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Personalized Treatment of Obsessive-Compulsive Disorder: Radiology, EEG, Pharmacogenetics and Biochemistry
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: Obsessive-compulsive disorder (OCD) is a common mental illness and a ubiquitous cause of disability. Approximately half of the patients with OCD only partially respond or do not respond at all to current ways of treatment. Even patients responding to treatment usually need high doses of medication and/or intense psychotherapy for a long time. It is obvious that therapeutic approaches to OCD need improving. In this article, we review the modalities of personalized medicine in OCD. </p><p> Methods: We conducted a search in PubMed (until June 2015) and Scopus (until June 2015) by using the following terms: “obsessive-compulsive disorder,” “personalized medicine,” “response prediction,” “pharmacogenetics,” “therapeutic drug monitoring,” “EEG,” “neuroimaging” and “serotonin.” The literature about neuroimaging including radiological techniques (positron emission tomography, single-photon emission tomography, functional and morphometric magnetic resonance imaging and magnetic resonance spectroscopy) and electroencephalography, therapeutic drug monitoring (measuring the plasma levels of drugs), pharmacogenetics (genes encoding cytochrome P450 enzymes, serotonin transporter, serotonin receptors, norepinephrine transporter, dopamine receptors, brain-derived neurotrophic factor [BDNF] and catechol-O-methyltransferase) and biochemistry (whole blood serotonin levels and neuroendocrine challenge tests) is investigated. </p><p> Results: Pre-treatment changes in glucose metabolism shown by radiological instruments might be related to response to medication. Increased alpha in EEG is predictive of good response whereas increased theta forecasts a poor response. BDNF, serotonin receptors and glutamatergic and serotonergic transmission have been found to be somewhat related to treatment response in OCD. Few studies on whole blood serotonin levels and hormone response to challenge with a serotonergic medication in patients seem to have a predictive value in OCD treatment. </p><p> Conclusion: Although the studies to elaborate a personalized treatment of OCD have produced some promising results, much more work is required to provide clinician with a reliable decision tree. </p><p>
Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids found in such plants as gender Berberis. Berberine is recognised to improve glucose and lipid metabolism disorders and preliminary clinical evidences suggest the ability of berberine to reduce endothelial inflammation improving vascular health, even in patients already affected by cardiovascular diseases, suggesting a possible interesting role of berberine and its metabolites in clinical practice. However, its physicochemical properties, pharmacokinetic, and metabolism are not fully elucidated and contradictory data have been reported. </p><p> This review provides a summary regarding the pharmacological and biological features of berberine, with a focus on berberine as well as their pharmacologically active metabolites and the different mechanisms underlying their activities in order to clarify the correct use of berberine supplementation, alone or in association with other nutraceuticals, for the management of metabolic disorders associated to increased cardiovascular disease risk. A particular attention has also been given to the available clinical trials assessing its short- and middle- term use tolerability, safety and efficacy in various conditions, such as dyslipidaemia, impaired fasting glucose, metabolic syndrome and type 2 diabetes. </p><p>
Editorial (Thematic Issue: New Therapeutic Targets for Autism Spectrum Disorders)
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Population Studies of Association Between Lithium and Risk of Neurodegenerative Disorders
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: Lithium shows neuroprotective and neurotrophic effects in vitro and in vivo. Due to its involvement in hippocampal neurogenesis and the interaction with beta-amyloid and neurofibrillary tangle metabolism it has been hypothesized that lithium could have the potential to influence the development of dementia. Method: Using the PubMed database and cross-reference search strategies our aim was to specifically identify population (cohort or case-control) studies investigating the association between lithium and dementia. Results: Data from large cohort studies suggest an association between lithium treatment and dementia risk reduction or reduced dementia severity. Studies with smaller sample sizes yield more variable findings. Conclusions: Lithium may reduce the risk of dementia among middle-aged and older people. Beneficial lithium effects are possibly limited to specific types of neurodegenerative processes.
