Miracle-dz/UniFAR-FTUs huggingface dataset:
REVIEW Heteromers of μ - δ opioid receptors: new pharmacology and novel therapeutic possibilities

Several studies suggest that heteromerization between μ (MOP) and δ (DOP) opioid receptors modulates the signalling properties of the individual receptors. For example, whereas activation of MOP receptors by an agonist induces G protein-mediated signalling, the same agonist induces β -arrestin-mediated signalling in the context of the MOP-DOP receptor heteromer. Moreover, heteromer-mediated signalling is allosterically modulated by a combination of MOP and DOP receptor ligands. This has implications in analgesia given that morphine-induced antinociception can be potentiated by DOP receptor ligands. Recently reagents selectively targeting the MOP-DOP receptor heteromer such as bivalent ligands, antibodies or membrane permeable peptides have been generated; these reagents are enabling studies to elucidate the contribution of endogenously expressed heteromers to analgesia as well as to the development of side-effects associated with chronic opioid use. Recent advances in drug screening technology have led to the identiﬁcation of a MOP-DOP receptor heteromer-biased agonist that activates both G protein-mediated and β -arrestin-mediated signalling. Moreover, this heteromer-biased agonist exhibits potent antinociceptive activity but with reduced side-effects, suggesting that ligands targeting the MOP-DOP receptor heteromer form a basis for the development of novel therapeutics for the treatment of pain. In this review, we summarize ﬁndings regarding the biological and functional characteristics of the MOP-DOP receptor heteromer and the in vitro and in vivo properties of heteromer-selective ligands.
Prediction of splice site using AdaBoost with a new sequence encoding approach

The Biological sequence data are increasing rapidly, so there is a vital need of effective method for gene detection. Predicting of splice site is an important part of gene finding. Therefore, attempts to improve the prediction accuracy of the computational methods for splice sites detection continue. In this paper we propose a hybrid algorithm for splice sites prediction by combining AdaBoost classifier with a novel nucleotide encoding method, namely FDDM. Our encoding method provides frequency difference between the true sites and false sites (FD) along with distance measure (DM). The proposed method produces an improvement in comparison with the result of current methods such as MM1-SVM, Reduced MM1-SVM, SVM-B, LVMM, DM-SVM, DM2-AdaBoost and MSC+Pos(+APR)-SVM, when applied to the HS3D dataset with repeated 10-fold cross validation. In addition, for demonstrating the stability of the method, we also applied it to NN269 dataset. The obtained results indicate that the new method is practicable and efficient.
Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer

Cannabinoids have been reported to possess antitumorogenic activity. Not much is known, however, about the effects and mechanism of action of synthetic nonpsychotic cannabinoids on breast cancer growth and metastasis. We have shown that the cannabinoid receptors CB1 and CB2 are overexpressed in primary human breast tumors compared with normal breast tissue. We have also observed that the breast cancer cell lines MDA-MB231, MDA-MB231-luc, and MDA-MB468 express CB1 and CB2 receptors. Furthermore, we have shown that the CB2 synthetic agonist JWH-133 and the CB1 and CB2 agonist WIN-55,212-2 inhibit cell proliferation and migration under in vitro conditions. These results were confirmed in vivo in various mouse model systems. Mice treated with JWH-133 or WIN-55,212-2 showed a 40% to 50% reduction in tumor growth and a 65% to 80% reduction in lung metastasis. These effects were reversed by CB1 and CB2 antagonists AM 251 and SR144528, respectively, suggesting involvement of CB1 and CB2 receptors. In addition, the CB2 agonist JWH-133 was shown to delay and reduce mammary gland tumors in the polyoma middle T oncoprotein (PyMT) transgenic mouse model system. Upon further elucidation, we observed that JWH-133 and WIN-55,212-2 mediate the breast tumor-suppressive effects via a coordinated regulation of cyclooxygenase-2/prostaglandin E2 signaling pathways and induction of apoptosis. These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis. [Mol Cancer Ther 2009;8(11):3117–29]
Think-pair-share based flipped classroom: A model for improving students’ learning achievement and self-efficacy

