All the GNB, including the ESBL-producers, were susceptible to ti

All the GNB, including the ESBL-producers, were susceptible to tigecycline with MIC(90) ranges of 0.25 to 2 mu g/ml. Imipenem and meropenem were very active against ESBL and non-ESBL producers; mean MIC(90)s of 0.19 and 0.09 mu g/ml and 0.05 mu g/ml and 0.02 mu

g/ml, respectively. The MIC(90)s of imipenem and meropenem for the Acinetobacter spp. were 16 and >32 mu g/ml, respectively with resistance rates of 64.3 and 66.1%. ESBL production 3MA was detected in 62% and 82.1% of the E. coli and K. pneumoniae isolates, respectively. Resistance to ciprofloxacin was higher among the ESBL-producing strains of E. coli and K. pneumoniae than the non-ESBL producers. Comparatively, tigecycline had excellent in vitro activities against ESBL-producing Enterobacteriaceae and demonstrated superior activity against Acinetobacter spp. Increasing ESBL production and resistance to ciprofloxacin and gentamicin in Enterobacteriaceae require careful selection of empirical JQ1 molecular weight therapy. Tigecycline holds promise as an alternative choice of therapy for infections caused by ESBL-producing isolates and multi-drug resistant Acinetobacter spp. Key words: Tigecycline, susceptibility, Gram-negative bacteria,

ESBL-producing bacteria.”
“The second edition of the International Classification of Headache Disorders makes a distinction between primary and secondary headaches. The diagnosis of a secondary headache is made if the underlying disease is thought to cause headache or if a close temporal relationship is present together with the occurrence of the headache. At first glance, this may allow clearly secondary headaches to be distinguished from primary headaches. However, by reviewing the available literature concerning several selected secondary headaches, we will discuss the hypothesis that some secondary headaches can also be understood as a variation of primary headaches in the sense that the underlying cause (e.g. infusion of glyceryl trinitrate [ICHD-II 8.1.1], epilepsy [7.6.2], brain tumours [7.4], craniotomy [5.7], etc.)

triggers the same neurophysiologic Vorasidenib order mechanisms that are responsible for the pain in primary headache attacks.”
“RNA editing is the alteration of RNA sequences via insertion, deletion and conversion of nucleotides. In flowering plants, specific cytidine residues of RNA transcribed from organellar genomes are converted into uridines. Approximately 35 editing sites are present in the chloroplasts of higher plants; six pentatricopeptide repeat genes involved in RNA editing have been identified in Arabidopsis. However, although approximately 500 editing sites are found in mitochondrial RNAs of flowering plants, only one gene in Arabidopsis has been reported to be involved in such editing. Here, we identified rice mutants that are defective in seven specific RNA editing sites on five mitochondrial transcripts. Their various phenotypes include delayed seed germination, retarded growth, dwarfism and sterility.


“Background: The French Nutrition and Health Survey (ENNS)


“Background: The French Nutrition and Health Survey (ENNS) was conducted in order to describe food consumption and levels of various biomarkers in the general population. In this paper, we aimed to assess the distribution of blood lead levels (BLL) in the adult population living in France.

Method: ENNS was a cross-sectional survey carried out in the general population. Participants (18-74 years of age) were sampled using a three-stage probability design stratified by geographical areas and degrees of urbanization. Collected data included biochemical samples,

anthropometric measurements, socio-demographic characteristics, and environmental and occupational exposure.

Results: In 2006/2007,2029 adults were included in the survey on lead. The blood lead PF-03084014 geometric mean (GM) in the population living in France was 25.7 mu g/L[24.9-26.5]. check details The overall prevalence

of elevated BLL (>100 mu g/L) was 1.7%[1.1-2.3%]. Levels were significantly higher in males than in females, and increased with age, smoking status and alcohol consumption. Other factors significantly associated with BLL were leisure activities, occupational category, age of housing unit, birth place and shellfish/crustacean consumption.

Conclusion: For the first time a survey provides national estimates of BLL for the adult population in France. Comparison with results from a previous study among men

aged 18-28 years showed that the GM dropped more than 60% in the last 10 years. The distribution of BLL in France was quite similar to that observed in NVP-HSP990 other European countries. (C) 2011 Elsevier Ltd. All rights reserved.”
“Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have emerged as a potential common cause for both sporadic and familial Parkinson’s Disease (PD) in different populations. The pleomorphic features exhibited by LRRK2 mutation carriers and the central role of Lrrk2 protein in the proper functioning of central nervous system suggest that mutations in this protein might be involved in multiple cellular processes leading to other neurodegenerative disorders than PD. The location of LRRK2 gene on chromosome 12, close to a linkage peak for familial late-onset Alzheimer’s Disease (AD), highlights that LRRK2 mutations might be involved in AD pathogenesis. We screened the most common LRRK2 mutation (p.G2019S) in a series of 180 consecutive patients clinically diagnosed with Alzheimer Disease (AD). We identified the p.G2019S in one AD patient with no PD signs, indicating that this mutation is not a common etiological factor for AD in our population (0.5%), corroborating recent data found in Norwegian, North American, Chinese and Italian populations.

Northern blotting analysis revealed that sarcoplasmic reticulum A

Northern blotting analysis revealed that sarcoplasmic reticulum ATPase (SERCA2) mRNA was decreased in ET-1-treated cardiomyocytes, and that this decrease was inhibited by BQ-123 but not by BQ-788. Moreover, pretreatment with chelerythrine partially restored the ET-1-induced decrease MK-4827 price in SERCA2 mRNA, whereas phorbol 12-myristate 13-acetate markedly reduced SERCA2 gene expression. Real-time RT-PCR analysis showed abundant ETA receptor gene expression in

cardiomyocytes. ET-1 reduces SERCA2 gene expression through the ETA receptor and PKC pathway, and prolongs intracellular calcium transient decay. Specific inhibition of the ETA receptor may be a possible therapeutic strategy for improving cardiac performance.”
“Background: Mandibular hypoplasia is one of the most frequently encountered craniofacial anomalies with a variety of etiologies, including congenital, developmental, and acquired. It can lead to significant functional issues at birth by creating an obstruction of the hypopharynx with the retropositioning of the base of the tongue, which lead to respiratory and feeding difficulties at birth. Later in life, mandibular hypoplasia may have a severe impact on the quality of life of the patient, affecting mastication, speech, and appearance. Distraction osteogenesis Selleck CB-5083 (DO) of the craniofacial skeleton emerged as an alternative

to orthognathic surgery. It is a topic of great interest; the technique is gaining enthusiasm for the treatment of a wide range of deformities and achieved wide acceptance in Selleckchem OSI744 orthopedics.

Aim: The objective of the study was to determine the changes in overbite, overjet, and midline shift following mandibular DO in Iraqi patients.

Methods: Nine patients (3 males and 6 females) underwent extraoral multidirectional mandibular DO after proper clinical evaluation. After performing the corticotomy and a mean of 5-day latency period, the distraction was performed at a rate of 0.5 mm twice a day. Subsequent consolidation period mean was 2 months.

Results:

The mandible was successfully elongated in 9 patients with significant decrease in overbite, overjet, and midline shift, and the actual horizontal movement needed in the correction of overjet is more than the horizontal distractor lengthening.”
“Objective: To evaluate the relationship between dynamic mechanical loading, as indicated by external knee adduction moment (KAM) measures during walking, and measures of articular cartilage morphology and subchondral bone size in people with medial knee osteoarthritis (OA).

Design: 180 individuals with radiographic medial tibiofemoral OA participated. Peak KAM and KAM angular impulse were measured by walking gait analysis. Tibial cartilage volume and plateau bone area, and tibiofemoral cartilage defects were determined from magnetic resonance imaging using validated methods.

Although the available family was small, we could show a signific

Although the available family was small, we could show a significant association between the heterozygous T101N mutation and obesity.”
“Background: Selleckchem JNK-IN-8 Multivitamins are frequently consumed by children, but it is unclear whether this affects the risk of allergic disease.

Objective:

We sought to study the association between multivitamin supplementation and allergic disease in 8-y-old children.

Design: Data were obtained from a Swedish birth cohort study. Information on lifestyle factors, including use of vitamin supplements, environmental exposures, and symptoms and diagnoses of allergic diseases, was obtained by parental TPCA-1 purchase questionnaires. In addition, allergen-specific IgE concentrations of food and airborne allergens were measured in blood samples collected at age 8 y. A total of 2423 children were included in the study. The association between use

of vitamin supplements and the selected health outcomes was analyzed with logistic regression.

Results: Overall, no strong and consistent associations were observed between current multivitamin use and asthma, allergic rhinitis, eczema, or atopic sensitization at age 8 y. However, children who reported that they started taking multivitamins before or at age 4 y had a decreased risk of sensitization to food allergens (odds ratio: 0.61; 95% CI: 0.39, 0.97) and tendencies toward inverse associations with allergic rhinitis. In contrast, there was no consistent association among children who started to use multivitamins at or after age 5 y.

Conclusion: Our results show no association between current use of multivitamins and risk of allergic disease but suggest that supplementation with multivitamins during the first years of life may reduce the risk of allergic disease at school age.

Am J Clin Nutr 2009;90:1693-8.”
“Background: Bacterial brain abscesses remain a serious Torin 2 in vivo central nervous system problem despite advances in neurosurgical, neuroimaging, and microbiological techniques and the availability of new antibiotics. The successful treatment of brain abscesses requires surgery, appropriate antibiotic therapy, and eradication of the primary source; nevertheless many controversial issues on the management of this serious infection remain unresolved.

Controversial issues: The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for some controversial issues using an evidence-based and analytical approach.

7 Of 58 limbs, 35%, 19% and 47% were of CEAP clinical stages C4,

7. Of 58 limbs, 35%, 19% and 47% were of CEAP clinical stages C4, C5 and C6, respectively. Previous deep vein thrombosis (DVT) was reported by 7% and major leg trauma by 9% of Givinostat clinical trial patients. The mean VCSS was 9.7 and mean VDS was 1.0. VDS 2 or 3 were found in 10% of patients. The VCSS 2 and 3 for pain, oedema and inflammation were found in 22%, 26% and 0% of C6 legs. The prevalence of combined superficial and deep vein reflux was 71%. The prevalence of isolated superficial and deep vein reflux were 8% and 17%, respectively. One patient had iliac vein occlusion. Compared

with the control group, risk factors that were found to be significant were physical findings of varicose veins, history of leg trauma, standing posture and BMI.

Conclusions: XMU-MP-1 cost Thai patients with CVI were relatively young. Visible varicose veins, pain, oedema and inflammation were uncommon and most patients could maintain their usual activities despite advanced venous disease. An association with obesity was not common. Despite a low prevalence of a history of previous DVT, the prevalence of deep vein reflux was high and commonly combined with superficial venous reflux. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.”
“The aim of this work was to assess the effect of inoculation with the non-symbiotic Agrobacterium

strain 10C2, previously isolated from root nodules of Phaseolus vulgaris, on nodulation, effectiveness and host range specificity. Two rhizobial strains, Ensifer meliloti 2011 and Ensifer medicae A321, were used in this study on the basis of their differential sensitivity to the in vitro antagonistic activity exercised by Agrobacterium sp. 10C2. Three host legumes, P. vulgaris, Medicago laciniata and M. polymorpha, were also selected for this experiment on the basis of their variable symbiotic specificity towards strains 2011 and A321. Cross inoculation experiments were conducted with or without co-inoculation with Agrobacterium sp. 10C2. Results showed that both rhizobial

strains induced ineffective nodules on P. vulgaris. Nevertheless, inoculation with Agrobacterium sp. 10C2 slightly increased shoot dry weight with both strains and enhanced nodule number with strain 2011 selleck screening library only. Inoculation of M. polymorpha with strain 10C2 significantly increased the nodule number induced by E. medicae A321 but did not affect biomass production. However, inoculation of M. laciniata by strain 10C2 enhanced nodule number and shoot dry weight with strain 2011 only. Agrobacterium sp. 10C2 did not affect the non-inoculated control, nor the contrasted host range of both rhizobial strains towards M. polymorpha and M. laciniata. The potential negative effect of the in vitro antagonistic activity of strain 10C2 on reduction of nodule number or symbiotic effectiveness was not proved. No evidence of symbiotic gene transfer from the rhizobial strains to Agrobacterium sp.

(C) 2013 Elsevier B V All rights reserved “
“Objectives: Gh

(C) 2013 Elsevier B.V. All rights reserved.”
“Objectives: Ghrelin has been implicated in the regulation of gastric growth and functional development, but it is yet to be determined whether and how ghrelin over-expression may modify gastric growth, gastric acid secretion and mRNA expression of other gastric endocrine hormones. 25-day-old mice were injected intra-muscularly with vacant plasmid (VP) or recombinant plasmid expressing secretory ghrelin at the doses of 50 mu g (LG) and 100 mu g (HG).

Results:

Expression of ghrelin mRNA was detected in muscles 15 days post-injection, being most abundant in HG mice. In accordance with the ghrelin expression, gastric weight increased (P < 0.05) in HG mice, compared with VP control group. Significant increase of gastric mucosa H+-K+-ATPase mRNA learn more expression was detected in HG mice compared to VP control group (P < 0.05). Compared with VP mice, gastric somatostatin (SS) mRNA expression decreased in LG and

HG mice (P < 0.05), while gastric gastrin expression had no significant difference.

Conclusions: I.M. injection of plasmid encoding ghrelin improved gastric growth and gastric acid secretion with decreased SS mRNA in weaned mice. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.”
“Ghrelin is an important gastrointestinal hormone involved in the regulation of feeding Talazoparib in both mammals and fish. In this study, the preproghrelin cDNA sequence was cloning in the gut of Schizothorax prenanti (S. prenanti). The preproghrelin gene, encoding 103-amino acids, was strongly expressed in the gut

and brain using real-time quantitative RT-PCR (qPCR). The S. prenanti preproghrelin was detected in embryonic developmental stages. Further, it was detectable Z-IETD-FMK cell line in unfertilized eggs, suggesting that ghrelin could be classified as maternal mRNA. An experiment was conducted to determine the expression profile of ghrelin during post-feeding and fasting status of the brain and gut. The results revealed a significant postprandial decrease in ghrelin mRNA expression in the gut 6 h post-feeding (hpf) and brain (1.5 and 9 hpf) compared to an unfed control group, indicating that food intake and processing affect the regulation of expression of ghrelin in S. prenanti. The constructed recombinant plasmid pMD-19 T-ghrelin was transformed to Escherichia coli BL21 and induced with IPTG, and the expressed product was identified by SDS-PAGE. The prokaryotic expression vector for ghrelin was constructed successfully, and fusion protein was expressed in E. coli BL21, which laid the foundation for the further study on the function of this protein and its mechanism. Overall, our results provide evidence for a highly conserved structure and biological actions of ghrelin in S. prenanti.

Laboratory Investigation (2010) 90, 1628-1636; doi:10 1038/labinv

Laboratory Investigation (2010) 90, 1628-1636; doi:10.1038/labinvest.2010.158;

published online 23 August 2010″
“Periodic sharp wave complexes observed on an electroencephalographic recording and the presence of a 14-3-3 protein in the cerebrospinal Selleckchem CHIR-99021 fluid (CSF) are both included in the diagnostic criteria for the Creutzfeldt-Jakob disease (CJD) supplied by the World Health Organization; however, the presence or absence of the 14-3-3 protein in the CSF is sometimes difficult to discern on a western blot because of equivocal bands. The goal of this study was to establish a standard 14-3-3 protein assay and to determine the threshold level of a 14-3-3 protein that can be assayed by western blot. We searched for the most suitable isoform of the 14-3-3 protein to test for in protein assays, and the most sensitive antibody among four antibodies with PD0332991 an affinity for 14-3-3. We measured the levels of all 14-3-3 isoforms in 112 patients with CJD and in 100 patients with other diseases. We compared the performances of four different

antibodies. We carried out a semi-quantitative analysis of gamma-isoform levels using the LAS 3000 system, which was capable of producing a digital image from the luminescence on a western blot. We determined that the most suitable isoform of the 14-3-3 protein for conducting a standardized assay was the gamma-isoform. Among the four commercially available antibodies for this protein, the most sensitive and specific was 18647 (IBL, Japan). We report the high repeatability of the detection of the 14-3-3 protein by this antibody to the gamma-isoform, showing that western blot can be used for semi-quantitative

analysis. Laboratory Investigation (2010) 90, 1637-1644; Epacadostat molecular weight doi:10.1038/labinvest.2009.68; published online 9 August 2010″
“In this study, we investigated the involvement of dystrophin-associated proteins (DAPs) and their relationship with the perivascular basement membrane in the brains of mdx mice and controls at the age of 2 months. We analyzed (1) the expression of glial DAPs alpha-beta-dystroglycan (DG), alpha-syntrophin, aquaporin-4 (AQP4) water channel, Kir 4.1 and dystrophin isoform (Dp71) by immunocytochemistry, laser confocal microscopy, immunogold electron microscopy, immunoblotting and RT-PCR; (2) the ultrastructure of the basement membrane and expression of laminin and agrin; and (3) the dual immunofluorescence colocalization of AQP4/alpha-beta-DG, and of Kir 4.1/agrin.


“We previously showed conjugated linoleic acids (CLA) inhi


“We previously showed conjugated linoleic acids (CLA) inhibited TNF-alpha-induced monocyte (THP-1) adhesion to human umbilical vein endothelial cells (HUVEC) in vitro which involved an increase in platelet activating factor (PAF). Here we show adhesion molecule (ADM) regulation by fatty acids and the differing role of nuclear factor kappa B (NF-kappa B) activation in HUVEC and vascular smooth muscle cells (vSMC). CLA and omega-3 long-chain polyunsaturated fatty acids (PUFA) (FA) reduced TNF-alpha-induced expression of ADMs (intercellular AZD4547 clinical trial adhesion molecule-1

(ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) but not E-selectin) on HUVEC and vSMC to different extents depending on FA type and concentration, cell type and method of analysis. I kappa B alpha phosphorylation in HUVEC and vSMC and transient transfection with NF-kappa

B-luciferase reporter plasmid (HUVEC only) indicated differential NF-kappa B involvement during FA modulation (cis-9, trans-11; trans-10, cis-12 and a 50:50 mix of both CLA isomers; eicosapentaenoic acid (EPA); docosahexaenoic acid (DHA)). TNF-a-induced ADM expression in both cell types by 2-10-fold. In HUVEC, CLA t10, c12 and CLA mix (50:50 mixture of CLA c9, t11 and t10, c12) and EPA and DHA reduced ICAM-I expression (15-35%) at 12.5, 25 and/or 50 mu M. VCAM-I expression SRT2104 in vivo was reduced by 25 mu M 00, c12 isomer and mix; omega-3 PUFA and other concentrations of CLA and TNF-a-induced E-selectin expression were unaffected. TNF alpha-induced inhibitor kappa B (I kappa B) phosphorylation was biphasic peaking at 5 min in both cell types and 60 and 120 min in HUVEC

and SMC, respectively. I kappa B alpha phosphorylation and NF-kappa B activity was reduced (29% and 30%, respectively) by 25 mu M CLA mix. n-3 PUFA did not reduce I kappa B alpha phosphorylation or NF-kappa B activity but reduced ADM expression. We show that n-3 PUFA and CLA reduce expression of ADM on HUVEC and vSMC. This reflected reduced adherence of monocytes to HUVEC previously reported by our group. Reduction of ICAM-1 and VCAM-1 protein expression by n-3 PUFA was less dependent on the NF-kappa B pathway than reduction by CLA which reflected the parallel attenuation of NF-kappa B activity. This indicated involvement of other SU5402 concentration transcription factors (i.e. AP-1) in the FA regulation of ADM expression and has, to our knowledge, not been previously reported. (C) 2007 Elsevier Ltd. All rights reserved.”
“The Epstein-Barr virus (EBV) genome is maintained as an extrachromosomal episome during latent infection of B lymphocytes. Episomal maintenance is conferred by the interaction of the EBV-encoded nuclear antigen 1 (EBNA1) with a tandem array of high-affinity binding sites, referred to as the family of repeats (FR), located within the viral origin of plasmid replication (OriP).

This structure of the early gene promoter might be selectively ma

This structure of the early gene promoter might be selectively maintained by allowing fast growth of the virus. With amino acid limitation, there exist finite optimal ratio of early/late gene promoter activity. (C) 2009 Elsevier Ltd. All rights reserved.”
“Repetitive transcranial magnetic stimulation (rTMS) has been increasingly evaluated as a therapeutic tool for the treatment of

depression, using various stimulation parameters and protocols. Heterogeneous results have been reported with regard to clinical outcome, at least partly due to the variety of procedures for buy NU7441 coil placement above the desired site of stimulation. This article reviews the strategies for coil positioning in the treatment of depression. Considering preliminary clinical evidence, neuronavigated rTMS appears desirable to treat

