bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing cell biomass in Saccharomyces cerevisiae increases recombinant protein yield: the use of a respiratory strain as a microbial cell factory
Authors: Ferndahl Cecilia , Bonander Nicklas , Logez Christel , Wagner Renaud , Gustafsson Lena , Larsson Christer , Hedfalk Kristina , Darby Richard AJ , Bill Roslyn M 
Published: June 2010

AbstractBackgroundRecombinant protein production is universally employed as a solution to obtain the milligram to gram quantities of a given protein required for applications as diverse as structural genomics and biopharmaceutical manufacture. Yeast is a well-established recombinant host cell for these purposes. In this study we wanted to investigate whether our respiratorySaccharomyces cerevisiaestrain, TM6*, could be used to enhance the productivity of recombinant proteins over that obtained from corresponding wild type, respiro-fermentative strains when cultured under the same laboratory conditions.ResultsHere we demonstrate at least a doubling in productivity over wild-type strains for three recombinant membrane proteins and one recombinant soluble protein produced in TM6* cells. In all cases, this was attributed to the improved biomass properties of the strain. The yield profile across the growth curve was also more stable than in a wild-type strain, and was not further improved by lowering culture temperatures. This has the added benefit that improved yields can be attained rapidly at the yeast's optimal growth conditions. Importantly, improved productivity could not be reproduced in wild-type strains by culturing them under glucose fed-batch conditions: despite having achieved very similar biomass yields to those achieved by TM6* cultures, the total volumetric yields were not concomitantly increased. Furthermore, the productivity of TM6* was unaffected by growing cultures in the presence of ethanol. These findings support the unique properties of TM6* as a microbial cell factory.ConclusionsThe accumulation of biomass in yeast cell factories is not necessarily correlated with a proportional increase in the functional yield of the recombinant protein being produced. The respiratoryS. cerevisiaestrain reported here is therefore a useful addition to the matrix of production hosts currently available as its improved biomass properties do lead to increased volumetric yields without the need to resort to complex control or cultivation schemes. This is anticipated to be of particular value in the production of challenging targets such as membrane proteins.
Fas (CD95) induces rapid, TLR4/IRAK4-dependent release of pro-inflammatory HMGB1 from macrophages
Authors: Wang Feng , Lu Ziyue , Hawkes Michael , Yang Huan , Kain Kevin C , Liles W Conrad 
Published: June 2010

AbstractAlthough Fas (CD95) is recognized as a death receptor that induces apoptosis, recent studies indicate that the Fas/FasL system can induce pro-inflammatory cytokine production by macrophages independent of conventional caspase-mediated apoptotic signaling. The precise mechanism(s) by which Fas activates macrophage inflammation is unknown. We hypothesized that Fas stimulates rapid release of high mobility group box 1 (HMGB1) that acts in an autocrine and/or paracrine manner to stimulate pro-inflammatory cytokine production via a Toll-like receptor-4 (TLR4)/Interleukin-1 receptor associated kinase-4 (IRAK4)-dependent mechanism. Following Fas activation, HMGB1 was released within 1 hr from viable RAW267.4 cells and primary murine peritoneal macrophages. HMGB1 release was more rapid following Fas activation compared to LPS stimulation. Neutralization of HMGB1 with an inhibitory anti-HMGB1 monoclonal antibody strongly inhibited Fas-induced production of tumor necrosis factor (TNF) and macrophage inflammatory protein-2 (MIP-2). Both Fas-induced HMGB1 release and associated pro-inflammatory cytokine production were significantly decreased fromTlr4-/-andIrak4-/-macrophages, but notTlr2-/-macrophages. These findings reveal a novel mechanism underlying Fas-mediated pro-inflammatory physiological responses in macrophages. We conclude that Fas activation induces rapid, TLR4/IRAK4-dependent release of HMGB1 that contributes to Fas-mediated pro-inflammatory cytokine production by viable macrophages.
Interleukin 11 is upregulated in uterine lavage and endometrial cancer cells in women with endometrial carcinoma
Authors: Yap Joanne , Salamonsen Lois A , Jobling Tom , Nicholls Peter K , Dimitriadis Evdokia 
Published: June 2010

Abstract

Background
Interleukin (IL) 11 is produced by human endometrium and endometrial cancer tissue. It has roles in endometrial epithelial cell adhesion and trophoblast cell invasion, two important processes in cancer progression. This study aimed to determine the levels of IL11 in uterine lavage fluid in women with endometrial cancer and postmenopausal women. It further aimed to determine the levels of IL11 protein and its signaling molecules in human endometrial cancer of varying grades, and endometrium from postmenopausal women and IL11 signalling mechanisms in endometrial cancer cell lines.

