bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomic approach for the isolation of a thermostable β-galactosidase with high tolerance of galactose and glucose from soil samples of Turpan Basin
Authors: Zhang Xia , Li He , Li Chang-Jie , Ma Teng , Li Gang , Liu Yu-Huan 
Published: October 2013

Abstract

Background
β-Galactosidases can be used to produce low-lactose milk and dairy products for lactose intolerant people. Although commercial β-galactosidases have outstanding lactose hydrolysis ability, their thermostability is low, and reaction products have strong inhibition to these enzymes. In addition, the β-galactosidases possessing simultaneously high thermostability and tolerance of galactose and glucose are still seldom reported until now. Therefore, identification of novel β-galactosidases with high thermostability and tolerance to reaction products from unculturable microorganisms accounting for over 99% of microorganisms in the environment via metagenomic strategy is still urgently in demand.

Results
In the present study, a novel β-galactosidase (Gal308) consisting of 658 amino acids was identified from a metagenomic library from soil samples of Turpan Basin in China by functional screening. After being overexpressed in Escherichia coli and purified to homogeneity, the enzymatic properties of Gal308 with N-terminal fusion tag were investigated. The recombinant enzyme displayed a pH optimum of 6.8 and a temperature optimum of 78°C, and was considerably stable in the temperature range of 40°C - 70°C with almost unchangeable activity after incubation for 60 min. Furthermore, Gal308 displayed a very high tolerance of galactose and glucose, with the highest inhibition constant K
i,gal (238 mM) and K
i,glu (1725 mM) among β-galactosidases. In addition, Gal308 also exhibited high enzymatic activity for its synthetic substrate o-nitrophenyl-β-D-galactopyranoside (ONPG, 185 U/mg) and natural substrate lactose (47.6 U/mg).

Conclusion
This study will enrich the source of β-galactosidases, and attract some attentions to β-galactosidases from extreme habitats and metagenomic library. Furthermore, the recombinant Gal308 fused with 156 amino acids exhibits many novel properties including high activity and thermostability at high temperatures, the pH optimum of 6.8, high enzyme activity for lactose, as well as high tolerance of galactose and glucose. These properties make it a good candidate in the production of low-lactose milk and dairy products after further study.
Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study
Authors: Kruk Mariusz , Menon Venu , Kądziela Jacek , Sadowski Zygmunt , Rużyłło Witold , Janas Jadwiga , Roik Marek , Opolski Grzegorz , Zmudka Krzysztof , Czunko Piotr , Kurowski Michal , Busz-Papież Benita , Zinka Elzbieta , Jablonski Wojciech , Jaworska Krystyna , Raczynska Anna , Skonieczny Grzegorz , Forman Sandra , Li Daner , Hochman Judith 
Published: October 2013

Abstract

Background
The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis.

Methods
Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3.

Results
Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted.

Conclusions
There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers’ release.
The impact of inappropriate antibiotics on bacteremia patients in a community hospital in Taiwan: an emphasis on the impact of referral information for cases from a hospital affiliated nursing home
Authors: Yang Chih-Jen , Chung Yu-Chieh , Chen Tun-Chieh , Chang Hsu-Liang , Tsai Ying-Ming , Huang Ming-Shyan , Chen Yen-Hsu , Lu Po-Liang 
Published: October 2013

Abstract

Background
Evidence for the impact of inappropriate antimicrobial therapy on bacteremia is mainly from studies in medical centers. We investigated the impact of inappropriate antimicrobial therapy on bacteremia in a community hospital. In particular, patients from the hospital’s affiliated nursing home were sent to the hospital with adequate referral information.

Methods
We performed a retrospective study to collect data of patients with bacteremia in a community hospital in Taiwan from 2005 to 2007.

Results
A total of 222 patients with blood stream infection were diagnosed, of whom 104 patients (46.8%) died. The rate of initial inappropriate antibiotic prescriptions was high (59%). Multivariate analysis revealed that patients with initial inappropriate antibiotics, patients with ventilator support and patients requiring ICU care were the independent predictors for inhospital mortality. Patients referred from the hospital-affiliated nursing home and patients with normal WBC counts had better survival outcome. More than 80% cases infected with methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis received initial inappropriate antimicrobial therapy. With the longer delay to administer appropriate antibiotic, a trend of higher mortality rates was observed.

Conclusions
Bacteremia patients from a hospital-affiliated nursing home had a better prognosis, which may have been due to the adequate referral information. Clinicians should be aware of the commonly ignored drug resistant pathogens, and efforts should be made to avoid delaying the administration of appropriate antibiotic therapy.
Detailed investigations of proximal tubular function in Imerslund-Gräsbeck syndrome
Authors: Storm Tina , Zeitz Christina , Cases Olivier , Amsellem Sabine , Verroust Pierre J , Madsen Mette , Benoist Jean-François , Passemard Sandrine , Lebon Sophie , Jønsson Iben Møller , Emma Francesco , Koldsø Heidi , Hertz Jens Michael , Nielsen Rikke , Christensen Erik I , Kozyraki Renata 
Published: October 2013

Abstract

Background
Imerslund-Gräsbeck Syndrome (IGS) is a rare genetic disorder characterised by juvenile megaloblastic anaemia. IGS is caused by mutations in either of the genes encoding the intestinal intrinsic factor-vitamin B12 receptor complex, cubam. The cubam receptor proteins cubilin and amnionless are both expressed in the small intestine as well as the proximal tubules of the kidney and exhibit an interdependent relationship for post-translational processing and trafficking. In the proximal tubules cubilin is involved in the reabsorption of several filtered plasma proteins including vitamin carriers and lipoproteins. Consistent with this, low-molecular-weight proteinuria has been observed in most patients with IGS. The aim of this study was to characterise novel disease-causing mutations and correlate novel and previously reported mutations with the presence of low-molecular-weight proteinuria.

Methods
Genetic screening was performed by direct sequencing of the CUBN and AMN genes and novel identified mutations were characterised by in silico and/or in vitro investigations. Urinary protein excretion was analysed by immunoblotting and high-resolution gel electrophoresis of collected urines from patients and healthy controls to determine renal phenotype.

Results
Genetic characterisation of nine IGS patients identified two novel AMN frameshift mutations alongside a frequently reported AMN splice site mutation and two CUBN missense mutations; one novel and one previously reported in Finnish patients. The novel AMN mutations were predicted to result in functionally null AMN alleles with no cell-surface expression of cubilin. Also, the novel CUBN missense mutation was predicted to affect structural integrity of the IF-B12 binding site of cubilin and hereby most likely cubilin cell-surface expression. Analysis of urinary protein excretion in the patients and 20 healthy controls revealed increased urinary excretion of cubilin ligands including apolipoprotein A-I, transferrin, vitamin D-binding protein, and albumin. This was, however, only observed in patients where plasma membrane expression of cubilin was predicted to be perturbed.

Conclusions
In the present study, mutational characterisation of nine IGS patients coupled with analyses of urinary protein excretion provide additional evidence for a correlation between mutation type and presence of the characteristic low-molecular-weight proteinuria.
Etiologic subtype predicts outcome in mild stroke: prospective data from a hospital stroke registry
Authors: Hao Zilong , Liu Ming , Wang Deren , Wu Bo , Tao Wendan , Chang Xueli 
Published: October 2013

Abstract

Background
Few studies on whether etiologic subtype can predict outcome in mild stroke are available. The study aim to explore the effect of different etiologic subtype on prognosis of these patients.

Methods
We prospectively registered consecutive cases of acute ischemic stroke from September. 01, 2009 to August. 31, 2011. Patients with National Institute of Health Stroke Scale (NIHSS) ≦3 and within 30 days of symptom onset were included. All cause death or disability (defined as modified Rankin Scale >2) were followed up at 3 months. The multivariate logistical regression model was used to analyse relationship between etiologic subtype and clinical outcomes.

Results
We included 680 cases, which accounted for 41.1% (680/1655) of the total registered cases. Mean age were 62.54 ± 13.51 years, and males were 65.4%. The median time of symptoms onset to admission was 72 hours. 3.8% (26/680) of cases admitted within 3 hours and 4.7% (32/680) admitted within 4.5 hours. However, no patient received intravenous thrombolysis. Of included patients, 21.5% large-artery atherosclerosis, 40.6% small-vessel disease, 7.5% cardioembolisms, 2.2% other causes and 28.2% undetermined causes. The rate of case fatality and death/disability was 2.2% and 10.1% respectively at 3 months. After adjustment of potential confounders, such as age, sex, NIHSS on admission and vascular risk factors et al., cardioembolism (RR = 3.395;95%CI 1.257 ~ 9.170) was the predictor of death or disability at 3 months and small vessel occlusion (RR = 0.412;95%CI 0.202 ~ 0.842) was the protective factor of death or disability at 3 months.