Recent Advances Using Phosphodiesterase 4 (PDE4) Inhibitors to Treat Inflammatory Disorders: Animal and Clinical Studies
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Phosphodiesterase 4 (PDE4) inhibitors can be effective drugs for treating inflammation in different tissues/organs caused by conditions such as asthma, chronic obstructive pulmonary disease (COPD), psoriasis, and Alzheimer’s disease. It has been demonstrated that PDE4 inhibitors used for drug therapy provide some advantages over conventional formulations, including sensitivity to selective inhibitors, unique tissue distribution, and ease of oral administration. To date, the U.S. Food and Drug Administration (USFDA) had approved two PDE4 inhibitors, roflumilast (Daxas®, Daliresp®) and apremilast (Otezla®), for treating respective COPD and plaque psoriasis. Several pharmaceutical companies and academic laboratories continuously develop novel PDE4 inhibitors for clinical application. A concern pertaining to the development of PDE4 inhibitors is the high occurrence rate of side effects such as emesis, nausea, and headache. This review describes recent developments using PDE4 inhibitors for inflammation management. Special attention is paid to the use of PDE4 inhibitors in treating pulmonary and cutaneous inflammation. This review article focuses on issues related to animal and human studies. The action mode of the inhibitors is also addressed.
Smell and Taste Disorders Resulting from Cancer and Chemotherapy
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Malnutrition is common in both adult and pediatric patients undergoing treatment for cancer. Patients commonly attribute difficulties maintaining food intake to an altered taste developed during treatment. This review summarizes what is known about taste and smell dysfunction in patients with undergoing chemotherapy as their main treatment modality. Self-reported taste and smell alterations are prevalent in upwards of 86% of cancer patients. There is some evidence for decreased taste sensitivity in cancer patients when assessed using common gustatory tests. In some patients, taste and smell alterations may continue well after their cancer treatment has been completed. Such disorders can increase distress, reduce appetite and contribute towards poor nutritional status in cancer patients. There remain no effective interventions for improving the appetite or nutritional intake of patients with cancer experiencing taste and smell changes. There is a lack of consistency in assessment methodologies for measuring taste and smell changes in cancer patients and we therefore recommend that future work use well-established methods. Research should also take into account the role of food hedonics, food flavor and texture in assessing the association between taste dysfunction, poor oral intake and malnutrition in cancer patients. Both adult and child cancer patients should be counselled on the potential impact taste and smell dysfunction can have on their appetite and oral intake.
Rate-Determining and Rate-Limiting Steps in the Clearance and Excretion of a Potent and Selective p21-Activated Kinase Inhibitor: A Case Study of Rapid Hepatic Uptake and Slow Elimination in Rat
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: Significant under-prediction of in vivo clearance in rat was observed for a potent p21-activated kinase (PAK1) inhibitor, GNE1. </p><p> Objective: Rate-determining (rapid uptake) and rate-limiting (slow excretion) steps in systemic clearance and elimination of GNE1, respectively, were evaluated to better understand the cause of the in vitro-in vivo (IVIV) disconnect. </p><p> Methods: A series of in vivo, ex vivo, and in vitro experiments were carried out: 1) the role of organic cation transporters (Oct or Slc22a) was investigated in transporter knock-out and wild-type animals with or without 1-aminobenzotriazole (ABT) pretreatment; 2) the concentration-dependent hepatic extraction ratio was determined in isolated perfused rat liver; and 3) excreta were collected from both bile duct cannulated and non-cannulated rats after intravenous injection. </p><p> Results: After intravenous dosing, the rate-determining step in clearance was found to be mediated by the active uptake transporter, Oct1. In cannulated rats, biliary and renal clearance of GNE1 accounted for only approximately 14 and 16% of the total clearance, respectively. N-acetylation, an important metabolic pathway, accounted for only about 10% of the total dose. In non-cannulated rats, the majority of the dose was recovered in feces as unchanged parent (up to 91%) overnight following intravenous administration. </p><p> Conclusion: Because the clearance of GNE1 is mediated through uptake transporters rather than metabolism, the extrahepatic expression of Oct1 in kidney and intestine in rat likely plays an important role in the IVIV disconnect in hepatic clearance prediction. The slow process of intestinal secretion is the rate-limiting step for in vivo clearance of GNE1. </p><p>
Untapped Potential of Disordered Proteins in Current Druggable Human Proteome
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Current efforts in design and characterization of drugs often rely on the structure of their protein targets. However, a large fraction of proteins lack unique 3-D structures and exist as highly dynamic structural ensembles. These intrinsically disordered proteins are involved in pathogenesis of various human diseases and are highly abundant in eukaryotes. Based on a comprehensive analysis of the current druggable human proteome covering 12 drug classes and 18 major classes of drug targets we show a significant bias toward high structural coverage and low abundance of intrinsic disorder. We review reasons for this bias including widespread use of the structural information in various stages of drug development and characterization process and difficulty with attaining structures for the intrinsically disordered proteins. We also discuss future of intrinsically disordered proteins as drug targets. Given the overall high disorder content of the human proteome and current bias of the druggable human proteome toward structural proteins, it is inevitable that disordered proteins will have to raise up on the list of prospective drug targets. The protein disorder-assisted drug design can draw from current rational drug design techniques and would also need novel approaches that no longer rely on a unique protein structure.
Prader-Willi Syndrome: Clinical Genetics and Diagnostic Aspects with Treatment Approaches
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: Prader-Willi syndrome (PWS) is a neuro-developmental genetic disorder due to lack of expression of genes inherited from the paternal chromosome 15q11-q13 region with three main genetic subtypes. These include paternal 15q11-q13 deletion (about 70% of cases), maternal uniparental disomy 15 or both 15s from the mother (20-30% of cases), and defects in the imprinting center (1-3%) which controls the expression of imprinted genes in this chromosome region. Clinical manifestations include infantile hypotonia with a poor suck resulting in failure to thrive, short stature, small hands/feet and hypogonadism/hypogenitalism due to growth and other hormone deficiencies, hyperphagia and excessive weight gain with obesity and cognitive and behavioral problems including obsessive compulsions, tantrums and self-injury. The phenotype is likely related to hypothalamic dysfunction. </p><p> Objective: Hyperphagia and obesity with related complications are major causes of morbidity and mortality in PWS requiring accurate diagnosis, appropriate medical management and treatment; the major objective of our report. </p><p> Methods and Results: An extensive review of the literature was undertaken including genetics, clinical and behavioral aspects, and updated health-related information addressing the importance of early diagnosis and treatment of individuals with Prader-Willi syndrome. A searchable, bulleted and formatted list of topics related to this obesity syndrome was provided utilizing a Table of Contents approach for the clinical practitioner. </p><p> Conclusions: Physicians and other health care providers can use this review with clinical, genetic and treatment summaries divided into sections that are pertinent in the context of clinical practice. Finally, frequently asked questions by clinicians, families and other interested participants will be addressed. </p><p>
Evaluation of a Dramatic Writing Workshop in Youth With or Without Psychiatric Disorders
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: Metacognitive difficulties are frequent among youth with a psychiatric disorder. The present study evaluates the effectiveness of a dramatic writing workshop on the metacognition of youth aged from 14 to 25 years, the majority presenting a stabilized psychiatric disorder. </p><p> Methods: Twenty-four youth were recruited for the study, 12 youth who received the workshop and 12 who did not. Among each group of 12 eligible participants, 10 presented with a stabilized psychiatric disorder and two did not. Metacognition, social cognition, psychological and social functioning measures as well as questionnaires about objectives and appreciation regarding the workshop were used. </p><p> Results: Analyses revealed no differences between groups after the workshop in regard to youth’s metacognition, social cognition, nor psychological and social functioning. On the other hand, youth who participated in the workshop appreciated their experience, and their psychological and social functioning didn’t deteriorate. </p><p> Conclusions: Study results suggest that the duration of the workshop and the number of sessions should be extended. </p><p>
An Improved U-Shaped Microstrip Meander-Line Slow Wave Structure for High Efficiency G-band Traveling Wave Tubes
Today, 12 Ιουλίου 2016, 3:02:35 μμ
In this paper, an improved U-shaped microstrip meander-line slow wave structure (SWS) for low-voltage high-efficiency miniature G-band traveling wave tubes (TWT) is presented. To increase the TWT efficiency, the synchronization between electromagnetic (EM) wave and the electron beam should be maintained. Since the velocity of the electron beam passing along the tube is gradually reduced, the EM wave phase velocity should be also slowed down. Therefore, we gradually lengthen the width of meander-line to make longer the EM wave path for decreasing the EM wave phase velocity. Meanwhile, a simple analysis for calculating the dispersion properties of this kind of SWS is presented and the analytical results are compared with those obtained from simulation using CST-microwave studio. In addition, the scattering parameters of the SWS and the interaction between electron sheet beam and the electromagnetic fields are investigated with the help of CSTmicrowave studio and CST-Particle Studio, respectively. Our study shows that the G-band TWT is capable of delivering several tens of watts output power with 3-dB frequency bandwidth of 17GHz, ranging from 210GHz to 227GHz. Additionally, the peak output power is about 50 W with the corresponding gain of 40 dB at 218 GHz.
Validation of a Rapid and Sensitive HPLC-UV Method for the Quantification of Eprosartan Mesylate in Bulk Drug, TeventenTM and Ultradeformable Lipid Based Vesicular System
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: Methods reported so far in literature, considered to be less sensitive, uneconomical and time consuming; overall run time more than 10 minutes. </p><p> Objective: From economic point of view and for the purpose of routine analysis, it was decided to develop a simple, more sensitive, rapid and economical HPLC method for estimation of EM. </p><p> Method: A HPLC analytical method has been developed for the quantification of eprosartan in bulk drugs and pharmaceutical formulations at 235 nm using HPLC-UV detector. Chromatographic separation was performed on a Waters<sup>®</sup> C<sub>18</sub> column (µBondapak<sup>TM</sup>5 µm, 150 mm x 3.9 mm i.d). The acetonitrile and potassium dihydrogen orthophosphate buffer (20mM, pH 3) in ratio of 35%: 65% respectively was used as mobile phase; which pumped at a flow rate of 1.2 ml/min. The developed analytical method was validated following ICH guidelines taking linearity, accuracy, precision, sensitivity, selectivity, robustness and stability of method into consideration. </p><p> Result: The calibration curves were found linear with regression coefficient (r<sup>2</sup>) of 0.99. The developed method was found to be rapid and sensitive; as the retention time for eprosartan was found to be lesser than 5 min and the LOD and LOQ were found to be 0.014 µg/ml and 0.042 µg/ml, respectively. Additionally, the developed method was successfully applied for the estimation of eprosartan in pharmaceutical formulations (bulk drug, tablet and ultradeformable lipid based formulation). </p><p> Conclusion: The developed method was found simple, rapid, accurate, and reproducible for the determination of eprosartan in bulk, tablet and in lipid based formulation.
Utilization of Evidence-Based Secondary Prevention Medications at the Time of Discharge in Patients with Acute Coronary Syndrome (ACS) in Qatar
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background and Objectives: In Qatar, ACS (Acute Coronary Syndrome) has become the leading cause of morbidity and mortality. Guidelines recommend that ACS patients should receive indefinite treatment with antiplatelets, -blockers, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and statins. The study objectives were to assess the use of evidence-based secondary prevention medication at discharge among ACS patients in Qatar and to determine the clinical and demographic characteristics associated with the use of these medications. </p><p> Setting and Methods: A retrospective medical record review was conducted at the Heart Hospital in Qatar. A random sample of 1068 ACS patients was selected. Patient characteristics were summarized. Prevalence of medications at discharge were computed for each medication as well as for medication combinations. Multiple logistic regression was used to detect patient variables that were associated with the outcomes. A p 0.05 was considered significant. </p><p> Main Outcome Measures: -Percentage of ACS patients discharged on each of the following medications: antiplatelets (aspirin, clopidogrel), -blockers, ACEI or ARBs and statins and on the combination of these medications-Association between the use of these medications and patient characteristics. </p><p> Results: In total, 1064 records were reviewed. The majority were males (85.3%) and about 1 in 5 (18.7%) were Qatari. At discharge, patients were prescribed the following: aspirin (96.0%), clopidogrel (92.0%), -blockers (90.6%) and statins (97.7%). ACEI and ARBs were prescribed to 63.5 and 11.3%, respectively. The concurrent 4 medications (aspirin or clopidogrel, statins or other lowering cholesterol medication, -blockers and ACEI or ARB) were prescribed to 773 patients (77.8%; 95% confidence interval: 75.2-80.4%). Being overweight or obese, and having PCI (percutaneous coronary intervention) or hypertension were associated with higher prescription of the concurrent medications. Those with diabetes had a 52% increase in the odds of prescribing the 4 medications. Those with kidney disease had a 67% reduction in the odds of prescribing. </p><p> Conclusion: Most ACS patients were prescribed antiplatelets, -blockers and statins, but the use of ACEIs or ARBs was suboptimal. Strategies are needed to enhance ACEI or ARB prescribing, especially for high risk patients who would have the greatest therapeutic benefit from these drugs. </p><p>
Editorial (Thematic Issue: Effective and Promising Treatments for Neurological Disorders and Cancer)
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Commentary: Neurorestoratology: A Concept and Emerging Discipline in the Treatment of Neurological Disorders