Methods
IL11 levels in uterine lavage were measured by ELISA. IL11, IL11 receptor(R) α, phosphorylated (p) STAT3 and SOCS3 were examined by immunohistochemistry in endometrial carcinomas and in control endometrium from postmenopausal women and normal cycling women. The effect of IL11 on pSTAT3/STAT3 and SOCS3 protein abundance in endometrial cancer cell lines and non-cancer endometrial epithelial cells was determined by Western blot.

Results
IL11 was present in uterine flushings and was significantly higher in women with Grade 1 carcinomas compared to postmenopausal women (p < 0.05). IL11 immunostaining was significantly elevated in the endometrial tumour epithelial cells from Grade 1 and 3 compared to endometrial epithelium from postmenopausal and cycling women. IL11Rα immunostaining intensity was increased in cancer epithelium in the Grades 1 and 2 tumours compared to epithelium from postmenopausal women. Both IL11 and IL11Rα localized to vascular endothelial and smooth muscle cells while IL11 also localized to subsets of leucocytes in the cancer tissues. pSTAT3 was found in both the tumour epithelial and stromal compartments but was maximal in the tumour epithelial cells, while SOCS3 was predominantly found in the tumour epithelial cells. pSTAT3 staining intensity was significantly higher in Grade 1 and 2 tumour epithelial cells compared to epithelial cells from cycling and postmenopausal women. SOCS3 staining intensity did not differ between between each tumour and postmenopausal endometrial epithelium but SOCS3 in cycling endometrium was significantly higher compared to postmonopausal and Tumour Grades 2 and 3. IL11 increased pSTAT3/STAT3 in all tumour cell lines, while SOCS3 abundance was increased only in one tumour cell line.

Conclusions
The present study suggests that IL11 in uterine washings may be useful as a diagnostic marker for early stage endometrial cancer. It indicates that IL11, along with its specific receptor, IL11Rα, and downstream signalling molecules, STAT3 and SOCS3, are likely to play a role in the progression of endometrial carcinoma. The precise role of IL11 in endometrial cancer remains to be elucidated.
Development and implementation of a lifestyle intervention to promote physical activity and healthy diet in the Dutch general practice setting: the BeweegKuur programme
Authors: Helmink Judith HM , Meis Jessie JM , de Weerdt Inge , Visser Femke N , de Vries Nanne K , Kremers Stef PJ 
Published: June 2010

Abstract

Background
The number of patients with diabetes is increasing. BeweegKuur (Dutch for 'Exercise Therapy') is a Dutch lifestyle intervention which aims to effectively and feasibly promote physical activity and better dietary behaviour in primary health care to prevent diabetes.

Methods
The goal of this paper is to present the development process and the contents of the intervention, using a model of systematic health promotion planning. The intervention consists of a 1-year programme for diabetic and prediabetic patients. Patients are referred by their general practitioner (GP) to a lifestyle advisor (LSA), usually the practice nurse or a physiotherapist. Based on specific inclusion criteria and in close collaboration with the patient, an individual exercise programme is designed and supervised by the LSA. This programme can be attended at existing local exercise facilities or (temporarily) under the supervision of a specialized exercise coach or physiotherapist. All participants are also referred to a dietician and receive diet-related group education. In the first pilot year (2008), the BeweegKuur programme was implemented in 7 regions in the Netherlands (19 GP practices and health centres), while 14 regions (41 GP practices and health centres) participated during the second year. The aim is to implement BeweegKuur in all regions of the Netherlands by 2012.

Discussion
The BeweegKuur programme was systematically developed in an evidence- and practice-based process. Formative monitoring studies and (controlled) effectiveness studies are needed to examine the diffusion process and the effectiveness and cost-effectiveness of the intervention.
Confocal analysis of nervous system architecture in direct-developing juveniles of Neanthes arenaceodentata (Annelida, Nereididae)
Authors: Winchell Christopher J , Valencia Jonathan E , Jacobs David K 
Published: June 2010

Abstract

Background
Members of Family Nereididae have complex neural morphology exemplary of errant polychaetes and are leading research models in the investigation of annelid nervous systems. However, few studies focus on the development of their nervous system morphology. Such data are particularly relevant today, as nereidids are the subjects of a growing body of "evo-devo" work concerning bilaterian nervous systems, and detailed knowledge of their developing neuroanatomy facilitates the interpretation of gene expression analyses. In addition, new data are needed to resolve discrepancies between classic studies of nereidid neuroanatomy. We present a neuroanatomical overview based on acetylated α-tubulin labeling and confocal microscopy for post-embryonic stages of Neanthes arenaceodentata, a direct-developing nereidid.

