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Emotional monitoring was essential in the development of sophisticated automobiles with advanced driver assistance systems (ADAS) to ensure safety and monitor potential collision trends for evaluating the driver's mental state. Factors affecting driver emotional identification include posture changes, illumination, and occlusions. Existing emotion recognition using CNN ResNet101 has low sensitivity, high false-positive rate, and error. To overcome these challenges, this paper proposes Driver Emotion Recognition (DER) using ShuffleNet V2 to effectively recognize emotions and determine the driver's mental condition. Initially, the facial images from different peoples are collected as a dataset and pre-processed using image resizing, Gaussian filter, median filter, histogram equalization and wiener filter for removing noise and enhancing the image quality. For segmentation and feature extraction of face images from a variety of datasets such as CK_Plus, FER_2013, TFEID, KMU_FED, and KDEF, the Region of Interest (ROI) and Kanade-Lucas-Tomasi (KLT) algorithm are used, which segments the face images based on region. Then, the ShuffleNet V2 classification is used to categorize emotions into six unique expressions such as happy, surprise, sad, fear, anger, disgust, and neutral. The performance of the proposed model is assessed by comparing it to that existing models. The proposed approach achieved an accuracy rate of 0.98% in CK_Plus, 0.97% in FER_2013, 0.97% in TFEID, 0.99% in KMU_FED, and 0.99% in KDEF. In comparison to other existing techniques, the proposed technique performs better. In order to determine the different emotions, the created model is the best choice. [ABSTRACT FROM AUTHOR]

Testing is a process of trying to find out every believable fault or weakness in a project. In today's world, software products and components play a vital part in our life. Software testing is a world, it contains its own life cycle consists of the following stages -- Requirements, Test Plan, Test Design, Test Execution, Defect reporting/tracking. The core of software testing lies in writing test cases based on specifications. Software testers play a vital role writing the test cases during test design phase of software testing life cycle. Research have proved that writing test cases is the most time killing and challenging activity among other testing life cycle phases. It is very crucial to sequence and write optimized test cases to increase the rate of fault identification during test design phase as early as possible. There are various proven test design techniques available which focuses on optimizing test cases in different test stages. Our key focus in this paper is to identify the optimized test cases minimizing the actual number of test cases with minimal effort using OATS (Orthogonal Array Test Strategy) techniques covering double mode and triple mode test combinations and Random Forest algorithm. [ABSTRACT FROM AUTHOR]

Aim and Objectives: To evaluate lipid profile in ABO blood group phenotypes. Materials and Method: This prospective study was conducted to find the association between different blood groups and their lipid profile, which can further be used for the strategy for prevention of risk factor of cardiovascular disease and atherosclerosis. Results: The mean cholesterol was significantly highest in individuals with blood group O (149.86±25.96) and lowest in individuals with blood group AB (92.79±26.93). The mean triglyceride was highest in O blood group (144.67±24.57) and lowest in AB blood group (108.67±32.70). The mean LDL was significantly highest in individuals with blood group O (108.50±24.01) and lowest in individuals with blood group AB (67.35±31.63). The mean VLDL was highest in O blood group (26.09±3.94) and lowest in AB blood group (21.71±4.65). The mean HDL was highest in B blood group (41.25±13.33) and lowest in O blood group (28.78±8.65). The mean cholesterol/HDL ratio was highest in individuals with blood group O (5.57±1.45) and lowest in individuals with blood group AB (3.34±1.02). Conclusion: The lipid profile has been found to vary significantly in different blood groups. As the levels of cholesterol, triglyceride, LDL, VLDL and HDL are directly associated with various cardiovascular diseases, the blood group of an individual can be used as a predictor for the development of those diseases. [ABSTRACT FROM AUTHOR]

A sensitive and specific diagnostic kit is crucial for the detection of human lymphatic filariasis at the early stage of infection as the existing diagnostic tools are inefficient and expensive. In the present study, we have cloned and expressed Brugia malayi HSP70 (BmHSP70) protein and characterized it as a potential antigen for diagnosis of the asymptomatic microfilariae stage of Wuchereria. bancrofti infection using ELISA, western blot, and bioinformatics tools. The antigenic efficacy of BmHSP70 was also compared with ScHSP70. The BmHSP70 and ScHSP70 peptide showed highly antigenic in nature and they showed immunogenic cross‐reactivity endemic normal (EN) < chronic (CH) < microfilaraemic (MF) in IgG, IgG1, and IgG4 ELISA. IgG4‐specific immunoblotting of BmHSP70 with MF sera further explicated its stage‐specific antigenic cross‐reactivity. These antigens (ScHSP70 and BmHSP70) showed a positive immunogenic correlation with the number of MF in blood samples. Thus, proposing BmHSP70 as a potential immunodiagnostic antigen against lymphatic filariasis. A triplet of GGMP tetrapeptide specific to the filarial HSP70 was also identified which was absent in human HSP70. In terms of sensitivity and specificity of antigens, these results suggest that recombinant BmHSP70 is a good antigen and could be used to diagnose early‐stage of microfilariae infection. [ABSTRACT FROM AUTHOR]

Prolyl oligopeptidase (POP) plays a crucial role in the processing and degradation of neuropeptides and regulates inositol trisphosphate (IP3) signaling in mammals. We have reported that POP inhibition leads to IP3-mediated calcium efflux leading to mitochondrial-mediated apoptosis in the filarial parasite Setaria cervi. This study further elucidates the effect of altered calcium homeostasis on the proteome of filarial parasites. Adult parasites were treated with POP's specific inhibitor, Z-Pro-prolinal (ZPP), for 7 h. Cytosolic and mitochondrial proteome was analyzed using 2D gel electrophoresis coupled with MALDI-MS/MS. Phosphoproteins were also analyzed in the cytosolic fraction of the parasites. The phosphoprotein analysis revealed 7, and 9 spots in the cytosolic fraction of control and ZPP-treated parasites, respectively. The two identified protein spots in the treated set were found to be involved in G protein signaling. In cytosolic fraction, 109 and 112 protein spots were observed in control and treated parasites, respectively. Of these, 56 upregulated and 32 downregulated protein spots were observed in the treated set. On the other hand, 50 and 47 protein spots were detected in the mitochondrial fraction of control and treated parasites, respectively. Of these spots, 18 upregulated and 12 down-regulated protein spots were found in treated parasites. In silico analysis showed that the identified proteins were involved in energy metabolism, calcium signaling, stress response, and cytoskeleton organization. These findings correlate with our previous results suggesting the important regulatory role of POP in signaling and different metabolic pathways of filarial parasites. [ABSTRACT FROM AUTHOR]

The available antifilarial medications are effective only against the larval stage of the filarial parasite. As a result, there is a pressing need for an adulticidal drug. The development of drugs requires the identification of molecular targets that are critical for parasite life. In this study, we observed the effect of 17‐N‐allyl‐17‐demethoxygeldanamycin on the survival of adult filarial parasites. The 17‐N‐allyl‐17‐demethoxygeldanamycin (17‐AAG) is a derivative of geldanamycin (GA), which is an inhibitor of heat shock protein (HSP)90. It is less toxic as compared to geldanamycin. The motility and viability of the adult filarial parasite Setaria cervi were decreased on exposure to 17‐AAG at 2.5 and 5.0 μM/ml concentrations. The 17‐AAG treated parasites showed induction of oxidative stress as evidenced by decreased activity of various antioxidant enzymes like glutathione s‐transferase, glutathione reductase, thioredoxin reductase, and an increase in ROS production in comparison to control. Oxidative stress may lead to altered calcium homeostasis. Indeed, in 17‐AAG treated worms, there was a rise in calcium in the cytosol and mitochondria, as well as a decrease in the ER. We also observed enhanced activity of phospholipase C in the treated parasite, suggesting the opening of calcium channels located on the ER membrane. ER stress is marked by a reduced level of protein disulfide isomerase. Further, 17‐AAG treated worms showed an increase in apoptotic marker enzyme activities like calpain, cyt‐c, and caspase‐3. The 2D‐gel electrophoresis technique showed 142 protein spots in the control and 112 spots in the 17‐AAG treated parasite. Thus, 17‐AAG induced oxidative stress, and altered calcium, and proteostasis of parasites, which led to apoptosis. [ABSTRACT FROM AUTHOR]

Internet of Vehicles (IoV) systems are vulnerable to a wide range of attacks because of the lack of security measures. IoV systems can be infiltrated by malicious and unauthorized nodes, which can cause the authenticity, accessibility, and privacy of shared information resources to be compromised. Indeed, the use of an access control system can help; as a result, it is unable to respond to such attacks on time. This paper introduces an artificial intelligence-enabled access control mechanism (AI-ACM) with vehicle nodes and roadside units (RSUs) to overcome these issues. Here, use vehicle nodes as lightweight nodes, while RSUs act as comprehensive and edge nodes to provide access control service. A generative adversarial network (GAN) is used in place of risk prediction (RP) due to the lack of training sets, resulting in a sequence generation rather than an accurate risk prediction. Afterward, the blockchain-based Internet of Vehicles (BIoV) approach is summarized for the security mechanisms of vehicles that are discussed from the aspects of access control and authentication to sustain the distributed processing architecture and solve security issues. The simulation results show that AI-ACM is more accurate than the previous GANs at predicting the future. In addition, the RP model's access control accuracy can be improved as a result of this technique. [ABSTRACT FROM AUTHOR]

Wireless Underground Networks comprise the ability to constantly monitor several physical parameters such as ground temperature, water level and soil condition, and these are required to know the underground surface. A major challenge in wireless underground sensor networks is limited coverage area, high deployment costs, complex network topology, and identifying the better position for node deployment. To overcome these challenges, this research design an effective approach of localization algorithm that detects the location of unknown node position and then it must be able to place optimally to provide extended signal strength and coverage. The proposed design consists of three phases: placement selection using RSSI, placement selection using maximum signal strength and coverage, and predicting location. The proposed model provides an optimal solution to solve localization issues using a metaheuristic optimization algorithm in Long Range Topology based sensor network. The proposed model is implemented in MATLAB environment provides 84% of accuracy, 16% of error values and local delay, localization time, path loss, Mean Square Error, RSSI simulation, number of transmitted packets also obtained, this reveals the effectiveness of the proposed model. [ABSTRACT FROM AUTHOR]

