bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Stride Frequency and Length on Running Mechanics
Authors: Schubert Amy G. , Kempf Jenny , Heiderscheit Bryan C.
Published: October 2013

Context:

A high number of recreational runners sustain a running-related injury each year. To reduce injury risk, alterations in running form have been suggested. One simple strategy for running stride frequency or length has been commonly advocated.

Objective:

To characterize how running mechanics change when stride frequency and length are manipulated.

Data Sources:

In January 2012, a comprehensive search of PubMed, CINAHL Plus, SPORTDiscus, PEDro, and Cochrane was performed independently by 2 reviewers. A second search of the databases was repeated in June 2012 to ensure that no additional studies met the criteria after the initial search.

Study Selection:

Inclusion criteria for studies were an independent variable including manipulation of stride frequency or length at a constant speed with outcome measures of running kinematics or kinetics.

Study Design:

Systematic review.

Level of Evidence:

Level 3.

Data Extraction:

Two reviewers independently appraised each article using a modified version of the Quality Index, designed for assessing bias of nonrandomized studies.

Results:

Ten studies met the criteria for this review. There was consistent evidence that increased stride rate resulted in decreased center of mass vertical excursion, ground reaction force, shock attenuation, and energy absorbed at the hip, knee, and ankle joints. All but 1 study had a limited number of participants, with several methodological differences existing among studies (eg, overground and treadmill running, duration of test conditions). Although speed was held constant during testing, it was individually self-selected or fixed. Most studies used only male participants.

Conclusion:

Despite procedural differences among studies, an increased stride rate (reduced stride length) appears to reduce the magnitude of several key biomechanical factors associated with running injuries.
Symmetric duality for nondifferentiable multiobjective fractional variational problems involving cones
Authors: Kang Young Min , Kim Do Sang , Kim Moon Hee
Published: October 2013

We introduce a pair of symmetric dual problems for nondifferentiable multiobjective fractional variational problems with cone constraints over arbitrary cones. On the basis of weak efficiency, we obtain symmetric duality relations for Mond-Weir-type problems under invexity and pseudoinvexity assumptions. Our symmetric duality results extend and improve some known results in Mishra et al. (J. Math. Anal. Appl. 333:1093-1110, 2007) to the cone constraints.

MSC:90C29, 90C32, 90C26.
MiR-155 promotes proliferation of human breast cancer MCF-7 cells through targeting tumor protein 53-induced nuclear protein 1
Authors: Zhang Chun-Mei , Zhao Jing , Deng Hua-Yu
Published: October 2013

Background

MiR-155 has emerged as an “oncomiR”, which is the most significantly up-regulated miRNA in breast cancer. However, the mechanisms of miR-155 functions as an oncomiR are mainly unknown. In this study, the aims were to investigate the effects of miR-155 on cell proliferation, cell cycle, and cell apoptosis of ERalpha (+) breast cancer cells and to verify whether TP53INP1 (tumor protein 53-induced nuclear protein 1) is a target of miR-155, and tried to explore the mechanisms of miR-155 in this process.

Results

The expression of miR-155 is significantly higher in MCF-7 cells compared with MDA-MB-231 cells. Ectopic expression of TP53INP1 inhibits growth of MCF-7 cells by inducing cell apoptosis and inhibiting cell cycle progression. Overexpression of miR-155 increases cell proliferation and suppress cell apoptosis, whereas abrogating expression of miR-155 suppress cell proliferation and promotes cell apoptosis of MCF-7 cells. In addition, miR-155 negatively regulates TP53INP1 mRNA expression and the protein expression of TP53INP1, cleaved-caspase-3, -8, -9, and p21, and luciferase reporter reveals that TP53INP1 is targeted by miR-155.

