypes for the traits conferring drought resistance. The genotypic coefficient of variation (GCV), phenotypic coefficient of variation (PCV), heritability in broad sense (h2bs) and genetic advance (GA) as percent mean were estimated for all the eight quantitative traits. Small difference between GCV and PCV estimates was observed for shoot length (cm), root length (cm), number of primary roots, shoot weight (g), number of tillers/plantand root:shoot ratio by length suggesting that these characters were little influenced by environment and could be substantially improved through selection breeding program. Out of 39 rice genotypes, 7 genotypes including 2 checks (Ranjit and Monohar Sail) were selected on the basis of morphometric traits for drought resistance. Fifteen day old seedlings of seven selected rice genotypes were subjected to different osmotics of PEG-6000 (0.0, -0.4 and -0.8 MPa) to evaluate the effect of drought stress on proline, protein and antioxidant enzyme catalase. Poline content and catalase activity analyses further suggested that five selected bold grained rice genotypes (excluding two checks) namely Halodhar, George Sail, Kapili Dhan, Karmi Sail and Baodum were potentially drought tolerant

Improved social functioning following social recovery therapy in first episode psychosis: Do social cognition and neurocognition change following therapy, and do they predict treatment response?

There is a need to develop and refine psychosocial interventions to improve functioning in First Episode Psychosis (FEP). Social cognition and neurocognition are closely linked to functioning in psychosis; examinations of cognition pre- and post- psychosocial intervention may provide insights into the mechanisms of these interventions, and identify which individuals are most likely to benefit. Method: Cognition was assessed within a multi-site trial of Social Recovery Therapy (SRT) for individuals with FEP experiencing poor functioning (<30 h weekly structured activity). Fifty-nine participants were randomly allocated to the therapy group (SRT + Early intervention), and 64 were allocated to treatment as usual group (TAU - early intervention care). Social cognition and neurocognition were assessed at baseline and 9 months; assessors were blind to group allocation. It was hypothesized that social cognition would improve following therapy, and those with better social cognition prior to therapy would benefit the most from SRT. Results: There was no significant impact of SRT on individual neurocognitive or social cognitive variables, however, joint models addressing patterns of missingness demonstrate improvement across a number of cognitive outcomes following SRT. Further, regression analyses showed those who had better social cognition at baseline were most likely to benefit from the therapy (ß = 0.350; 95% CI = 0.830 to 8.891; p = .019). Conclusion: It is not clear if SRT impacts on social cognitive or neurocognitive function, however, SRT may be beneficial in those with better social cognition at baseline

Identification of miR-379/miR-656 (C14MC) cluster downregulation and associated epigenetic and transcription regulatory mechanism in oligodendrogliomas

Introduction Although role of individual microRNAs (miRNAs) in the pathogenesis of gliomas has been well studied, their role as a clustered remains unexplored in gliomas. Methods In this study, we performed the expression analysis of miR-379/miR-656 miRNA-cluster (C14MC) in oligodendrogliomas (ODGs) and also investigated the mechanism underlying modulation of this cluster. Results We identified significant downregulation of majority of the miRNAs from this cluster in ODGs. Further data from The Cancer Genome Atlas (TCGA) also confirmed the global downregulation of C14MC. Furthermore, we observed that its regulation is maintained by transcription factor MEF2. In addition, epigenetic machinery involving DNA and histone-methylation are also involved in its regulation, which is acting independently or in synergy. The post- transcriptionally regulatory network of this cluster showed enrichment of key cancer-related biological processes such as cell adhesion and migration. Also, there was enrichment of several cancer related pathways viz PIK3 signaling pathway and glioma pathways. Survival analysis demonstrated association of C14MC (miR-487b and miR-409-3p) with poor progression free survival in ODGs. Conclusion Our work demonstrates tumor-suppressive role of C14MC and its role in pathogenesis of ODGs and therefore could be relevant for the development of new therapeutic strategies

Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition.

