MOLECULAR AND CELLULAR MECHANISMS UNDERLYING THE CLEFT PALATE PHENOTYPE OF TRPS1 MUTANT MICE

Trichorhinophalangeal syndrome (TRPS) is an autosomal dominantly inherited condition caused by heterozygous mutations of the TRPS1 gene. This gene codes for the GATA transcriptional factor TRPS1. Patients with TRPS exhibit multiple skeletal, hair, dental and craniofacial defects, including cleft palate. Using mouse models, one of the goals of this study is to characterize the skeletal abnormalities of Trps1-deficient mice. Skeletal staining using Alcian blue/Alizarin red revealed apparent underdevelopment of the zygomatic arch, sternum, vertebrae and anterior cranial base in Trps1-/- mice. We also found that the nose and mandible of Trps1-/- mice were significantly shorter. Additionally, cleft palate was detected in Trps1-/- mice. In order to understand the role of Trps1 in palatogenesis, immunohistochemistry was used to delineate the expression pattern of Trps1 protein in wildtype (WT) mouse tissues. We demonstrated that Trps1 was expressed in palatal shelf mesenchyme and epithelium, specifically at the medial edge epithelium. Along the anterior-posterior axis, epithelial Trps1 signal appeared to be increased in the posterior region of the palate. Lack of fusion observed in Trps1-/- mouse palatal shelves led us to examine proteins involved in the fusion process. Thus, immunohistochemistry was used to compare the expression of Tgfβ3, Twist1, and β-catenin in WT and Trps1-/- mice. Tgfβ3, β-catenin and Twist1 were all expressed in WT palatal epithelium as well but were downregulated in Trps1-/- palatal epithelium. In summary, Trps1 plays a vital role in proper skeletal and craniofacial development, including palatal shelf fusion. Trps1 is also involved in the regulation of other proteins required for palatal fusion

Association of gut microbiota with obesity in children and adolescents

Pediatric obesity is among the most serious global health problems whose prevalence has increased over the past decade. Pediatric obesity increases concomitant health problems, including type 2 diabetes mellitus, hypertension, dyslipidemia, fatty liver disease, and psychological problems, which often progress into adulthood. The gut microbiota is a new factor in the development of obesity, which is affected by renowned risk factors such as diet, lifestyle, and socioeconomic status. This review aimed to describe the association between the gut microbiota and childhood obesity. According to advances in gene sequencing technologies, many findings of experimental animal and human studies of adults and children demonstrated that compositional and functional changes in the gut microbiota (dysbiosis) are associated with the development of obesity. Many studies have reported that an increased Firmicutes/Bacteroidetes (F/B) ratio is a biomarker of obesity susceptibility; however, with the rapid accumulation of data, meta-analyses of human gut microbiota and obesity showed no clear association between F/B ratio and obesity status. The contribution of the microbiota to obesity has been considered using multifactorial approaches, such as supplying additional calories to the host, modulating blood lipopolysaccharide levels, favoring fat storage, and affecting satiety. Probiotics are proposed to manipulate the gut microbiota population to improve obesity; however, their clinical application remains limited because trials have shown different results. Further studies are required to better understand the mechanisms underlying the observed association between the gut microbiota and pediatric obesity

How can the R.E.N.A.L. nephrometry scoring system aid management of a solid renal mass?

OBJECTIVES. To investigate use of the R.E.N.A.L. nephrometry score in relation to the choice of treatment and postoperative complications for renal masses. DESIGN. Case series. SETTING. A tertiary referral hospital in Hong Kong. PATIENTS. Data of patients undergoing nephrectomy were collected retrospectively from a clinical database and analysed. A R.E.N.A.L. nephrometry score was allocated to each renal tumour by a blinded qualified radiologist, utilising computerised imaging systems. Patient demographics, choice of surgery (radical vs partial), and approaches (open vs minimally invasive) were analysed with respect to their R.E.N.A.L. score. RESULTS. In all, 74 patients were included during the study period, of which 38 underwent partial nephrectomy and 36 underwent radical nephrectomy. No differences between the groups were found with respect to patient demographics. There were significant differences between the partial and radical nephrectomy groups in terms of their mean nephrometry score (6.9 vs 9.3, P<0.001). The mean nephrometry sum was also significantly different in the open approach versus the minimally invasive approach in patients having partial nephrectomy (7.8 vs 6.0, P=0.001). There was no difference in the postoperative 90-day morbidity and mortality in the partial nephrectomy and radical nephrectomy groups. CONCLUSIONS. The R.E.N.A.L. nephrometry score of a renal mass correlated significantly with our choice of surgery (partial vs radical) and our approach to surgery (open vs minimally invasive surgery), particularly in the partial nephrectomy group. It does not, however, correlate with postoperative complications. The nephrometry score provides a useful tool for objectively describing renal mass characteristics and enhancing better communication for the operative planning directed at renal masses.published_or_final_versio

Diagnostic value of the Vesikari Scoring System for predicting the viral or bacterial pathogens in pediatric gastroenteritis

