bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of microbial diversity determined with the same variable tag sequence extracted from two different PCR amplicons
Authors: He Yan , Zhou Ben-Jie , Deng Guan-Hua , Jiang Xiao-Tao , Zhang Hai , Zhou Hong-Wei 
Published: September 2013

Abstract

Background
Deep sequencing of the variable region of 16S rRNA genes has become the predominant tool for studying microbial ecology. As sequencing datasets have accumulated, meta-analysis of sequences obtained with different variable 16S rRNA gene targets and by different sequencing methods has become an intriguing prospect that remains to be evaluated experimentally.

Results
We amplified a group of fecal samples using both V4F-V6R and V6F-V6R primer sets, excised the same V6 fragment from the two sets of Illumina sequencing data, and compared the resulting data in terms of the α-diversity, β-diversity, and community structure. Principal component analysis (PCA) comparing the microbial community structures of different datasets, including those with simulated sequencing errors, was very reliable. Procrustes analysis showed a high degree of concordance between the different datasets for both abundance-weighted and binary Jaccard distances (P < 0.05), and a meta-analysis of individual datasets resulted in similar conclusions. The Shannon’s diversity index was consistent as well, with comparable values obtained for the different datasets and for the meta-analysis of different datasets. In contrast, richness estimators (OTU and Chao) varied significantly, and the meta-analysis of richness estimators was also biased. The community structures of the two datasets were obviously different and led to significant changes in the biomarkers identified by the LEfSe statistical tool.

Conclusions
Our results suggest that beta-diversity analysis and Shannon’s diversity are relatively reliable for meta-analysis, while community structures and biomarkers are less consistent. These results should be useful for future meta-analyses of microbiomes from different data sources.
Pre-existing Schistosoma japonicum infection alters the immune response to Plasmodium berghei infection in C57BL/6 mice
Authors: Wang Mei-lian , Cao Ya-ming , Luo En-jie , Zhang Ying , Guo Ya-jun 
Published: September 2013

Abstract

Background
Since helminths and malaria parasites are often co-endemic, it is important to clarify the immunoregulatory mechanism that occurs during the process of co-infection. A previous study confirmed that dendritic cells (DCs) are involved in the establishment and regulation of the T-cell-mediated immune response to malaria infection. In the current study, distinct response profiles for splenic DCs and regulatory T cell (Treg) responses were assessed to evaluate the effects of a pre-existing Schistosoma japonicum infection on malaria infection.

Methods
Malaria parasitaemia, survival rate, brain histopathology and clinical experimental cerebral malaria (ECM) were assessed in both Plasmodium berghei ANKA-mono-infected and S. japonicum-P. berghei ANKA-co-infected mice. Cell surface/intracellular staining and flow cytometry were used to analyse the level of splenic DC subpopulations, toll-like receptors (TLRs), DC surface molecules, Tregs (CD4+CD25+Foxp3+), IFN-γ/IL-10-secreting Tregs, and IFN-γ+/IL-10+-Foxp3-CD4+ T cells. IFN-γ, IL-4, IL-5, IL-10 and IL-13 levels were determined in splenocyte supernatants using enzyme-linked immunosorbent assay (ELISA).

Results
The co-infected mice had significantly higher malaria parasitaemia, compared with the mono-infected mice, on days 2, 3, 7 and 8 after P. berghei ANKA infection. M ono-infected mice had a slightly lower survival rate, while clinical ECM symptoms, and brain pathology, were significantly more severe during the period of susceptibility to ECM. On days 5 and 8 post P. berghei ANKA infection, co-infected mice had significantly lower levels of CD11c+CD11b+, CD11c+CD45R/B220+, CD11c+TLR4+, CD11c+TLR9+, CD11c+MHCII+, CD11c+CD86+, IFN-γ-secreting Tregs, and IFN-γ+Foxp3-CD4+ T cells in single-cell suspensions of splenocytes when compared with P. berghei ANKA-mono-infected mice. Co-infected mice also had significantly lower levels of IFN-γ and higher levels of IL-4, IL-5, and IL-13 in splenocyte supernatants compared to mono-infected mice. There were no differences in the levels of IL-10-secreting Tregs or IL-10+Foxp3-CD4+ T cells between co-infected and mono-infected mice.

