Hufflange7238

Retinoic acid (RA) and 2-phospho-L-ascorbic acid trisodium salt (AscPNa) promote the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. In the current studies, the lower abilities of RA and AscPNa to promote reprogramming in the presence of each other suggested that they may share downstream pathways at least partially. The hypothesis was further supported by the RNA-seq analysis which demonstrated a high-level overlap between RA-activated and AscPNa activated genes during reprogramming. In addition, RA upregulated Glut1/3, facilitated the membrane transportation of dehydroascorbic acid, the oxidized form of L-ascorbic acid, and subsequently maintained intracellular L-ascorbic acid at higher level and for longer time. On the other hand, AscPNa facilitated the mesenchymal-epithelial transition during reprogramming, downregulated key mesenchymal transcriptional factors like Zeb1 and Twist1, subsequently suppressed the expression of Cyp26a1/b1 which mediates the metabolism of RA, and sustained the intracellular level of RA. Furthermore, the different abilities of RA and AscPNa to induce mesenchymal-epithelial transition, pluripotency, and neuronal differentiation explain their complex contribution to reprogramming when used individually or in combination. Therefore, the current studies identified a positive feedback between RA and AscPNa, or possibility between vitamin A and C, and further explored their contributions to reprogramming.The original article was published with an incorrect presentation of all author names.Multiple phenotypic states of single cells often co-exist in the presence of positive feedbacks. Stochastic gene-state switchings and low copy numbers of proteins in single cells cause considerable fluctuations. The chemical master equation (CME) is a powerful tool that describes the dynamics of single cells, but it may be overly complicated. Among many simplified models, a fluctuating-rate (FR) model has been proposed recently to approximate the full CME model in the realistic intermediate region of gene-state switchings. However, only the scenario with two gene states has been carefully analysed. In this paper, we generalise the FR model to the case with multiple gene states, in which the mathematical derivation becomes more complicated. The leading order of fluctuations around each phenotypic state, as well as the transition rates between phenotypic states, in the intermediate gene-state switching region is characterized by the rate function of the stationary distribution of the FR model in the Freidlin-Wentzell-type large deviation principle (LDP). Under certain reasonable assumptions, we show that the derivative of the rate function is equal to the unique nontrivial solution of a dominant generalised eigenvalue problem, leading to a new numerical algorithm for obtaining the LDP rate function directly. Furthermore, we prove the Lyapunov property of the rate function for the corresponding deterministic mean-field dynamics. Finally, through a tristable example, we show that the local fluctuations (the asymptotic variance of the stationary distribution at each phenotypic state) in the intermediate and rapid regions of gene-state switchings are different. Finally, a tri-stable example is constructed to illustrate the validity of our theory.

In mental health care, patients and their care providers may conceptualize the nature of the disorder and appropriate action in profoundly different ways. This may lead to dropout and lack of compliance with the treatments being provided, in particular in young patients with more severe disorders. This study provides detailed information about patient-provider (dis)agreement regarding the care needs of children and adolescents.

We used the Camberwell Assessment of Need (CANSAS) to assess the met and unmet needs of 244 patients aged between 6 and 18years. These needs were assessed from the perspectives of both patients and their care providers. Our primary outcome measure was agreement between the patient and care provider on unmet need. By comparing a general outpatient sample (n = 123) with a youth-ACT sample (n = 121), we were able to assess the influence of severity of psychiatric and psychosocial problems on the extent of agreement on patient's unmet care needs.

In general, patients reported unmet care needs less often than care providers did. Patients and care providers had the lowest extents of agreement on unmet needs with regard to "mental health problems" (k = 0.113) and "information regarding diagnosis/treatment" (k = 0.171). Comparison of the two mental healthcare settings highlighted differences for three-quarters of the unmet care needs that were examined. Agreement was lower in the youth-ACT setting.

Clarification of different views on patients' unmet needs may help reduce nonattendance of appointments, noncompliance, or dropout. Routine assessment of patients' and care providers' perceptions of patients' unmet care needs may also help provide information on areas of disagreement.

Clarification of different views on patients' unmet needs may help reduce nonattendance of appointments, noncompliance, or dropout. #link# Routine assessment of patients' and care providers' perceptions of patients' unmet care needs may also help provide information on areas of disagreement.Infectious diseases are one of the major drivers of coral reef decline worldwide. Reparixin -like disease (WPL) is a widespread disease with a complex etiology that infects several coral species, including the Brazilian endemic species Mussismilia braziliensis. Gene expression profiles of healthy and WPL-affected M. braziliensis were analyzed in winter and summer seasons. The de novo assembly of the M. braziliensis transcriptome from healthy and white plague samples produced a reference transcriptome containing 119,088 transcripts. WPL-diseased samples were characterized by repression of immune system and cellular defense processes. Autophagy and cellular adhesion transcripts were also repressed in WPL samples, suggesting exhaustion of the coral host defenses. Seasonal variation leads to plasticity in transcription with upregulation of intracellular signal transduction, apoptosis regulation, and oocyte development in the summer. Analysis of the active bacterial rRNA indicated that Pantoea bacteria were more abundant in WPL corals, while Tistlia, Fulvivirga, and Gammaproteobacteria Ga0077536 were more abundant in healthy samples.