Melanin-concentrating hormone (MCH) is a 19-aa cyclic neuropeptide originally isolated from chum salmon pituitaries. Besides its effects on the aggregation of melanophores in fish several lines of ...evidence suggest that in mammals MCH functions as a regulator of energy homeostasis. Recently, several groups reported the identification of an orphan G protein-coupled receptor as a receptor for MCH (MCH-1R). We hereby report the identification of a second human MCH receptor termed MCH-2R, which shares about 38% amino acid identity with MCH-1R. MCH-2R displayed high-affinity MCH binding, resulting in inositol phosphate turnover and release of intracellular calcium in mammalian cells. In contrast to MCH-1R, MCH-2R signaling is not sensitive to pertussis toxin and MCH-2R cannot reduce forskolin-stimulated cAMP production, suggesting an exclusive Gα qcoupling of the MCH-2R in cell-based systems. Northern blot and in situ hybridization analysis of human and monkey tissue shows that expression of MCH-2R mRNA is restricted to several regions of the brain, including the arcuate nucleus and the ventral medial hypothalamus, areas implicated in regulation of body weight. In addition, the human MCH-2R gene was mapped to the long arm of chromosome 6 at band 6q16.2-16.3, a region reported to be associated with cytogenetic abnormalities of obese patients. The characterization of a second mammalian G protein-coupled receptor for MCH potentially indicates that the control of energy homeostasis in mammals by the MCH neuropeptide system may be more complex than initially anticipated.
Glucagon maintains glucose homeostasis during the fasting state by promoting hepatic gluconeogenesis and glycogenolysis. Hyperglucagonemia and/or an elevated glucagon-to-insulin ratio have been ...reported in diabetic patients and animals. Antagonizing the glucagon receptor is expected to result in reduced hepatic glucose overproduction, leading to overall glycemic control. Here we report the discovery and characterization of compound 1 (Cpd 1), a compound that inhibits binding of 125I-labeled glucagon to the human glucagon receptor with a half-maximal inhibitory concentration value of 181 +/- 10 nmol/l. In CHO cells overexpressing the human glucagon receptor, Cpd 1 increased the half-maximal effect for glucagon stimulation of adenylyl cyclase with a KDB of 81 +/- 11 nmol/l. In addition, Cpd 1 blocked glucagon-mediated glycogenolysis in primary human hepatocytes. In contrast, a structurally related analog (Cpd 2) was not effective in blocking glucagon-mediated biological effects. Real-time measurement of glycogen synthesis and breakdown in perfused mouse liver showed that Cpd 1 is capable of blocking glucagon-induced glycogenolysis in a dosage-dependent manner. Finally, when dosed in humanized mice, Cpd 1 blocked the rise of glucose levels observed after intraperitoneal administration of exogenous glucagon. Taken together, these data suggest that Cpd 1 is a potent glucagon receptor antagonist that has the capability to block the effects of glucagon in vivo.
DESIDOC Journal of Library & Information Technology (DJLIT) formerly known as DESIDOC Bulletin of Information Technology is a peer-reviewed, open access, bimonthly journal. This paper presents a ...bibliometric analysis of the journal to assess the pattern of growth of the research output published in the journal, pattern of authorship and geographic distribution of output, subjects covered and citation analysis of the references attached to the papers and change in them over two different periods (2001-2006) and (2007-2012). It is found that 391 papers were published during the period of study (2001-2012). The maximum number of articles (65) was published in 2012. The maximum number of contributions is joint collaborations with 61.4 %. Most of the contributions (88 %) are from India and 12 % are foreign contributions. The study revealed that majority of the authors preferred journals as the source of information providing the highest number of citations. Dr BM Gupta has published maximum number of articles (26) in the Journal during the period under study. The maximum number of articles (65 %) has the length of 6-10 pages. Maximum number of special issues (5) was published in 2012.
Abstract
Interleukin-22 (IL-22), an IL-10 cytokine family member, is produced by a variety of immune cells including Th1, Th17 and Th22 T helper cells, CD8+ T-cells, NK cells, ILC3, neutrophils and ...macrophages. Interleukin-22 crucially participates in regulating the integrity of epithelial barriers by modulating inflammation, mucus production, additional aspects of wound healing and has been noted to be substantially induced in patients with various chronic inflammatory conditions. Upregulation of IL-22 in psoriasis (PS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) inflammatory bowel disease, Crohn’s disease, cystic fibrosis and atopic dermatitis (AD) has been well documented, with IL-22 often considered a hallmark of IL-1-driven immune responses. Furthermore, IL-22 protein has been proposed as a stratification biomarker for psoriatic arthritis therapeutic choice between IL-17 and TNF inhibitions, to correlate with the severity of clinical sequelae of Sjogren’s Syndrome, and IL-22 mRNA expression stratifies AD responses to fezakinumab. In healthy individuals, IL-22 activity resulting from low level expression may be functionally neutralized, at least in selected tissues such as the intestinal tract, by binding to soluble IL-22 binding protein (IL-22BP) expressed locally by dendritic cells. However, in these pathologies, inhibition of IL-22 by IL-22BP is presumably overcome by elevated expression of IL-22 protein. Explore ranges of IL-22 serum concentrations to differentiate between healthy donors (HD) and select autoimmune disease patients with a simple-to-use, high sensitivity ELISA. A commercial sandwich ELISA (PBL Assay Science, 41701-1) quantifying human IL-22 was characterized and used to assess IL-22 concentration in sera from HD and patients exhibiting one of several autoimmune diseases. This high sensitivity ELISA, having a manufacturer-stated LLOQ of 0.78 pg/ml, exhibited good assay precision, dilutional linearity and spike recovery using HD serum. Parallelism was demonstrated using serum samples from four patients with AD and three HD. Addition of a 10- to 100-fold mass excess of exogenous recombinant IL-22BP reduced the ability of the assay to quantify IL-22 suggesting that at least one antigenic region recognized by ELISA antibodies may be sterically hindered by IL-22BP