Conclusions

TP53INP1 is the direct target of miR-155. MiR-155, which is overexpressed in MCF-7 cells, contributes to proliferation of MCF-7 cells possibly through down-regulating target TP53INP1.
Quantitative trait loci-dependent analysis of a gene co-expression network associated with Fusarium head blight resistance in bread wheat (Triticum aestivumL.)
Authors: Kugler Karl G , Siegwart Gerald , Nussbaumer Thomas , Ametz Christian , Spannagl Manuel , Steiner Barbara , Lemmens Marc , Mayer Klaus FX , Buerstmayr Hermann , Schweiger Wolfgang
Published: October 2013

Background

Fusarium head blight (FHB) caused byFusarium graminearumSchwabe is one of the most prevalent diseases of wheat (Triticum aestivumL.) and other small grain cereals. Resistance against the fungus is quantitative and more than 100 quantitative trait loci (QTL) have been described. Two well-validated and highly reproducible QTL,Fhb1andQfhs.ifa-5Ahave been widely investigated, but to date the underlying genes have not been identified.

Results

We have investigated a gene co-expression network activated in response toF. graminearumusing RNA-seq data from near-isogenic lines, harboring either the resistant or the susceptible allele forFhb1andQfhs.ifa-5A. The network identified pathogen-responsive modules, which were enriched for differentially expressed genes between genotypes or different time points after inoculation with the pathogen. Central gene analysis identified transcripts associated with either QTL within the network. Moreover, we present a detailed gene expression analysis of four gene families (glucanases, NBS-LRR, WRKY transcription factors and UDP-glycosyltransferases), which take prominent roles in the pathogen response.

Conclusions

A combination of a network-driven approach and differential gene expression analysis identified genes and pathways associated withFhb1andQfhs.ifa-5A. We find G-protein coupled receptor kinases and biosynthesis genes for jasmonate and ethylene earlier induced forFhb1. Similarly, we find genes involved in the biosynthesis and metabolism of riboflavin more abundant forQfhs.ifa-5A.
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

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

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

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

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

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

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

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

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

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

Background

Differently 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.

Results

CD4+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.

Conclusion

Our 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

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.
Status of selected nutrients in obese dogs undergoing caloric restriction
Authors: Linder Deborah E , Freeman Lisa M , Holden Shelley L , Biourge Vincent , German Alexander J
Published: October 2013

Background

The purpose of this study was to test the hypothesis that dog plasma concentrations of selected nutrients decrease after undergoing caloric restriction for weight loss. Thirty-one overweight dogs that had successfully lost at least 15% of initial body weight were included in the study. Nutrients that had been previously identified to be at potential risk of deficiency during caloric restriction were measured in plasma (choline, amino acids) and urine (selenium) at the initiation and completion of a standardized weight loss regimen in dogs.

Results

Dogs remained healthy throughout the study, and no signs attributable to nutrient deficiency were noted. Percentage weight loss was 28.3% (16.0-40.1%) starting body weight, over a period of 250 days (91–674 days). Median energy intake during the weight loss period was 62 (44 to 74) Kcal/kg0.75 target weight per day. Choline (P = 0.046) and threonine (P = 0.02) decreased after weight loss. Glycine (P = 0.041), and urinary selenium:creatinine ratio (P = 0.006) both increased after weight loss. There were no other significant differences in plasma nutrient concentrations.

Conclusions

Since concentrations of most measured nutrients did not change significantly, the data are not consistent with widespread nutrient deficiency in dogs undergoing caloric restriction using a diet formulated for weight loss. However, the significance of the decrease in plasma choline concentration requires further assessment.
Engineering biodegradable and multifunctional peptide-based polymers for gene delivery
Authors: Shi Julie , Schellinger Joan G , Pun Suzie H
Published: October 2013

The complex nature of in vivo gene transfer establishes the need for multifunctional delivery vectors capable of meeting these challenges. An additional consideration for clinical translation of synthetic delivery formulations is reproducibility and scale-up of materials. In this review, we summarize our work over the last five years in developing a modular approach for synthesizing peptide-based polymers. In these materials, bioactive peptides that address various barriers to gene delivery are copolymerized with a hydrophilic backbone of N-(2-hydroxypropyl)methacrylamide (HPMA) using reversible-addition fragmentation chain-transfer (RAFT) polymerization. We demonstrate that this synthetic approach results in well-defined, narrowly-disperse polymers with controllable composition and molecular weight. To date, we have investigated the effectiveness of various bioactive peptides for DNA condensation, endosomal escape, cell targeting, and degradability on gene transfer, as well as the impact of multivalency and polymer architecture on peptide bioactivity.
Tumor hypoxia as a driving force in genetic instability
Authors: Luoto Kaisa R , Kumareswaran Ramya , Bristow Robert G
Published: October 2013