Deep learning models depend on sizeable labelled training samples, and it is a common challenge that affects image retrieval based applications. Applications that are affected by these issues are computer vision and search engines. In the traditional system, the Convolutional Neural Network (CNN) is applied for designing high-quality RGB images retrieval. These techniques provided better classification performance, but the learning process of these deep learning algorithms are more complex than the conventional classifiers. Moreover, a practical technique has been raised to alleviate the low training samples called data augmentation. By increasing the learning features of CNN, very high-resolution images can be classified. This paper proposed an effective Content Based Image Retrieval (CBIR) based on CNN (IRB_CNN) with advantages from data augmentation. In IRB_CNN, feature generation is done by using pre-trained CNN without fully connected layers to get a better result than the overfitting issue of CNN. The training data augmentation method is employed to expand training images. The performance of CNN is enhanced using metaheuristic optimisation for weight optimisation in the training phase. Then CNN as a classifier is used to classify and evaluate the proposed CNN in the testing phase. The proposed model is evaluated using Swiss mountain and arbogreen datasets. The evaluation results have shown that the proposed IRB_CNN achieved an accuracy of 98% and reduced retrieval loss retrieval. Hence the proposed model better for real-time image retrieval than other conventional methods. [ABSTRACT FROM AUTHOR]

AMP-activated protein kinase (AMPK) is an evolutionarily conserved energy sensor. Activation of AMPK leads to a number of metabolic benefits, including improved mitochondrial function in skeletal muscle and lowering of serum glucose levels in type-2 diabetes models. However, direct activation of AMPK leads to cardiac enlargement, and an alternative strategy that activates AMPK without affecting the heart is needed. Inhibition of phosphodiesterase 4 (PDE4), which is poorly expressed in the human heart, activates AMPK in other tissues. In a screen to identify novel PDE4 inhibitors, we discovered compound CBU91, which is 5–10 fold more potent than rolipram, the best characterized PDE4 inhibitor. CBU91, like rolipram, is able to activate AMPK and Sirt1 and increase mitochondrial function in myotubes. These findings suggest that activation of AMPK in myotubes is a general property of PDE4 inhibition and that PDE4 inhibition may activate AMPK in metabolically relevant tissues without affecting the heart. [ABSTRACT FROM AUTHOR]

Over the past few decades multimedia content, particularly digital images, has increased at a rapid pace, with several complex images being uploaded to various social websites such as Instagram, Facebook and Twitter. Therefore, it is difficult to search and retrieve the relevant image in seconds. Search engines retrieve images based on traditional textbased methods that depend on metadata and captions. In the last few years, a wide range of research has focused on content-based image retrieval (CBIR) based on image mining approaches. This is a challenging research area due to the ever-increasing multimedia database and other image libraries. In order to offer an effective search and retrieval, a novel CBIR system is proposed using the image mining-based deep belief neural network (IMDBN) technique. The proposed method is designed to enhance retrieval accuracy while diminishing the semantic gap between human visual understanding and image feature representation. To achieve this objective, the proposed system carries several steps like preprocessing, feature extraction, classification, and feature matching. Initially, the input database images are fed into the proposed image mining-based CBIR system, whereas colour-shape-texture (CST) feature extraction technique is applied to extract relevant feature set. The extracted features are fused and stored in the feature vector and are subjected to the proposed IMDBN classification step to retrieve similar images in one label. Whenever a new query content is created, the most relevant images are retrieved. This, in turn, achieves 94% accuracy, which is higher than in existing approaches. [ABSTRACT FROM AUTHOR]

Aim: Identification of a 29 kDa heat stress protein in filarial parasite Setaria cervi and evaluation of its diagnostic potential against lymphatic filariasis. Methods and results: The Heat shock proteins (HSPs) were induced in filarial parasite S cervi by incubated at 42°C for 2 hours. The 10% SDS‐PAGE of cytosolic extract showed several over‐expressed bands. The MALDI‐LC/MS analysis of 29 kDa band showed 100% similarity with Bm14‐3‐3 like protein 2. Multiple sequence alignment of Bm14‐3‐3 like protein 2 sequence with W bancrofti, Caenorhabditis elegans; Loa loa and Homo sapiens showed 100%, 86%, 83% and 78%, sequence similarity respectively. The antigenic efficacy of Sc14‐3‐3 protein was evaluated with different filarial sera using ELISA which showed cross‐reactivity in order to Endemic Normal (EN) < Microfilaraemic (MF) < Chronic(CH) with IgG1 and EN < CH < MF in IgG4 ELISA. IgG1‐ and IgG4‐specific immunoblotting with CH and MF sera further explicated its specific antigenic cross‐reactivity. Conclusion: A 29 kDa heat shock protein of S cervi was identified as 14‐3‐3 protein having 100% homology to human filarial parasite B malayi. It showed strong reactivity with IgG1 and IgG4 subclass antibodies of W bancrofti‐infected human sera suggesting that 14‐3‐3 protein could be used as a vaccine/ diagnostic marker. [ABSTRACT FROM AUTHOR]

