133 research outputs found
Four small puzzles that Rosetta doesn't solve
A complete macromolecule modeling package must be able to solve the simplest
structure prediction problems. Despite recent successes in high resolution
structure modeling and design, the Rosetta software suite fares poorly on
deceptively small protein and RNA puzzles, some as small as four residues. To
illustrate these problems, this manuscript presents extensive Rosetta results
for four well-defined test cases: the 20-residue mini-protein Trp cage, an even
smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease
inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies,
several lines of evidence indicate that conformational sampling is not the
major bottleneck in modeling these small systems. Instead, approximations and
omissions in the Rosetta all-atom energy function currently preclude
discriminating experimentally observed conformations from de novo models at
atomic resolution. These molecular "puzzles" should serve as useful model
systems for developers wishing to make foundational improvements to this
powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special
Collectio
A Systematic Review of Online Sex Addiction and Clinical Treatments Using CONSORT Evaluation
Researchers have suggested that the advances of the Internet over the past two decades have gradually eliminated traditional offline methods of obtaining sexual material. Additionally, research on cybersex and/or online sex addictions has increased alongside the development of online technology. The present study extended the findings from Griffithsβ (2012) systematic empirical review of online sex addiction by additionally investigating empirical studies that implemented and/or documented clinical treatments for online sex addiction in adults. A total of nine studies were identified and then each underwent a CONSORT evaluation. The main findings of the present review provide some evidence to suggest that some treatments (both psychological and/or pharmacological) provide positive outcomes among those experiencing difficulties with online sex addiction. Similar to Griffithsβ original review, this study recommends that further research is warranted to establish the efficacy of empirically driven treatments for online sex addiction
Pharmacotherapeutic intervention in impulsive preschool children: The need for a comprehensive therapeutic approach
Impulsive and aggressive behaviour symptoms often are serious problems in children, even already at preschool age. Thus, effective treatment approaches are requested. In this comment pharmacotherapeutic treatment approaches, first of all risperidone, their limitations and alternative psychotherapeutic approaches are outlined
Crystal Structure Analysis Reveals Functional Flexibility in the Selenocysteine-Specific tRNA from Mouse
Selenocysteine tRNAs (tRNA(Sec)) exhibit a number of unique identity elements that are recognized specifically by proteins of the selenocysteine biosynthetic pathways and decoding machineries. Presently, these identity elements and the mechanisms by which they are interpreted by tRNA(Sec)-interacting factors are incompletely understood.We applied rational mutagenesis to obtain well diffracting crystals of murine tRNA(Sec). tRNA(Sec) lacking the single-stranded 3'-acceptor end ((ΞGCCA)RNA(Sec)) yielded a crystal structure at 2.0 Γ
resolution. The global structure of (ΞGCCA)RNA(Sec) resembles the structure of human tRNA(Sec) determined at 3.1 Γ
resolution. Structural comparisons revealed flexible regions in tRNA(Sec) used for induced fit binding to selenophosphate synthetase. Water molecules located in the present structure were involved in the stabilization of two alternative conformations of the anticodon stem-loop. Modeling of a 2'-O-methylated ribose at position U34 of the anticodon loop as found in a sub-population of tRNA(Sec)in vivo showed how this modification favors an anticodon loop conformation that is functional during decoding on the ribosome. Soaking of crystals in Mn(2+)-containing buffer revealed eight potential divalent metal ion binding sites but the located metal ions did not significantly stabilize specific structural features of tRNA(Sec).We provide the most highly resolved structure of a tRNA(Sec) molecule to date and assessed the influence of water molecules and metal ions on the molecule's conformation and dynamics. Our results suggest how conformational changes of tRNA(Sec) support its interaction with proteins
Capsaicin-Induced Changes in LTP in the Lateral Amygdala Are Mediated by TRPV1
The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms
Knowledge of psychiatric nurses about the potentially lethal side-effects of clozapine
Clozapine is an antipsychotic with superior efficacy in the treatment refractory patients, unique antisuicidal
properties and a low propensity to cause extrapyramidal side-effects. Despite these advantage,clozapine utilization is low. This can in part be explained by a number of potentially lethal side-effects of the compound.
Next to psychiatrists nurses play a crucial role in the long-term management of patients with schizophrenia. It is therefore important that nurses know, inform and monitor patients about the specific side-effects of clozapine.
A recent study in psychiatrists has shown that there was a gap in the knowledge about side-effects of clozapine. The knowledge about side-effects of clozapine in nurses has never been studied.
This cross-sectional study evaluated the knowledge base regarding the safety of clozapine, and its
potential mediators, of psychiatric nurses in 3 psychiatric hospitals in Belgium with a specifically developed questionnaire based on the literature and expert opinion (3 clozapine experts).
A total of 85 nurses completed the questionnaire. The mean total score was 6.1 of a potential maximum score of 18. Only 3 of the 18 multiple choice questions were answered correctly by more than 50% of nurses. Only 24.9% of participants passed the test (>50% correct answers). Nurses working on psychosis units were more likely to pass the test (p=0.0124). There was a trend that nurse with a lower
nursing diploma were more likely to fail the test (p=0,0561).
Our study clearly identifies a large gap in the basic knowledge of psychiatric nurses about clozapine and its side-effects. Knowledge could be increased by more emphasis on the topic in nurse's training curricula as well as targeted onsite training. Only 23.5% of participants indicate that there was sufficient information in their basic nursing training.publisher: Elsevier
articletitle: Knowledge of Psychiatric Nurses About the Potentially Lethal Side-Effects of Clozapine
journaltitle: Archives of Psychiatric Nursing
articlelink: http://dx.doi.org/10.1016/j.apnu.2015.09.003
content_type: article
copyright: Copyright Β© 2015 Elsevier Inc. All rights reserved.status: publishe
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