Conclusion
Different etiologic subtype can predict the outcome in patients with mild stroke and it can help to stratify these patients for individual decision-making.
Si-Wu-tang extract stimulates bone formation through PI3K/Akt/NF-κB signaling pathways in osteoblasts
Authors: Wu Chi-Ming , Chen Po-Chun , Li Te-Mao , Fong Yi-Chin , Tang Chih-Hsin 
Published: October 2013

Abstract

Background
Si-Wu-Tang (SWT), a Traditional Chinese Medicine (TCM) formula, is widely used for the treatment of gynopathies diseases such as menstrual discomfort, climacteric syndrome, dysmenorrhea, and other estrogen-related diseases. Recent studies have shown that SWT can treat primary dysmenorrhea, have anti-pruritic anti-inflammatory effects, and protect against radiation-induced bone marrow damage in an animal model. It has been reported that anti-inflammatory and anti-oxidant agents have the potential to treat osteoporosis by increasing bone formation and/or suppressing bone resorption. However, the effect of SWT on bone cell function has not yet been reported.

Methods
Alkaline phosphatase (ALP), bone morphogenetic proteins (BMP)-2, and osteopontin (OPN) mRNA expression was analyzed by qPCR. The mechanism of action of SWT extract was investigated using western blotting. The in vivo anti-osteoporotic effect of SWT extract was assessed in ovariectomized mice.

Results
Here, we report that SWT increases ALP, BMP-2, and OPN expression as well as bone mineralization. In addition, we show that the PI3K, Akt, and NF-κB signaling pathways may be involved in the SWT-mediated increase in gene expression and bone mineralization. Notably, treatment of mice with SWT extract prevented bone loss induced by ovariectomy in vivo.

Conclusion
SWT may be used to stimulate bone formation for the treatment of osteoporosis.
Protective activity of Panduratin A against Thioacetamide-induced oxidative damage: demonstration with in vitro experiments using WRL-68 liver cell line
Authors: Salama Suzy M , AlRashdi Ahmed S , Abdulla Mahmood A , Hassandarvish Pouya , Bilgen Mehmet 
Published: October 2013

Abstract

Background
Chalcone Panduratin A (PA) has been known for its antioxidant property, but its merits against oxidative damage in liver cells has yet to be investigated. Hence, the paper aimed at accomplishing this task with normal embryonic cell line WRL-68.

Methods
PA was isolated from Boesenbergia rotunda rhizomes and its 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and ferric reducing power (FRAP) activities were measured in comparison with that of the standard reference drug Silymarin (SI). Oxidative damage was induced by treating the cells with 0.04 g/ml of toxic thioacetamide for 60 minutes followed by treatment with 1, 10 and 100 μg/ml concentrations of either PA or SI. The severities of oxidative stress in the control and experimental groups of cells were measured by Malondialdehyde (MDA) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities.

Results
PA exhibited an acceptable DPPH scavenging and FRAP activities close to that of Silymarin. Treating the injured cells with PA significantly reduced the MDA level and increased the cell viability, comparable to SI. The activities of SOD, CAT and GPx were significantly elevated in the PA-treated cells in a dose dependent manner and again similar to SI.

Conclusion
Collectively, data suggested that PA has capacity to protect normal liver cells from oxidative damage, most likely via its antioxidant scavenging ability.
A novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation
Authors: Chan King Chi , Ting Choi Man , Chan Pui Shan , Lo Ming Chu , Lo Kwok Wai , Curry Jayne E , Smyth Tomoko , Lee Anne Wing Mui , Ng Wai Tong , Tsao George Sai Wah , Wong Ricky Ngok Shun , Lung Maria Li , Mak Nai Ki 
Published: October 2013

Abstract

Background
Nasopharyngeal carcinoma (NPC) is an epithelial malignancy strongly associated with Epstein-Barr virus (EBV). AT13387 is a novel heat shock protein 90 (Hsp90) inhibitor, which inhibits the chaperone function of Hsp90 and reduces expression of Hsp90-dependent client oncoproteins. This study aimed to evaluate both the in vitro and in vivo antitumor effects of AT13387 in the EBV-positive NPC cell line C666-1.

Results
Our results showed that AT13387 inhibited C666-1 cell growth and induced cellular senescence with the downregulation of multiple Hsp90 client oncoproteins EGFR, AKT, CDK4, and restored the protein expression of negative cell cycle regulator p27. We also studied the ability of AT13387 to restore p27 expression by downregulation of AKT and the p27 ubiquitin mediator, Skp2, using AKT inhibitor and Skp2 siRNA. In the functional study, AT13387 inhibited cell migration with downregulation of a cell migration regulator, HDAC6, and increased the acetylation and stabilization of α-tubulin. We also examined the effect of AT13387 on putative cancer stem cells (CSC) by 3-D tumor sphere formation assay. AT13387 effectively reduced both the number and size of C666-1 tumor spheres with decreased expression of NPC CSC-like markers CD44 and SOX2. In the in vivo study, AT13387 significantly suppressed tumor formation in C666-1 NPC xenografts.