Today, 12 Ιουλίου 2016, 3:02:35 μμ
A Review of Rehabilitation Devices to Promote Upper Limb Function Following Stroke
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: Stroke is a major contributor to the reduced ability to carry out activities of daily living (ADL) post cerebral infarct. There has been a major focus on understanding and improving rehabilitation interventions in order to target cortical neural plasticity to support recovery of upper limb function. Conventional therapies delivered by therapists have been combined with the application of mechanical and robotic devices to provide controlled and assisted movement of the paretic upper limb. The ability to provide greater levels of intensity and reproducible repetitive task practice through the application of intervention devices are key mechanisms to support rehabilitation efficacy. </p><p> Results: This review of literature published in the last decade identified 141 robotic or mechanical devices. These devices have been characterised and assessed by their individual characteristics to provide a review of current trends in rehabilitation device interventions. Correlation of factors identified to promote positive targeted neural plasticity has raised questions over the benefits of expensive robotic devices over simple mechanical ones. </p><p> Conclusion: A mechanical device with appropriate functionality to support the promotion of neural plasticity after stroke may provide an effective solution for both patient recovery and to stimulate further research into the use of medical devices in stroke rehabilitation. These findings indicate that a focus on simple, cost effective and efficacious intervention solutions may improve rehabilitation outcomes. </p><p>
Aptamer-Quantum Dot Lateral Flow Test Strip Development for Rapid and Sensitive Detection of Pathogenic Escherichia coli via Intimin, O157- Specific LPS and Shiga Toxin 1 Aptamers
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Background: The use of DNA aptamers to replace antibodies in lateral flow (LF) test strip assays coupled to quantum dots (QDs) has demonstrated enhanced sensitivity for the rapid and portable detection of several foodborne pathogenic bacterial species with simple ultraviolet (UV) illumination and visual assessment (Bruno, Pathogens, 2014; 3: 341-355). </p><p> Objectives: The present report extends and focuses development on detection of O157- specific lipopolysaccharide (LPS), intimin protein and Shiga toxin 1 (Stx 1) using the same aptamer-QD LF assay approach to aid in rapid and sensitive detection of E. coli O157:H7 and other pathogenic serotypes of E. coli. </p><p> Methods: Numerous anti-O157 LPS, intimin and anti-Stx 1 aptamer DNA sequence candidates were developed and screened by enzyme-linked aptamer assay (ELASA) followed by further screening of the best candidates in less expensive aptamer- latex particle or aptamer-colloidal gold (CG) LF formats. The highest affinity and most specific aptamer candidates were incorporated into the aptamer-QD LF format. </p><p> Results: Several high affinity and specific aptamers against intimin, Stx1, and O157 LPS were developed and found to work well in various capture-reporter conjugate combinations using latex particles, CG and QDs with detection limits as low as 100 E. coli O157:H7 bacterial cells and 10 ng of Stx 1 in buffer by visual assessment. </p><p> Conclusion: The seminal work in this aptamer-QD LF area has been extended to sensitive detection of E. coli O157 cells as well as detection of other pathogenic E. coli serotypes by targeting intimin and Stx 1. </p><p>
Aporphines and Parkinson’s Disease: Medical Tools for the Future
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Parkinson’s disease is a motor dysfunction that has been widely studied but many of the reports on commercial drugs for the treatment of this disease have afforded some undesirable side effects that generate an extensive and unviable treatment by economic costs and due to the bioavailability of the assayed compounds. At present, some molecules are used as L-DOPA agonists or can change the dopamine concentrations in the CNS. Thus, the use of aporphine-type alkaloids has given a real alternative due to the diverse natural sources where can be isolated or to obtain them by means of conventional syntheses. Isoquinoline alkaloids as liriodenine, phenanthrene-type alkaloids, alkoxy-hydroxyaporphine, aminothiazole-aporphine or lipoic ester aporphine derivatives are some of the examples to be considered in this mini-review, wherein the applied pharmacological effects to reduce the motor disorders and the possible medical properties of these alkaloids on the dopaminergic receptors are analyzed.
Medication-Induced Nephrotoxicity in Older Patients
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Objective: To summarize current evidence about mechanisms, clinical features, diagnostic issues, and strategies for prevention of medication-induced nephrotoxicity among older people. </p><p> Methods: A Pubmed search was performed, and studies concerning age-related changes in kidney structure and function predisposing to nephrotoxicity, pathophysiological mechanisms, kidney drug metabolism enzymes, clinical epidemiology of medication-induced kidney damage, biomarkers for early identification of nephrotoxicity and strategies for prevention of medication-induced nephrotoxicity among older people were selected. Finally, 245 papers were included in the review. </p><p> Results: Medications may induce nephrotoxicity through several pathophysiological mechanisms. People aged 75 or more are especially exposed to potential nephrotoxic medications or combinations of medications in the context of complex polypharmacy regimens. Estimated glomerular filtration rate (eGFR) may be useful to identify medication-induced alterations in kidney function, but creatinine-based methods have important limitation in older patients. Several innovative biomarkers have been proposed to identify AKI but these methodologies are not standardized and older people have not been evaluated systematically. Factors related to patient, medication, and interactions should be taken into account for effective prevention. </p><p> Conclusions: Medication-induced nephrotoxicity is a relevant problem in older populations. Nevertheless, several areas of uncertainty remain to be explored, including the impact of nephrotoxicity on functional outcomes relevant to older patients, the reliability of currently recommended methods for diagnosing and staging AKI, the use of innovative biomarkers in such a heterogeneous population, the effectiveness of preventing strategies and treatments and their impact on functional outcomes. </p><p>
PDZ Binding Domains, Structural Disorder and Phosphorylation: A Menage-a-trois Tailing Dcp2 mRNA Decapping Enzymes
Today, 12 Ιουλίου 2016, 3:02:35 μμ
Diverse cellular activities are mediated through the interaction of protein domains and their binding partners. One such protein domain widely distributed in the higher metazoan world is the PDZ domain, which facilitates abundant protein–protein interactions. The PDZ domain-PDZ binding domain interaction has been implicated in several pathologies including Alzheimer’s disease, Parkinson’s disease and Down syndrome. PDZ domains bind to C-terminal peptides/proteins which have either of the following combinations: S/T-X-hydrophobic-COOH for type I, hydrophobic-Xhydrophobic- COOH for type II, and D/E-X-hydrophobic-COOH for type III, although hydrophobicity in the termini form the key characteristic of the PDZ-binding domains. We identified and characterized a Dcp2 type mRNA decapping enzyme from Arabidopsis thaliana, a protein containing a putative PDZ-binding domain using mutagenesis and protein biochemistry. Now we are using bioinformatics to study the Cterminal end of mRNA decapping enzymes from complex metazoans with the aim of (1) identifying putative PDZ-binding domains (2) Correlating structural disorder with PDZ binding domains and (3) Demonstrating the presence of phosphorylation sites in C-terminal extremities of Dcp2 type mRNA decapping enzymes. It is proposed here that the trinity of PDZbinding domains, structural disorder and phosphorylation-susceptible sites are a feature of the Dcp2 family of decapping enzymes and perhaps is a wider trick in protein evolution where scaffolding/tethering is a requirement for localization and function. It is critical though laboratory-based supporting evidence is sought to back-up this bioinformatics exploration into tail regions of mRNA decapping enzymes.
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