bluuebunny/crossref_metadata_2025_split huggingface dataset:
High yield recombinant thermostable α-amylase production using an improved Bacillus licheniformis system
Authors: Niu Dandan , Zuo Zhirui , Shi Gui-Yang , Wang Zheng-Xiang 
Published: October 2009

Abstract

Background
Some strains of Bacillus licheniformis have been improved by target-directed screening as well as by classical genetic manipulation and used in commercial thermostable α-amylase and alkaline protease production for over 40 years. Further improvements in production of these enzymes are desirable.

Results
A new strain of B. licheniformis CBBD302 carrying a recombinant plasmid pHY-amyL for Bacillus licheniformis α-amylase (BLA) production was constructed. The combination of target-directed screening and genetic recombination led to an approximately 26-fold improvement of BLA production and export in B. licheniformis. Furthermore, a low-cost fermentation medium containing soybean meal and cottonseed meal for BLA production in shake-flasks and in a 15 liter bioreactor was developed and a BLA concentration of up to 17.6 mg per ml growth medium was attained.

Conclusion
This production level of BLA by B. licheniformis CBBD302(pHY-amyL) is amongst the highest levels in Gram-positive bacteria reported so far.
EM011 activates a survivin-dependent apoptotic program in human non-small cell lung cancer cells
Authors: Karna Prasanthi , Sharp Starlette M , Yates Clayton , Prakash Satya , Aneja Ritu 
Published: October 2009

Abstract

Background
Lung cancer remains a leading cause of cancer death among both men and women in the United States. Treatment modalities available for this malignancy are inadequate and thus new drugs with improved pharmacological profiles and superior therapeutic indices are being continually explored. Noscapinoids constitute an emerging class of anticancer agents that bind tubulin but do not significantly alter the monomer/polymer ratio of tubulin. EM011, a rationally-designed member of this class of non-toxic agents, is more potent than the lead molecule, noscapine.

Results
Here we report that EM011 inhibited proliferation of a comprehensive panel of lung cancer cells with IC50's ranging from 4-50 μM. In A549 human non-small cell lung cancer cells, the antiproliferative activity was mediated through blockage of cell-cycle progression by induction of a transient but robust mitotic arrest accompanied by activation of the spindle assembly checkpoint. The mitotically-arrested A549 cells then override the activated mitotic checkpoint and aberrantly exit mitosis without cytokinesis resulting in pseudo G1-like multinucleated cells that either succumb directly to apoptosis or continue another round of the cell-cycle. The accumulated enormous DNA perhaps acts as genotoxic stress to trigger cell death. EM011-induced apoptotic cell death in A549 cells was associated with a decrease of the Bcl2/BAX ratio, activation of caspase-3 and cleavage of PARP. Furthermore, EM011 induced downregulation of survivin expression over time of treatment. Abrogation of survivin led to an increase of cell death whereas, overexpression caused decreased apoptosis.

Conclusion
These in vitro data suggest that EM011 mediates antiproliferative and proapoptotic activity in non-small cell A549 lung cancer cells by impeding cell-cycle progression and attenuating antiapoptotic signaling circuitries (viz. Bcl2, survivin). The study provides evidence for the potential usefulness of EM011 in chemotherapy of lung cancer.
Cleavage of functional IL-2 receptor alpha chain (CD25) from murine corneal and conjunctival epithelia by MMP-9
Authors: De Paiva Cintia S , Yoon Kyung-Chul , Pangelinan Solherny B , Pham Sapa , Puthenparambil Larry M , Chuang Eliseu Y , Farley William J , Stern Michael E , Li De-Quan , Pflugfelder Stephen C 
Published: October 2009

Abstract

Background
IL-2 has classically been considered a cytokine that regulates T cell proliferation and differentiation, signaling through its heterotrimeric receptor (IL-2R) consisting of α (CD25), β (CD122), γ chains (CD132). Expression of IL-2R has also been detected in mucosal epithelial cells. Soluble IL-2Rα (CD25) has been reported as an inflammatory marker. We evaluated the expression of CD25 and CD122 in the ocular surface epithelium and investigated the mechanism of proteolytic cleavage of CD25 from these cells.