Sub-regions of hypoxia exist within all tumors and the presence of intratumoral hypoxia has an adverse impact on patient prognosis. Tumor hypoxia can increase metastatic capacity and lead to resistance to chemotherapy and radiotherapy. Hypoxia also leads to altered transcription and translation of a number of DNA damage response and repair genes. This can lead to inhibition of recombination-mediated repair of DNA double-strand breaks. Hypoxia can also increase the rate of mutation. Therefore, tumor cell adaptation to the hypoxic microenvironment can drive genetic instability and malignant progression. In this review, we focus on hypoxia-mediated genetic instability in the context of aberrant DNA damage signaling and DNA repair. Additionally, we discuss potential therapeutic approaches to specifically target repair-deficient hypoxic tumor cells.
Analyses of Arabidopsis ecotypes reveal metabolic diversity to convert D-amino acids
Authors: Gördes Dirk , Koch Grit , Thurow Kerstin , Kolukisaoglu Üner
Published: October 2013

For a long time D-enantiomers of proteinogenic L-amino acids were assumed to be physiologically irrelevant for plants. But there is growing evidence that D-amino acids (D-AAs) also fulfil important physiological functions in these organisms. However, the knowledge about the metabolic fate of D-AAs in plants is still scarce and more information about it is needed. To close this gap we established an optimized protocol for the processing and analysis of D- and L-AAs from large numbers of Arabidopsis lines. This included the application of 18 different D-AAs to seedlings, the extraction of free amino acids from the samples and the determination of 16 L-AAs and their corresponding D-enantiomers. To validate our approach we searched for genetic accessions with aberrant amino acid metabolism. Therefore we applied D-AAs on 17 ecotypes of Arabidopsis thaliana and analysed their free amino acid contents. These analyses confirmed the suitability of the system for the analysis of large sets of plant samples with enhanced velocity and improved accuracy. Furthermore, the resulting data led to the definition of standard amino acid profiles in response to D-AAs of Arabidopsis seedlings. Within these analyses the ecotype Landsberg erecta was found with aberrant metabolic patterns like drastically reduced capabilities to convert different D-AAs to D-alanine and D-glutamate. The presented experimental setup and results of this study offer starting points to dissect the metabolic pathway of D-AAs in plants.
Biomarkers of lung epithelial injury and inflammation distinguish severe sepsis patients with acute respiratory distress syndrome
Authors: Ware Lorraine B , Koyama Tatsuki , Zhao Zhiguo , Janz David R , Wickersham Nancy , Bernard Gordon R , May Addison K , Calfee Carolyn S , Matthay Michael A
Published: October 2013

Introduction

Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.

Methods

This was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.

Results

Using the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.

Conclusions

Abnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.
Effect of erythropoietin on the incidence of acute kidney injury following complex valvular heart surgery: a double blind, randomized clinical trial of efficacy and safety
Authors: Kim Ji-Ho , Shim Jae-Kwang , Song Jong-Wook , Song Young , Kim Hye-Bin , Kwak Young-Lan
Published: October 2013

Introduction

Recombinant human erythropoietin (EPO) is known to provide organ protection against ischemia-reperfusion injury through its pleiotropic properties. The aim of this single-site, randomized, case-controlled, and double-blind study was to investigate the effect of pre-emptive EPO administration on the incidence of postoperative acute kidney injury (AKI) in patients with risk factors for AKI undergoing complex valvular heart surgery.

Methods

We studied ninety-eight patients with preoperative risk factors for AKI. The patients were randomly allocated to either the EPO group (n = 49) or the control group (n = 49). The EPO group received 300 IU/kg of EPO intravenously after anesthetic induction. The control group received an equivalent volume of normal saline. AKI was defined as an increase in serum creatinine >0.3 mg/dl or >50% from baseline. Biomarkers of renal injury were serially measured until five days postoperatively.

