SYNTHESIS, CHARACTERIZATION AND BIOCIDAL ACTIVITY OF NOVEL HALOGENATED -4-[(SUBSTITUTED-BENZOTHIAZOL-2-YL) HYDRAZONO]-2- (SUBSTITUTED-PHENYL)-5-METHYL /ETHOXY -2,4-DIHYDRO-PYRAZOL-3-ONE DERIVATIVES

ABSTRACT Some new 4-[(substituted-benzothiazol-2-yl)hydrazono]-2-(substituted-phenyl)-5-methyl/ethoxy-2,4-dihydro-pyrazol-3-one(4) have been synthesized by reacting substituted 2-amino benzothiazol (1) with acetoacetic ester and malonic ester (2). 2-[(substituted-benzothiazol-2-yl)hydrazono]-3-oxo-butyric acid ethyl ester and 2-[(substituted-benzothiazol-2-yl)hydrazono]-malonic acid diethyl ester (3) react with different hydrazines to give the title compounds(4). These compounds are evaluated for their antifungal and insecticidal activity

Hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of mesenchymal stem cells

Allogeneic mesenchymal stem cells (MSCs) are immunoprivileged and are being investigated in phase I and phase II clinical trials to treat different degenerative and autoimmune diseases. In spite of encouraging outcome of initial trials, the long-term poor survival of transplanted cells in the host tissue has declined the overall enthusiasm. Recent analyses of allogeneic MSCs based studies confirm that after transplantation in the hypoxic or ischemic microenvironment of diseased tissues, MSCs become immunogenic and are rejected by recipient immune system. The immunoprivilege of MSCs is preserved by absence or negligible expression of cell surface antigen, human leukocyte antigen (HLA)-DRα. We found that in normoxic MSCs, 26S proteasome degrades HLA-DRα and maintains immunoprivilege of MSCs. The exposure to hypoxia leads to inactivation of 26S proteasome and formation of immunoproteasome in MSCs, which is associated with upregulation and activation of HLA-DRα, and as a result, MSCs become immunogenic. Furthermore, inhibition of immunoproteasome formation in hypoxic MSCs preserves the immunoprivilege. Therefore, hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of allogeneic MSCs. The outcome of the current study may provide molecular targets to plan interventions to preserve immunoprivilege of allogeneic MSCs in the hypoxic or ischemic environment

A putative heat-responsive transcription factor (TaHD97) and its targets in wheat (Triticum aestivum) providing thermotolerance

214-223Transcription factors (TFs) are protein, which perform their role at transcriptional level by affecting the expression of various genes associated with metabolic pathways, growth and stress-associated genes (SAGs) at different developmental stages. Here, we identified 38 novel heat-responsive transcription factor genes from wheat cv. HD2985 by mining the de novo transcriptome data derived from heat shock (HS) treated wheat. Based on digital gene expression (DGE), a putative transcript (TaHD97) of ~1.1 kbas amplified and cloned from wheat cv. HD2985. The presence of heat stress transcription factor (HSF) DNA binding domain was observed in the amino acid sequence. Differential expression of TaHD97 was observed in HD2985 (thermotolerant) and HD2329 (thermosensitive) under heat stress. Tissue specific expression analysis showed up-regulation of TaHD97 in leaves, stem and endospermic tissues and down-regulation in root under HS. A positive correlation was established between the expression of TaHD97 and its target gene (HSP17 and HSP90) in wheat under heat stress. HSP17 transcripts were observed more in leaves of HD2985, as compared to HD2329. Thermotolerance related biochemical enzymes (SOD, CAT, GPX and TBARS) were observed higher in wheat cv. HD2985 showing maximum expression of TaHD97 under heat stress. There is a need for the functional validation of the gene TaHD97 in order to use it for the regulation of sHSP (catalytic chaperone) - a novel approach towards augmenting thermotolerance in wheat under heat stress

An evaluation of large group cognitive behaviour therapy with mindfulness (CBTm) classes

Abstract Background Ensuring equitable and timely access to Cognitive Behaviour Therapy (CBT) is challenging within Canada’s service delivery model. The current study aims to determine acceptability and effectiveness of 4-session, large, Cognitive Behaviour Therapy with Mindfulness (CBTm) classes. Methods A retrospective chart review of adult outpatients (n = 523) who attended CBTm classes from 2015 to 2016. Classes were administered in a tertiary mental health clinic in Winnipeg, Canada and averaged 24 clients per session. Primary outcomes were (a) acceptability of the classes and retention rates and (b) changes in anxiety and depressive symptoms using Generalized Anxiety Disorder 7-item (GAD-7) and Patient Health Questionnaire 9-item (PHQ-9) scales. Results Clients found classes useful and > 90% expressed a desire to attend future sessions. The dropout rate was 37.5%. A mixed-effects linear regression demonstrated classes improved anxiety symptoms (GAD-7 score change per class = − 0.52 [95%CI, − 0.74 to − 0.30], P < 0.001) and depressive symptoms (PHQ-9 score change per class = − 0.65 [95%CI, − 0.89 to − 0.40], P < 0.001). Secondary analysis found reduction in scores between baseline and follow-up to be 2.40 and 1.98 for the GAD-7 and PHQ-9, respectively. Effect sizes were small for all analyses. Conclusions This study offers preliminary evidence suggesting CBTm classes are an acceptable strategy to facilitate access and to engage and maintain clients’ interest in pursuing CBT. Clients attending CBTm classes experienced improvements in anxiety and depressive symptoms. Symptom improvement was not clinically significant. Study limitations, such as a lack of control group, should be addressed in future research.https://deepblue.lib.umich.edu/bitstream/2027.42/148879/1/12888_2019_Article_2124.pd