Results
At hatching (2-3 chaetigers), the nervous system has developed much of the complexity of the adult (large brain, circumesophageal connectives, nerve cords, segmental nerves), and the stomatogastric nervous system is partially formed. By the 5-chaetiger stage, the cephalic appendages and anal cirri are well innervated and have clear connections to the central nervous system. Within one week of hatching (9-chaetigers), cephalic sensory structures (e.g., nuchal organs, Langdon's organs) and brain substructures (e.g., corpora pedunculata, stomatogastric ganglia) are clearly differentiated. Additionally, the segmental-nerve architecture (including interconnections) matches descriptions of other, adult nereidids, and the pharynx has developed longitudinal nerves, nerve rings, and ganglia. All central roots of the stomatogastric nervous system are distinguishable in 12-chaetiger juveniles. Evidence was also found for two previously undescribed peripheral nerve interconnections and aspects of parapodial muscle innervation.

Conclusions

N. arenaceodentata has apparently lost all essential trochophore characteristics typical of nereidids. Relative to the polychaete Capitella, brain separation from a distinct epidermis occurs later in N. arenaceodentata, indicating different mechanisms of prostomial development. Our observations of parapodial innervation and the absence of lateral nerves in N. arenaceodentata are similar to a 19th century study of Alitta virens (formerly Nereis/Neanthes virens) but contrast with a more recent study that describes a single parapodial nerve pattern and lateral nerve presence in A. virens and two other genera. The latter study apparently does not account for among-nereidid variation in these major neural features.
Genetic characterization of wild-type measles viruses isolated in China, 2006-2007
Authors: Ji Yixin , Xu Songtao , Zhang Yan , Zhu Zhen , Mao Naiying , Jiang Xiaohong , Ma Chao , Lu Peishan , Wang Changyin , Liang Yong , Zheng Huanying , Liu Yang , Dai Defang , Zheng Lei , Zhou Jianhui , Wang Shuang , Zhang Zhenying , Wu Shengwei , Nan Lijuan , Li Li , Liang Xiaofeng , Featherstone David Alexander , Rota Paul A , Bellini William J , Xu Wenbo 
Published: June 2010

Abstract
Molecular characterization of wild-type measles viruses in China during 1995-2004 demonstrated that genotype H1 was endemic and widely distributed throughout the country. H1-associated cases and outbreaks caused a resurgence of measles beginning in 2005. A total of 210,094 measles cases and 101 deaths were reported by National Notifiable Diseases Reporting System (NNDRS) and Chinese Measles Laboratory Network (LabNet) from 2006 to 2007, and the incidences of measles were 6.8/100,000 population and 7.2/100,000 population in 2006 and 2007, respectively. Five hundred and sixty-five wild-type measles viruses were isolated from 24 of 31 provinces in mainland China during 2006 and 2007, and all of the wild type virus isolates belonged to cluster 1 of genotype H1. These results indicated that H1-cluster 1 viruses were the predominant viruses circulating in China from 2006 to 2007. This study contributes to previous efforts to generate critical baseline data about circulating wild-type measles viruses in China that will allow molecular epidemiologic studies to help measure the progress made toward China's goal of measles elimination by 2012.
Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population
Authors: Kong Fanjun , Liu Jie , Liu Yongheng , Song Bao , Wang Hualing , Liu Wenchao 
Published: June 2010

AbstractBackgroudInterleukin-10(IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population.MethodsWe genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP).ResultsThere were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN) involvement (P= 0.041) and larger tumor size (P= 0.039) at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p= 0.022) and higher tumor stage(p= 0.028) of breast cancer at the time of diagnosis compared with others.ConclusionsOur findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.
Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti‐TNF therapy
Authors: Bowen Catherine J , Edwards Christopher J , Hooper Lindsey , Dewbury Keith , Sampson Madeleine , Sawyer Sally , Burridge Jane , Arden Nigel K 
Published: June 2010

AbstractBackgroundInhibition of tumour necrosis factor (TNF) is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA), yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti‐TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability.MethodsConsecutive RA patients starting anti‐TNF therapy (infliximab, etanercept, adalimumab) were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso‐phalangeal (MTP) joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US) images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI).Results31 patients (24 female, 7 male) with RA (12 seronegative, 19 seropositive) completed the study: mean age 59.6 (SD 10.1) years, disease duration 11.1 (SD 10.5) years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6). Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p < 0.001), C‐reactive protein (t = 3.889, p = 0.001), 28 joint Disease Activity Score (t = 3.712, p = 0.0001), Visual Analog Scale (t = 2.735, p = 0.011) and Manchester Foot Pain and Disability Index (t = 3.712, p = 0.001).Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar) this was not significant.ConclusionsSignificant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.
Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival
Authors: Nodin Björn , Zendehrokh Nooreldin , Brändstedt Jenny , Nilsson Elise , Manjer Jonas , Brennan Donal J , Jirström Karin 
Published: June 2010

Abstract

Background
Altered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear.

