Connections Underlying Translation and mRNA Stability.

Gene expression and regulation in organisms minimally depends on transcription by RNA polymerase and on the stability of the RNA product (for both coding and non-coding RNAs). For coding RNAs, gene expression is further influenced by the amount of translation by the ribosome and by the stability of the protein product. The stabilities of these two classes of RNA, non-coding and coding, vary considerably: tRNAs and rRNAs tend to be long lived while mRNAs tend to be more short lived.

An audit of the predictors of outcome in status epilepticus from a resource-poor country: a comparison with developed countries.

Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010.

Early resective surgery causes favorable seizure outcome in malformations of cortical development.

Purpose: We analyzed consecutive cases of a large cohort of the spectrum of malformations of cortical development (MCDs) including focal cortical dysplasias (FCDs) who underwent presurgical evaluation through our epilepsy program from January 2000-December 2010. We analyzed factors predicting surgical candidacy, predictors of seizure outcome and reasons for deferring surgery.

Methods: 148 patients with MCD underwent detailed presurgical evaluation and 69 were operated.

Direct Demonstration That Loop1 of Scap Binds to Loop7: A CRUCIAL EVENT IN CHOLESTEROL HOMEOSTASIS.

Cholesterol homeostasis is mediated by Scap, a polytopic endoplasmic reticulum (ER) protein that transports sterol regulatory element-binding proteins from the ER to Golgi, where they are processed to forms that activate cholesterol synthesis. Scap has eight transmembrane helices and two large luminal loops, designated Loop1 and Loop7. We earlier provided indirect evidence that Loop1 binds to Loop7, allowing Scap to bind COPII proteins for transport in coated vesicles.

Dysregulation of splicing proteins in head and neck squamous cell carcinoma.

Signaling plays an important role in regulating all cellular pathways. Altered signaling is one of the hallmarks of cancers. Phosphoproteomics enables interrogation of kinase mediated signaling pathways in biological systems.

Surgery for "Long-term epilepsy associated tumors (LEATs)": Seizure outcome and its predictors.

Objectives: "Long-term epilepsy associated tumors (LEATs)" by definition are tumors primarily causing drug-resistant seizures for two years or more. They include low-grade glial and glioneuronal tumors with normal life expectancy. We studied a large cohort of patients with LEATs who underwent surgery through our epilepsy program.

MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours.

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development.

Advances in Flexible Endoscopy.

Flexible endoscopy, a minimally invasive diagnostic and potentially therapeutic tool, has become more available over the past decades. A fiberscope is used to visualize the lumen of the area of interest and collect tissue or fluid samples for evaluation. Samples can be submitted for histopathology, cytologic analysis, and bacterial culture.

A Clinical Decision Support System for Chronic Pain Management in Primary Care: Usability testing and its relevance.

Background: Clinical decision support systems (CDSSs) that are integrated into electronic medical records may be useful for encouraging practice change compliant with clinical practice guidelines.

Objective: To engage end users to inform early phase CDSS development through a process of usability testing.

Methods: A sequential exploratory mixed method approach was used.

Protective Mechanisms of Flavonoids in Parkinson's Disease.

Parkinson's disease is a chronic, debilitating neurodegenerative movement disorder characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta region in human midbrain. To date, oxidative stress is the well accepted concept in the etiology and progression of Parkinson's disease. Hence, the therapeutic agent is targeted against suppressing and alleviating the oxidative stress-induced cellular damage.

PEG-penetrated chitosan-alginate co-polysaccharide-based partially and fully cross-linked hydrogels as ECM mimic for tissue engineering applications.

The emerging strategy of tissue engineering for the management of end-stage organ failure and associated complications mainly relies on ECM mimicking scaffolds for neo-tissue genesis. In the current study, novel polyethylene glycol interpenetrated cross-linked hydrogel scaffold based on a co-polysaccharide (PIAC) synthesized from two marine heteropolysaccharides, alginate and chitosan, was designed. Partially cross-linked (PIAC-P) and fully cross-linked hydrogels (PIAC-F) were prepared.

Protective effects of quercetin glycosides, rutin, and isoquercetrin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in rat pheochromocytoma (PC-12) cells.

There is increasing evidence that free radicals induced oxidative stress is a major causative agent in the pathogenesis of neurodegenerative diseases, particularly Parkinson's disease. Quercetin glycosides, namely rutin and isoquercitrin, are flavonoid polyphenol compounds found ubiquitously in fruits and vegetables and have been known to possess antioxidant effects. This study was designed to compare the neuroprotective effects of quercetin glycosides rutin and isoquercitrin in 6-OHDA-induced rat pheochromocytoma (PC-12) cells.