PurposeTo evaluate the diagnostic value of the Vesikari Scoring System (VSS) as an early predictor of pathogens in children with acute gastroenteritis (AG).MethodsIn this retrospective study, the VSS score, absolute neutrophil count (ANC), and C-reactive protein (CRP) levels were analyzed in 107 hospitalized children with AG, aged 6 months to 17 years. Patients were divided into nonspecific, viral, and bacterial groups according to the pathogens detected using a multiplex polymerase chain reaction (PCR) test.ResultsPatients in the bacterial group had significantly higher CRP values and VSS scores compared to those in the viral group and significantly higher VSS scores compared to those in the nonspecific group (P<0.05). Patients in the viral group had significantly higher VSS scores than those in the nonspecific group (P<0.05). Logistic regression analysis revealed that VSS was the most effective diagnostic tool for predicting the type of pathogen (P<0.05). The area under the receiver operating characteristics curve of VSS was significantly greater than that for ANC and CRP (P<0.05). At a cutoff point of 10 in the VSS, an acceptable diagnostic accuracy could be achieved for distinguishing between bacterial and viral pathogens in AG.ConclusionVSS can be considered a useful and reliable infectious marker for pediatric gastroenteritis. VSS may be a good early predictor of the type of pathogen, enabling development of a treatment plan before results from a stool culture or PCR test are available

Grain Boundary Induced Bias Instability in Soluble Acene-Based Thin-Film Transistors

Since the grain boundaries (GBs) within the semiconductor layer of organic field-effect transistors (OFETs) have a strong influence on device performance, a substantial number of studies have been devoted to controlling the crystallization characteristics of organic semiconductors. We studied the intrinsic effects of GBs within 5,11-bis(triethylsilylethynyl) anthradithiophene (TES-ADT) thin films on the electrical properties of OFETs. The GB density was easily changed by controlling nulceation event in TES-ADT thin films. When the mixing time was increased, the number of aggregates in as-spun TES-ADT thin films were increased and subsequent exposure of the films to 1,2-dichloroethane vapor led to a significant increase in the number of nuleation sites, thereby increasing the GB density of TES-ADT spherulites. The density of GBs strongly influences the angular spread and crystallographic orientation of TES-ADT spherulites. Accordingly, the FETs with higher GB densities showed much poorer electrical characteristics than devices with lower GB density. Especially, GBs provide charge trapping sites which are responsible for bias-stress driven electrical instability. Dielectric surface treatment with a polystyrene brush layer clarified the GB-induced charge trapping by reducing charge trapping at the semiconductor-dielectric interface. Our study provides an understanding on GB induced bias instability for the development of high performance OFETs

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

SMART: Unique splitting-while-merging framework for gene clustering

Copyright @ 2014 Fa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Successful clustering algorithms are highly dependent on parameter settings. The clustering performance degrades significantly unless parameters are properly set, and yet, it is difficult to set these parameters a priori. To address this issue, in this paper, we propose a unique splitting-while-merging clustering framework, named “splitting merging awareness tactics” (SMART), which does not require any a priori knowledge of either the number of clusters or even the possible range of this number. Unlike existing self-splitting algorithms, which over-cluster the dataset to a large number of clusters and then merge some similar clusters, our framework has the ability to split and merge clusters automatically during the process and produces the the most reliable clustering results, by intrinsically integrating many clustering techniques and tasks. The SMART framework is implemented with two distinct clustering paradigms in two algorithms: competitive learning and finite mixture model. Nevertheless, within the proposed SMART framework, many other algorithms can be derived for different clustering paradigms. The minimum message length algorithm is integrated into the framework as the clustering selection criterion. The usefulness of the SMART framework and its algorithms is tested in demonstration datasets and simulated gene expression datasets. Moreover, two real microarray gene expression datasets are studied using this approach. Based on the performance of many metrics, all numerical results show that SMART is superior to compared existing self-splitting algorithms and traditional algorithms. Three main properties of the proposed SMART framework are summarized as: (1) needing no parameters dependent on the respective dataset or a priori knowledge about the datasets, (2) extendible to many different applications, (3) offering superior performance compared with counterpart algorithms.National Institute for Health Researc

Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation

In higher eukaryotes, one of the two arginyl-tRNA synthetases (ArgRSs) has evolved to have an extended N-terminal domain that plays a crucial role in protein synthesis and cell growth and in integration into the multisynthetase complex (MSC). Here, we report a crystal structure of the MSC subcomplex comprising ArgRS, glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)/p43. In this complex, the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. Mutation of AIMP1 destabilized the N-terminal helix of ArgRS and abrogated its catalytic activity. Mutation of the N-terminal helix of ArgRS liberated GlnRS, which is known to control cell death. This ternary complex was further anchored to AIMP2/p38 through interaction with AIMP1. These findings demonstrate the importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex.open111315Ysciescopu

Successful Combined Treatment with Total Parenteral Nutrition Fluid Extravasation Injuries in Preterm Infants

Extravasation injuries in the neonatal intensive care unit are not rare during parenteral hyperalimentation. There have been many different methods of management. We report five premature infants with wounds of hyperalimentation fluid extravasation managed by the antibacterial ointment (Terramycin ophthalmic ointment™) and sesame oil and a antiinflammatory herbal mixture (MEBO™). The mean gestational age of patients was 31+2 weeks (range, 28+4 to 35+6 weeks), and the mean weight at extravasation was 1,930 g (range, 1,140 to 2,680 g). Extravasation occurred within the mean of 32 days (range, 17 to 50 days). The method of dressing was application of a thick layer of this mixture covered by vaseline and wet gauze renewed at an interval of 8-12 hr after irrigating the wounds thoroughly with normal saline. The mean duration of dressing was 30 days (range, 20-50 days). The wounds had healed completely leaving a small size of contracture without functional abnormality. We conclude that this therapy may be considered for an alternative treatment and warrants clinical trials for the confirmation of the local management of extravasation injury