The lack of clear instruction and teaching strategy during the in-class learning activities of flipped classroom (FC) model has affected the model’s efficacy. This study aims to improve FC model by proposing the think-pair-share-based flipped classroom model (TPS-FCM). This study investigates the effect of TPS-FCM on students’ academic achievement and self-efficacy in an information and communications technology (ICT) in education course. One hundred and seventy-three students were involved in the quasi-experimental study. The students in the experimental group (n=91) learned with TPS-FCM, and students in the control group (n=82) used the conventional flipped classroom model (CFCM). Pre-test, post-test, and survey were employed. Results showed that TPS-FCM significantly improved students’ ICT learning achievement and self-efficacy compared to CFCM. Gender was found to have been significantly affected by TPS-FCM in students’ learning achievement but not in self-efficacy. This study recommends think-pair-share (TPS) strategy to improve in-class activities in FC model. Moreover, the study has limitations because of using two different teachers, which might affect students’ learning achievement and self-efficacy. Nonetheless, this study contributed that integrating TPS into FC model improves in-class learning activities. Integrating TPS into the in-class learning activities proved the budding support to enhance the efficacy of FC model. Based on the results of this study, the authors suggested that flipped practitioners can use the think-pair-share strategy to minimize in-class issues, particularly the lack of clear instruction and teaching strategy. Many practical studies of FC model have already been conducted. The originality of this work is in the fact that it proposes a suitable strategy (TPS) to improve the in-class learning activities of the model. The study also explores the effect of the proposed model on students’ learning achievement and self-efficacy, which enrich the current literature.
Deep learning and ecology: what practices, what values for the neuroimaging scientific community?

The investigation we are proposing took place as part of an engineering school internship within the UNITAE ecological redirection project [1] at the Neuromarseille institute. This project is part of a global movement in higher education and research (e.g. [2] ; [3] in computer science and [4] in neuroscience) which aims at 1) quantifying the impact of research activity and 2) through a reflexive approach, identifying the issues at stake within different epistemic communities in order to envisage their future in relation to planetary limits. In this context, part of this study focused on the use of deep/machine learning methods (AI in the following) in neuroscience laboratories, and more generally in medical research. In this we proposed exchanges with those involved in the research of this field. The goal is to analyze scientists' practices from two angles: the first aims to quantify precisely the energy consumption of deep learning algorithms [5]; the second questions the motivations that might drive researchers to rethink the production of knowledge coming from AI.
Biocidal Activity of Bacillus thuringiensis on Plutella xylostella L.

Fifty native Bacillus thuringiensis isolates of Dharwad were evaluated for their insecticidal activity against third instar larvae of Plutella xylostella. Toxicity of these isolates ranged from nill to 92.00 per cent. Most promising ones are DBT-388 (92.00%) and DBT-772 (86%) comparable with reference strain HD1 (84%). Crude protein extraction was done from DBT-388 and DBT-772 isolates along with HD-1. LC 50 values were 1738, 2113 and 2427 ppm for DBT-388, DBT-772 and HD-1 respectively. Spore crystal complex count also taken from DBT-388 and HD-1 to calculate the International Unit (IU) /ml and to to find out its potency. DBT-388 and HD-1 had a count of 42,000 and 32,000 IU/ml, respectively when measured on P. xylostella . DBT-388 produced more spores than the HD-1. Effective isolates (mortality greater than 75%) were screened to know the spectrum of cry 1, cry 2, cry 8, cry 9 and cry 20 genes present in them. cry 1 gene was amplified in eleven isolates, cry 2 in eight isolates whereas cry 8 and cry 9 in three and six isolates, respectively. cry 20 was not amplified in any of the twelve isolates.
Enhanced Bandwidth and Diversity in Real-Time Analog Signal Processing (R-ASP) Using Nonuniform C-Section Phasers

