bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptomic profile analysis of fed-batch cultures expressing different recombinant proteins in Escherichia coli
Authors: Sharma Ashish K , Mahalik Shubhashree , Ghosh Chaitali , Singh Anuradha B , Mukherjee Krishna J 
Published: October 2011

AbstractThere is a need to elucidate the product specific features of the metabolic stress response of the host cell to the induction of recombinant protein synthesis. For this, the method of choice is transcriptomic profiling which provides a better insight into the changes taking place in complex global metabolic networks. The transcriptomic profiles of three fed-batch cultures expressing different proteins viz. recombinant human interferon-beta (rhIFN-β), Xylanase and Green Fluorescence Protein (GFP) were compared post induction. We observed a depression in the nutrient uptake and utilization pathways, which was common for all the three expressed proteins. Thus glycerol transporters and genes involved in ATP synthesis as well as aerobic respiration were severely down-regulated. On the other hand the amino acid uptake and biosynthesis genes were significantly repressed only when soluble proteins were expressed under different promoters, but not when the product was expressed as an inclusion body (IB). High level expression under the T7 promoter (rhIFN-β and xylanase) triggered the cellular degradation machinery like the osmoprotectants, proteases and mRNA degradation genes which were highly up-regulated, while this trend was not true with GFP expression under the comparatively weakerarapromoter. The design of a better host platform for recombinant protein production thus needs to take into account the specific nature of the cellular response to protein expression.
Surface cooling for induction of mild hypothermia in conscious healthy volunteers - a feasibility trial
Authors: Testori Christoph , Sterz Fritz , Behringer Wilhelm , Spiel Alexander , Firbas Christa , Jilma Bernd 
Published: October 2011

Abstract
Introduction
Animal and human studies suggest beneficial outcome effects of mild hypothermia for stroke, for acute myocardial infarction, and for cardiogenic shock. The aim of this study was to investigate the feasibility and safety of non-invasive surface cooling for induction and maintenance of mild hypothermia (32 to 34°C) in healthy, conscious volunteers.

Methods
The trial was set at a clinical research ward in a tertiary care center, and included 16 healthy male volunteers 18 to 70 years old. Surface cooling was established by a novel non-invasive cooling pad with an esophageal target temperature of 32 to 34°C and maintenance for six hours. Shivering-control was achieved with meperidine and buspirone and additional administration of magnesium in eight subjects.

Results
The primary endpoint to reach a target temperature of 32 to 34°C was only reached in 6 of the 16 participating subjects. Temperatures below 35°C were reached after a median cooling time of 53 minutes (38 to 102 minutes). Cooling rate was 1.1°C/h (0.7 to 1.8°C). Additional administration of magnesium had no influence on cooling rate. At no time during the cooling procedure did the participants report uncomfortable conditions for which termination of cooling had to be considered. No severe skin damage was reported.

Conclusions
Cooling to body temperature below 35°C by the use of non-invasive surface cooling is feasible and safe in conscious healthy volunteers. Further studies are needed to investigate an altered cooling protocol to achieve temperatures below 35°C.

Trial Registration
ISRCTN: ISRCTN50530495
Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism and circulating ACE levels are not associated with outcome in critically ill septic patients
Authors: Tsantes Argirios , Tsangaris Iraklis , Kopterides Petros , Nikolopoulos Georgios , Kalamara Eleni , Antonakos Georgios , Kapsimali Violetta , Gialeraki Argiri , Dimopoulou Ioanna , Orfanos Stylianos , Dima Kleanthi , Travlou Anthi , Armaganidis Apostolos 
Published: October 2011