Results

Patient characteristics and operative data, including the duration of cardiopulmonary bypass, were similar between the two groups. Incidence of postoperative AKI (32.7% versus 34.7%, P = 0.831) and biomarkers of renal injury including cystatin C and neutrophil gelatinase-associated lipocalin showed no significant differences between the groups. The postoperative increase in interleukin-6 and myeloperoxidase was similar between the groups. None of the patients developed adverse complications related to EPO administration, including thromboembolic events, throughout the study period.

Conclusions

Intravenous administration of 300 IU/kg of EPO did not provide renal protection in patients who are at increased risk of developing AKI after undergoing complex valvular heart surgery.

Trial registration

Clinical Trial.gov, NCT01758861
Procalcitonin biomarker kinetics fails to predict treatment response in perioperative abdominal infection with septic shock
Authors: Jung Boris , Molinari Nicolas , Nasri Mourad , Hajjej Zied , Chanques Gerald , Jean-Pierre Helene , Panaro Fabrizio , Jaber Samir
Published: October 2013

Introduction

Procalcitonin (PCT) biomarker is suggested to tailor antibiotic therapy in the medical intensive care unit (ICU) but studies in perioperative medicine are scarce. The aim of this study was to determine whether PCT reported thresholds are associated with the initial treatment response in perioperative septic shock secondary to intra-abdominal infection.

Methods

This single ICU, observational study included patients with perioperative septic shocks secondary to intra-abdominal infection. Demographics, PCT at days 0, 1, 3, 5, treatment response and outcome were collected. Treatment failure included death related to the initial infection, second source control treatment or a new onset intra-abdominal infection. The primary endpoint was to assess whether PCT thresholds (0.5 ng/ml or a drop from the peak of at least 80%) predict the initial treatment response.

Results

We included 101 consecutive cases. Initial treatment failed in 36 patients with a subsequent mortality of 75%. Upon admission, PCT was doubled when treatment ultimately failed (21.7 ng/ml ± 38.7 vs. 41.7 ng/ml ± 75.7; P = 0.04). Although 95% of the patients in whom PCT dropped down below 0.5 ng/ml responded to treatment, 50% of the patients in whom PCT remained above 0.5 ng/ml also responded successfully to treatment. Moreover, despite a PCT drop of at least 80%, 40% of patients had treatment failure.

Conclusions

In perioperative intra-abdominal infections with shock, PCT decrease to 0.5 ng/ml lacked sensitivity to predict treatment response and its decrease of at least 80% from its peak failed to accurately predict treatment response. Studies in perioperative severe infections are needed before using PCT to tailor antibiotic use in this population.
Adaptive multiple subtraction based on 3D blind separation of convolved mixtures
Authors: Li Zhong-xiao , Lu Wen-kai
Published: October 2013

Multiple removal is one of the important preprocessing steps in a seismic data processing sequence. For an accurate multiple prediction, a full 3D method is required. However, the application of such methods is often limited by practical and economic constraints. Therefore, in practical situations, 2D prediction methods are used, such as 2D surface-related multiple elimination. However, the resulting predicted multiples may have significant temporal shift, spatial mismatch, and amplitude inconsistency, compared with true 3D multiples. Adaptive multiple subtraction based on 2D blind separation of convolved mixtures (BSCM) has been proposed to estimate the 2D matching filter in a single gather. To improve the flexibility of the adaptive multiple subtraction for the inconsistencies between the 2D predicted multiples and true 3D multiples, we evaluated the adaptive multiple subtraction as a problem of 3D BSCM. In the proposed method, the predicted multiples were modeled as the convolution of the true multiples with a 3D kernel, whose third dimension is in the gather direction. By maximizing the non-Gaussianity of the estimated primaries, the iterative reweighted least-squares algorithm was exploited to obtain the 3D matching filter, which is the inverse of the 3D kernel. To avoid the possible overfitting problem introduced by the 3D matching filter, the proposed method fit several seismic gathers using one 3D matching filter. In addition, by using the non-Gaussian maximization criterion, the proposed method alleviated the orthogonality assumption used by the least-squares subtraction method. Furthermore, the proposed method can eliminate the temporal and spatial mismatches between the 2D predicted multiples and true 3D multiples better than the 2D BSCM subtraction method. Tests on synthetic and field data sets demonstrated the effectiveness of the 3D BSCM subtraction method.
Seismic characterization of a Mississippi Lime resource play in Osage County, Oklahoma, USA
Authors: Dowdell Benjamin L. , Kwiatkowski J. Tim , Marfurt Kurt J.
Published: October 2013