We show that a continuously nonuniform coupled-line C-section phaser, as the limiting case of the step-discontinuous coupled-line multisection commensurate and non-commensurate phasers, provides enhanced bandwidth and diversity in real-time analog signal processing (R-ASP). The phenomenology of the component is explained in comparison with the step-discontinuous using multiple-reflection theory and a simple synthesis procedure is provided. The bandwidth enhancement results from the suppression of spurious group delay harmonics or quasi-harmonics, while the diversity enhancement results from the greater level of freedom provided by the continuous nature of the nonuniform profile of the phaser. These statements are supported by theoretical and experimental results.
Structure of a Pheromone Receptor-Associated MHC Molecule with an Open and Empty Groove

Neurons in the murine vomeronasal organ (VNO) express a family of class Ib major histocompatibility complex (MHC) proteins (M10s) that interact with the V2R class of VNO receptors. This interaction may play a direct role in the detection of pheromonal cues that initiate reproductive and territorial behaviors. The crystal structure of M10.5, an M10 family member, is similar to that of classical MHC molecules. However, the M10.5 counterpart of the MHC peptide-binding groove is open and unoccupied, revealing the first structure of an empty class I MHC molecule. Similar to empty MHC molecules, but unlike peptide-filled MHC proteins and non-peptide–binding MHC homologs, M10.5 is thermally unstable, suggesting that its groove is normally occupied. However, M10.5 does not bind endogenous peptides when expressed in mammalian cells or when offered a mixture of class I–binding peptides. The F pocket side of the M10.5 groove is open, suggesting that ligands larger than 8–10-mer class I–binding peptides could fit by extending out of the groove. Moreover, variable residues point up from the groove helices, rather than toward the groove as in classical MHC structures. These data suggest that M10s are unlikely to provide specific recognition of class I MHC–binding peptides, but are consistent with binding to other ligands, including proteins such as the V2Rs.
Sleep Health: Journal of the National Sleep Foundation

Objective: Sleep undergoes major changes during the first year of life, but the characteristics of sleep among infants in low and middle-income countries are not well documented. This study describes sleep characteristics and changes in sleep patterns in infants at 6 and 12 months of age from Bhaktapur, Nepal. Methods: This was a community-based longitudinal study comprising 735 infants. Sleep characteristics were obtained by interview with the mother using the Brief Infant Sleep Questionnaires. The stability of sleep duration and night awakenings were estimated by logistic regression analysis. Results: Cosleeping in the parent’s bed at 6 and 12 months of age was almost universal (> 97%). At 6 months of age, 254 (35%) and at 12 months of age, 341 (46%) infants had a total 24-hour sleep duration < 12 hours. Night awakenings > 3 times per night were common (65%) both at 6 and 12 months of age. Infants with frequent nightly awakenings at 6 months had increased odds of frequent nightly awakenings at 12 months (OR = 2.2; 95% CI: 1.6, 2.9). Very few (< 3%) mothers reported sleep problems in their infants at 6 and 12 months of age. Conclusions: Cosleeping was almost universal among Nepalese infants, and very few of the mothers re-ported sleep problems in their infants. Infants at 6 and 12 months had similar patterns for both sleep duration and nocturnal awakenings. For infants, there were increased odds of having similar sleep duration and nocturnal awakening at 6 and 12 months. © 2024 The Author(s). Published by Elsevier Inc. on behalf of National Sleep Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Application of Broad-Spectrum Resequencing Microarray for Genotyping Rhabdoviruses