Conclusion
AT13387 suppressed cell growth, cell migration, tumor sphere formation and induced cellular senescence on EBV-positive NPC cell line C666-1. Also, the antitumor effect of AT13387 was demonstrated in an in vivo model. This study provided experimental evidence for the preclinical value of using AT13387 as an effective antitumor agent in treatment of NPC.
Effect of a prescriptive dietary intervention on psychological dimensions of eating behavior in obese adolescents
Authors: Ho Mandy , Gow Megan , Halim Jocelyn , Chisholm Kerryn , Baur Louise A , Noakes Manny , Steinbeck Katherine , Kohn Michael R , Cowell Chris T , Garnett Sarah P 
Published: October 2013

Abstract

Background
Overweight adolescents are more likely to have dysfunctional eating behaviours compared to normal weight adolescents. Little is known about the effects of obesity treatment on the psychological dimensions of eating behavior in this population.

Objective
To examine the effects of a prescriptive dietary intervention on external eating (eating in response to food cues, regardless of hunger and satiety), emotional eating and dietary restraint and their relation to weight loss. Parental acceptability was also examined.

Method
This is a secondary study of a 12-month randomized trial, the RESIST study, which examined the effects of two diets on insulin sensitivity. Participants were 109 obese 10- to 17-year-olds with clinical features of insulin resistance. The program commenced with a 3-month dietary intervention using a structured meal plan, with the addition of an exercise intervention in the next 3 months and followed by a 6 month maintenance period.This paper presents changes in eating behaviors measured by the Eating Pattern Inventory for Children and parent rated diet acceptability during the first 6 months of the trial. As there was no difference between the diets on outcome of interest, both diet groups were combined for analyses.

Results
After 6 months, the proportion of participants who reported consuming more in response to external eating cues decreased from 17% to 5% (P = 0.003), whereas non- emotional eating increased from 48% to 65% (p = 0.014). Dietary restraint and parental pressure to eat remained unchanged. A reduction in external eating (rho = 0.36, P < 0.001) and a reduction in dietary restraint (r = 0.26, P = 0.013) were associated with greater weight loss at 3 and 6 months, respectively. Overall this approach was well accepted by parents with 72% of parents considered that their child would be able to follow the meal plan for the longer term.

Conclusions
In the short to medium term, a prescriptive dietary intervention approach is a well-accepted and suitable option for obese adolescents with clinical features of insulin resistance. It may reduce external and emotional eating, led to modest weight loss and did not cause any adverse effect on dietary restraint.

Trial registration
Australian New Zealand Clinical Trial Registration Number (ACTRN) 12608000416392 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=83071
Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response
Authors: Rocha Cheila , Calado Rita , Borrego Pedro , Marcelino José Maria , Bártolo Inês , Rosado Lino , Cavaco-Silva Patrícia , Gomes Perpétua , Família Carlos , Quintas Alexandre , Skar Helena , Leitner Thomas , Barroso Helena , Taveira Nuno 
Published: October 2013

AbstractBackgroundDifferently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth.ResultsCD4+T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies.ConclusionOur data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.
S100A9 protein is a novel ligand for the CD85j receptor and its interaction is implicated in the control of HIV-1 replication by NK cells
Authors: Arnold Vincent , Cummings Jean-Saville , Moreno-Nieves Uriel Y , Didier Céline , Gilbert Adrien , Barré-Sinoussi Françoise , Scott-Algara Daniel 
Published: October 2013

Abstract

Background
The reportedly broad expression of CD85j across different immune cell types suggests an importance for this molecule in the human immune system. Previous reports have shown that this receptor interacts with several HLA class-I molecules, as well as with some viral proteins. We have demonstrated that the subset of CD85j + Natural Killer (NK) cells efficiently controls human immunodeficiency virus type 1 (HIV-1) replication in monocyte-derived dendritic cells (MDDC) in vitro and this led us to hypothesize that the CD85j + NK cell-mediated anti-HIV activity in MDDC is specifically dependent on the interaction between the CD85j receptor and unknown non-HLA class-I ligand(s).

Results
In this study, we focused our efforts on the identification of these non-described ligands for CD85j. We found that the CD85j receptor interacts with a calcium-binding proteins of the S100 family; namely, S100A9. We further demonstrated that HIV-1 infection of MDDC induces a modulation of S100A9 expression on surface of the MDDC, which potentially influences the anti-HIV-1 activity of human NK cells through a mechanism involving CD85j ligation. Additionally, we showed that stimulation of NK cells with exogenous S100A9 enhances the control of HIV-1 infection in CD4+ T cells.

Conclusions
Our data show that S100A9 protein, through ligation with CD85j, can stimulate the anti-HIV-1 activity of NK cells.