This paper is a literature survey (Review Paper) of comparative analysis on various definitions and concept explanations on software complexity, software deliverability and Software usability published recently (till date) in different international papers and books. This paper also includes the basic introduction of soft computing and its approaches. This paper explains how the software usability gets affected by the software complexity. [ABSTRACT FROM AUTHOR]

Introduction: In light of literature and controversy that exists in various cervical lesions, this prospective study was designed to explore the expression of Human Epidermal Growth Factor Receptor-2 (HER-2/neu) in the cervical lesions and its correlation with the histopathological grade and type of tumour. Immunohistochemistry (IHC) was performed to evaluate HER-2/neu expression as it is the most reliable method of detecting overexpression of HER-2/neu. Aim: To assess the role of HER-2/neu expression in premalignant and malignant lesions of uterine cervix. Materials and Methods: Seventy cases of premalignant and malignant cervical lesions received in our department from January 2015 to December 2016, were included in study and Polyclonal Rabbit Anti-Human c-erbB-2 oncoprotein from DAKO was used. Standard streptovidin-biotin peroxidase method of IHC was followed. A golden brown membrane and cytoplasmic staining was taken as a positive reaction and intensity of expression was graded according to the 2014 ASCO/CAP guidelines for HER-2/neu reporting. Results: Out of total 70 cases, HER-2/neu expression scores were 0 in 64.3% {23 cases of Cervical Intraepithelial Neoplasia (CIN) and 22 of Squamous Cell Carcinoma (SCC)}, +1 in 22.9%, (04 cases of CIN and 12 of SCC) +2 in 10% (06 cases of SCC and 01 of adenosquamous carcinoma) and +3 in 2.9% (02 cases of adenocarcinoma) cases. HER-2/neu overexpression rate was significantly higher in malignant (48.8%) as compared to pre malignant (14.8%) cases (p=0.004) and expression scores were higher (+2 and +3) in 20.9% of malignant cases as compared to none of pre malignant cases (p=0.020). Significant higher HER-2/neu scores are seen (+2 and +3) in all the adenocarcinoma cases as compared to 15% cases of SCC (p<0.001). Among malignant cases, HER-2/neu expression was statistically significantly higher in {Moderately Differentiated (MD) + Poorly Differentiated (PD)} 59.09% as compared to {Well Differentiated (WD)} 38.09% cases (p=0.090). Conclusion: Study shows that expression of HER-2/neu is relatively lower in cervical lesions. However, the results of our study show that with shift from well to poorly differentiated lesions; the HER-2/neu expression rate shows an incremental trend. [ABSTRACT FROM AUTHOR]

Oxidative stress plays a pivotal role in pathogenesis of cardiovascular diseases and diabetes; however, the roles of protein kinase A (PKA) and human phosphodiesterase 3A (hPDE3A) remain unknown. Here, we show that yeast expressing wild-type (WT) hPDE3A or K13R hPDE3A (putative ubiquitinylation site mutant) exhibited resistance or sensitivity to exogenous hydrogen peroxide (H2O2), respectively. H2O2-stimulated ROS production was markedly increased in yeast expressing K13R hPDE3A (Oxidative stress Sensitive 1, OxiS1), compared with yeast expressing WT hPDE3A (Oxidative stress Resistant 1, OxiR1). In OxiR1, YAP1 and YAP1-dependent antioxidant genes were up-regulated, accompanied by a reduction in thioredoxin peroxidase. In OxiS1, expression of YAP1 and YAP1-dependent genes was impaired, and the thioredoxin system malfunctioned. H2O2 increased cyclic adenosine monophosphate (cAMP)-hydrolyzing activity of WT hPDE3A, but not K13R hPDE3A, through PKA-dependent phosphorylation of hPDE3A, which was correlated with its ubiquitinylation. The changes in antioxidant gene expression did not directly correlate with differences in cAMP-PKA signaling. Despite differences in their capacities to hydrolyze cAMP, total cAMP levels among OxiR1, OxiS1, and mock were similar; PKA activity, however, was lower in OxiS1 than in OxiR1 or mock. During exposure to H2O2, however, Sch9p activity, a target of Rapamycin complex 1-regulated Rps6 kinase and negative-regulator of PKA, was rapidly reduced in OxiR1, and Tpk1p, a PKA catalytic subunit, was diffusely spread throughout the cytosol, with PKA activation. In OxiS1, Sch9p activity was unchanged during exposure to H2O2, consistent with reduced activation of PKA. These results suggest that, during oxidative stress, TOR-Sch9 signaling might regulate PKA activity, and that post-translational modifications of hPDE3A are critical in its regulation of cellular recovery from oxidative stress. [ABSTRACT FROM AUTHOR]