Methods
Desiccating stress (DS) was used as an inducer of matrix metalloproteinase 9 (MMP-9). DS was created by subjecting C57BL/6 and MMP-9 knockout (BKO) mice and their wild-type littermates (WT) mice to a low humidity and drafty environment for 5 days (DS5). A separate group of C57BL/6 mice was subjected to DS5 and treatment with topical 0.025% doxycycline, a MMP inhibitor, administered QID. The expression of CD25 and CD122 was evaluated in cryosections by dual-label laser scanning confocal microscopy. Western blot was used to measure relative levels of CD25 in epithelial lysates. Gelatinase activity was evaluated by in situ zymography. Soluble CD25 in tear fluid was measured by an immunobead assay.

Results
CD25 and CD122 were abundantly expressed in cornea (all layers) and conjunctiva epithelia (apical and subapical layers) in nonstressed control mice. After desiccating stress, we found that immunoreactivity to CD25, but not CD122, decreased by the ocular surface epithelia and concentration of soluble CD25 in tears increased as MMP-9 staining increased. CD25 was preserved in C57BL/6 mice topically treated with an MMP-9 inhibitor and in MMP-9 knock-out mice. MMP-9 treatment of human cultured corneal epithelial cells decreased levels of CD25 protein in a concentration dependent fashion.

Conclusion
Our results indicate that functional IL-2R is produced by the ocular surface epithelia and that CD25 is proteolytic cleaved to its soluble form by MMP-9, which increases in desiccating stress. These findings provide new insight into IL-2 signaling in mucosal epithelia.
Using the ratio of means as the effect size measure in combining results of microarray experiments
Authors: Hu Pingzhao , Greenwood Celia MT , Beyene Joseph 
Published: November 2009

AbstractBackgroundDevelopment of efficient analytic methodologies for combining microarray results is a major challenge in gene expression analysis. The widely used effect size models are thought to provide an efficient modeling framework for this purpose, where the measures of association for each study and each gene are combined, weighted by the standard errors. A significant disadvantage of this strategy is that the quality of different data sets may be highly variable, but this information is usually neglected during the integration. Moreover, it is widely known that the estimated standard deviations are probably unstable in the commonly used effect size measures (such as standardized mean difference) when sample sizes in each group are small.ResultsWe propose a re-parameterization of the traditional mean difference based effect measure by using the log ratio of means as an effect size measure for each gene in each study. The estimated effect sizes for all studies were then combined under two modeling frameworks: the quality-unweighted random effects models and the quality-weighted random effects models. We defined the quality measure as a function of the detection p-value, which indicates whether a transcript is reliably detected or not on the Affymetrix gene chip. The new effect size measure is evaluated and compared under the quality-weighted and quality-unweighted data integration frameworks using simulated data sets, and also in several data sets of prostate cancer patients and controls. We focus on identifying differentially expressed biomarkers for prediction of cancer outcomes.ConclusionOur results show that the proposed effect size measure (log ratio of means) has better power to identify differentially expressed genes, and that the detected genes have better performance in predicting cancer outcomes than the commonly used effect size measure, the standardized mean difference (SMD), under both quality-weighted and quality-unweighted data integration frameworks. The new effect size measure and the quality-weighted microarray data integration framework provide efficient ways to combine microarray results.
A selective eradication of human nonhereditary breast cancer cells by phenanthridine-derived polyADP-ribose polymerase inhibitors
Authors: Inbar-Rozensal Dana , Castiel Asher , Visochek Leonid , Castel David , Dantzer Françoise , Izraeli Shai , Cohen-Armon Malka 
Published: November 2009

Abstract
Introduction
PARP-1 (polyADP-ribose polymerase-1) is known to be activated in response to DNA damage, and activated PARP-1 promotes DNA repair. However, a recently disclosed alternative mechanism of PARP-1 activation by phosphorylated externally regulated kinase (ERK) implicates PARP-1 in a vast number of signal-transduction networks in the cell. Here, PARP-1 activation was examined for its possible effects on cell proliferation in both normal and malignant cells.

Methods
In vitro (cell cultures) and in vivo (xenotransplants) experiments were performed.

