Finite mixture clustering of human tissues with different levels of IGF-1 splice variants mRNA transcripts

BACKGROUND: This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a finite mixture of multivariate Gaussian densities. However, given we had more technical replicates from the same tissue for each quantitative measurement, we also employed a finite mixture of linear mixed models, with tissue-specific random effects. RESULTS: A panel of human tissues was analysed through quantitative real-time PCR methods, to quantify the relative amount of mRNA encoding different IGF-1 alternative splicing variants. After an appropriate, preliminary, equalization of the quantitative data, we provided an estimate of the distribution of the observed concentrations for the different IGF-1 mRNA splice variants in the cohort of tissues by employing suitable kernel density estimators. We observed that the analysed IGF-1 mRNA splice variants were characterized by multimodal distributions, which could be interpreted as describing the presence of several sub-population, i.e. potential tissue clusters. In this context, a formal clustering approach based on a finite mixture model (FMM) with Gaussian components is proposed. Due to the presence of potential dependence between the technical replicates (originated by repeated quantitative measurements of the same mRNA splice isoform in the same tissue) we have also employed the finite mixture of linear mixed models (FMLMM), which allowed to take into account this kind of within-tissue dependence. CONCLUSIONS: The FMM and the FMLMM provided a convenient yet formal setting for a model-based clustering of the human tissues in sub-populations, characterized by homogeneous values of concentrations of the mRNAs for one or multiple IGF-1 alternative splicing isoforms. The proposed approaches can be applied to any cohort of tissues expressing several alternatively spliced mRNAs generated by the same gene, and can overcome the limitations of clustering methods based on simple comparisons between splice isoform expression levels

Sea level rise scenarios in a changing climate. Learning from the past to predict the future

Geological investigations of Holocene (last 12 ka) sea-level stands represent a crucial contribution to quantify any possible post-industrial (i.e., last 150 years) acceleration in sea-level rise and provide new constrains into the effects of on-going global change on the coastal areas. In particular, definition of both the pattern and the magnitude of the land vertical motions is controlled by the isostatic adjustment along the global coastlines. We present here the results of a number of recent studies that were carried out along the coast of north and south America and of the Mediterranean Sea. These data allowed quantifying the recent acceleration in sea-level rise and to define future scenarios of coastal inundation along the global coastlines

Assessing understanding of sexual assault resources and response among health sciences students

Background: The widely published statistic of 1 in 5 represents the number of women on college campuses who have been sexually assaulted (White House Office of the Press Secretary, 2014). Many colleges and universities have been attempting to address the sensitive topic of sexual assault for quite some time; however, sexual violence still remains prevalent on campuses throughout the United States (Allen, Ridgeway, & Swan, 2015). Many of the roadblocks an institution faces in its efforts may stem from a lack of understanding of the true nature of student attitudes surrounding the topic of sexual assault. The specific needs of community members, such as student knowledge on reporting policies, attitudes towards prevention, knowledge of existing survivor resources, and perception of community attitudes, must be understood and examined in order to improve campus response in terms of prevention, resources, and support (The White House Task Force to Protect Students from Sexual Assault, 2014). Therefore, it is the aim of this study to assess students’ existing knowledge of policies and procedures at JMU. Additionally, this study aims to identify resources and individuals, whether they be peers, professors, law enforcement, and the like, which students feel most inclined to turn in the aftermath of a sexual assault, as well as to understand why they feel as such. Methods: A total of 13 focus groups were held, each consisting of 5-11 Health Science major students at James Madison University (JMU). Semi-structured questions were posed as prompts during a facilitated discussion during focus group meetings. With participant consent, the in-person group meetings were recorded utilizing a digital recorder. The recorded data research file was then encrypted and transcribed by the researcher post meeting. Results: Overall, students were able to identify sexual assault survivor resources available at JMU; however, unless students were part of residence life, they did not seem to know very much about the services they actually provide. A call for advertisement and increased visibility of reactive resources was made evident as many of the identified qualities desired in an ideal survivor resource could be found in already existing resources available on campus. Additionally, students indicated a desire for the prevention program Dukes Step Up to be more comprehensive and take on a more serious tone, as well as the desire for a follow up continued education prevention program. Participants showed high interest in meeting with administration to gain knowledge about their strides towards combating sexual violence

The “I belong in the LLB” program: Animation and promoting law student well-being

This article argues that the growing body of empirical evidence on law students’ high levels of psychological distress creates an imperative for curricular and extra-curricular strategies to address this issue. We highlight recent initiatives at QUT Law School designed to support law student well-being that are informed by insights from positive psychology. In particular, we explain our use of animation, which is an engaging medium to promote students’ appreciation of the importance of psychological well-being in law school and beyond

Phenolic composition of hydrophilic extract of manna from sicilian Fraxinus angustifolia vahl and its reducing, antioxidant and anti-inflammatory activity in vitro

Manna, a very singular vegetable product derived from the spontaneous solidification of the sap of some Fraxinus species, has long been known for its mild laxative and emollient properties. In this work, a hydro-alcoholic extract of manna (HME) from Sicilian Fraxinus angustifolia Vahl was investigated using HPLC-DAD to find phenol components and using chemical and biological in vitro assays to determine its reducing, antioxidant and anti-inflammatory capacity. We identified elenolic acid, tyrosol, hydroxytyrosol, catechin, fraxetin, verbascoside, gallic acid, procyanidin-B1, and luteolin 3,7 glucoside, in order of abundance. Measurements of total antioxidant activity by Folin-Ciocalteu reaction and ferric reducing ability (FRAP), as well as of scavenger activity towards ABTS•+, DPPH•, and perferryl-myoglobin radicals, showed that the phytocomplex effectively reduced oxidants with different standard potentials. When compared with vitamin E, HME also behaved as an efficient chain-breaking antioxidant against lipoperoxyl radicals from methyl linoleate. In cellular models for oxidative stress, HME counteracted membrane lipid oxidation of human erythrocytes stimulated by tert-butyl hydroperoxide and prevented the generation of reactive oxygen species, as well as the GSH decay in IL-1β–activated intestinal normal-like cells. Moreover, in this in vitro intestinal bowel disease model, HME reduced the release of the pro-inflammatory cytokines IL-6 and IL-8. These findings may suggest that manna acts as an antioxidant and anti-inflammatory natural product in humans, beyond its well-known effects against constipation

PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?

BACKGROUND: Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders. CASE PRESENTATION: We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing. CONCLUSION: Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation