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Variants of the melanocortin-4 receptor (MC4R) gene are the most common cause of monogenic obesity. In this situation; while obesity cannot be controlled with diet and exercise, it was shown that Glucagon-like-peptide-1 receptor agonists (GLP-1 RA) provide weight loss in short term. In this paper, we present our experience with Liraglutide treatment in an adolescent patient carrying MC4R gene variant. A female patient had admitted first at the age of 12.5 years with a complaint of progressive weight gain. She had a marked excess of appetite since infancy. In the physical examination of the pubertal female patient with a body mass index (BMI) of 36.1kg/m2 (3.48 SDS), there was no pathological finding except diffuse acanthosis nigricans. Laboratory examinations revealed only insulin resistance. Weight loss couldn't be achieved with lifestyle changes, metformin and orlistat treatments In genetic examination, a sporadic heterozygous c.206T>G(p.I69R) variant (reported previously) was found in the MC4R gene. GLP-1 RA Liraglutide treatment was initiated and a loss of 19.2% reduction was achieved in the patient's body weight and BMI at the end of 32 weeks. However, the patient, whose treatment compliance was disrupted due to significant gastrointestinal complaints, returned to her former weight within a few months after treatment was stopped. In our case carrying a pathogenic variant in the MC4R gene, decrease of appetite and weight loss were achieved with Liraglutide treatment, but this situation could not be maintained. In such cases, there is a need for effective and tolerable treatment options.Targeted sequencing for somatic mutations across the hotspots of 50 cancer-related genes was performed using biopsy specimens to investigate whether clinicopathological factors and genomic alterations correlated with prognosis in locally advanced cervical cancer. Seventy patients diagnosed with International Federation of Obstetrics and Gynecology (FIGO) stage III to IVA cervical cancer underwent radiotherapy or concurrent chemoradiotherapy at the National Cancer Center Hospital between January 2008 and December 2017. Mutations were detected in 47 of 70 [67% of cases; frequency of genetic alterations was as follows PIK3CA (51%), FBXW7 (10%), PTEN (7.1%), and TP53 (5.7%)]. The Cancer Genome Atlas (TCGA) datasets showed a similar distribution of somatic mutations, but PIK3CA mutation frequency was significantly higher in our cohort than in TCGA datasets (P = 0.028). Patients with TP53 mutation were significantly related to poor progression-free survival (PFS) (hazard ratio [HR] = 3.53, P = 0.042). Patients with tumor diameters > 70 mm were associated with poor prognosis (HR = 2.96, P = 0.0048). Patients with non-HPV16/18 genotypes had worse prognosis than those with HPV16/18 genotypes (HR = 2.15, P = 0.030). Hence, patients with locally advanced cervical cancer, TP53 mutation, large tumor diameter, and non-HPV16/18 genotype were independently correlated with poor PFS, despite concurrent chemoradiotherapy.Gastric cancer (GC) is one of the most lethal malignant tumors. To improve the prognosis of GC, the identification of novel driver genes as therapeutic targets is in urgent need. Here, we aimed to identify novel driver genes and clarify their roles in gastric cancer. OSBPL3 was identified as a candidate driver gene by in silico analysis of public genomic datasets. OSBPL3 expression was analyzed by RT-qPCR and immunohistochemistry in GC cells and tissues. The biological functions and mechanisms of OSBPL3 in GC were examined in vitro and in vivo using GC cells. The association between OSBPL3 expression and clinical outcome in GC patients was also evaluated. Overexpression of OSBPL3 was detected in GC cells with OSBPL3 DNA copy number gains and promoter hypomethylation. OSBPL3-knockdown reduced GC cell growth in vitro and in vivo by inhibiting cell cycle progression. Moreover, an active Ras pull-down assay and western blotting demonstrated that OSBPL3 activates the R-Ras/Akt signaling pathway in GC cells. In a clinical analysis of two GC datasets, high OSBPL3 expression was predictive of a poor prognosis. Our findings suggest that OSBPL3 is a novel driver gene stimulating the R-Ras/Akt signaling pathway and a potential therapeutic target in GC patients.Separation related disorder in dogs is a multi-faceted phenomenon. Dogs can react to the absence of their owner due to different inner states such as fear, panic or frustration. We hypothesized that dogs that are prone to frustration or fearfulness in other contexts would show a different behavioral response to separation from the owner. We investigated the association between inner states in different contexts and separation behaviors by combining a questionnaire with a separation test. Fear-related questionnaire components were rather associated with whining and the absence of barking. Dogs that received higher scores in the demanding component of the questionnaire, which might be in association of the frustration threshold of the dog, barked more and were more likely to scratch the door. Finally, dogs that were more prone to phobic reactions whined somewhat more and tried to escape. We provide empirical support for the assumption that separation-related behavioral responses of dogs might be triggered by different emotions.The extent to which women differ in the course of blood cell counts throughout pregnancy, and the importance of these changes to pregnancy outcomes has not been well defined. Here, we develop a series of statistical analyses of repeated measures data to reveal the degree to which women differ in the course of pregnancy, predict the changes that occur, and determine the importance of these changes for post-partum hemorrhage (PPH) which is one of the leading causes of maternal mortality. We present a prospective cohort of 4082 births recorded at the University Hospital, Lausanne, Switzerland between 2009 and 2014 where full labour records could be obtained, along with complete blood count data taken at hospital admission. We find significant differences, at a [Formula