Inhibition of Apoptosis Blocks Human Motor Neuron Cell Death in a Stem Cell Model of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC) lines generated from two Type I SMA subjects–one produced with lentiviral constructs and the second using a virus-free plasmid–based approach–recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients

Fog computing security: a review of current applications and security solutions

Fog computing is a new paradigm that extends the Cloud platform model by providing computing resources on the edges of a network. It can be described as a cloud-like platform having similar data, computation, storage and application services, but is fundamentally different in that it is decentralized. In addition, Fog systems are capable of processing large amounts of data locally, operate on-premise, are fully portable, and can be installed on heterogeneous hardware. These features make the Fog platform highly suitable for time and location-sensitive applications. For example, Internet of Things (IoT) devices are required to quickly process a large amount of data. This wide range of functionality driven applications intensifies many security issues regarding data, virtualization, segregation, network, malware and monitoring. This paper surveys existing literature on Fog computing applications to identify common security gaps. Similar technologies like Edge computing, Cloudlets and Micro-data centres have also been included to provide a holistic review process. The majority of Fog applications are motivated by the desire for functionality and end-user requirements, while the security aspects are often ignored or considered as an afterthought. This paper also determines the impact of those security issues and possible solutions, providing future security-relevant directions to those responsible for designing, developing, and maintaining Fog systems

Beyond technology: A research agenda for social sciences and humanities research on renewable energy in Europe

This article enriches the existing literature on the importance and role of the social sciences and humanities (SSH) in renewable energy sources research by providing a novel approach to instigating the future research agenda in this field. Employing a series of in-depth interviews, deliberative focus group workshops and a systematic horizon scanning process, which utilised the expert knowledge of 85 researchers from the field with diverse disciplinary backgrounds and expertise, the paper develops a set of 100 priority questions for future research within SSH scholarship on renewable energy sources. These questions were aggregated into four main directions: (i) deep transformations and connections to the broader economic system (i.e. radical ways of (re)arranging socio-technical, political and economic relations), (ii) cultural and geographical diversity (i.e. contextual cultural, historical, political and socio-economic factors influencing citizen support for energy transitions), (iii) complexifying energy governance (i.e. understanding energy systems from a systems dynamics perspective) and (iv) shifting from instrumental acceptance to value-based objectives (i.e. public support for energy transitions as a normative notion linked to trust-building and citizen engagement). While this agenda is not intended to be—and cannot be—exhaustive or exclusive, we argue that it advances the understanding of SSH research on renewable energy sources and may have important value in the prioritisation of SSH themes needed to enrich dialogues between policymakers, funding institutions and researchers. SSH scholarship should not be treated as instrumental to other research on renewable energy but as intrinsic and of the same hierarchical importance.acceptedVersio

Alteration of the phospho- or neutral lipid content and fatty acid composition in Listeria monocytogenes due to acid adaptation mechanisms for hydrochloric, acetic and lactic acids at pH 5.5 or benzoic acid at neutral pH

This study provides a first approach to observe the effects on Listeria monocytogenes of cellular exposure to acid stress at low or neutral pH, notably how phospho- or neutral lipids are involved in this mechanism, besides the fatty acid profile alteration. A thorough investigation of the composition of polar and neutral lipids from L. monocytogenes grown at pH 5.5 in presence of hydrochloric, acetic and lactic acids, or at neutral pH 7.3 in presence of benzoic acid, is described relative to cells grown in acid-free medium. The results showed that only low pH values enhance the antimicrobial activity of an acid. We suggest that, irrespective of pH, the acid adaptation response will lead to a similar alteration in fatty acid composition [decreasing the ratio of branched chain/saturated straight fatty acids of total lipids], mainly originating from the neutral lipid class of adapted cultures. Acid adaptation in L. monocytogenes was correlated with a decrease in total lipid phosphorus and, with the exception of cells adapted to benzoic acid, this change in the amount of phosphorus reflected a higher content of the neutral lipid class. Upon acetic or benzoic acid stress the lipid phosphorus proportion was analysed in the main phospholipids present: cardiolipin, phosphatidylglycerol, phosphoaminolipid and phosphatidylinositol. Interestingly only benzoic acid had a dramatic effect on the relative quantities of these four phospholipids

Phosphatase and tensin homologue: a therapeutic target for SMA

Spinal muscular atrophy (SMA) is one of the most common juvenile neurodegenerative diseases, which can be associated with child mortality. SMA is caused by a mutation of ubiquitously expressed gene, Survival Motor Neuron1 (SMN1), leading to reduced SMN protein and the motor neuron death. The disease is incurable and the only therapeutic strategy to follow is to improve the expression of SMN protein levels in motor neurons. Significant numbers of motor neurons in SMA mice and SMA cultures are caspase positive with condensed nuclei, suggesting that these cells are prone to a process of cell death called apoptosis. Searching for other potential molecules or signaling pathways that are neuroprotective for central nervous system (CNS) insults is essential for widening the scope of developmental medicine. PTEN, a Phosphatase and Tensin homologue, is a tumor suppressor, which is widely expressed in CNS. PTEN depletion activates anti-apoptotic factors and it is evident that the pathway plays an important protective role in many neurodegenerative disorders. It functions as a negative regulator of PIP3/AKT pathway and thereby modulates its downstream cellular functions through lipid phosphatase activity. Moreover, previous reports from our group demonstrated that, PTEN depletion using viral vector delivery system in SMN delta7 mice reduces disease pathology, with significant rescue on survival rate and the body weight of the SMA mice. Thus knockdown/depletion/mutation of PTEN and manipulation of PTEN medicated Akt/PKB signaling pathway may represent an important therapeutic strategy to promote motor neuron survival in SMA