Synthesis at the Speed of Codons.

The possibility that different mRNA sequences encoding identical peptides are translated dissimilarly has long been of great interest. Recent work by Yu and co-workers provides striking evidence that mRNA sequences influence the rate of protein synthesis, and lends support to the emerging idea that mRNA sequence informs protein folding.

A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

Background And Purpose: Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis.

Materials And Methods: Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI.

Modulatory effects of mesenchymal stem cells on leucocytes and leukemic cells: A double-edged sword?

Mesenchymal stem cells (MSCs) have drawn much attention amongst stem cell researchers in the past few decades. The ability of the MSC to differentiate into cells of mesodermal and non-mesodermal origins has made them an attractive approach for cell-based therapy and regenerative medicine. The MSCs have immunosuppressive activities that may have considerable therapeutic values in autoimmune diseases.

Crystal structure of a conserved domain in the intermembrane space region of the plastid division protein ARC6.

The chloroplast division machinery is composed of numerous proteins that assemble as a large complex to divide double-membraned chloroplasts through binary fission. A key mediator of division-complex formation is ARC6, a chloroplast inner envelope protein and evolutionary descendant of the cyanobacterial cell division protein Ftn2. ARC6 connects stromal and cytosolic contractile rings across the two membranes through interaction with an outer envelope protein within the intermembrane space (IMS).

Structural Basis for the Regulation of the MmpL Transporters of Mycobacterium tuberculosis.

The mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the MmpL (mycobacterial membrane protein large) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complex regulatory network, including the TetR family transcriptional regulators Rv3249c and Rv1816.

Chronic exposure to chewing tobacco selects for overexpression of stearoyl-CoA desaturase in normal oral keratinocytes.

Chewing tobacco is a common practice in certain socio-economic sections of southern Asia, particularly in the Indian subcontinent and has been well associated with head and neck squamous cell carcinoma. The molecular mechanisms of chewing tobacco which leads to malignancy remains unclear. In large majority of studies, short-term exposure to tobacco has been evaluated.

Crystal structure of the Mycobacterium tuberculosis transcriptional regulator Rv0302.

Mycobacterium tuberculosis is a pathogenic bacterial species, which is neither Gram positive nor Gram negative. It has a unique cell wall, making it difficult to kill and conferring resistance to antibiotics that disrupt cell wall biosynthesis. Thus, the mycobacterial cell wall is critical to the virulence of these pathogens.

Does F-18 FDG-PET substantially alter the surgical decision-making in drug-resistant partial epilepsy?

Objective: There is a dearth of information on the critical utility of positron emission tomography (PET) in choosing candidates for epilepsy surgery especially in resource-poor countries where it is not freely available. This study aimed to critically analyze the utility of FDG-PET in the presurgical evaluation and surgical selection of patients with DRE based on the results obtained through its use in our comprehensive epilepsy program.

Methods: From 2008 to 2012, 117 patients with drug-resistant epilepsy underwent F-18 fluoro-deoxy-glucose (FDG) PET in our center.

PROTEIN STRUCTURE. Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels.

Insulin-induced gene 1 (Insig-1) and Insig-2 are endoplasmic reticulum membrane-embedded sterol sensors that regulate the cellular accumulation of sterols. Despite their physiological importance, the structural information on Insigs remains limited. Here we report the high-resolution structures of MvINS, an Insig homolog from Mycobacterium vanbaalenii.

Extracranial metastasis of gliobastoma: Three illustrative cases and current review of the molecular pathology and management strategies.

Glioblastoma (GBM) is the most common and the most malignant primary brain tumor in adults, accounting for ~12-15% of all intracranial neoplasms. Despite advances in surgical, medical and radiation therapies, the mortality of GBM remains high, with a median survival ranging between 40 and 70 weeks. Similar to other primary brain tumors, the extracranial metastasis of GBM is extremely rare, occurring in <2% of patients.

Safe sedation practices among gastroenterology registrars: do we need more training?

Endoscopy training is a central component of gastroenterology training for the vast majority of UK trainees, and integral to this is the practice of safe sedation. The majority of endoscopic procedures are performed with the patient under conscious sedation with a benzodiazepine, often combined with an opioid. Little data exists on the practice of sedation among gastroenterology trainees, including their degree of knowledge of the common sedation agents used and their actions.