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High-resolution mapping of cis-regulatory variation in budding yeast [Genetics]

Original post: http://www.pnas.org/content/114/50/E10736.short?rss=1

Genetic variants affecting gene-expression levels are a major source of phenotypic variation. The approximate locations of these variants can be mapped as expression quantitative trait loci (eQTLs); however, a major limitation of eQTLs is their low resolution, which precludes investigation of the causal variants and their molecular mechanisms. Here we…

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Interaction of intramembrane metalloprotease SpoIVFB with substrate Pro-{sigma}K [Biochemistry]

Original post: http://www.pnas.org/content/114/50/E10677.short?rss=1

Intramembrane proteases (IPs) cleave membrane-associated substrates in nearly all organisms and regulate diverse processes. A better understanding of how these enzymes interact with their substrates is necessary for rational design of IP modulators. We show that interaction of Bacillus subtilis IP SpoIVFB with its substrate Pro-σK depends on particular residues…

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Good News, Guys: Viagra Prices to Tumble Today

Original post: https://www.webmd.com/erectile-dysfunction/news/20171211/good-news-guys-viagra-prices-to-tumble-today?src=RSS_PUBLIC

One of the new generics is made by Teva Pharmaceuticals, and the other by Greenstone, a subsidiary of Pfizer, the company that manufactures Viagra.

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Often, Opioid Abuse Becomes a Family Affair

Original post: https://www.webmd.com/mental-health/addiction/news/20171211/often-opioid-abuse-becomes-a-family-affair?src=RSS_PUBLIC

If someone is taking prescription opioids for pain, such as OxyContin, it’s more likely that others living in the home will also get an opioid prescription, the researchers found.

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Sharing and reuse of individual participant data from clinical trials: principles and recommendations

Original post: http://bmjopen.bmj.com/cgi/content/short/7/12/e018647?rss=1

Objectives

We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach.

Design and methods

This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique. The consensus was reached in a series of three workshops held over 1 year, supported by exchange of documents and teleconferences within focused subgroups when needed. This work was set within the Horizon 2020-funded project CORBEL (Coordinated Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European.

Outcome

We developed principles and practical recommendations on

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Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis [Developmental Biology]

Original post: http://www.pnas.org/content/114/50/E10717.short?rss=1

The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. During neuronal differentiation, the Ryk intracellular domain (ICD) is cleaved. Cleavage of Ryk and nuclear translocation of Ryk-ICD are required for neuronal differentiation. However, the mechanism of translocation and how it regulates neuronal differentiation…

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Protocol of a single group prospective observational study on the diagnostic value of 3T susceptibility weighted MRI of nigrosome-1 in patients with parkinsonian symptoms: the N3iPD study (nigrosomal iron imaging in Parkinsons disease)

Original post: http://bmjopen.bmj.com/cgi/content/short/7/12/e016904?rss=1

Introduction

Parkinson’s disease (PD) is the most common movement disorder in the elderly and is characterised clinically by bradykinesia, tremor and rigidity. Diagnosing Parkinson’s can be difficult especially in the early stages. High-resolution nigrosome MRI offers promising diagnostic accuracy of patients with established clinical symptoms; however, it is unclear whether this may help to establish the diagnosis in the early stages of PD, when there is diagnostic uncertainty. In this scenario, a single photon emission CT scan using a radioactive dopamine transporter ligand can help to establish the diagnosis, or clinical follow-up may eventually clarify the diagnosis. A non-invasive, cost-effective diagnostic test that could replace this would be desirable. We therefore aim to prospectively test whether nigrosome MRI is as useful as DaTSCAN to establish the correct diagnosis in people with minor or unclear symptoms suspicious for PD.

Methods and analysis

In a prospective study we will recruit 145 patients with unclear symptoms possibly caused by Parkinson’s from three movement disorder centres in the UK to take part in the study. We will record the M

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Influence of overstated abstract conclusions on clinicians: a web-based randomised controlled trial

Original post: http://bmjopen.bmj.com/cgi/content/short/7/12/e018355?rss=1

Objectives

To investigate whether overstatements in abstract conclusions influence primary care physicians’ evaluations when they read reports of randomised controlled trials (RCTs)

Design

RCT setting: This study was a parallel-group randomised controlled survey, conducted online while masking the study hypothesis.

Participants

Volunteers were recruited from members of the Japan Primary Care Association in January 2017. We sent email invitations to 7040 primary care physicians. Among the 787 individuals who accessed the website, 622 were eligible and automatically randomised into ‘without overstatement’ (n=307) and ‘with overstatement’ (n=315) groups.

Interventions

We selected five abstracts from published RCTs with at least one non-significant primary outcome and overstatement in the abstract conclusion. To construct a version without overstatement, we rewrote the conclusion sections. The methods and results sections were standardised to provide the necessary information of primary outcome information when it was missing in the original abstract. Participants were randomly assigned to read an abstract either with or without

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Zika Babies Facing More Health Problems With Age

Original post: https://www.webmd.com/a-to-z-guides/news/20171214/zika-babies-facing-more-health-problems-with-age?src=RSS_PUBLIC

Their findings come from a study of 19 Zika-infected children in Brazil, the epicenter of a Zika outbreak that began in 2015.

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Phosphorylation of CENP-C by Aurora B facilitates kinetochore attachment error correction in mitosis [Biochemistry]

Original post: http://www.pnas.org/content/114/50/E10667.short?rss=1

Kinetochores are superprotein complexes that orchestrate chromosome segregation via a dynamic interaction with spindle microtubules. A physical connection between CENP-C and the Mis12–Ndc80–Knl1 (KMN) protein network is an important pathway that is used to assemble kinetochores on CENP-A nucleosomes. Multiple outer kinetochore components are phosphorylated by Aurora B kinase to…

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