Conclusions
A Tregs-associated Th2 response plays an important role in protecting against ECM pathology. Pre-existing S. japonicum infection suppressed TLR ligand-induced DC maturation and had an anti-inflammatory effect during malaria infection not only by virtue of its ability to induce Th2 responses, but also by directly suppressing the ability of DC to produce pro-inflammatory mediators.
Homology modeling and ligand docking of Mitogen-activated protein kinase-activated protein kinase 5 (MK5)
Authors: Lindin Inger , Wuxiuer Yimingjiang , Kufareva Irina , Abagyan Ruben , Moens Ugo , Sylte Ingebrigt , Ravna Aina Westrheim 
Published: September 2013

AbstractBackgroundMitogen-activated protein kinase-activated protein kinase 5 (MK5) is involved in one of the major signaling pathways in cells, the mitogen-activated protein kinase pathway. MK5 was discovered in 1998 by the groups of Houng Ni and Ligou New, and was found to be highly conserved throughout the vertebrates. Studies, both in vivo and in vitro, have shown that it is implicated in tumor suppression as well as tumor promotion, embryogenesis, anxiety, locomotion, cell motility and cell cycle regulation.MethodsIn order to obtain a molecular model of MK5 that can be used as a working tool for development of chemical probes, three MK5 models were constructed and refined based on three different known crystal structures of the closely related MKs; MK2 [PDB: 2OZA and PDB: 3M2W] and MK3 [PDB: 3FHR]. The main purpose of the present MK5 molecular modeling study was to identify the best suited template for making a MK5 model. The ability of the generated models to effectively discriminate between known inhibitors and decoys was analyzed using receiver operating characteristic (ROC) curves.ResultsAccording to the ROC curve analyzes, the refined model based on 3FHR was most effective in discrimination between known inhibitors and decoys.ConclusionsThe 3FHR-based MK5 model may serve as a working tool for development of chemical probes using computer aided drug design. The biological function of MK5 still remains elusive, but its role as a possible drug target may be elucidated in the near future.
Dengue 2 infection of HepG2 liver cells results in endoplasmic reticulum stress and induction of multiple pathways of cell death
Authors: Thepparit Chutima , Khakpoor Atefeh , Khongwichit Sarawut , Wikan Nitwara , Fongsaran Chanida , Chingsuwanrote Pimjai , Panraksa Patcharee , Smith Duncan R 
Published: September 2013

AbstractBackgroundA number of studies have implicated the direct involvement of the liver in dengue virus (DENV) infection, and it has been widely shown that liver cells subsequently undergo apoptosis. The mechanism by which liver cells undergo apoptosis in response to DENV infection remains unclear. To provide further information on the mechanism of apoptosis in DENV infected liver cells, HepG2 cells were infected with DENV 2 and analyzed for the induction of ER stress, apoptosis and autophagy.ResultsIn response to DENV infection, HepG2 cells showed the induction of both the ER resident unfolded protein response as well as the Noxa/PUMA stress response pathways. Proteolytic activation of caspases 4, 7, 8 and 9 was observed as well as changes in mitochondrial transmembrane potential. Increased monodansylcadaverine staining was observed in DENV infected cells, consistent with the previously reported induction of autophagy.ConclusionsThese results are consistent with a model in which the induction of multiple ER stress pathways is coupled with the induction of multiple cell death pathways as a mechanism to ensure the removal of infected liver cells from the system.
Time course of soluble P-selectin and von Willebrand factor levels in trauma patients: a prospective observational study
Authors: Tang Ning , Yin Shiyu , Sun Ziyong , Pan Yingying 
Published: September 2013

