Receptor Identification: Advances in Ligands and Transmitters Discovery

Receptor identification is an integral part of drug discovery and development. By the beginning of the next millennium, the search for the natural ligands of the orphan G-protein-coupled receptors will lead to the discovery of so many new peptides that it may well double their present number. It has recently become evident that all types of chemical messengers, hormones and transmitters act through membrane receptors which constitute our largest superfamily of proteins, i.e. the G protein-coupled receptors. The development of targeted therapies has revolutionized the treatment of various chronic diseases. Receptors have well-conserved regions that are recognized and activated by hormones and neurotransmitters. These ligands are peptides, lipids or biogenic amines, and act as transmitter molecules. Identification of orphan receptors include screening, binding and reverse engineering that help to find out cysteinyl leukotriene CysLT1 and Cys T2, hepatointestinal leukotriene B4, motilin, Ghrelin, Growth hormone-releasing peptide and growth hormone secretagogue receptor and many more. Techniques involved in screening of receptors include low stringency hybridization followed by PCR-derived approaches helps to discover various orphan g protein couple recptors (oGPCR). The discovery of the oGPCR represents a hallmark in neuroscience research, and the exploitation of its numerous physiological and pathophysiological functions is a promising avenue for therapeutic applications

Complex Composite Odontoma with Characteristic Histology

Odontomas are the most commonly occurring odontogenic tumors, which are considered by many to be hamartomas rather than neoplasms. These clinically asymptomatic tumors are classified into complex and compound odontomas. They are usually discovered in radiographs and rarely cause bony expansion or infection. This paper discusses a case report of a complex odontoma exhibiting all the structural features and defects of enamel, dentine, and cementum in succession, with an overview on its etiology

Youth futures and a masculine development ethos in the regional story of Uttarakhand

Research on the Uttarakhand region, which became a new state in 2000, has focused largely on agrarian livelihoods, religious rituals, development demands, ecological politics and the role of women in regional social movements. This essay discusses another dimension of the regional imaginary—that of a masculine development ethos. Based on ethnographic research and print media sources, this essay focuses on stories, politics, mobilities and imaginations of young men in the years immediately after the achievement of statehood. Despite increased outmigration of youth in search of employment, many young men expressed the dream of maintaining livelihoods in the familiar towns and rural spaces of Uttarakhand, describing their home region as a source of power and agency. In rallies and in print media, young (mostly upper caste) men expressed their disillusionment with the government and the promises of statehood, arguing that their aspirations for development and employment were left unfulfilled. Gendered stories of the region, told in Hindi in rallies and print media, contained references to local places, people and historical events and were produced through local connections and know-how, fostering a regional youth politics. The article argues that Uttarakhand as a region is shaped by the politics of local actors as well as embodied forms of aspiration, affiliation and mobility.IS

Reduction en-masse of inguinal hernia with strangulated obstruction

“Reduction en masse of inguinal hernia” means reduction/migration of a hernial sac into the properitoneal space. We report the CT findings in a case of reduction en masse with strangulated obstruction. CT scan demonstrated a hernial sac with fibrous constriction band at the neck, situated in the properitoneal space superior to the inguinal region, causing closed-loop obstruction. The hernial sac contained thickened bowel loop with wall enhancement and fluid suggestive of incarceration/strangulation. We propose to call this, ‘The properitoneal hernial sac sign’, defined as “Presence of a hernial sac in the properitoneal space (and not in the inguinal/femoral canal) containing an obstructed/incarcerated bowel loop and causing small bowel obstruction” to identify “reduction en masse of inguinal hernia”

Prolactin and DNA damage trigger an anti-breast cancer cell immune response

IntroductionThe role of prolactin (PRL) in breast cancer and its role within the context of the tumor microenvironment are not well understood. In our previous study, we demonstrated a cross-talk between the ataxia telangiectasia-mutated (ATM) DNA damage response pathway and the PRL-Janus-kinase-2 (JAK2)-signal transducer and activator of transcription-5 (STAT5)-heat shock protein-90 (HSP90) pathway. Here we investigated the role of PRL in tumor initiation and the effect of DNA damage.MethodsWe used an in vivo model to assess the ability of breast cancer cells to initiate orthotopic xenograft tumor formation after DNA damage. Breast cancer cells engineered to secrete human PRL were treated with the DNA damaging agent doxorubicin and injected into the mammary fat pad of immune-deficient severe combined immunodeficiency disease (SCID) mice.ResultsDoxorubicin and PRL combination increased the tumor latency, although PRL secretion alone did not change the tumor latency compared to the controls. Depletion of glycolipid asialo ganglioside-GM1-positive immune cells using anti-asialo GM1 antibody resulted in faster tumor formation only in the PRL-secreting breast cancer cells that were pre-treated with doxorubicin. Additionally, doxorubicin plus the PRL treatment of breast cancer cells was shown in vitro to attract cytotoxic NK cells compared to the controls, and this was dependent on the PRLR.DiscussionThese results demonstrate that combined breast cancer cell DNA damage and PRL exposure results in the anti-tumor cell activity of asialo-GM1-positive immune cells