Feed aggregator

Toxicology App Has Great Content, Poor Execution

Headlines from MedPage Today® - Wed, 08/17/2016 - 5:30pm
(MedPage Today) -- User interface is not ideal, says Iltifat Husain, MD

Ocaliva Efficacy, Safety in PBC Affirmed (CME/CE)

Headlines from MedPage Today® - Wed, 08/17/2016 - 5:00pm
(MedPage Today) -- Publication of phase III data confirms earlier reports

No Meaningful Risk of Birth Defects Seen With Antipsychotic Drugs (CME/CE)

Headlines from MedPage Today® - Wed, 08/17/2016 - 4:30pm
(MedPage Today) -- But risk varied by drug type

Reckless Report Exaggerates Flaws in fMRI Software

Headlines from MedPage Today® - Wed, 08/17/2016 - 4:00pm
(MedPage Today) -- An in-depth look at problems with recent study

TAVR Bests Surgery for Survival in Lower-Risk Patients

Headlines from MedPage Today® - Wed, 08/17/2016 - 3:30pm
(MedPage Today) -- Surgery, CoreValve otherwise on par for those with STS PROM below 7%

One-man band: the solo physicist who models black holes in sound

news@nature - Wed, 08/17/2016 - 2:21pm

Working alone, Jeff Steinhauer has created a sonic analogue of Hawking radiation.

Nature News doi: 10.1038/nature.2016.20437

SLE Patients Benefit From Routine Echocardiography (CME/CE)

Headlines from MedPage Today® - Wed, 08/17/2016 - 2:00pm
(MedPage Today) -- Cardiac involvement common in systemic lupus erythematosus

CardioBrief: Imprecise Medicine? Genetic Tests Led to Misdiagnosis

Headlines from MedPage Today® - Wed, 08/17/2016 - 1:20pm
(MedPage Today) -- Some black Americans wrongly told of high risk for hypertrophic cardiomyopathy

Risk of Some Cancers Rises With Duration of Obesity (CME/CE)

Headlines from MedPage Today® - Wed, 08/17/2016 - 1:00pm
(MedPage Today) -- Extent of overweight intensifies risk

CAD Outcomes, Costs Better Off With Better Med Adherence (CME/CE)

Headlines from MedPage Today® - Wed, 08/17/2016 - 12:30pm
(MedPage Today) -- Rx fill rates important in MI and atherosclerosis, study affirms

Morphing neutrinos provide clue to antimatter mystery

news@nature - Wed, 08/17/2016 - 12:21pm

Excitement rises over chance of new physics from particle-du-jour.

Nature 536 261 doi: 10.1038/nature.2016.20405

Opinion Makers: The Current State of Disappearing Stents

Headlines from MedPage Today® - Wed, 08/17/2016 - 12:00pm
(MedPage Today) -- Ajay Kirtane, MD, separates hype from reality of Absorb

At Some Catholic Hospitals, Taboos Extend to Referrals

Headlines from MedPage Today® - Wed, 08/17/2016 - 11:30am
(MedPage Today) -- Docs forbidden to make referrals for contraception, abortion

Biologics Seem to Protect Against Sepsis in RA (CME/CE)

Headlines from MedPage Today® - Wed, 08/17/2016 - 11:00am
(MedPage Today) -- Sepsis risk spikes with discontinuation of biologics

Why the US decision to expand marijuana supply for research matters

news@nature - Wed, 08/17/2016 - 10:21am

Policy change could accelerate development of treatments derived from the drug.

Nature News doi: 10.1038/nature.2016.20410

Morning Break: EpiPen or Food? Missing 'Type'; Medicaid Lottery

Headlines from MedPage Today® - Wed, 08/17/2016 - 9:45am
(MedPage Today) -- Health news and commentary from around the Web, gathered by the MedPage Today staff

Polio eradication faces setback as Nigeria records first cases in two years

news@nature - Wed, 08/17/2016 - 9:21am

Health officials launch emergency immunization campaign.

