Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

An Analysis of Nucleotide-Amyloid Interactions Reveals Selective Binding to Codon-Sized RNA.

Interactions between RNA and proteins are the cornerstone of many important biological processes from transcription and translation to gene regulation, yet little is known about the ancient origin of said interactions. We hypothesized that peptide amyloids played a role in the origin of life and that their repetitive structure lends itself to building interfaces with other polymers through avidity. Here, we report that short RNA with a minimum length of three nucleotides binds in a sequence-dependent manner to peptide amyloids.

Structural basis for recognition of transcriptional terminator structures by ProQ/FinO domain RNA chaperones.

The ProQ/FinO family of RNA binding proteins mediate sRNA-directed gene regulation throughout gram-negative bacteria. Here, we investigate the structural basis for RNA recognition by ProQ/FinO proteins, through the crystal structure of the ProQ/FinO domain of the Legionella pneumophila DNA uptake regulator, RocC, bound to the transcriptional terminator of its primary partner, the sRNA RocR. The structure reveals specific recognition of the 3' nucleotide of the terminator by a conserved pocket involving a β-turn-α-helix motif, while the hairpin portion of the terminator is recognized by a conserved α-helical N-cap motif.

Branch site bulge conformations in domain 6 determine functional sugar puckers in group II intron splicing.

Although group II intron ribozymes are intensively studied the question how structural dynamics affects splicing catalysis has remained elusive. We report for the first time that the group II intron domain 6 exists in a secondary structure equilibrium between a single- and a two-nucleotide bulge conformation, which is directly linked to a switch between sugar puckers of the branch site adenosine. Our study determined a functional sugar pucker equilibrium between the transesterification active C2'-endo conformation of the branch site adenosine in the 1nt bulge and an inactive C3'-endo state in the 2nt bulge fold, allowing the group II intron to switch its activity from the branching to the exon ligation step.

Access routes and reported decision criteria for lumbar epidural drug injections: a systematic literature review.

Purpose: To review lumbar epidural drug injection routes in relation to current practice and the reported criteria used for selecting a given approach.

Material And Methods: This was a HIPPA-compliant study. Employing a systematic search strategy, the MEDLINE and EMBASE databank as well as the Cochrane Library were searched for studies on epidural drug injections.

Agonist-biased trafficking of somatostatin receptor 2A in enteric neurons.

Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored.

Protease- and acid-catalyzed labeling workflows employing (18)O-enriched water.

Stable isotopes are essential tools in biological mass spectrometry. Historically, (18)O-stable isotopes have been extensively used to study the catalytic mechanisms of proteolytic enzymes(1-3). With the advent of mass spectrometry-based proteomics, the enzymatically-catalyzed incorporation of (18)O-atoms from stable isotopically enriched water has become a popular method to quantitatively compare protein expression levels (reviewed by Fenselau and Yao(4), Miyagi and Rao(5) and Ye et al.

Targeting proteases in cardiovascular diseases by mass spectrometry-based proteomics.

Proteases hydrolyze peptide bonds, thereby controlling the function of proteins and peptides on the posttranslational level. In the cardiovascular system, proteases play pivotal roles in the regulation of blood pressure, coagulation and other essential physiological processes. Accordingly, proteases are prime targets for therapeutic interventions and diagnostics.

Profiling protease activities by dynamic proteomics workflows.

Proteases play prominent roles in many physiological processes and the pathogenesis of various diseases, which makes them interesting drug targets. To fully understand the functional role of proteases in these processes, it is necessary to characterize the target specificity of the enzymes, identify endogenous substrates and cleavage products as well as protease activators and inhibitors. The complexity of these proteolytic networks presents a considerable analytic challenge.

Radical nephrectomy performed by open, laparoscopy with or without hand-assistance or robotic methods by the same surgeon produces comparable perioperative results.

Purpose: Radical nephrectomy can be performed using open or laparoscopic (with or without hand assistance) methods, and most recently using the da Vinci Surgical Robotic System. We evaluated the perioperative outcomes using a contemporary cohort of patients undergoing radical nephrectomy by one of the above 4 methods performed by the same surgeon.

Materials And Methods: The relevant clinical information on 57 consecutive patients undergoing radical nephrectomy from September 2000 until July 2004 by a single surgeon was entered in a Microsoft Access Database and queried.

Tissue transglutaminase interacts with protein kinase A anchor protein 13 in prostate cancer.