With the advent of horizontal drilling and hydraulic fracturing in the Midcontinent, USA, fields once thought to be exhausted are now experiencing renewed exploitation. However, traditional Midcontinent seismic analysis techniques no longer provide satisfactory reservoir characterization for these unconventional plays; new seismic analysis methods are needed to properly characterize these radically innovative play concepts. Time processing and filtering is applied to a raw 3D seismic data set from Osage County, Oklahoma, paying careful attention to velocity analysis, residual statics, and coherent noise filtering. The use of a robust prestack structure-oriented filter and spectral whitening greatly enhances the results. After prestack time migrating the data using a Kirchhoff algorithm, new velocities are picked. A final normal moveout correction is applied using the new velocities, followed by a final prestack structure-oriented filter and spectral whitening. Simultaneous prestack inversion uses the reprocessed and time-migrated seismic data as input, along with a well from within the bounds of the survey. With offsets out to 3048 m and a target depth of approximately 880 m, we can invert for density in addition to P- and S-impedance. Prestack inversion attributes are sensitive to lithology and porosity while surface seismic attributes such as coherence and curvature are sensitive to lateral changes in waveform and structure. We use these attributes in conjunction with interpreted horizontal image logs to identify zones of high porosity and high fracture density.
Azimuthal variations in attributes for induced fracture detection in the Barnett Shale
Authors: Trumbo Amanda , Rich Jamie P.
Published: October 2013

Wide azimuth seismic data acquisition has become standard in many plays where azimuthal characterization of fractures or stress is important for fully understanding reservoir behavior. Usually, the desire is to image preexisting fracture networks, but, in artificially stimulated reservoirs, it is also desirable to understand the fracture state after completion. To characterize the induced fractures in a heavily drilled area of the Barnett Shale, a wide azimuth survey was acquired and processed to generate four separate azimuthal stacks. Attributes exploiting variations in amplitude and waveform were independently calculated for each azimuthal stack. Azimuthal variations in the attributes were then quantified through ellipse fitting. The attributes with the most statistical significance in azimuthal variability were those related to frequency such as the wavelet dominant frequency. These attributes were consistent with each other but show a wide distribution over azimuths across the survey. In addition, random distribution of orientations within the Barnett shale compared to the over and underlying Marble Falls and Viola Limestones indicate a difference in orientation for the induced as opposed to preexisting fractures. With the ability to map the induced fractures, it becomes feasible to take an intelligent approach to planning infill locations to avoid the previously fractured areas.
Black/Feminist Futures: Reading Beauvoir inBlack Skin, White Masks
Authors: Adkins Amey Victoria
Published: October 2013

While Simone de Beauvoir and Frantz Fanon are icons of the French existential movement—each being the influential progenitors of feminist theory and postcolonial studies, respectively—their names, lives, and works are rarely examined in concert. This essay argues for the intertextuality of The Second Sex and Black Skin, White Masks as inextricably bound discourses on subject formation and the other. Via close reading, I address the long-standing citational elision of Beauvoir from Fanon’s analysis of alienation, with particular address to the famous “Look! A Negro!” scene. Through this analysis I point out the question of Fanon’s voicing of the self toward the white male intellectual figured through Jean-Paul Sartre, which marks the question of citational practice as particular to feminist and critical race concerns, particularly in addressing the black woman. Drawing on Clare Hemmings’s notion of recitation, I read theologically Fanon’s and Beauvoir’s respective turns to liberation and as such consider the critical-constructive possibilities for black and feminist futures in viewing these works of Beauvoir and Fanon as kindred texts.