see text] level, among women in how blood count values change through pregnancy for mean corpuscular hemoglobin, mean corpuscular volume, mean platelet volume, platelet count and red cell distribution width. We find evidence that almost all complete blood count values show trimester-specific associations with PPH. For example, high platelet count (OR 1.20, 95% CI 1.01-1.53), high mean platelet volume (OR 1.58, 95% CI 1.04-2.08), and high erythrocyte levels (OR 1.36, 95% CI 1.01-1.57) in trimester 1 increased PPH, but high values in trimester 3 decreased PPH risk (OR 0.85, 0.79, 0.67 respectively). We show that differences among women in the course of blood cell counts throughout pregnancy have an important role in shaping pregnancy outcome and tracking blood count value changes through pregnancy improves identification of women at increased risk of postpartum hemorrhage. This study provides greater understanding of the complex changes in blood count values that occur through pregnancy and provides indicators to guide the stratification of patients into risk groups.Highly selective and sensitive 2,7-naphthyridine based colorimetric and fluorescence "Turn Off" chemosensors (L1-L4) for detection of Ni2+ in aqueous media are reported. The receptors (L1-L4) showed a distinct color change from yellow to red by addition of Ni2+ with spectral changes in bands at 535-550 nm. The changes are reversible and pH independent. The detection limits for Ni2+ by (L1-L4) are in the range of 0.2-0.5 µM by UV-Visible data and 0.040-0.47 µM by fluorescence data, which is lower than the permissible value of Ni2+ (1.2 µM) in drinking water defined by EPA. The binding stoichiometries of L1-L4 for Ni2+ were found to be 21 through Job's plot and ESI-MS analysis. Moreover the receptors can be used to quantify Ni2+ in real water samples. Formation of test strips by the dip-stick method increases the practical applicability of the Ni2+ test for "in-the-field" measurements. DFT calculations and AIM analyses supported the experimentally determined 21 stoichiometries of complexation. TD-DFT calculations were performed which showed slightly decreased FMO energy gaps due to ligand-metal charge transfer (LMCT).Biogenic amines play an important role in the regulation of appetitive responses in insects. Ertugliflozin Among them, serotonin (5-HT) regulates feeding-related processes in numerous insect species. In carpenter ants, 5-HT administration has been shown to depress feeding behavior, thus opening the possibility of using 5-HT modulation in control strategies against those species considered as pest. Here we studied if administration of a 5-HT antagonist, ketanserin, promotes feeding of a sucrose solution and a toxic bait in carpenter ants Camponotus mus. We found that 3 h after a single oral administration of ketanserin, the mass of sucrose solution consumed by carpenter ants increased significantly. A similar effect was found after a chronic administration that lasted 5 days. Yet, ketanserin did neither affect the intake rates nor the activity of the pharyngeal pump that mediates feeding dynamics. In addition, ketanserin promoted the consumption of a toxic bait based on boric acid. Our results thus show that feeding motivation and consumption of both sucrose solution and a toxic bait can be enhanced via prior administration of ketanserin. We discuss the possible mechanisms underlying these effects and conclude that understanding basic physiological and neural principles that underlie feeding motivation allows establishing more efficient control strategies for pest insects.To better understand the decline of one of earth's most biodiverse habitats, coral reefs, many survey programs employ regular photographs of the benthos. An emerging challenge is the time required to annotate the large volume of digital imagery generated by these surveys. Here, we leverage existing machine-learning tools (CoralNet) and develop new fit-to-purpose programs to process and score benthic photoquadrats using five years of data from the Smithsonian MarineGEO Network's biodiversity monitoring program at Carrie Bow Cay, Belize. Our analysis shows that scleractinian coral cover on forereef sites (at depths of 3-10 m) along our surveyed transects increased significantly from 6 to 13% during this period. More modest changes in macroalgae, turf algae, and sponge cover were also observed. Community-wide analysis confirmed a significant shift in benthic structure, and follow-up in situ surveys of coral demographics in 2019 revealed that the emerging coral communities are dominated by fast-recruiting and growing coral species belonging to the genera Agaricia and Porites. While the positive trajectory reported here is promising, Belizean reefs face persistent challenges related to overfishing and climate change. Open-source computational toolkits offer promise for increasing the efficiency of reef monitoring, and therefore our ability to assess the future of coral reefs in the face of rapid environmental change.This study presents a comprehensive study of the genetic bases controlling variation in the rice ionome employing genome-wide association studies (GWAS) with a diverse panel of indica accessions, each genotyped with 5.2 million markers. GWAS was performed for twelve elements including B, Ca, Co, Cu, Fe, K, Mg, Mn, Mo, Na, P, and Zn and four agronomic traits including days to 50% flowering, grain yield, plant height and thousand grain weight. GWAS identified 128 loci associated with the grain elements and 57 associated with the agronomic traits. There were sixteen co-localization regions containing QTL for two or more traits. Fourteen grain element quantitative trait loci were stable across growing environments, which can be strong candidates to be used in marker-assisted selection to improve the concentrations of nutritive elements in rice grain. Potential candidate genes were revealed including OsNAS3 linked to the locus that controls the variation of Zn and Co concentrations. The effects of starch synthesis and grain filling on multiple grain elements were elucidated through the likely involvement of OsSUS1 and OsGSSB1 genes.