Results
Phenanthridine-derived PARP inhibitors interfered with cell proliferation by causing G2/M arrest in both normal (human epithelial cells MCF10A and mouse embryonic fibroblasts) and human breast cancer cells MCF-7 and MDA231. However, whereas the normal cells were only transiently arrested, G2/M arrest in the malignant breast cancer cells was permanent and was accompanied by a massive cell death. In accordance, treatment with a phenanthridine-derived PARP inhibitor prevented the development of MCF-7 and MDA231 xenotransplants in female nude mice. Quiescent cells (neurons and cardiomyocytes) are not impaired by these PARP inhibitors.

Conclusions
These results outline a new therapeutic approach for a selective eradication of abundant nonhereditary human breast cancers.
CD57+ T lymphocytes and functional immune deficiency
Authors: Focosi Daniele , Bestagno Marco , Burrone Oscar , Petrini Mario 
Published: October 2009

Abstract
CD57 marker on T lymphocytes is a promising marker of functional immune deficiency whose clinical value is under scrutiny.
CD57+ expression in T lymphocytes has been recognized for decades as a marker of in vitro replicative senescence. In recent years, accumulating evidences have pointed on the utility of this marker to measure functional immune deficiency in patients with autoimmune disease, infectious diseases, and cancers. We review here the relevant literature and implications in clinical settings.
Second-generation antipsychotic long-acting injections: Systematic review
Authors: Fleischhacker W. Wolfgang 
Published: October 2009

BackgroundSecond-generation antipsychotics (SGAs) represent an advance in the long-term management of schizophrenia.AimsTo review the available evidence concerning SGA long-acting injections (LAIs).MethodA systematic review of the literature was conducted using PubMed.ResultsRisperidone long-acting injection was the first licensed SGA–LAI compound and is effective in the long-term management of schizophrenia, with a safety profile similar to that of oral risperidone. Olanzapine pamoate has recently been approved in Europe. In terms of efficacy, at injection intervals of up to 4 weeks it appears comparable to oral olanzapine, although the potential for ‘post-injection syndrome’ (delirium) calls for additional safety considerations. Paliperidone palmitate is currently under review with the licensing authorities. It also affords the potential advantage of monthly dosing.ConclusionsMore long-term comparisons of SGA–LAIs with oral SGAs as well as with first-generation antipsychotic LAIs are needed. These studies should include cost-effectiveness data.
Antipsychotic long-acting injections: Prescribing practice in the UK
Authors: Barnes Thomas R. E. , Shingleton-Smith Amber , Paton Carol 
Published: October 2009

BackgroundData from the USA, Australia and Europe suggest that the proportion of patients with schizophrenia prescribed an antipsychotic long-acting injection (LAI) varies from around a quarter to a third. Use of LAIs has been associated with male gender and younger age.AimsTo characterise the use of LAIs in people with schizophrenia in three clinical settings in the UK.MethodThe study used audit data from quality improvement programmes conducted by the Prescribing Observatory for Mental Health.ResultsLong-acting injections were found to be prescribed for between a quarter and a third of patients, depending on the clinical setting. Flupentixol, risperidone and zuclopenthixol were most commonly prescribed and were combined with an oral antipsychotic in half of cases, frequently constituting high-dose prescribing. The use of LAIs was not consistently associated with age, gender or ethnicity.ConclusionsAntipsychotic LAIs are commonly prescribed. We did not replicate previous findings with respect to demographic variables associated with their use.
Attitudes of patients and mental health staff to antipsychotic long-acting injections: Systematic review
Authors: Waddell Linda , Taylor Mark 
Published: October 2009

BackgroundThe attitudes of staff and patients have been demonstrated to influence the acceptance of long-acting injections (LAIs) or depot antipsychotics.AimsTo examine the attitudes of patients and staff to LAIs.MethodA systematic review was carried out. Studies included contained quantitative data for attitudes of patients or staff to LAIs.ResultsTwelve studies published subsequent to the systematic review reported in 2001 were identified. Five studies conveyed an overall positive attitude. The most positive attitudes among patients were seen in those already prescribed an LAI. Positive attitudes of staff correlated closely with the extent of their knowledge of LAIs.ConclusionsLong-acting injections continue to have an image problem, arguably perpetuated by manufacturers of oral second-generation antipsychotic drugs, and exacerbated by the predominant use of these medications as a ‘last resort’ often for the most stigmatised individuals. The introduction of better-tolerated LAIs and better education of both staff and patients may encourage individuals to re-examine their attitudes.
Knowledge about antipsychotic long-acting injections: Bridging that gap
Authors: Burns Tom 
Published: October 2009