Methods
In this study, the prognostic impact of AR expression was investigated using immunohistochemistry in tissue microarrays from 154 incident cases of epithelial ovarian cancer (EOC) in the prospective, population-based cohorts Malmö Diet and Cancer Study and Malmö Preventive Project. A subset of corresponding fallopian tubes (n = 36) with no histopathological evidence of disease was also analysed.

Results
While abundantly expressed in the majority of fallopian tubes with more than 75% positive nuclei in 16/36 (44%) cases, AR was absent in 108/154 (70%) of EOC cases. AR expression was not related to prognosis in the entire cohort, but in the serous subtype (n = 90), AR positivity (> 10% positive nuclei) was associated with a prolonged disease specific survival in univariate (HR= 0.49; 95% CI 0.25-0.96; p= 0.038) and multivariate (HR= 0.46; 95% CI 0.22-0.97; p= 0.042) analysis, adjusted for age, grade and clinical stage.

Conclusions
AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.
Sex Steroid Hormones in Older Men: Longitudinal Associations with 4.5-Year Change in Hip Bone Mineral Density—The Osteoporotic Fractures in Men Study
Authors: Cauley Jane A. , Ewing Susan K. , Taylor Brent C. , Fink Howard A. , Ensrud Kristine E. , Bauer Douglas C. , Barrett-Connor Elizabeth , Marshall Lynn , Orwoll Eric S. ,   for the Osteoporotic Fractures in Men Study (MrOS) Research Group
Published: June 2010

Context: There is limited information on the association between sex hormones and bone loss in older men.Objective: Our objective was to determine the longitudinal association between sex steroid hormones and bone mineral density (BMD).Design and Setting: We conducted a prospective study of 5995 men aged at least 65 yr old at six U.S. clinical centers.Participants: Sex steroid hormones were measured in a random sample of 1602 men. After exclusions, 1238 men were included in cross-sectional analyses and 969 in longitudinal analyses. Baseline sex hormones were measured using liquid chromatography-mass spectrometry. Bioavailable (Bio) estradiol (BioE2) and testosterone (BioT) were calculated from mass action equations. SHBG was measured using chemiluminescent substrate.Main Outcome Measures: BMD of the total hip, measured at baseline and once or twice afterward over 4.6 yr of follow-up, was evaluated.Results: The annualized percent change in hip BMD increased with decreasing BioE2 (P trend = 0.03). Men with the lowest BioE2 (&lt;39.7 pmol/liter) compared with the highest BioE2 (≥66.0 pmol/liter) experienced 38% faster rate of BMD loss (P &lt; 0.05). There was no association between BioT and hip BMD loss. Men with lowest BioE2, lowest BioT, and highest SHBG experienced a 3-fold faster rate of BMD loss compared with men with higher levels (P = 0.02). A threshold effect of SHBG was observed; the rate of hip BMD loss increased in men with SHBG of 49–60 nm.Conclusions: Low BioE2 and high SHBG levels were associated with lower BMD and faster hip BMD loss. The combination of low BioE2, low BioT, and high SHBG was associated with significantly faster rates of BMD loss.
Characterization of and Risk Factors for the Acute-Phase Response after Zoledronic Acid
Authors: Reid I. R. , Gamble G. D. , Mesenbrink P. , Lakatos P. , Black D. M. 
Published: June 2010

Context: Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied.
Objective: The objective of the study was to characterize the APR and determine its frequency and the risk factors for its development.
Design: The study was an analysis of adverse events from a large randomized trial.
Setting: This was a multicenter international trial.
Patients: Patients included 7765 postmenopausal women with osteoporosis.
Intervention: Zoledronic acid 5 mg annually or placebo was the intervention.
Main Outcome Measure: Adverse events occurring within 3 d of zoledronic acid infusion were measured.
Results: More than 30 adverse events were significantly more common in the zoledronic acid group and were regarded collectively as constituting an APR. These were clustered into five groups: fever; musculoskeletal (pain and joint swelling); gastrointestinal (abdominal pain, vomiting, diarrhea); eye inflammation; and general (including fatigue, nasopharyngitis, edema). A total of 42.4% of the zoledronic acid group had an APR after the first infusion, compared with 11.7% of the placebo group. All APR components had their peak onset within 1 d, the median duration of the APR was 3 d, and severity was rated as mild or moderate in 90%. Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P &lt; 0.05 for all).
Conclusion: This analysis identifies new components of the APR and provides the first assessment of risk factors for it. Despite its frequency, APR rarely resulted in treatment discontinuation in this study.