Cloning characterisation and expression of a G-protein-couple receptor from Lymnaea stagnalis and identification of a leucokinin-like peptide PSFHSWSamide as its endogenous ligand

No description supplie

The Lymnaea Cardioexcitatory Peptide (LyCEP) Receptor: A G-Protein–Coupled Receptor for a Novel Member of the RFamide Neuropeptide Family

A novel G-protein–coupled receptor (GRL106) resembling neuropeptide Y and tachykinin receptors was cloned from the molluscLymnaea stagnalis. Application of a peptide extract from the Lymnaea brain to Xenopus oocytes expressing GRL106 activated a calcium-dependent chloride channel. Using this response as a bioassay, we purified the ligand for GRL106,Lymnaea cardioexcitatory peptide (LyCEP), an RFamide-type decapeptide (TPHWRPQGRF-NH2) displaying significant similarity to the Achatina cardioexcitatory peptide (ACEP-1) as well as to the recently identified family of mammalian prolactin-releasing peptides. In the Lymnaeabrain, the cells that produce egg-laying hormone are the predominant site of GRL106 gene expression and appear to be innervated by LyCEP-containing fibers. Indeed, LyCEP application transiently hyperpolarizes isolated egg-laying hormone cells. In theLymnaea pericardium, LyCEP-containing fibers end blindly at the pericardial lumen, and the heart is stimulated by LyCEPin vitro. These data confirm that LyCEP is an RFamide ligand for GRL10

Cancer cells under immune attack acquire CD47-mediated adaptive immune resistance independent of the myeloid CD47-SIRP alpha axis

Cancer cells exploit CD47 overexpression to inhibit phagocytic elimination and neoantigen processing via the myeloid CD47-SIRPα axis and thereby indirectly evade adaptive T cell immunity. Here, we report on a hitherto unrecognized direct immunoinhibitory feature of cancer cell-expressed CD47. We uncovered that in response to IFNγ released during cognate T cell immune attack, cancer cells dynamically enhance CD47 cell surface expression, which coincides with acquiring adaptive immune resistance toward pro-apoptotic effector T cell mechanisms. Indeed, CRISPR/Cas9-mediated CD47-knockout rendered cancer cells more sensitive to cognate T cell immune attack. Subsequently, we developed a cancer-directed strategy to selectively overcome CD47-mediated adaptive immune resistance using bispecific antibody (bsAb) CD47xEGFR-IgG2s that was engineered to induce rapid and prolonged cancer cell surface displacement of CD47 by internalization. Treatment of CD47(pos) cancer cells with bsAb CD47xEGFR-IgG2s potently enhanced susceptibility to cognate CD8(pos) T cells. Targeting CD47-mediated adaptive immune resistance may open up new avenues in cancer immunotherapy

An adaptive meta-search engine considering the user’s field of interest

AbstractExisting meta-search engines return web search results based on the page relevancy to the query, their popularity and content. It is necessary to provide a meta-search engine capable of ranking results considering the user’s field of interest. Social networks can be useful to find the users’ tendencies, favorites, skills, and interests. In this paper we propose MSE, a meta-search engine for document retrieval utilizing social information of the user. In this approach, each user is assumed to have a profile containing his fields of interest. MSE extracts main phrases from the title and short description of receiving results from underlying search engines. Then it clusters the main phrases by a Self-Organizing Map neural network. Generated clusters are then ranked on the basis of the user’s field of interest. We have compared the proposed MSE against two other meta-search engines. The experimental results show the efficiency and effectiveness of the proposed method

Assessing professionals' adoption readiness for eMental health:Development and validation of the eMental health adoption readiness scale