Collagen assembly during development is essential for successful matrix mineralisation, which determines bone quality and mechanocompetence. However, the biochemical and structural perturbations that drive pathological skeletal collagen configuration remain unclear. Deletion of vascular endothelial growth factor (VEGF) in bone forming osteoblasts (OBs) induces sex-specific alterations in extracellular matrix (ECM) conformation and mineralisation coupled to vascular changes, which are augmented in males. Whether this phenotypic dimorphism arises as a result of the divergent control of ECM composition and its subsequent arrangement is unknown and is the focus of this study. Herein, we have used a murine osteocalcin-specific Vegf knockout (OcnVEGFKO) and performed ex vivo multiscale analysis at the tibiofibular junction of both sexes. Furthermore, we also deleted Vegf in vitro in OBs extracted from male and female mice in an attempt to link sex-specific matrix signatures to deviations in gene expression. Label-free and non-destructive polarisation-resolved second harmonic generation microscopy (p-SHG) revealed a reduction in collagen fibre number in males following the loss of VEGF, complemented by observable defects in matrix organisation by backscattered electron scanning electron microscopy. This was accompanied only in males by localised divergence in collagen orientation, determined by p-SHG anisotropy measurements, as a result of OcnVEGFKO. Raman spectroscopy confirmed the effect on collagen was linked to molecular dimorphic VEGF effects on collagen-specific proline and hydroxyproline, and collagen intra-stand stability, in addition to matrix carbonation and mineralisation. Vegf deletion in male and female murine OB cultures in vitro further highlighted divergence in genes regulating local ECM structure including Adamts2, Spp1, Mmp9 and Lama1 The current results demonstrate the utility of macromolecular imaging and spectroscopic modalities for the detection of collagen arrangement and ECM composition in pathological bone. Linking the sex-specific genetic regulators to matrix signatures could be important for treatment of dimorphic bone disorders which clinically manifest in both pathological nano and macro-level disorganisation

Engineering simulations of a super-complex cultural heritage building: Ica Cathedral in Peru

The Cathedral of Ica, Peru, is one of the four prototype buildings involved in the ongoing Seismic Retrofitting Project, initiative of the Getty Conservation Institute. The complex historical building, which was heavily damaged by earthquakes in 2007 and 2009, can be divided into two substructures: an external masonry envelope and an internal timber frame built by a construction method known as quincha technique. This study makes use of the information available in literature and the results obtained from experimental campaigns performed by Pontificia Universidad Catlica del PerA and University of Minho. Nonlinear behaviour of masonry is simulated in the numerical models by considering specified compressive and tensile softening behaviour, while isotropic homogeneous and linear behaviour is adopted for modelling timber with appropriate assumptions on the connections. A single representative bay was initially studied by performing linear elastic analysis and verifying the compliance with the various criteria specified by the applicable normative to discuss the actual failure of Ica Cathedral. Afterwards, the structural behaviour of the two substructures composing the Cathedral is evaluated independently. Finally, the interaction of these two substructures is investigated by performing structural analysis on the entire structure of Ica Cathedral. Several structural analysis techniques, including eigenvalue, nonlinear static and dynamic analyses, are performed in order to: (1) evaluate the dominant mode shapes of the structure; (2) validate the numerical models by reproducing the structural damage observed in situ; (3) estimate the structural performance; and (4) identify the main failure mechanisms.This work was carried out with funding from the Getty Seismic Retrofitting Project under the auspices of the Getty Conservation Institute (GCI). This work is also partially financed by FEDER funds through the Competitivity Factors Operational Programme-COMPETE and by national funds through FCT-Foundation for Science and Technology within the scope of the projects POCI-01-0145-FEDER-007633 and PTDC/ECM-EST/2777/2014.info:eu-repo/semantics/publishedVersio

Prevalence of treatment resistance and clozapine use in early intervention services

