Suicide and suicidal behaviour are a major health concern worldwide particularly in patients with mood disorders. Family, adoption and twin studies show that genetics influences suicidal behaviour. ...The serotonin transporter (5HTT) plays an important role in the pathophysiology of mood disorders and may also be involved in suicidal behaviour since 5HTT binding is decreased in the brain of suicide completers. Because the effect of genomic imprinting in the 5HTT gene on suicidal behaviour has not been investigated, we analysed the parent-of-origin effect (POE) of four 5HTT markers and the differential expression of the 5HTT G2651T (rs1042173) alleles in suicide attempters affected by bipolar disorder. We performed a family based association study and ETDT/QTDT analyses of the rs25531, HTTLPR, VNTR-2 and G2651T polymorphisms in 312 nuclear families with at least one subject affected by bipolar disorder. The main outcomes investigated in this study are bipolar disorder diagnosis, suicide attempts, suicidal behaviour severity and age at onset of bipolar disorder. We also compared the allele-specific mRNA levels in lymphoblastoid cells from 13 bipolar suicide attempters and 8 bipolar non-suicide attempters. Allele 2651T was transmitted significantly more often to bipolar patients (
P
= 0.042). There was no significant difference between maternal and paternal transmission ratios. Furthermore, there was no significant difference in the ratio of T/G-specific mRNA expression between bipolar attempters and non-attempters. These data do not support a role for differential allelic expression of 5HTT for suicidal behaviour in bipolar disorder. Small sample size and the fact that RNA was obtained from lymphoblastoid cell lines were some of the limitations of this study.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Plants display an immense diversity of specialized metabolites, many of which have been important to humanity as medicines, flavors, fragrances, pigments, insecticides and other fine chemicals. ...Apparently, much of the variation in plant specialized metabolism evolved through events of gene duplications followed by neo- or sub-functionalization. Most of the catalytic diversity of plant enzymes is unexplored since previous biochemical and genomics efforts have focused on a relatively small number of species. Interdisciplinary research in plant genomics, microbial engineering and synthetic biology provides an opportunity to accelerate the discovery of new enzymes. The massive identification, characterization and cataloguing of plant enzymes coupled with their deployment in metabolically optimized microbes provide a high-throughput functional genomics tool and a novel strain engineering pipeline.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Breast implant-associated lymphoma (BIA-ALCL) has recently been recognized as an independent peripheral T-cell lymphoma (PTCL) entity. In this study, we generated the first BIA-ALCL patient-derived ...tumor xenograft (PDTX) model (IL89) and a matching continuous cell line (IL89_CL#3488) to discover potential vulnerabilities and druggable targets. We characterized IL89 and IL89_CL#3488, both phenotypically and genotypically, and demonstrated that they closely resemble the matching human primary lymphoma. The tumor content underwent significant enrichment along passages, as confirmed by the increased variant allele frequency (VAF) of mutations. Known aberrations (JAK1 and KMT2C) were identified, together with novel hits, including PDGFB, PDGFRA, and SETBP1. A deep sequencing approach allowed the detection of mutations below the Whole Exome Sequencing (WES) sensitivity threshold, including JAK1G1097D, in the primary sample. RNA sequencing confirmed the expression of a signature of differentially expressed genes in BIA-ALCL. Next, we tested IL89's sensitivity to the JAK inhibitor ruxolitinib and observed a potent anti-tumor effect, both in vitro and in vivo. We also implemented a high-throughput drug screening approach to identify compounds associated with increased responses in the presence of ruxolitinib. In conclusion, these new IL89 BIA-ALCL models closely recapitulate the primary correspondent lymphoma and represent an informative platform for dissecting the molecular features of BIA-ALCL and performing pre-clinical drug discovery studies, fostering the development of new precision medicine approaches.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The large family of cytochrome P450 enzymes are heme containing proteins generally associated with the cytoplasmic face of the endoplasmic reticulum in Eukaryotic cells. They play essential roles in ...detoxification mechanisms of cellular processes and are key components in biosynthesis and evolution of specialized metabolites having various biological activities in the plant kingdom. The assembly of complex monoterpenoid indole alkaloids and benzylisoquinoline alkaloids involves numerous cytochrome P450 enzymes that participate in their chemical diversification and that act as central scaffolds for recruitment of the biosynthetic enzymes required for their production. The present review discusses the roles played by different CYP families (-71, -72, -75, -76, 80-, 82-, -86 and -719) in the diversification of MIA and BIA pathways that have been discovered and characterized. Recent studies using homology model guided site-directed mutagenesis coupled with determination of biochemical function are described that provide insights about how small modifications in protein structures allowed the evolution of new substrate specificity and the appearance of new monoterpenoid indole alkaloids and benzylisoquinoline alkaloids in Nature.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The common functional single-nucleotide polymorphism (rs324420, C385A) of the endocannabinoid inactivating enzyme fatty acid amide hydrolase (FAAH) has been associated with anxiety disorder relevant ...phenotype and risk for addictions. Here, we tested whether the FAAH polymorphism affects in vivo binding of the FAAH positron emission tomography (PET) probe 11CCURB (11C-carbonyl-6-hydroxy-1,10-biphenyl-3-yl cyclohexylcarbamate (URB694)). Participants (n = 24) completed one 11CCURB/PET scan and were genotyped for rs324420. Relative to C/C (58%), A-allele carriers (42%) had 23% lower 11CCURB binding (λk3) in brain. We report evidence that the genetic variant rs324420 in FAAH is associated with measurable differences in brain FAAH binding as per PET 11CCURB measurement.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The aim of this study was to evaluate in vitro the behavior and the biocompatibility of primary human osteoblasts (HOs) grown onto different implant surface.