SummaryAntipsychotics in depot (or ‘long-acting injection’, LAI) form are shown in this supplement to be a significant component of clinical practice. They are comparatively underresearched, which may reflect their frequent use witih poorly adherent patients. This supplement clearly demonstrates the need for that research, highlighting the variations in dosing and the absence of established, specific guidelines in their use. Traditional evidence-based approaches to systematic reviews are of limited utility in this area so this supplement's blending of experimental trials with observational research is particularly appropriate and effective. After a brief decline in their use with the introduction of oral atypical antipsychotics, LAIs are regaining a central position in the care of long-term psychosis. This comprehensive review of current knowledge makes a timely contribution.
Community treatment orders and antipsychotic long-acting injections
Authors: Lambert Tim J. , Singh Bruce S. , Patel Maxine X. 
Published: October 2009

BackgroundThe community treatment order (CTO) is the legal framework by which people in the community are compelled to accept treatment. Both antipsychotic long-acting injections (LAIs) and CTOs are used to address treatment non-adherence.AimsTo investigate the relationship between CTOs and LAI use in patients with schizophrenia.MethodPrescribing, demographic and CTO data were collected for patients from four community mental health clinics in Melbourne, Australia, in 1998 and 2002.ResultsAgainst a background of increasing use of oral second-generation antipsychotic (SGA) medication and decreasing use of LAIs, the rates of CTO implementation doubled from 13% to 26% of patients with schizophrenia between 1998 and 2002. Proportionally more patients with a CTO are prescribed LAIs rather than oral SGAs.ConclusionsThe relationship between receiving an LAI and being subject to a CTO is significant, and reflects the consideration given to enhancing adherence in a community mental health setting.
Androgen Regulates Brain-Derived Neurotrophic Factor in Spinal Motoneurons and Their Target Musculature
Authors: Verhovshek Tom , Cai Yi , Osborne Mark C. , Sengelaub Dale R. 
Published: October 2009

AbstractTrophic factors maintain motoneuron morphology and function in adulthood. Brain-derived neurotrophic factor (BDNF) interacts with testosterone to maintain dendritic morphology of spinal motoneurons. In addition, testosterone regulates BDNF’s receptor (trkB) in motoneurons innervating the quadriceps muscles as well as in motoneurons of the highly androgen-sensitive spinal nucleus of the bulbocavernosus (SNB). Given these interactive effects, we examined whether androgen might also regulate BDNF in quadriceps and SNB motoneurons and their corresponding target musculature. In both motoneuron populations, castration of males reduced BDNF immunolabeling, and this effect was prevented with testosterone replacement. ELISA for BDNF in the target musculature of quadriceps (vastus lateralis, VL) and SNB (bulbocavernosus, BC) motoneurons revealed that BDNF in the VL and BC muscles was also regulated by androgen. However, although castration significantly decreased BDNF concentration in the VL muscle, BDNF concentration in the BC muscle was significantly increased in castrates. Treatment of castrated males with testosterone maintained BDNF levels at those of intact males in both sets of muscles. Together, these results demonstrate that androgens regulate BDNF in both a sexually dimorphic, highly androgen-sensitive neuromuscular system as well as a more typical somatic neuromuscular system. Furthermore, in addition to the regulation of trkB, these studies provide another possible mechanism for the interactive effects of testosterone and BDNF on motoneuron morphology. More importantly, by examining both the motoneurons and the muscles they innervate, these results demonstrate that within a neural system, BDNF levels in different components are differentially affected by androgen manipulation.
A Novel Distal Enhancer Mediates Cytokine Induction of Mouse Rankl Gene Expression
Authors: Bishop Kathleen A. , Meyer Mark B. , Pike J. Wesley 
Published: October 2009