ABSTRACT The rapid and accurate identification of pathogens is critical in the control of infectious disease. To this end, we analyzed the capacity for viral detection and identification of a newly described high-density resequencing microarray (RMA), termed PathogenID, which was designed for multiple pathogen detection using database similarity searching. We focused on one of the largest and most diverse viral families described to date, the family Rhabdoviridae. We demonstrate that this approach has the potential to identify both known and related viruses for which precise sequence information is unavailable. In particular, we demonstrate that a strategy based on consensus sequence determination for analysis of RMA output data enabled successful detection of viruses exhibiting up to 26% nucleotide divergence with the closest sequence tiled on the array. Using clinical specimens obtained from rabid patients and animals, this method also shows a high species level concordance with standard reference assays, indicating that it is amenable for the development of diagnostic assays. Finally, 12 animal rhabdoviruses which were currently unclassified, unassigned, or assigned as tentative species within the family Rhabdoviridae were successfully detected. These new data allowed an unprecedented phylogenetic analysis of 106 rhabdoviruses and further suggest that the principles and methodology developed here may be used for the broad-spectrum surveillance and the broader-scale investigation of biodiversity in the viral world.
Association between serum procalcitonin level with exacerbation severity Association between serum procalcitonin level with exacerbation severity in chronic obstructive pulmonary disease patients in chronic obstructive pulmonary disease patients

Background : There is a signi ﬁ cant impact on morbidity, mortality, and quality of life due to chronic obstructive pulmonary disease (COPD) exacerbations. Individuals with acute exacerbation of COPD had considerably higher mean serum procalcitonin (PCT) levels compared to individuals with stable COPD, according to previous investigations. Objective : This study aimed to assess whether PCT levels were associated with the severity of exacerbations in patients with COPD. Patients and methods : Thirty-nine patients who were suffering from an acute exacerbation of COPD were included. Included patients were classi ﬁ ed as having either acute respiratory failure non life threatening or acute respiratory failure life threatening. Serum PCT level was measured. Results : PCT serum levels were not substantially associated with the severity of exacerbation in studied patients ( P ¼ 0.4). There was no correlation between PCT level and pack-year index, modi ﬁ ed medical research council dyspnea, COPD assessment test, exacerbation history, exacerbation severity, respiratory rate, or pCO 2 level. Conclusion : The results of our research proved a nonsigni ﬁ cant association between PCT level and exacerbation severity of COPD patients.
Narrative Review of Multifaceted Approaches to Managing Recurrent Implantation Failure: Insights and Innovations

Objective : We aimed to explore the multifaceted etiology of recurrent implantation failure (RIF) and evaluate the efficacy of various management strategies, with a focus on refining examination protocols and treatment pathways to improve implantation success rates in patients undergoing in vitro fertilization-embryo transfer. Mechanism : The development of RIF can be attributed to a complex causal network of factors. Chromosomal anomalies, such as aneuploidies, directly impact the genetic viability of embryos. Immune system dysregulation, marked by the presence of autoantibodies, disrupts the normal immunological tolerance required for successful implantation. Endocrine disruptions interfere with the hormonal balance essential for preparing the endometrium for implantation. Anatomical irregularities in the female reproductive tract can physically impede the embryo’s ability to implant. Lifestyle factors, including diet, stress, and environmental exposures, influence both male and female reproductive health, affecting gamete quality and implantation potential. These diverse factors interact in a multifaceted manner, making a personalized diagnostic and therapeutic approach essential for addressing the specific causes in each case of RIF. Findings in brief : The review synthesizes current understanding of RIF’s etiology, highlighting the need for innovative interventions and adjustments in clinical practice. It emphasizes the significance of a highly personalized approach in managing RIF, incorporating refined examination protocols and tailor-made treatment pathways to address the unique combination of factors present in each case. Conclusions : Effective management of RIF requires innovative interventions and a shift in clinical practice towards personalized care. Identifying gaps in the current understanding of RIF points towards a clear direction for future research, aimed at refining treatment protocols and improving outcomes for patients. This contributes significantly to the broader field of reproductive medicine, aiming to alleviate the clinical and psychological burdens of RIF.
Host response modulation in the management of periodontal diseases.