HOs were cultured onto ...sandblasted/acid-etched (control group) and sandblasted/acid-etched followed by coating with inorganic ions (test group) experimental titanium discs. At established times, SEM analysis, LDH assay, MTT assay, and enzyme-linked immunosorbent assay for type 1 collagen, interleukin (IL)-6, and PGE2 secretion were performed.
Both surfaces promote HOs adhesion and proliferation. After 21 days, cells on test surfaces are well spread, flattened, and attached by cellular extensions, whereas cells on control discs appear mainly elongated. Lower LDH levels and higher values of MTT assay are recorded for cells on test respect to control surfaces at each experimental time. Type 1 collagen release increases until 14 days, significantly decreasing at day 21 in cells grown on both surfaces. IL-6 and PGE2 secretion shows a peak in control group samples at day 7, whereas their levels do not significantly modify in both groups at days 14 and 21.
Results indicate that the test group surface is more biocompatible, well tolerated, and suitable for supporting osteoblasts growth and proliferation.
In science, bezoar is a mass of hair or undigested vegetable matter, found in a human or animal's intestines, similar to a hairball. Usually, it is found trapped in every part of the gastrointestinal ...system and must be distinguished by pseudobezoar which is an indigestive object voluntarily introduced into the digestive tract. The term Bezoar is from Arabic bāzahr, “bezoar” or ultimately from Middle Persian pʾtzhl pādzahr, “antidote, bezoar”ægagropile o egagropile It should be a universal antidote that works against any poison, and could neutralize any poison. Otherwise, the name could derive from a kind of Turkish goat whose name is just bezoar. Authors report a case of fecal impaction by pumpkin seeds bezoar with abdominal pain: a difficulty to void with subsequent rectal inflammation and hemorrhoid enlargement was observed. The patient underwent a successful manual disimpaction. Guidelines do not require IRB approval Authors examined the literature about occlusion from bezoar The most common causes of occlusion from bezoar are: a previous gastric surgery such as a gastric band (for weight loss) or gastric bypass, a reduced stomach acid (hypochlorhydria) or decreased stomach size, a delayed gastric emptying, typically due to diabetes, autoimmune disorders, or mixed connective tissue disease. Seed bezoars are usually found in the rectum of patients without predisposing factors, causing constipation and pain. Rectal impaction is common after ingestion of seeds while a true occlusion is rare. Although several cases of phytobezoars composed of various types of seeds are reported in literature, bezoars of pumpkin seeds have rarely been reported.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Difficulty in controlling SARS-CoV-2 transmission made the ability to inactivate viruses in aerosols and fomites to be an important and attractive risk reduction measure. Evidence that light ...frequencies have the ability to inhibit microorganisms has already been reported by many studies which, however, focused on ultraviolet (UV) wavelengths, which are known to induce potential injury in humans. In the present study, the effect on suspensions of SARS-CoV-2 of a Light Emitting Diode (LED) device capable of radiating frequencies in the non-hazardous visible light spectrum (VIS) was investigated. In order to evaluate the efficiency of viral inactivation, plaque assay and western blot of viral proteins were performed. The observed results showed a significant reduction in infectious particles that had been exposed to the LED irradiation of visible light. Furthermore, the analysis of the intracellular expression of viral proteins confirmed the inactivating effect of this irradiation technology. This in vitro study revealed for the first time the inactivation of SARS-CoV-2 through LED irradiation with multiple wavelengths of the visible spectrum. However additional and more in-depth studies can aim to demonstrate the data obtained during these experiments in different matrices, in mutable environmental conditions and on other respiratory viruses such as the influenza virus. The type of LED technology can decisively contribute on reducing virus transmission through the continuous sanitation of common environments without risks for humans and animals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BackgroundWe report a study of machine learning applied to the phenotyping of psychiatric diagnosis for research recruitment in youth depression, conducted with 861 labelled electronic medical ...records (EMRs) documents. A model was built that could accurately identify individuals who were suitable candidates for a study on youth depression.ObjectiveOur objective was a model to identify individuals who meet inclusion criteria as well as unsuitable patients who would require exclusion.MethodsOur methods included applying a system that coded the EMR documents by removing personally identifying information, using two psychiatrists who labelled a set of EMR documents (from which the 861 came), using a brute force search and training a deep neural network for this task.FindingsAccording to a cross-validation evaluation, we describe a model that had a specificity of 97% and a sensitivity of 45% and a second model with a specificity of 53% and a sensitivity of 89%. We combined these two models into a third one (sensitivity 93.5%; specificity 68%; positive predictive value (precision) 77%) to generate a list of most suitable candidates in support of research recruitment.ConclusionOur efforts are meant to demonstrate the potential for this type of approach for patient recruitment purposes but it should be noted that a larger sample size is required to build a truly reliable recommendation system.Clinical implicationsFuture efforts will employ alternate neural network algorithms available and other machine learning methods.
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