Inhibition of adipocyte lipolysis by insulin is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance and type 2 diabetes mellitus. The main target of the antilipolytic action of insulin is believed to be phosphodiesterase 3B (PDE3B), whose phosphorylation by Akt leads to accelerated degradation of the prolipolytic second messenger cyclic AMP (cAMP). To test this hypothesis genetically, brown adipocytes lacking PDE3B were examined for their regulation of lipolysis. In Pde3b knockout (KO) adipocytes, insulin was unable to suppress β-adrenergic receptor- stimulated glycerol release. Reexpressing wild-type PDE3B in KO adipocytes fully rescued the action of insulin against lipolysis. Surprisingly, a mutant form of PDE3B that ablates the major Akt phosphorylation site, murine S273, also restored the ability of insulin to suppress lipolysis. Taken together, these data suggest that phosphorylation of PDE3B by Akt is not required for insulin to suppress adipocyte lipolysis. [ABSTRACT FROM AUTHOR]

Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolysis of cyclic AMP and cyclic GMP, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signalling pathways and, consequently, myriad biological responses in health and disease. Currently, a small number of PDE inhibitors are used clinically for treating the pathophysiological dysregulation of cyclic nucleotide signalling in several disorders, including erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, intermittent claudication and chronic obstructive pulmonary disease. However, pharmaceutical interest in PDEs has been reignited by the increasing understanding of the roles of individual PDEs in regulating the subcellular compartmentalization of specific cyclic nucleotide signalling pathways, by the structure-based design of novel specific inhibitors and by the development of more sophisticated strategies to target individual PDE variants. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Hashimoto's thyroiditis is the most common form of acquired hypothyroidism. Fine needle aspiration cytology is one important tool in diagnosing Hashimoto's thyroditis, along with clinical, biochemical, immunological and ultrasonographical modalities. The present study examines cytological aspects of Hashimoto's thyroiditis along with their correlation with clinical, biochemical and immunological findings, whenever available. MATERIALS AND METHODS: This is a retrospective study of 50 cases of Hashimoto's thyroiditis. Cytological findings were reviewed and correlated with clinical, biochemical and immunological findings whenever available. RESULTS: The majority of the patients were middle-aged females, with a female to male ratio of 6.14:1. Most patients presented with diffuse thyromegaly (68%) and/or hypothyroidism (56.09%).The antibody profile was available in 22% of patients. Of these, anti-thyroid peroxidase antibodies were raised in 81.81% of patients and anti-thyroglobulin antibodies were raised in 63.63% of patients. In the present study, high lymphoid to epithelial cell ratio was seen in 78% of cases, and 74% of cases showed Hurthle cell change. Follicular atypia was seen in 36% of cases. Lymphoid follicle formation was seen in seen in 54% of cases. Follicular cell infiltration by lymphocytes, eosinophils and neutrophils was seen in 72%, 48% and 26% of cases, respectively. Plasma cells were seen in 18% of cases. CONCLUSION: Thyroid function tests and immunological tests cannot diagnose all cases of Hashimoto's thyroiditis. Fine needle aspiration cytology continues to be a diagnostic tool of significance in diagnosing Hashimoto's thyroiditis. The presence of inflammatory cells, particularly lymphocytes and eosinophils, was detected in a significant proportion of cases. [ABSTRACT FROM AUTHOR]

Inhibitors of cyclic nucleotide phosphodiesterase (PDE) PDE3A have inotropic actions in human myocardium, but their long-term use increases mortality in patients with heart failure. Two isoforms in cardiac myocytes, PDE3A1 and PDE3A2, have identical amino acid sequences except for a unique N-terminal extension in PDE3A1. We expressed FLAG-tagged PDE3A1 and PDE3A2 in HEK293 cells and examined their regulation by PKA- and PKC-mediated phosphorylation. PDE3A1, which is localized to intracellular membranes, and PDE3A2, which is cytosolic, were phosphorylated at different sites within their common sequence. Exposure to isoproterenol led to phosphorylation of PDE3A1 at the 14-3-3-binding site S312, whereas exposure to PMA led to phosphorylation of PDE3A2 at an alternative 14-3-3-binding site, S428. PDE3A2 activity was stimulated by phosphorylation at S428, whereas PDE3A1 activity was not affected by phosphorylation at either site. Phosphorylation of PDE3A1 by PKA and of PDE3A2 by PKC led to shifts in elution on gel-filtration chromatography consistent with increased interactions with other proteins, and 2D electrophoresis of coimmunoprecipitated proteins revealed that the two isoforms have distinct protein interactomes. A similar pattern of differential phosphorylation of endogenous PDE3A1 and PDE3A2 at S312 and S428 is observed in human myocardium. The selective phosphorylation of PDE3A1 and PDE3A2 at alternative sites through different signaling pathways, along with the different functional consequences of phosphorylation for each isoform, suggest they are likely to have distinct roles in cyclic nucleotide-mediated signaling in human myocardium, and raise the possibility that isoform-selective inhibition may allow inotropic responses without an increase in mortality. [ABSTRACT FROM AUTHOR]