binding to IL-22. However, such high levels of 10 and 100 ng/ml of IL-22BP are unlikely to be achieved in vivo, and therefore may not adversely affect quantitation of physiological levels of IL-22 protein by this assay. Commercially sourced HD sera concentrations of IL-22 exceeded the assay LLOQ in 23 of 24 samples (96%) with a mean IL-22 concentration of 1.84 ± 1.33 pg/ml. Commercial sera from patients with AD (n = 10, 100%), PS (n = 10, 100%), RA (n = 10, 100%), SLE (n = 10, 100%) were similarly analysed and yielded mean levels of 14.8 ± 11.2, 5.1 ± 2.4, 5.6 ± 0.91 and 3.1 ± 0.74 pg/mL, respectively. Interleukin-22 measured in AD (and PS) sera exhibited sufficiently broad ranges of concentrations such that statistical differences between AD and all other groups were not readily achievable with this number of samples. Notably, these commercially obtained serum samples were not controlled for overall severity of any disease at the time of sample collection. Sample sets were randomly obtained from a population of individuals self-identifying as AD sufferers, as were the other patient samples. With mean serum IL-22 in AD appearing to trend as substantially elevated, an opportunity exists to explore IL-22 trends along with other biomarkers in clinically identified and possibly symptom-stratified populations of patients with AD. Should this trend toward IL-22 elevation be fully substantiated in AD, therapeutic stratification and precision medicine approaches may be conceivable based on serum IL-22 protein concentrations, supporting other investigators’ earlier work examining IL-22 mRNA. The baseline readability of endogenous IL-22 in HD sera using this ELISA is also highly advantageous.
Marketing is not all about selling or making profit. It is a mix of pricing, promotion, development of markets, selling as well as distribution and one most important term that has been added in ...recently is after sales service and most successful marketing is considered to have a feedback mechanism. Feedback, not for the sake of getting the feedback, but careful analysis of the requirements of the clients, analysis of the feedback and then taking appropriate action on that. Marketing is all about creating awareness, making the customer delight and satisfaction with product/service. It is true for all be it design, product development, or service. Defence Scientific Information & Documentation Centre (DESIDOC), on behalf of DRDO brings out a journal--DESIDOC Journal of Library & Information Technology (DJLIT). It is a well known journal in the field of Library & Information Science. DESIDOC has taken certain initiatives for DJLIT in terms of tools and techniques applied for online and offline marketing of the Journal. The study points out the initiatives taken for marketing of the Journal for its all stakeholders and plans for the future. The study has provided some recommendations also. The article will help the LIS professionals to explore various forums to market their products and services. http://dx.doi.org/10.14429/djlit.36.2.9714
Gene therapy and its applications Bansal, Alka; Prakash, Ravi; Agarwal, Swati ...
Journal of Medical Evidence,
01/2023, Letnik:
4, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Gene therapy is the treatment of abnormal or mutated genes present in cells through the addition of healthy genes or replacement/deletion/site-specific modification of faulty genes. Deoxyribonucleic ...acid, messenger ribonucleic acid (RNA), small interference RNA, microsomal RNA and antisense oligonucleotides are the genetic materials implicated in gene therapy. They are inserted into the diseased cells using viral or non-viral vectors through an in vivo or ex vivo transduction. Gamma retrovirus, lentivirus, herpesvirus, adenovirus and adeno-associated virus are common viral vectors, while transposons, cationic polymers, dendrimers and cell-penetrating peptides or liposomes are common non-viral vectors. Allologous or autologous T cells, haematopoietic stem cells and chimeric antigen receptor T cells are used for ex vivo gene transduction. Conventional gene therapy of inserting new genetic material shows toxicity such as off-target effects, altered immune responses, inflammatory reactions and possible oncogenic transformation in the recipient. Newer gene editing techniques such as zinc-finger nuclease, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats allow the site-specific correction or control of expression of mutated genes present in cells. Until August 2020, 23 gene-based medicines received approval from drug regulatory agencies in various countries and 362 were in development. Single-gene disorders have shown encouraging results, but evidence of using gene therapy in polygenic and common age-related diseases is still required. Recently, the horizon of gene therapy widened to include COVID vaccines and as an adjunct to chemotherapy. If we could overcome its limitations such as immunogenicity, mutagenicity and high costs, gene therapy can be the medicine of the next generation.
Libraries have adopted information technology be that IT-enabled content development, content management tools, content access and delivery tools or long term presentation tools. Libraries are always ...in the fore front where the adoption and usage of new technologies are concerned. Internet of Things (IoT) is enabling objects to collect data and transfer the data over a network without human intervention by using internet, sensors, and RFID. It is being used in various fields and is still emerging. Various innovative solutions are created. This paper explores the concept of IoT, its historical background and its potential applications in libraries. Some of the challenges which will be faced by the library professional while implementing it are also discussed.
"Survival of the Fittest" as quoted by Charles Darwin fits and suits in all walks of life. As on date, big debate is on regarding the existence and survival of libraries. Libraries need to adopt ...emerging tools and technologies to provide best services to the users on time with precision. Artificial intelligence has placed itself everywhere in everyday life. This paper is an attempt to expedite AI applications in libraries, not only for providing services to the existing users but also finding innovative ways to attract new users. The paper discusses AI, basic requisites, its applications in libraries, and barriers in its implementations. The paper concludes that AI is the need of today for libraries.
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