AbstractIn critically ill patients independent studies have shown contradictory findings regarding the prognostic significance of the D/D genotype of the I/D angiotensin converting enzyme (ACE) polymorphism. The study aim was to evaluate the effect of both ACE I/D polymorphism and ACE serum levels on the clinical outcomes of critically ill septic patients.This study recruited 186 Caucasian patients with sepsis, severe sepsis or septic shock. Epidemiological, clinical data, co-morbidities and severity scores were recorded. Measurements of serum ACE activity and genotyping for ACE I/D polymorphism were carried out. Primary outcomes were the 28- and the 90-day mortality; secondary outcomes included the number of days without renal or cardiovascular failure and ventilation-free days over the 28-day period following study enrolment.Neither 28- nor 90-day mortality were associated with ACE I/D polymorphism (p=0.59 and 0.34, respectively) or circulating ACE levels (p=0.17 and 0.25, respectively). Similarly, ACE polymorphism and levels were not related to ventilation-free days (p=0.14 and 0.25, respectively), days without cardiovascular failure (p=0.14 and 0.81, respectively) and days without renal failure (p=0.64 and 0.27, respectively).Neither ACE I/D polymorphism nor serum ACE levels seem to be significant prognostic factors of clinical outcomes in septic, critically ill patients.
Relevance of pharmacogenomics for developing countries in Europe
Authors: Mitropoulos Konstantinos , Johnson Lindsey , Vozikis Athanassios , Patrinos George P. 
Published: October 2011

Abstract
Pharmacogenomics holds promise of personalized treatment for patients suffering from many common diseases, particularly those with multiple treatment modalities. Owing to recent advances in the deciphering of the human genome sequence, high throughput genotyping technology has led to the reduction of the overall costs of genetic testing and allowed the inclusion of genotype-related dosing recommendations into drug package inserts, hence enabling the integration of pharmacogenomics into clinical practice. Although pharmacogenomics gradually assumes an important part in routine clinical practice in developed countries, many countries, particularly from the developing world, still do not have access either to the knowledge or the resources to individualize drug therapy. The PharmacoGenetics for Every Nation Initiative (PGENI) aims to fill this gap, by making pharmacogenomics globally applicable, not only by defining population-specific pharmacogenomic marker frequency profiles but also by formulating country-specific recommendations for drug efficacy and safety. This article aims to highlight the PGENI activities in Europe in an effort to make pharmacogenomics readily applicable in the European healthcare systems, particularly those in developing countries.
Method for regeneration of hormones: 17β-estradiol, 21α-hydroxyprogesterone and corticosterone. A pathway for a possible medical application
Authors: Getoff Nikola , Brenn Eric , Hartmann Johannes , Danielova Iren 
Published: October 2011

Abstract
The hormones 17β-estradiol (17βE2), 21α-hydroxyprogesterone (21α-HOPRG) and corticosterone (CORT) were used as representative models for the study. As a source for hormone excitation in singlet state serviced monochromatic UV-light (λ=254 nm), it was stated that the transients resulting by e–
aq emission in air-free mixture water/ethanol 40/60, as long as they are in “status nascendi”, can be regenerated by electron transfer from a potent electron donor, e.g., vitamin C. The hormone regeneration (%) strongly depends, after all, on specific hormone molecular structure, concentration, temperature, etc. Because of the large heterogenic molecular structures, the substrates dissolved in the solvent mixture form “associates” (unstable complexes) in concentrations >109 mol/L hormone. The hormones eject, but they also consume e–
aq with a rather high reaction rate constant (k≈109 up to 2×1010 L/mol.s), therefore, they act as “electron mediators”. It was also observed that the hormones by dissolution in aerated solvent mixture are sensitive towards oxygen. For an explanation of the results, probable reaction mechanisms are presented. The described method offers a new pathway and possibilities for application in medicine.
Polypropylene-based long-life insecticide-treated mosquito netting
Authors: Focke Walter W. , van Pareen Walter 
Published: October 2011

Abstract
The World Health Organization (WHO) is promoting the use of insecticide treated nets (ITNs) in order to roll back malaria. Long-life netting (LLIN) is preferred and this study investigated the possibility of incorporating the insecticide in the fiber polymer. Multifilament polypropylene (PP) yarn, containing up to 0.76% of pyrethroid insecticide, was successfully produced on a conventional production-scale fiber-spinning machine. The insecticides were incorporated via masterbatches that contained up to 18.8% active with low-density polyethylene (LDPE) as the carrier. Nets knitted from the yarns were tested using bioassays with mosquitoes. Initial efficacy complied with WHO specifications but the performance deteriorated with the number of wash cycles. Crystalline insecticides, featuring a melting point above the wash temperature of 60°C (e.g., β-cyfluthrin), provided better wash resistance than amorphous insecticides (e.g., cyfluthrin).
A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndrome
Authors: Wei Wei , Zhao Hongmin , Wang Aili , Sui Ming , Liang Kun , Deng Haiyun , Ma Yukun , Zhang Yajuan , Zhang Hongxiu , Guan Yuanyuan 
Published: October 2011

ObjectivePolycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance (IR). Berberine (BBR) is an isoquinoline derivative alkaloid extracted from Chinese medicinal herbs that has been used as an insulin sensitizer. BBR may have a potential therapeutic value for PCOS. The aim of this study was to evaluate the effects of BBR in comparison to metformin (MET) on the metabolic features of women with PCOS.Design and methodsEighty-nine subjects with PCOS and IR subjects were randomized into one of three treatment groups: BBR+compound cyproterone acetate (CPA; n=31), MET+CPA (n=30), and placebo+CPA (n=28) for 3 months. Clinical characteristics of the women and metabolic and hormonal parameters were assessed before and after the period of treatment.ResultsTreatment with BBR in comparison to MET showed decrease in waist circumference and waist-to-hip ratio (WHR; P<0.01), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDLC; P<0.05) as well as increase in high-density lipoprotein cholesterol (HDLC) and sex hormone-binding globulin (SHBG; P<0.05). Similarly, treatment with BBR in comparison to placebo showed decrease in WHR, fasting plasma glucose, fasting insulin, homeostasis model assessment for IR, area under the curve of insulin, TC, LDLC, and TG (P<0.05) as well as increase in HDLC and SHBG (P<0.01).ConclusionsIntake of BBR improved some of the metabolic and hormonal derangements in a group of treated Chinese women with PCOS. Main effects could be related to the changes in body composition in obesity and dyslipidemia. Further controlled studies are needed for the assessment of the potential favorable metabolic effects of BBR in women with PCOS.
Molecular Characterization of Vegetative Incompatibility Genes That Restrict Hypovirus Transmission in the Chestnut Blight Fungus Cryphonectria parasitica
Authors: Choi Gil H , Dawe Angus L , Churbanov Alexander , Smith Myron L , Milgroom Michael G , Nuss Donald L 
Published: October 2011

Abstract
Genetic nonself recognition systems such as vegetative incompatibility operate in many filamentous fungi to regulate hyphal fusion between genetically dissimilar individuals and to restrict the spread of virulence-attenuating mycoviruses that have potential for biological control of pathogenic fungi. We report here the use of a comparative genomics approach to identify seven candidate polymorphic genes associated with four vegetative incompatibility (vic) loci of the chestnut blight fungus Cryphonectria parasitica. Disruption of candidate alleles in one of two strains that were heteroallelic at vic2, vic6, or vic7 resulted in enhanced virus transmission, but did not prevent barrage formation associated with mycelial incompatibility. Detailed characterization of the vic6 locus revealed the involvement of nonallelic interactions between two tightly linked genes in barrage formation, heterokaryon formation, and asymmetric, gene-specific influences on virus transmission. The combined results establish molecular identities of genes associated with four C. parasitica vic loci and provide insights into how these recognition factors interact to trigger incompatibility and restrict virus transmission.
Triple-Negative Breast Cancer in Lebanon: A Case Series
Authors: Ghosn Marwan , Hajj Carla , Kattan Joseph , Farhat Fadi , El Karak Fadi , Nasr Fadi , Abadjian Gerard , Chahine Georges 
Published: October 2011

Abstract

Objectives.
To determine the incidence, characteristics, and survival outcomes of triple-negative breast cancer patients in a medical oncology practice in Lebanon.

Methods.
The pathology reports of all breast cancer cases diagnosed or treated in 1997–2008 were reviewed.

Results.
One hundred seventy breast cancer cases (9.3%) of the 1,834 cases that were identified in this practice over a 10-year span had a triple-negative phenotype, with a median age at diagnosis of 52 years. The pathology distribution of those cases was as follows: invasive ductal carcinoma, 85%; medullary carcinoma, 5%; invasive lobular carcinoma, 5%; 95 cases (63%) were grade III. At diagnosis, 17% presented with stage I, 47% had stage II, 24% had stage III, and 12% had stage IV disease, whereas 11% had an inflammatory component. After a median follow-up of 17 months, 43 patients (25.3%) had relapsed and the most common sites of relapse were the brain (19%), lungs (19%), and bones (12%). The risk for recurrence peaked at 1.5 years and became almost nil after 3 years. Twenty patients received induction chemotherapy, among whom six (42.9%) had a complete response and six (42.9%) had a partial response to treatment. None of the patients progressed on neoadjuvant chemotherapy. The 5-year disease-free survival rate was 75% for stage I, 58% for stage II, and 40% for stage III patients, whereas the 5-year overall survival rate was 88% for stage I, 72% for stage II, and 63% for stage III patients. Adjuvant therapy was administered to 96% of patients, using a taxane-based regimen in 38% of cases. The median survival time for stage IV patients was 19 months, with a first line taxane-based regimen used in 50% of cases.