Introduction: Extra pulmonary TB can be encountered in various organ systems, like lymph nodes, serous cavities, genitourinary tract, skeletal. Musculoskeletal TB can cause significant functional impairment. The clinical symptoms are variable, pain and swelling being common symptomatology. Investigations for suspected cases include radiological imaging, histopathological examination, bacteriological examination, and polymerase chain reaction. The mainstay of treatment is multidrug antitubercular chemotherapy. Aim: To study the cases of osteoarticular TB diagnosed on biopsy, to analyse the various microscopic patterns, results of microbiological investigations, correlate the clinical and radiological features and the response to ATT. Setting and Designs: A teaching tertiary medical institute in North India in catchment area, where prevalence of tuberculosis is high. A retrospective study of cases with a biopsy diagnosis of bone and/joint TB, retrieved from Histopathology section of Department of Pathology of the tertiary institute. Material and Methods: The study was retrospective and the data was collected for the preceding 3 years. The cases were retrieved from the records of the department of Pathology. A total of 16 cases were diagnosed as/suspected to be tuberculosis of bones and/joints. The clinical information were noted from the case files. Results of laboratory investigations along with relevant microbiologic investigations were noted. The biopsy samples were processed according to protocol. Ziehl-Neelsen stain to detect tubercle bacilli and PAS stain to rule out fungal infection were done. Microscopic features were noted. Results and Conclusion: Sixteen cases with a diagnosis of bone and/joint tuberculosis were found. The average age was 23.6 years. The most common presentation was pain and swelling. Knee joint was most commonly involved (7 cases) followed by spine and ankle (3 each). All the cases showed epithelioid granulomas which was necrotising in 11. AFB positivity was found only in 4 cases. ATT was started in 12 cases with a good response. It is important to suspect osteoarticular TB clinically and investigate accordingly. In resource poor setting, study of biopsy material can aid in diagnosis, further guiding the management. [ABSTRACT FROM AUTHOR]

ADP-ribosylation factors (ARFs) have crucial roles in vesicular trafficking. Brefeldin A-inhibited guanine nucleotide-exchange proteins (BIG)1 and BIG2 catalyze the activation of class I ARFs by accelerating replacement of bound GDP with GTP. Several additional and differing actions of BIG1 and BIG2 have been described. These include the presence in BIG2 of 3 A kinase-anchoring protein (AKAP) domains, one of which is identical in BIG1. Proteins that contain AKAP sequences act as scaffolds for the assembly of PKA with other enzymes, substrates, and regulators in complexes that constitute molecular machines for the reception, transduction, and integration of signals from CAMP or other sources, which are initiated, propagated, and transmitted by chemical, electrical, or mechanical means. Specific depletion of HeLa cell PDE3A with small interfering RNA significantly decreased membrane-associated BIG1 and BIG2, which by confocalimmunofluorescence microscopy were widely dispersed from an initial perinuclear Golgi concentration. Concurrently, activated ARF1-GTP was significantly decreased. Selective inhibition of PDE3A by 1-h incubation of cells with cilostamide similarly decreased membrane-associated BIG1. We suggest that decreasing PDE3A allowed cAMP to accumulate in microdomains where its enzymatic activity limited cAMP concentration. There, cAMP-activated PKA phosphorylated BIG1 and BIG2 (AKAP5 for assembly of PKA. PDE3A, and other molecules), which decreased their GEP activity and thereby amounts of activated ARF1GTP. Thus, PDE3A in these BIG1 and BIG2 AKAP complexes may contribute to the regulation of ARF function via limitation of cAMP effects with spatial and temporal specificity. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-alpha (TNF-alpha) stimulates lipolysis in human adipocytes. However, the mechanisms regulating this process are largely unknown. We demonstrate that TNF-alpha increases lipolysis in differentiated human adipocytes by activation of mitogen-activated protein kinase kinase (MEK), extracellular signal-related kinase (ERK), and elevation of intracellular cAMP. TNF-alpha activated ERK and increased lipolysis; these effects were inhibited by two specific MEK inhibitors, PD98059 and U0126. TNF-alpha treatment caused an electrophoretic shift of perilipin from 65 to 67 kDa, consistent with perilipin hyperphosphorylation by activated cAMP-dependent protein kinase A (PKA). Coincubation with TNF-alpha and MEK inhibitors caused perilipin to migrate as a single 65-kDa band. Consistent with the hypothesis that TNF-alpha induces perilipin hyperphosphorylation by activating PKA, TNF-alpha increased intracellular cAMP approximately 1.7-fold, and the increase was abrogated by PD98059. Furthermore, H89, a specific PKA inhibitor, blocked TNF-alpha-induced lipolysis and the electrophoretic shift of perilipin, suggesting a role for PKA in TNF-alpha-induced lipolysis. Finally, TNF-alpha decreased the expression of cyclic-nucleotide phosphodiesterase 3B (PDE3B) by approximately 50%, delineating a mechanism by which TNF-alpha could increase intracellular cAMP. Cotreatment with PD98059 restored PDE3B expression. These studies suggest that in human adipocytes, TNF-alpha stimulates lipolysis through activation of MEK-ERK and subsequent increase in intracellular cAMP. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNF-α) stimulates lipolysis in human adipocytes. However, the mechanisms regulating this process are largely unknown. We demonstrate that TNF-α increases lipolysis in differentiated human adipocytes by activation of mitogen-activated protein kinase (MEK), extracellular signal-related kinase (ERK), and elevation of intracellular cAMP. TNF-α activated ERK and increased lipolysis; these effects were inhibited by two specific MEK inhibitors, PD98059 and U0126. TNF-α treatment caused an electrophoretic shift of perilipin from 65 to 67 kDa, consistent with perilipin hyperphosphorylation by activated cAMP dependent protein kinase A (PKA). Coincubation with TNF-α and MEK inhibitors caused perilipin to migrate as a single 65-kDa band. Consistent with the hypothesis that TNF-α induces perilipin hyperphosphorylation by activating PKA, TNF-α increased intracellular cAMP ∼l.7-fold, and the increase was abrogated by PD98059. Furthermore, H89, a specific PKA inhibitor, blocked TNF-α-induced lipolysis and the electrophoretic shift of perilipin, suggesting a role for PKA in TNF-α-induced lipolysis. Finally, TNF-α decreased the expression of cyclic-nucleotide phosphodiesterase 3B (PDE3B) by ∼50%, delineating a mechanism by which TNF-α could increase intracellular cAMP. Cotreatment with PD98059 restored PDE3B expression. These studies suggest that in human adipocytes, TNF-α stimulates lipolysis through activation of MEK-ERK and subsequent increase in intracellular cAMP. [ABSTRACT FROM AUTHOR]