We have previously described that tissue transglutaminase (tTG) is a high level phenotypic biomarker in prostate cancer, which is down regulated in prostate cancer and surrounding premalignant field compared to benign prostate glands. To understand the function of tTG in prostate cancer, we sought to identify proteins that interact with the transglutaminase moiety of tTG using a human prostate cancer complementary deoxyribonucleic acid library in a Yeast 2-Hybrid system. The Yeast 2-Hybrid experiments identified a strong and novel interaction between the transglutaminase moiety and protein kinase A anchor protein 13 (AKAP13), which was quantified by beta-galactosidase assay, confirmed in vitro by immunoprecipitation experiments using PC3 prostate cancer cell lysates, and in vivo colocalization was confirmed by immunofluorescence studies in PC3 cells.

High-resolution gas chromatography retention data as a basis for estimation of the octanol-water distribution coefficients (Kow) of PCB: the effect of experimental conditions.

The semi-experimental approach to approximating physicochemical data relevant to environmental distribution (vapor pressure and gas-octanol distribution) by correlation with gas chromatography (GC) retention data has been extended to the determination of Kow values. We estimated Kow values >10(4) for polychlorinated biphenyls (PCB), which are often derived by liquid chromatography, by correlation with gas chromatographic retention data. Selecting a set of reference compounds with known Kow values for relative retention time (RRT) correlation enables easy and accurate semi-empirical calculation of further Kow values for a given group of congeners.

Feasibility of robotic radical nephrectomy--initial results of single-institution pilot study.

Objectives: To report our initial experience and the utility of the da Vinci surgical robotic system (DSRS) for performing robotic radical nephrectomy (RRN). The DSRS has been increasingly evaluated to determine its feasibility for assisting surgeons in major urologic procedures.

Methods: The perioperative outcomes of the first five RRNs performed at our institution were analyzed to establish the safety and utility of the DSRS in performing RRN.

One-year prevalence of migraine in Austria: a nation-wide survey.

This study presents the first nation-wide survey of migraine in Austria. A sample of 997 Austrian > or = 15 years old were interviewed personally (face-to-face) in a random sample in the whole country. Diagnosis of migraine was based on the International Headache Society (IHS) classification.

Perceptions of chest pain differ by race.

Background: African American patients are less likely to receive thrombolytic therapy and coronary revascularization than are white patients. Delay and clinical presentation may be keys to understanding differences in care.

Objective: To determine how symptom recognition and perception influence clinical presentation as a function of race, we characterized symptoms and care-seeking behavior in African American and white patients seen in the ED with chest pain.

[Incidence and cost estimation of diseases of the nervous system and the psyche. An evaluation of non-profit hospitals].

There were 273,722 hospitalizations due to neurological disorders reported in Austria's nonprofit hospitals in 1997, including the related operated cases (14.12% of all 1.9 million hospitalizations).

Hospitalization of patients with neurological disorders and estimation of the need of beds and of the related costs in Austria's non-profit hospitals.

In 1997, 273 722 hospitalizations as a result of neurological disorders, including the related operated cases, were reported in Austria's non-profit hospitals (80% of all hospitals). They represent 14.12% of all 1.

A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease.

Cerebrolysin (Cere) is a compound with neurotrophic activity which has been shown to be effective in the treatment of Alzheimer's disease (AD) in earlier trials. The efficacy and safety of repeated treatments with Cere were investigated in this randomized, double-blind, placebo-controlled, parallel-group study. One hundred and forty-nine patients were enrolled (76 Cere; 73 placebo).

Migraine-like headache in bacterial meningitis.

The effect of sumatriptan has not been previously described in the treatment of the headache of meningitis, although this headache has similarities to migraine. This study presents the clinical features of two patients who had fulminant bacterial meningitis with migraine-like headache and who experienced no improvement in headache intensity after administration of sumatriptan 6 mg s.c.

Transcutaneous electrical nerve stimulation in the treatment of chronic pain: predictive factors and evaluation of the method.

Objective: Transcutaneous electrical nerve stimulation (TENS) is a widely used therapeutic approach in acute and chronic pain syndromes. The aim of this study was to investigate the influence of patient management as well as other factors on the outcome of TENS treatment.

Design: The study was carried out as a retrospective analysis of the course of treatment and the therapeutic results of transcutaneous electric nerve stimulation (TENS) in 482 patients with chronic pain of various origins.

Clinical case report: opiate antagonist and event-related desynchronization in 2 autistic boys.

Event-related desynchronization and visual orientational behavior were examined in 2 autistic boys to determine if blockade of endogenous opioid activity facilitates cognitive processing at a cortical level. Before naltrexone, the boys showed no selective alpha blocking during exposure to either mother's pictures or white light. Unlike normals, they exhibited strong alpha band enhancement at temporocentral recording sites.