OBJECTIVE To review the biological mechanisms and clinical utility of therapeutic modulation of the host response in the management of periodontal diseases. MATERIAL AND METHODS A search of MEDLINE-PubMed was performed up to and including December 2004. The search was limited to in vitro, experimental animal and clinical studies published in English. The selection criteria included all levels of available evidence: systematic reviews, randomised-controlled clinical trials, controlled clinical trials, prospective and retrospective cohort studies and case reports of human and experimental animal studies. RESULTS Six targets for non-microbial chemotherapeutic intervention were identified. Clinical trials have demonstrated the ability of non-steroidal anti-inflammatory drugs to slow periodontal disease progression. However, recently reported serious adverse effects preclude the use of cyclooxygenase-2 inhibitors as an adjunct to periodontal therapy. Adjunctive use of subantimicrobial dose doxycycline to non-surgical periodontal therapy is beneficial in the management of chronic periodontitis over 12 months. Controversial data exist on the effects of bisphosphonate administration as an adjunct to periodontal therapy. Evidence on modulation of other host mediators including lipoxins, cytokines and nitric oxide synthase is limited to animal research. CONCLUSION After validation in long-term clinical trials, adjunctive host modulation therapy may prove advantageous in the management of periodontal diseases.
Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila

The JAK/STAT pathway is a key signaling pathway in the regulation of development and immunity in metazoans. In contrast to the multiple combinatorial JAK/STAT pathways in mammals, only one canonical JAK/STAT pathway exists in Drosophila. It is activated by three secreted proteins of the Unpaired family (Upd): Upd1, Upd2 and Upd3. Although many studies have established a link between JAK/STAT activation and tissue damage, the mode of activation and the precise function of this pathway in the Drosophila systemic immune response remain unclear. In this study, we used mutations in upd2 and upd3 to investigate the role of the JAK/STAT pathway in the systemic immune response. Our study shows that haemocytes express the three upd genes and that injury markedly induces the expression of upd3 by the JNK pathway in haemocytes, which in turn activates the JAK/STAT pathway in the fat body and the gut. Surprisingly, release of Upd3 from haemocytes upon injury can remotely stimulate stem cell proliferation and the expression of Drosomycin-like genes in the intestine. Our results also suggest that a certain level of intestinal epithelium renewal is required for optimal survival to septic injury. While haemocyte-derived Upd promotes intestinal stem cell activation and survival upon septic injury, haemocytes are dispensable for epithelium renewal upon oral bacterial infection. Our study also indicates that intestinal epithelium renewal is sensitive to insults from both the lumen and the haemocoel. It also reveals that release of Upds by haemocytes coordinates the wound-healing program in multiple tissues, including the gut, an organ whose integrity is critical to fly survival.
Macroinvertebrate Biodiversity Trends and Habitat Relationships within Headwater Rivers of the Qinghai-Tibet Plateau

Highland running-water biodiversity has gained growing interest around the world, because of the more pristine conditions and higher sensitivity to environmental changes of highland rivers compared to the lowland rivers. This study presents the findings of systematic investigations and analyses on running-water biodiversity of macroinvertebrate assemblages in the most important headwater streams in the Yalutsangpo and Sanjiangyuan River basins in the Qinghai-Tibet Plateau and the lowland headwaters of the Songhua River, Juma River, and East River during the non-flood seasons of 2012 to 2016. The results indicated that the headwaters on the plateau had a higher regional biodiversity compared to the lowland rivers with the similar flow and substrate conditions. Even though the local diversity of the highland rivers was not significantly different at each single site, the taxonomic composition was significantly different with several rarely seen species scattering among the different sites, resulting in a high regional biodiversity. The biodiversity and composition of macroinvertebrates were strongly affected by the altitude gradient and the environmental variables associated with altitude. To be specific, for the Yalutsangpo River, canonical correspondence analyses of the macroinvertebrate assemblages and their environmental variables indicated that altitude, stream condition (represented by river pattern, riverbed structures, substrate composition), and water temperature influence macroinvertebrate taxa composition. Because of the restrictive plateau conditions including low water temperature, poor aquatic and riparian vegetation, and low runoff, the macroinvertebrate assemblages showed low biodiversity and were vulnerable to potential human disturbance/climate change. Therefore, it is essential to conserve suitable conditions of the determinative environmental variables to protect the unique and high regional biodiversity of the headwaters on the Qinghai-Tibet Plateau.