Background: Abdominal tuberculosis (TB) is the sixth most common form of extra-pulmonary site of infection after lymphatic, genitourinary, bone and joint, miliary and meningeal TB with a rising incidence in recent years. TB can affect any part of the gastro-intestinal (GI) tract including anus, peritoneum and hepato-biliary system. The clinical manifestations of abdominal tuberculosis are non-specific and mimic various GI disorders and cause delay in diagnosis and management. Aim: To evaluate the various clinical, radiological and microbiological findings of abdominal tuberculosis and to define the role of histopathological examination in establishing the diagnosis in resource poor settings and to analyze the compliance and response to anti-tubercular treatment. Materials and Methods: A five year retrospective study (January 2010 to December 2014) was done in a tertiary teaching hospital in Northern India and all the cases diagnosed as abdominal tuberculosis during the study period, were included. The relevant clinical informations, laboratory results, microbiological and radiological investigations were recorded. Histopathological examination of all the resected / excised specimens was done and Ziehl-Neelsen (ZN) staining to detect the tubercular bacilli and Periodic acid-Schiff (PAS) stain to rule out fungal infection was done in all the cases. Results: Out of 48 cases with abdominal tuberculosis, the average age of presentation was 27.4 years with a slight male predominance (Male:Female=1.4:1). Abdominal pain (100%) was the most common presenting symptom followed by anorexia (98%), fever (88%) and intestinal obstruction (88%). The ileum was the most common site of involvement. All the 45 resected / excised tissue specimens (34 cases of intestinal resection and 11 cases of intesinal, omental and lymph nodes biopsies) showed epithelioid granulomas along with necrosis (in 38 cases) and Langhans giant cells (in 42 cases). Acid Fast Bacilli (AFB) positivity was seen in 5 tissue specimens only. All patients were put on anti-tubercular treatment and majority showed good response to therapy. Conclusion: Abdominal tuberculosis should be considered as a differential diagnosis in patients with vague GI symptoms. Study of histopathological findings can aid in the diagnosis in the settings where advanced molecular methods of diagnosis are not available, leading to early diagnosis and management. [ABSTRACT FROM AUTHOR]

Water extract of the bark of plant of Pterocarpus marsupium Roxb is used as an antidiabetic drug in indigenous medicine in India. (−) Epicatechin, its active principle, has been found to be insulinogenic. The present in vitro study reports some insulin like activities of (−) epicatechin. Like insulin, (−) epicatechin stimulates oxygen uptake in fat cells and tissue slices of various organs, increases glycogen content of rat diaphragm in dose-dependent manner with corresponding increase in U-C glucose uptake, and inhibits theophylline induced lipolysis in isolated fat pads in dose-dependent manner. Experiments on competitive binding ofI-insulin and (−) epicatechin to liver cell plasma membrane indicate that insulin does not share binding site with (−) epicatechin. (−) Epicatechin at a concentration of up to 1 mM does not effect the release of glucagon from the islets in vitro. Thus, (−) epicatechin has insulinogenic as well as insulin like properties. [ABSTRACT FROM AUTHOR]

The biologic activities of three synthetic analogues of CCK-4 (Trp-Met-Asp-Phe-NH) in which (i) the C-terminal residue Phe was N-methylated (peptide I); (ii) the C-terminal Phe residue was N-methylated and Ser is substituted for Met in position 2 (peptide II); (iii) Pro was substituted for Trp in position 1 and the C-terminal amino nitrogen was methylated (peptide III), have been described. Peptides I and II have been found to inhibit the release of both insulin and glucagon, while peptide III was found to be a potent releasing agent for insulin and an inhibitor for glucagon. [ABSTRACT FROM AUTHOR]

