Identification of Somatic Mutations in Parathyroid Tumors Using Whole-Exome Sequencing

ContextThe underlying molecular alterations causing sporadic parathyroid adenomas that drive primary hyperparathyroidism have not been thoroughly defined.ObjectiveThe aim of the study was to investigate the occurrence of somatic mutations driving tumor formation and progression in sporadic parathyroid adenoma using whole-exome sequencing.DesignEight matched tumor-constitutional DNA pairs from patients with sporadic parathyroid adenomas underwent whole-exome capture and high-throughput sequencing. Selected genes were analyzed for mutations in an additional 185 parathyroid adenomas.ResultsFour of eight tumors displayed a frame shift deletion or nonsense mutation in MEN1, which was accompanied by loss of heterozygosity of the remaining wild-type allele. No other mutated genes were shared among the eight tumors. One tumor harbored a Y641N mutation of the histone methyltransferase EZH2 gene, previously linked to myeloid and lymphoid malignancy formation. Targeted sequencing in the additional 185 parathyroid adenomas revealed a high rate of MEN1 mutations (35%). Furthermore, this targeted sequencing identified an additional parathyroid adenoma that contained the identical, somatic EZH2 mutation that was found by exome sequencing.ConclusionThis study confirms the frequent role of the loss of heterozygosity of chromosome 11 and MEN1 gene alterations in sporadic parathyroid adenomas and implicates a previously unassociated methyltransferase gene, EZH2, in endocrine tumorigenesis

Bbookx: An automatic book creation framework

ABSTRACT As more educational resources become available online, it is possible to acquire more up-to-date knowledge and information. We propose BBookX, a novel computer facilitated system that automatically and collaboratively builds free open online books using publicly available educational resources such as Wikipedia. BBookX has two separate components: one creates an open version of existing books by linking different book chapters to Wikipedia articles, while another with an interactive user interface supports interactive realtime book creation where users are allowed to modify a generated book from explicit feedback

Microvascular cerebral hemodynamics in pediatric sickle cell disease with Diffuse Correlation Spectroscopy

Sickle cell disease is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro- and micro-vascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels, increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in sickle cell disease patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with sickle cell disease than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography, magnetic resonance imaging) given their high-cost, requirement for sedation in children \u3c 6y, and need for trained personnel. In this pilot study, we first assess the feasibility of a low-cost, noninvasive optical technique known as Diffuse Correlation Spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow in 11 children with SCD along with 11 sex- and age-matched healthy controls. As expected, blood flow index was significantly higher in sickle subjects compared to healthy controls (p \u3c 0.001). Within sickle subjects, blood flow index was inversely proportional to resting-state arterial hemoglobin levels (p = 0.012), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with transcranial Doppler ultrasound, DCS-measured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery (Rs = 0.68), although the trend was not statistically significant (p=0.11). These results are consistent with those of several previous studies using traditional neuroimaging techniques to quantify cerebral blood flow, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level cerebral blood flow in pediatric sickle cell disease. Finally, given that sickle cell disease is often associated with severe anemia, we next assessed the potentially confounding effects of hematocrit on the DCS-measured blood flow index using a microfluidic tissue-simulating phantom. For a fixed flow rate in the microfluidic channels, we show that blood flow index is inversely correlated with hematocrit, and we present a means to correct the measured blood flow index for hematocrit in anemic conditions

Optimal experience and personal growth. Flow and the consolidation of place identity

This study examined the relationship between flow experience and place identity, based on eudaimonistic identity theory (EIT) which prioritizes self-defining activities as important for an individual's identification of his/her goals, values, beliefs, and interests corresponding to one's own identity development or enhancement. This study focuses on place identity, the identity's features relating to a person's relation with her/his place. The study is also based on flow theory, according to which some salient features of an activity experience are important for happiness and well-being. Questionnaire surveys on Italian and Greek residents focused on their perceived flow and place identity in relation to their own specific local place experiences. The overall findings revealed that flow experience occurring in one's own preferred place is widely reported as resulting from a range of self-defining activities, irrespective of gender or age, and it is positively and significantly associated with one's own place identity. Such findings provide the first quantitative evidence about the link between flow experienced during meaningfully located self-defining activities and identity experienced at the place level, similarly to the corresponding personal and social levels that had been previously already empirically tested. Results are also discussed in terms of their implications for EIT's understanding and enrichment, especially by its generalization from the traditional, personal identity level up to that of place identity. More generally, this study has implications for maintaining or enhancing one's own place identity, and therefore people place relations, by means of facilitating a person's flow experience within psychologically meaningful place

PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation

P21-activated kinases (PAKs) are multifunctional effectors of Rho GTPases with both kinase and scaffolding activity. Here, we investigated the effects of inflammation on PAK1 signaling and its role in colitis-driven carcinogenesis. PAK1 and p-PAK1 (Thr423) were assessed by immunohistochemistry, immunofluorescence, and Western blot. C57BL6/J wildtype mice were treated with a single intraperitoneal TNFα injection. Small intestinal organoids from these mice and from PAK1-KO mice were cultured with TNFα. NF-κB and PPARγ were analyzed upon PAK1 overexpression and silencing for transcriptional/translational regulation. PAK1 expression and activation was increased on the luminal intestinal epithelial surface in inflammatory bowel disease and colitis-associated cancer. PAK1 was phosphorylated upon treatment with IFNγ, IL-1β, and TNFα. In vivo, mice administered with TNFα showed increased p-PAK1 in intestinal villi, which was associated with nuclear p65 and NF-κB activation. p65 nuclear translocation downstream of TNFα was strongly inhibited in PAK1-KO small intestinal organoids. PAK1 overexpression induced a PAK1–p65 interaction as visualized by co-immunoprecipitation, nuclear translocation, and increased NF-κB transactivation, all of which were impeded by kinase-dead PAK1. Moreover, PAK1 overexpression downregulated PPARγ and mesalamine recovered PPARγ through PAK1 inhibition. On the other hand PAK1 silencing inhibited NF-κB, which was recovered using BADGE, a PPARγ antagonist. Altogether these data demonstrate that PAK1 overexpression and activation in inflammation and colitis-associated cancer promote NF-κB activity via suppression of PPARγ in intestinal epithelial cells

CiteSeer x : A Scholarly Big Dataset

Abstract. The CiteSeerx digital library stores and indexes research ar-ticles in Computer Science and related fields. Although its main purpose is to make it easier for researchers to search for scientific information, CiteSeerx has been proven as a powerful resource in many data min-ing, machine learning and information retrieval applications that use rich metadata, e.g., titles, abstracts, authors, venues, references lists, etc. The metadata extraction in CiteSeerx is done using automated tech-niques. Although fairly accurate, these techniques still result in noisy metadata. Since the performance of models trained on these data highly depends on the quality of the data, we propose an approach to CiteSeerx metadata cleaning that incorporates information from an external data source. The result is a subset of CiteSeerx, which is substantially cleaner than the entire set. Our goal is to make the new dataset available to the research community to facilitate future work in Information Retrieval

Social determinants of place attachment at a World Heritage site

While the work on place attachment is extensive, it neglects to focus on residents' and tourists' perspectives of the construct concurrently. Additionally, the role that social factors play in forging attachment to place is lacking within the tourism literature. This work focuses on whether residents' (n = 469) and tourists' (n = 461) degree of place attachment at the Osun Oshogbo Cultural Festival (Nigeria) were significantly different. Examining the psychometric properties of the place attachment scale in an international context was a second aim. The final purpose of this work was to assess whether social factors (i.e., frequency of interaction and emotional closeness) between residents and tourists could explain the resulting CFA place attachment factors. MANOVA results revealed tourists demonstrated a significantly higher degree of attachment. Each social determinant predicted the attachment factors for both samples, with the two independent variables explaining higher degrees of variance among residents

A Student\u27s Guide to giant Viruses Infecting Small Eukaryotes: From Acanthamoeba to Zooxanthellae

The discovery of infectious particles that challenge conventional thoughts concerning “what is a virus” has led to the evolution a new field of study in the past decade. Here, we review knowledge and information concerning “giant viruses”, with a focus not only on some of the best studied systems, but also provide an effort to illuminate systems yet to be better resolved. We conclude by demonstrating that there is an abundance of new host–virus systems that fall into this “giant” category, demonstrating that this field of inquiry presents great opportunities for future research

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179