depression, compared to the standard targeting SHP099 cell line procedure (5 cm anterior to the motor cortex). Coil positioning strategy might improve in the future by taking into consideration the individual abnormalities revealed by functional neuroimaging data. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“Tinnitus affects 10% of the population, its pathophysiology remains incompletely understood, and treatment is elusive. Both animal models and functional imaging data in tinnitus patients suggest that tinnitus is associated with increased neuronal activity, increased synchronicity and functional reorganisation in the auditory cortex. Therefore, targeted modulation of auditory cortex has Selleck VE-822 been proposed as a new therapeutic approach for chronic tinnitus. Repetitive

transcranial magnetic stimulation (rTMS), a non invasive method for modulation of cortical activity, has been applied in different ways in patients with chronic tinnitus. Single sessions of high-frequency rTMS over the temporal cortex have been used to transiently interfere with the intensity of tinnitus. Repeated sessions of low-frequency rTMS have been investigated as a treatment for tinnitus. Here, we review data from clinical trials and discuss potential neurobiological mechanisms with special focus on the relevance of the stimulation target and the method of TMS coil positioning. Different functional neuroimaging techniques are used for detecting tinnitus-related changes in brain activity. They converge in the finding of increased neuronal activity in the central auditory system, but they differ in the exact localisation of these changes, which in turn results in uncertainty about the optimal target for rTMS treatment. In this context, it is not surprising that the currently available studies do not demonstrate clear evidence for superiority of neuronavigational coil positioning. Further development of rTMS as a treatment for tinnitus will depend on a more detailed understanding of both the neuronal correlates of the different forms of tinnitus and of the neurobiological effects mediating the benefit of TMS on tinnitus perception. (C) 2009 Elsevier Masson SAS. All rights reserved.

When a single generalized seizure was elicited 10 min following

When a single generalized seizure was elicited 10 min following

phenytoin administration, average phenytoin brain dialysate levels were significantly lower (up to 45%) than those of control animals. During a self-sustained status epilepticus, phenytoin access to the site of seizure initiation tended to be lower in the early phase following drug administration, but reached control level 2 h later.

The data clearly demonstrate that seizure-induced alterations in BBB integrity and function do not increase extracellular brain levels of phenytoin in affected brain regions, but rather tend to decrease the eFT-508 ic50 free concentration of phenytoin in the extracellular compartment. (C) 2011 Elsevier Ltd. All rights reserved.”
“Nuclear factor E2 related Evofosfamide purchase factor-2 (Nrf2) transcription factor is one of the main regulators of intracellular redox balance and a sensor of oxidative and electrophilic stress. Low Nrf2 activity is usually associated with carcinogenesis, but Nrf2 is also considered as an oncogene because it increases survival of transformed cells. Because intracellular redox balance alterations :ire involved in both senescence and tumorigenesis, we investigated the impact of Nrf2 genetic deletion on cellular immortalization and life span of murine embryonic Fibroblasts. We report that Nrf2 genetic deletion promotes immortalization due to

an early loss of p53-dependent gene expression. However, compared with control cells, immortalized Nrf2-/- murine embryonic fibroblasts exhibited decreased growth, lower cycl in E levels, and impaired expression of NQO1 and cytochrome b(5) reductase. Moreover, SirT1 was also significantly reduced in immortalized Nrf2-/- murine embryonic fibroblasts, and these cells exhibited shorter life

span. Our results underscore the dual role of Nrf2 in protection against carcinogenesis and in the delay of cellular aging.”
“Two-pore-domain K(+) (K(2)P) channels are highly expressed in neurons and cardiac myocytes. In this JIB04 concentration study we investigated the potency of the antidepressant fluoxetine to inhibit brain and cardiac K(2)P channels, TREK-1, TASK-1 and THIK-1. Maximal sensitivity was detected for TREK-1, which was inhibited by 77% when expressed in HEK-293 cells and Xenopus oocytes. Alternative translation initiation (ATI) generates two different protein products from a single transcript of TREK-1. Electrophysiological analysis of two polypeptides engineered by mutagenesis (TREK-1[M53I], TREK-1[Delta N52]) revealed reduced current amplitude and K(+) selectivity of the truncated TREK-1 isoform. The sensitivity of TREK-1[Delta N52] to fluoxetine decreased by 70%, indicating that the first 52 amino acids are essential for TREK-1 sensitivity to this drug. (C) 2011 Elsevier Ltd. All rights reserved.”
“Werner syndrome is a premature aging disorder caused by mutations in a RecQ-like DNA helicase.