Conclusions.
The incidence of triple-negative breast cancer in Lebanon is similar to that described in the literature. In order to determine targets for future therapeutic options, it is essential to understand the biology of this particular breast cancer subtype.
Integrating Molecular Mechanisms and Clinical Evidence in the Management of Trastuzumab Resistant or Refractory HER-2+ Metastatic Breast Cancer
Authors: Wong Hilda , Leung Roland , Kwong Ava , Chiu Joanne , Liang Raymond , Swanton Charles , Yau Thomas 
Published: October 2011

AbstractHuman epidermal growth factor receptor (HER)-2+ breast cancer is a distinct molecular and clinical entity, the prognosis of which is improved by trastuzumab. However, primary resistance to trastuzumab is observed in &gt;50% of patients with HER-2+ advanced breast cancer, and the majority of patients who initially respond to treatment eventually develop disease progression. To facilitate crosstrial comparisons and the understanding of resistance mechanisms, we propose a unifying definition of trastuzumab resistance as progression at first radiological reassessment at 8–12 weeks or within 3 months after first-line trastuzumab in the metastatic setting or new recurrences diagnosed during or within 12 months after adjuvant trastuzumab. In contrast, we define trastuzumab-refractory breast cancer as disease progression after two or more lines of trastuzumab-containing regimens that initially achieved disease response or stabilization at first radiological assessment. We review mechanisms of trastuzumab resistance mediated by p95HER-2 overexpression, phosphoinositide 3-kinase pathway activation, and signaling pathway activation driven by HER-3, epidermal growth factor receptor, and insulin-like growth factor 1 receptor. We distinguish in vitro from in vivo evidence, highlighting that most data describing trastuzumab resistance are derived from preclinical studies or small retrospective patient cohorts, and discuss targeted therapeutic approaches to overcome resistance. Prospective analysis through clinical trials with robust tissue collection procedures, prior to and following acquisition of resistance, integrated with next-generation tumor genome sequencing technologies, is identified as a priority area for development. The identification of predictive biomarkers is of paramount importance to optimize health economic costs and enhance stratification of anti-HER-2 targeted therapies.
Postnatal Depression and Socio-Demographic Risk: Factors Associated with Edinburgh Depression Scale Scores in a Metropolitan Area of New South Wales, Australia
Authors: Eastwood John G. , Phung Hai , Barnett Bryanne 
Published: October 2011

Objective: The aim of this study was to determine the prevalence and risk factors for postnatal depressive symptoms in women living in metropolitan Sydney, Australia. Method: A population-based cross-sectional study of mothers of newborn infants was undertaken during home and community clinic visits in South West Sydney from 2000 to 2004. A comprehensive 45 item survey questionnaire was completed by 29 405 mothers. A self-report Edinburgh Postnatal Depression Scale (EPDS) of depressive symptoms was completed by 25 455 mothers at the first child and family nurse visit. The primary study outcome measures were EPDS scores greater than 9 and greater than 12. Results: At a mean infant age of 2.16 weeks the prevalence of EPDS >9 was 12% and EPDS >12 was 6.2%. Results from multiple logistic regression revealed that EPDS >9 and EPDS > 2 were associated with a maternal country of birth other than Australia, difficult financial situation, living in the suburb one year or less, ‘no regret leaving the suburb’, unplanned pregnancy, not breastfeeding, and poor rating of mother's own health. Other social demographic factors such as marital status, maternal age, education of mother, or being Aboriginal or a Torres Strait Islander show no significant association with postnatal depressive symptoms. Conclusions: The results confirm prevalence rates and maternal individual-level risk factors from previous studies. The study contributes to the limited number of studies of postnatal depression and socio-demographic factors. Neighbourhood and community group-level factors may be important and should be studied further.
The Class III Kinase Vps34 Promotes T Lymphocyte Survival through Regulating IL-7Rα Surface Expression
Authors: McLeod Ian X. , Zhou Xiang , Li Qi-Jing , Wang Fan , He You-Wen 
Published: October 2011