AbstractChronic inflammatory states are associated with increased bone loss. This increase is often linked to an elevation in receptor activator of nuclear factor-κB ligand (RANKL), a TNFα-like factor essential to osteoclast formation. In this study, we document the ability of IL-6 in combination with IL-6 soluble receptor (IL-6/IL-6sR) and oncostatin M to induce Rankl expression in stromal cells via signal transducer and activator of transcription 3 (STAT3). We used chromatin immunoprecipitation-tiled DNA microarray analysis to determine sites of action of STAT3 at the Rankl locus and to assess the consequences of binding on histone H4 acetylation and RNA polymerase II recruitment. Both IL-6/IL-6 soluble receptor and oncostatin M stimulated STAT3 binding upstream of the Rankl transcriptional start site. Although previously identified enhancers bound STAT3, a more distal enhancer termed mRLD6 was a particular focus of STAT3 binding. When fused to a heterologous promoter, this enhancer was highly active, containing two functionally active STAT response elements. Importantly, small interfering RNA knockdown of Stat3 mRNA and protein, but not that of Stat1 or Stat5a, was effective in limiting Rankl mRNA up-regulation. Interestingly, although RNA polymerase II and histone H4 acetylation marked many of the enhancers under basal conditions, the levels of both were strongly increased after cytokine treatment, particularly at mRLD6. Finally, mRLD6 was also a target for forskolin-induced cellular response element-binding protein (CREB) recruitment, which potentiated cytokine activity. Our studies provide new insight into mechanisms by which glycoprotein 130 activating cytokines induce RANKL expression.
Survival of patients with skeletal metastases from hepatocellular carcinoma after surgical management
Authors: Cho H. S. , Oh J. H. , Han I. , Kim H.-S. 
Published: October 2009

Skeletal metastases from hepatocellular carcinoma are highly destructive vascular lesions which severely reduce the quality of life. Pre-existing liver cirrhosis presents unique challenges during the surgical management of such lesions. We carried out a retrospective study of 42 patients who had been managed surgically for skeletal metastases from hepatocellular carcinoma affecting the appendicular skeleton between January 2000 and December 2006. There were 38 men and four women with a mean age of 60.2 years (46 to 77). Surgery for a pathological fracture was undertaken in 30 patients and because of a high risk of fracture in 12. An intralesional surgical margin was achieved in 36 and a wide margin in six. Factors influencing survival were determined by univariate and multivariate analyses. The survival rates at one, two and three years after surgery were 42.2%, 25.8% and 19.8%, respectively. The median survival time was ten months (95% confidence interval 6.29 to 13.71). The number of skeletal metastases and the Child-Pugh grade were identified as independent prognostic factors by Cox regression analysis. The method of management of the hepatocellular carcinoma, its status in the liver, the surgical margin for skeletal metastases, the presence of a pathological fracture and adjuvant radiotherapy were not found to be significantly related to the survival of the patient, which was affected by hepatic function, as represented by the Child-Pugh grade.
Two-stage revision arthroplasty of the hip for infection using an interim articulated Prostalac hip spacer
Authors: Biring G. S. , Kostamo T. , Garbuz D. S. , Masri B. A. , Duncan C. P. 
Published: October 2009

We report the outcome at ten to 15 years of two-stage revision for hip infection in 99 patients using the Prostalac articulated hip spacer system. All the patients were contacted to determine their current functional and infection status using the Oxford-12, Short form-12, and Western Ontario and McMaster University Osteoarthritis Index questionnaires. A total of 11 of the 99 patients had a further infection, of whom seven responded to repeat surgery with no further sequelae. The mean interval between the stages was five months (1 to 36). We were able to review 48 living patients, with a mean age of 72 years (46 to 86), 34 (71%) of whom provided health-related quality-of-life outcome scores. The mean follow-up was 12 years (10 to 15). The long-term success rate was 89% and with additional surgery this rose to 96%. The mean global Western Ontario and McMaster University Osteoarthritis Index score was 80.6 (sd 18.3). The mean Oxford-12 score was 74.0 (sd 22.3), and the mean Short form-12 score was 53.1 (sd 9.4) (mental) and 33.5 (sd 13.5) (physical). The mean satisfaction score was 90.5 (sd 15.3). Two-stage revision for hip infection using a Prostalac interim spacer offers a predictable and lasting solution for patients with this difficult problem.