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Lotus plumule, the embryo of the seed of the sacred lotus (Nelumbo nucifera), contains a high accumulation of secondary metabolites including flavonoids and possesses important pharmaceutical value. Flavonoid C-glycosides, which accumulate exclusively in lotus plumule, have attracted considerable attention in recent decades due to their unique chemical structure and special bioactivities. As well as mono-C-glycosides, lotus plumule also accumulates various kinds of di-C-glycosides by mechanisms which are as yet unclear. selleck chemical In this study we identified two C-glycosyltransferase (CGT) genes by mining sacred lotus genome data and provide in vitro and in planta evidence that these two enzymes (NnCGT1 and NnCGT2, also designated as UGT708N1 and UGT708N2, respectively) exhibit CGT activity. Recombinant UGT708N1 and UGT708N2 can C-glycosylate 2-hydroxyflavanones and 2-hydroxynaringenin C-glucoside, forming flavone mono-C-glycosides and di-C-glycosides, respectively, after dehydration. In addition, the above reactions were successfully catalysed by cell-free extracts from tobacco leaves transiently expressing NnCGT1 or NnCGT2. Finally, enzyme assays using cell-free extracts of lotus plumule suggested that flavone di-C-glycosides (vicenin-1, vicenin-3, schaftoside and isoschaftoside) are biosynthesized through sequentially C-glucosylating and C-arabinosylating/C-xylosylating 2-hydroxynaringenin. Taken together, our results provide novel insights into the biosynthesis of flavonoid di-C-glycosides by proposing a new biosynthetic pathway for flavone C-glycosides in N. nucifera and identifying a novel uridine diphosphate-glycosyltransferase (UGT708N2) that specifically catalyses the second glycsosylation, C-arabinosylating and C-xylosylating 2-hydroxynaringenin C-glucoside.

The prevalence of cognitive impairment is high among alcohol-dependent patients. Although the clinical presentation of alcohol-related cognitive disorder (ARCD) may resemble that of Alzheimer's disease (AD), the prognosis and treatment of the 2 diseases are different. Cerebrospinal fluid (CSF) biomarkers (tau, phosphorylated tau, and amyloid β) have high diagnostic accuracy in AD and are currently being used to discriminate between psychiatric disorders and AD, but are not used to diagnose ARCD. The aim of this study was to characterize CSF biomarkers in a homogeneous, cognitively impaired alcohol-dependent population.

This single-center study was conducted in an addiction medicine department of a Parisian Hospital. We selected patients with documented persistent cognitive impairment whose MoCA (Montreal Cognitive Assessment) score was below 24/30 after at least 1 month of documented inpatient abstinence from alcohol. We measured the CSF biomarkers (tau, phosphorylated tau, and amyloid β 1-42 and 1-40) inuse CSF biomarkers in addition to imaging and neuropsychological testing to evaluate alcohol-related cognitive impairment.

Evidence suggests that prenatal alcohol exposure (PAE) may adversely impact insulin production and signaling but there is limited information on the range of these effects and their future health consequences.

A prospective cohort of predominantly African-American individuals identified while in utero and followed into adulthood were used to evaluate differences in various indicators of diabetes, including fasting plasma glucose, hemoglobin A1c (HbA1c), and insulin levels. The homeostatic model assessment of insulin resistance (HOMA-IR) was also computed. Body mass index (BMI) was calculated and normal defined as<25kg/m

. Participants were categorized as having PAE (n=39) if their mothers drank at least 1 ounce of absolute alcohol per week or more during the 1

trimester of pregnancy and as Controls (n=22) if their mothers reported abstaining from alcohol consumption during pregnancy.

Mean age of the sample was 36.0±1.5years. Indices of glucose metabolism, including fasting plasma glucose and hemos may contribute to the metabolic disease risk associated with PAE.

Pachyonychia congenita (PC) refers to a group of autosomal dominant disorders caused by mutations in five keratin genes (KRT16,KRT6A,KRT17,KRT6B or KRT6C). Current disease classification is based on the gene harbouring disease-causing variants.

We harnessed the International Pachyonychia Congenita Research Registry (IPCRR) containing both clinical and molecular data on patients with PC worldwide, to identify genetic variants predicting disease severity.

We ascertained 815 individuals harbouring keratin mutations registered in the IPCRR. We looked for statistically significant associations between genetic variants and clinical manifestations in a subgroup of patients carrying mutations found in at least 10% of the cohort. Data were analysed using χ

and Kruskal-Wallis tests.

We identified five mutations occurring in at least 10% of the patients registered in the IPCRR. The KRT16 p.L132P mutation was significantly associated with younger age of onset, presence of palmar keratoderma oral leucokeratosis and a higher number of involved nails. By contrast, the KRT16 p.N125S and p.R127C mutations resulted in a milder phenotype featuring a decreased number of involved nails and older age of onset. Patients carrying the p.N125S mutation were less likely to develop palmar keratoderma while p.R127C was associated with an older age of palmoplantar keratoderma onset. Moreover, the KRT17 p.L99P mutation resulted in an increased number of involved fingernails and patients demonstrating 20-nail dystrophy, while the opposite findings were observed with KRT17 p.N92S mutation.

We have identified novel and clinically useful genetic predictive variants in the largest cohort of patients with PC described to date.

We have identified novel and clinically useful genetic predictive variants in the largest cohort of patients with PC described to date.

Clinicians' negative emotional responses to suicidal patients are predictive of near-term suicidality. This study aimed to explore the underlying pathway of this association by investigating the potential relationship between clinicians' emotional responses and the Narrative Crisis Model of suicide, which comprises long-term risk factors (LTRF) of suicidal thoughts and behaviors, Suicidal Narrative, and the Suicide Crisis Syndrome (SCS), a presuicidal affective state.

One thousand and One patient participants and 169 clinician participants were recruited. Patients' Suicidal Narrative, SCS, and LTRF were assessed at intake using the Suicidal Narrative Inventory (SNI), the Suicide Crisis Inventory, and a composite score of three separate scales, respectively. Clinicians' emotional responses were measured immediately after patient intake using the Therapist Response Questionnaire-Suicide Form (TRQ-SF).

Multilevel regression analyses, which controlled for clinician differences, found that only patients' SNI total score and perceived burdensomeness subscale score were significantly associated with clinicians' TRQ-SF total score.