Abstract
IL-7Rα–mediated signals are essential for naive T lymphocyte survival. Recent studies show that IL-7Rα is internalized and either recycled to cell surface or degraded. However, how the intracellular process of IL-7Rα trafficking is regulated is unclear. In this paper, we show that Vps34, the class III PI3K, plays a critical role in proper IL-7Rα intracellular trafficking. Mice lacking Vps34 in T lymphocytes had a severely reduced T lymphocyte compartment. Vps34-deficient T lymphocytes exhibit increased death and reduced IL-7Rα surface expression, although three major forms of autophagy remain intact. Intracellular IL-7Rα in normal T lymphocytes at steady state is trafficked through either early endosome/multivesicular bodies to the late endosome-Golgi for surface expression or to the lysosome for degradation. However, Vps34-deficient T cells have mislocalized intracellular Eea1, HGF-regulated tyrosine kinase substrate, and Vps36 protein levels, the combined consequence of which is the inability to mobilize internalized IL-7Rα into the retromer pathway for surface display. Our studies reveal that Vps34, though dispensable for autophagy induction, is a critical regulator of naive T cell homeostasis, modulating IL-7Rα trafficking, signaling, and recycling.
Hck Tyrosine Kinase Regulates TLR4-Induced TNF and IL-6 Production via AP-1
Authors: Smolinska Maria J. , Page Theresa H. , Urbaniak Ania M. , Mutch Brenda E. , Horwood Nicole J. 
Published: October 2011

Abstract
The TLRs play a key role in host defense against infection and injury, and mounting evidence suggests that these receptors may also play a role in diseases such autoimmunity, atherosclerosis, and cancer. Activation of TLRs on macrophages results in the production of multiple soluble mediators including the key inflammatory cytokines, TNF and IL-6. Thus, the intracellular signaling mechanism by which TLRs signal is a subject of great interest. As well as activating the NF-κB and MAPK pathways, TLR engagement leads to tyrosine kinase activation within minutes. Src family kinases (SFKs) are the largest nonreceptor tyrosine kinase family with nine members: Src, Hck, Lyn, Fyn, Fgr, Blk, Lck, Yes, and Ylk. The role of the SFKs in TLR signaling has been an area of much controversy, with conflicting findings between studies using chemical inhibitors and knockout mice. Using primary human macrophages in combination with adenoviral overexpression and small interfering RNA knockdown studies, we show that the SFK, Hck, has a pre-eminent role in LPS/TLR4-induced TNF and IL-6 production. Hck kinase mediates TLR4-induced transcription of both TNF and IL-6 by a mechanism that involves neither the NF-κB nor the MAPK pathways, but rather leads to AP-1 binding with a complex of c-fos and JunD. These data highlight the importance of Hck as an active component in LPS-induced TLR signaling and suggest the possibility of targeting this kinase for the alleviation of excessive inflammation.
TOX Is Required for Development of the CD4 T Cell Lineage Gene Program
Authors: Aliahmad Parinaz , Kadavallore Asha , de la Torre Brian , Kappes Dietmar , Kaye Jonathan 
Published: October 2011

Abstract
The factors that regulate thymic development of the CD4+ T cell gene program remain poorly defined. The transcriptional regulator ThPOK is a dominant factor in CD4+ T cell development, which functions primarily to repress the CD8 lineage fate. Previously, we showed that nuclear protein TOX is also required for murine CD4+ T cell development. In this study, we sought to investigate whether the requirement for TOX was solely due to a role in ThPOK induction. In apparent support of this proposition, ThPOK upregulation and CD8 lineage repression were compromised in the absence of TOX, and enforced ThPOK expression could restore some CD4 development. However, these “rescued” CD4 cells were defective in many aspects of the CD4+ T cell gene program, including expression of Id2, Foxo1, and endogenous Thpok, among others. Thus, TOX is necessary to establish the CD4+ T cell lineage gene program, independent of its influence on ThPOK expression.