Agaricus bisporus lectin (PHA-B) stimulates insulin release in vitro. The stimulation is associated with increased conversion of proinsulin to insulin in the isolated islets of Langerhans of rats. Both these functions are directly proportional to the binding of I PHA-B, which is more marked in the islets from younger rats. The lectin binding to islets is not affected by glucose concentration in the medium. [ABSTRACT FROM AUTHOR]

Protein-tyrosine phosphatases (PTPases) have been implicated in the physiological regulation of the insulin signalling pathway. In cellular and molecular studies, the transmembrane, receptor-type PTPase LAR and the intracellular, non-receptor enzyme PTP1B have been shown to have a direct impact on insulin action in intact cell models. Since insulin signalling can be enhanced by reducing the abundance or activity of specific PTPases, pharmaceutical agents directed at blocking the interaction between individual PTPases and the insulin receptor may have potential clinical relevance to the treatment of insulin-resistant states such as obesity and Type II diabetes mellitus. [ABSTRACT FROM AUTHOR]

Synthetic analogues of CCK-4 in which Trp was replaced by D-Pro (peptide I), Thz (peptide II) and ΔPro (peptide III) have been studied for their insulin and glucagon releasing activities from the islets of Langerhans in vitro. Peptide I has been found to be the most potent insulin releaser among the three analogues and its activity is comparable to that of CCK-4. Unlike CCK-4, its three analogues (peptides I-III) do not stimulate the release of glucagon with basal concentration of glucose in the medium. However, with increasing glucose concentration, all the three analogues potentiate the glucose stimulus for insulin release. [ABSTRACT FROM AUTHOR]

Colenol, a diterpenoid isolated from the roots of Coleus forskohlii stimulates the release of insulin and glucagon from the islets both in vitro and in vivo. Coleonol-stimulated release of glucagon from islets in vitro is much more pronounced as compared to that of insulin. Glucose concentration of 5.6 mM in the medium is required for the coleonol stimulation of insulin release. Feeding of coleonol to alloxan diabetic rats cause 36.5% increase in blood glucose level as compared to alloxan diabetic control. Oral feeding of coleonol for 7 days to normal rats causes increase in blood glucose, serum insulin, glucagon and free fatty acid levels with corresponding increase in glucose-6-phosphatase activity and depletion of liver glycogen. Predominant stimulation of A-cells by coleonol is suggested for the above effects. [ABSTRACT FROM AUTHOR]

Brooke-Spiegler syndrome is a rare entity. It is an autosomal dominant syndrome in which multiple trichoepitheliomas, cylindromas, or other adnexal tumors are seen. Very few cases of Brooke-Spiegler syndrome are reported in the literature. We came across a 40 -year-old female in which multiple trichoepitheliomas and cylindromas were seen on scalp. In view of clinical history and histopathological examination it was diagnosed as Brooke-Spiegler syndrome. We report this case because of its rarity. [ABSTRACT FROM AUTHOR]

Brooke-Spiegler syndrome is a rare entity. It is an autosomal dominant syndrome in which multiple trichoepitheliomas, cylindromas, or other adnexal tumors are seen. Very few cases of Brooke-Spiegler syndrome are reported in the literature. We came across a 40 -year-old female in which multiple trichoepitheliomas and cylindromas were seen on scalp. In view of clinical history and histopathological examination it was diagnosed as Brooke-Spiegler syndrome. We report this case because of its rarity. [ABSTRACT FROM AUTHOR]

Understanding mechanisms by which a population of beige adipocytes is increased in white adipose tissue (WAT) reflects a potential strategy in the fight against obesity and diabetes. Cyclic adenosine monophosphate (cAMP) is very important in the development of the beige phenotype and activation of its thermogenic program. To study effects of cyclic nucleotides on energy homeostatic mechanisms, mice were generated by targeted inactivation of cyclic nucleotide phosphodiesterase 3b (Pde3b) gene, which encodes PDE3B, an enzyme that catalyzes hydrolysis of cAMP and cGMP and is highly expressed in tissues that regulate energy homeostasis, including adipose tissue, liver, and pancreas. In epididymal white adipose tissue (eWAT) of PDE3B KO mice on a SvJ129 background, cAMP/protein kinase A (PKA) and AMP-activated protein kinase (AMPK) signaling pathways are activated, resulting in 'browning' phenotype, with a smaller increases in body weight under high-fat diet, smaller fat deposits, increased β-oxidation of fatty acids (FAO) and oxygen consumption. Results reported here suggest that PDE3B and/or its downstream signaling partners might be important regulators of energy metabolism in adipose tissue, and potential therapeutic targets for treating obesity, diabetes and their associated metabolic disorders. [ABSTRACT FROM AUTHOR]

An abstract of the article "Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases," by Sung-Jun Park, Faiyaz Ahmad, Andrew Philp, Keith Baar, Tishan Williams, Haibin Luo, Hengming Ke, Holger Rehmann, Ronald Taussig, and Alexandra L. Brown is presented.