Nature News doi: 10.1038/nature.2016.20416

Web Apps: Helpful or Harmful?

Headlines from MedPage Today® - Wed, 08/17/2016 - 8:39am
(MedPage Today) -- Is there an app for your patients?

The Identification and Targeting of Partially-Folded Conformations on the Folding Free-Energy Landscapes of ALS-Linked Proteins for Therapeutic Intervention: A Dissertation

eScholarship@UMMS - Wed, 08/17/2016 - 8:27am

The hallmark feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), is the accumulation of cytoplasmic inclusions of key disease-linked proteins. Two of these proteins, TDP-43 and SOD1, represent a significant proportion of sporadic and familial ALS cases, respectively. The population of potentially aggregation-prone partially-folded states on the folding free-energy landscape may serve as a common mechanism for ALS pathogenesis. A detailed biophysical understanding of the folding and misfolding energy landscapes of TDP-43 and SOD1 can provide critical insights into the design of novel therapeutics to delay onset and progression in ALS.

Equilibrium unfolding studies on the RNA recognition motif (RRM) domains of TDP-43 revealed the population of a stable RRM intermediate in RRM2, with residual structure localized to the N-terminal half of the domain. Other RRM domains from FUS/TLS and hnRNP A1 similarly populate RRM intermediates, suggesting a possible connection with disease. Mutations, which enhance the population of the RRM2 intermediate, could serve as tools for deciphering the functional and misfolding roles of this partially-folded state in disease models, leading to the development of new biomarkers to track ALS progression.

ALS mutations in SOD1 have been shown to destabilize the stable homodimer to result in increased populations of the monomeric and unfolded forms of SOD1. Mechanistic insights into the misfolding of SOD1 demonstrated that the unfolded state is a key species in the initiation and propagation of aggregation, suggesting that limiting these populations may provide therapeutic benefit to ALS patients. An in vitro time-resolved Förster Resonance Energy Transfer assay to screen small molecules that stabilize the native state of SOD1 has identified several lead compounds, providing a pathway to new therapeutics to treat ALS.

XIST and CoT-1 Repeat RNAs are Integral Components of a Complex Nuclear Scaffold Required to Maintain SAF-A and Modify Chromosome Architecture: A Dissertation

eScholarship@UMMS - Wed, 08/17/2016 - 8:27am

XIST RNA established the precedent for a noncoding RNA that stably associates with and regulates chromatin, however it remains poorly understood how such RNAs structurally associate with the interphase chromosome territory. I demonstrate that transgenic XIST RNA localizes in cis to an autosome as it does to the inactive X chromosome, hence the RNA recognizes a structure common to all chromosomes. I reassess the prevalent thinking in the field that a single protein, Scaffold Attachment Factor-A (SAF-A/hnRNP U), provides a single molecule bridge required to directly tether the RNA to DNA. In an extensive series of experiments in multiple cell types, I examine the effects of SAF-A depletion or different SAF-A mutations on XIST RNA localization, and I force XIST RNA retention at mitosis to examine the effect on SAF-A. I find that SAF-A is not required to localize XIST RNA but is one of multiple proteins involved, some of which frequently become lost or compromised in cancer. I additionally examine SAF-A’s potential role localizing repeat-rich CoT-1 RNA, a class of abundant RNAs that we show tightly and stably localize to euchromatic interphase chromosome territories, but release upon disruption of the nuclear scaffold. Overall, findings suggest that instead of “tethering” chromosomal RNAs to the scaffold, SAF-A is one component of a multi-component matrix/scaffold supporting interphase nuclear architecture. Results indicate that Cot-1 and XIST RNAs form integral components of this scaffold and are required to maintain the chromosomal association of SAF-A, substantially advancing understanding of how chromatin-associated RNAs contribute to nuclear structure.

Syndicate content