BACKGROUND: Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics. AIMS: This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services. METHOD: Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points. RESULTS: A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine. CONCLUSIONS: Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The N-terminal protease of pestiviruses, N(pro) is a unique viral protein, both because it is a distinct autoprotease that cleaves itself from the following polyprotein chain, and also because it binds and inactivates IRF3, a central regulator of interferon production. An important question remains the role of N(pro) in the inhibition of apoptosis. In this study, apoptotic signals induced by staurosporine, interferon, double stranded RNA, sodium arsenate and hydrogen peroxide were inhibited by expression of wild type N(pro), but not by mutant protein N(pro) C112R, which we show is less efficient at promoting degradation of IRF3, and led to the conclusion that N(pro) inhibits the stress-induced intrinsic mitochondrial pathway through inhibition of IRF3-dependent Bax activation. Both expression of N(pro) and infection with Bovine Viral Diarrhea Virus (BVDV) prevented Bax redistribution and mitochondrial fragmentation. Given the role played by signaling platforms during IRF3 activation, we have studied the subcellular distribution of N(pro) and we show that, in common with many other viral proteins, N(pro) targets mitochondria to inhibit apoptosis in response to cell stress. N(pro) itself not only relocated to mitochondria but in addition, both N(pro) and IRF3 associated with peroxisomes, with over 85% of N(pro) puncta co-distributing with PMP70, a marker for peroxisomes. In addition, peroxisomes containing N(pro) and IRF3 associated with ubiquitin. IRF3 was degraded, whereas N(pro) accumulated in response to cell stress. These results implicate mitochondria and peroxisomes as new sites for IRF3 regulation by N(pro), and highlight the role of these organelles in the anti-viral pathway

Structure and stability of symptoms in first episode psychosis: a longitudinal network approach

Early psychosis is characterised by heterogeneity in illness trajectories, where outcomes remain poor for many. Understanding psychosis symptoms and their relation to illness outcomes, from a novel network perspective, may help to delineate psychopathology within early psychosis and identify pivotal targets for intervention. Using network modelling in first episode psychosis (FEP), this study aimed to identify: (a) key central and bridge symptoms most influential in symptom networks, and (b) examine the structure and stability of the networks at baseline and 12-month follow-up. Data on 1027 participants with FEP were taken from the National EDEN longitudinal study and used to create regularised partial correlation networks using the ‘EBICglasso’ algorithm for positive, negative, and depressive symptoms at baseline and at 12-months. Centrality and bridge estimations were computed using a permutation-based network comparison test. Depression featured as a central symptom in both the baseline and 12-month networks. Conceptual disorganisation, stereotyped thinking, along with hallucinations and suspiciousness featured as key bridge symptoms across the networks. The network comparison test revealed that the strength and bridge centralities did not differ significantly between the two networks (C = 0.096153; p = 0.22297). However, the network structure and connectedness differed significantly from baseline to follow-up (M = 0.16405, p = <0.0001; S = 0.74536, p = 0.02), with several associations between psychosis and depressive items differing significantly by 12 months. Depressive symptoms, in addition to symptoms of thought disturbance (e.g. conceptual disorganisation and stereotyped thinking), may be examples of important, under-recognized treatment targets in early psychosis, which may have the potential to lead to global symptom improvements and better recovery

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

Androgen secreting steroid cell tumor of the ovary in a young lactating women with acute onset of severe hyperandrogenism: a case report and review of literature

<p>Abstract</p> <p>Introduction</p> <p>Steroid cell tumors of the ovary account for less than 0.1% of all ovarian tumors <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and these tumours may present at any age in association with interesting presentations related to the hormonal activity and virilizing properties of tumor. Hayes and Scully <abbrgrp><abbr bid="B2">2</abbr></abbrgrp> reported 63 cases in patients ranging from 2 to 80 years of age. The subtype, not otherwise specified, is associated with androgenic changes in approximately one half of patients with this tumour <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. In a series of 63 cases from Massachusetts General Hospital, 94% of the tumors were found to be unilateral and 28.6% were malignant <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. As most of these tumors are diagnosed at an early stage and do not recur or metastasize, little is known about their response to therapies such as chemotherapy or radiation <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Case Presentation</p> <p>We present the case of a 22-year old lactating woman who presented with four months of amenorrhea associated with signs of virilization. Clinical and diagnostic evaluation revealed a right adenexal mass and elevated serum levels of testosterone and she was diagnosed as having a stage 1A androgen secreting steroid cell tumor. In view of the early stage of the disease, she underwent right salpingo-oopherectomy. Histopathological examination and immunohistochemistry confirmed the diagnosis. Two months after surgery she regained normal menses and showed regression of the androgenic changes.</p> <p>Conclusion</p> <p>Surgery remains the mainstay of the treatment of gonadotrophin receptor positive steroid cell tumors although medical therapy using Gonadotrophin Releasing Hormone [GnRH analogues has been tried recently in recurrent or inoperable cases. There is no described effective chemotherapy or radiotherapy for this condition.</p