BACKGROUND: The last few decades have witnessed significant advances in the development of digital tools and applications for mental health care. Despite growing evidence for their effectiveness, acceptance and use of these tools in clinical practice remain low. Hence, a validated and easy-to-use instrument for assessing professionals’ readiness to adopt eMental health (EMH) is necessary to gain further insights into the process of EMH adoption and facilitate future research on this topic. OBJECTIVE: The aim of this study is to develop and validate an instrument for assessing mental health care professionals’ readiness to adopt EMH. METHODS: Item generation was guided by literature and inputs from mental health care professionals and experts in survey development. Exploratory factor analyses were conducted on an initial set of 29 items completed by a sample of mental health care professionals (N=432); thereafter, the scale was reduced to 15 items in an iterative process. The factor structure thus obtained was subsequently tested using a confirmatory factor analysis with a second sample of mental health care professionals (N=363). The internal consistency, convergent validity, and predictive validity of the eMental Health Adoption Readiness (eMHAR) Scale were assessed. RESULTS: Exploratory factor analysis resulted in a 3-factor solution with 15 items. The factors were analyzed and labeled as perceived benefits and applicability of EMH, EMH proactive innovation, and EMH self-efficacy. These factors were confirmed through a confirmatory factor analysis. The total scale and subscales showed a good internal consistency (Cronbach α=.73-.88) along with acceptable convergent and predictive relationships with related constructs. CONCLUSIONS: The constructed eMHAR Scale showed a conceptually interpretable 3-factor structure having satisfactory characteristics and relationships with relevant concepts. Its ease of use allows for quick acquisition of data that can contribute to understanding and facilitating the process of adoption of EMH by clinical professionals

Collective nostalgia: A group-level emotion that confers unique benefits on the group.

This research established collective nostalgia as a group-level emotion and ascertained the benefits it confers on the group. In Study 1, participants who reflected on a nostalgic event they had experienced together with ingroup members (collective nostalgia) evaluated the ingroup more positively and reported stronger intentions to approach (and not avoid) ingroup members than those who recalled a nostalgic event they had experienced individually (personal nostalgia), those who reflected on a lucky event they had experienced together with ingroup members (collective positive), and those who did not recall an event (no recall). In Study 2, collective (vs. personal) nostalgia strengthened behavioral intentions to support the ingroup more so than did recalling an ordinary collective (vs. personal) event. Increased collective self-esteem mediated this effect. In Study 3, collective nostalgia (compared with recall of an ordinary collective event) led participants to sacrifice money in order to punish a transgression perpetrated against an ingroup member. This effect of collective nostalgia was more pronounced when social identification was high (compared with low). Finally, in Study 4, collective nostalgia converged toward the group average (i.e., was socially shared) when participants thought of themselves in terms of their group membership. The findings underscore the viability of studying nostalgia at multiple levels of analysis and highlight the significance of collective nostalgia for understanding group-level attitudes, global action tendencies, specific behavioral intentions, and behavior

Cardiac Catheterizations in Patients With Prior Coronary Bypass Surgery:Impact of Access Strategy on Short-Term Safety and Long-Term Efficacy Outcomes

Little data are available on access strategy outcomes for cardiac catheterizations in patients with prior coronary artery bypass graft surgery (CABG). We investigated the effect of transradial access (TRA) and transfemoral access (TFA) on short-term major vascular complications (MVC) and long-term major adverse cardiovascular events (MACE). In this single-center, retrospective cohort study, 1084 patients met our inclusion criteria (TRA = 469; TFA = 615). The cumulative incidence for the primary safety endpoint MVC at 30 days (a composite of major bleeding, retroperitoneal hematoma, dissection, pseudoaneurysm, and arteriovenous fistula) was lower with TRA (0.7% vs 3.0%, P &lt;.01) and this difference remained significant after propensity score adjustment (odds ratio: 0.24; 95% CI, 0.07-0.83; P =.024). The cumulative incidence for the primary efficacy endpoint MACE at 36 months (a composite of all-cause mortality, myocardial infarction, stroke, and urgent target vessel revascularization) was 28.6% with TRA and 27.6% with TFA, respectively. Kaplan-Meier curves showed no difference for the primary efficacy endpoint (P =.65). Contrast use (mL) was significantly lower with TRA (130 [100-180] vs 150 [100-213], P &lt;.01). In conclusion, in patients with prior CABG, TRA was associated with significantly fewer short-term MVC and contrast use, but not with a difference in long-term MACE, compared with TFA.</p