Abstract

Background
Coagulopathy often develops in patients with serious trauma and is correlated with the clinical outcome. The contribution of platelet activity and endothelial dysfunction to trauma-induced coagulopathy remain to be defined. The purpose of this study was to investigate the time courses of soluble P-selectin (sPsel, an index of platelet activation) and von Willebrand factor (VWF, an index of endothelial dysfunction) in trauma patients and elucidate their relationship to coagulation parameter levels, the presence of coagulopathy, and patient outcome.

Methods
This prospective observational study, which took place in a university hospital intensive care unit (ICU), included 82 severely injured trauma patients. The sPsel, VWF antigen, protein C, and factor VII levels were measured and routine coagulation tests were performed upon admission to ICU and daily within the first week. The 30-day mortality rate was also determined.

Results
Thirty-seven (45.1%) patients developed coagulopathy upon admission to the ICU, and the 30-day mortality rate was 20.7% (n = 17). Both the admission sPsel and VWF levels were lower in patients with coagulopathy than in those without (p < 0.05) and were significantly correlated with the protein C and factor VII levels, respectively (all p < 0.05). The VWF levels were lower during the first 3 days and higher on day 7 after admission in nonsurvivors than in survivors (all p < 0.05). No significant differences in sPsel levels were found between nonsurvivors and survivors on each day during the first week.

Conclusion
In severely injured trauma patients in the ICU, lower levels of sPsel and VWF on admission were associated with the presence of coagulopathy and might not predict a better outcome. An increase in the VWF level at the end of the first week after admission to ICU was associated with increased 30-day mortality.
Association between radiological findings and severity of community-acquired pneumonia in children
Authors: Patria Maria Francesca , Longhi Benedetta , Lelii Mara , Galeone Carlotta , Pavesi Maria Angela , Esposito Susanna 
Published: September 2013

Abstract

Background
There are few published data concerning radiological findings and their relationship with community-acquired pneumonia (CAP) severity. The aim if this study was to assess radiographic findings in children with CAP of different severity in order to evaluate whether some parameters are associated with severe CAP.

Methods
We analysed the characteristics of parenchymal densities in 335 chest radiographs of otherwise healthy children (173 males; mean age ± standard deviation, 7.5 ± 4.5 years) admitted to our Emergency Room for CAP. Upon admission, chest radiographs were obtained in the two standard projections, and the children with severe or mild/moderate CAP were compared in order to identify any correlations between CAP severity and the radiological findings.

Results
Seventy-six of the 335 enrolled children (22.7%) fulfilled the criteria for severe CAP. In comparison with the children with mild/moderate CAP, in severe CAP there was a significantly greater frequency of a bilateral multifocal distribution (p = 0.01), the simultaneous involvement of ≥3 sites (p = 0.007), and the involvement of the right hilum (p = 0.02). The same results were confirmed in the multiple logistic regression model.

Conclusions
This study shows that radiological findings such as a multifocal bilateral distribution, the simultaneous involvement of at least three sites, and right hilar consolidation are associated with severe CAP in otherwise healthy children, and could be considered markers of disease severity in children with CAP.
The tumor suppressor gene DAPK2 is induced by the myeloid transcription factors PU.1 and C/EBPα during granulocytic differentiation but repressed by PML-RARα in APL
Authors: Humbert Magali , Federzoni Elena A , Britschgi Adrian , Schläfli Anna M , Valk Peter J M , Kaufmann Thomas , Haferlach Torsten , Behre Gerhard , Simon Hans-Uwe , Torbett Bruce E , Fey Martin F , Tschan Mario P 
Published: September 2013

ABSTRACTDAPK2 is a proapoptotic protein that is mostly expressed in the hematopoietic tissue. A detailed DAPK2 expression analysis in two large AML patient cohorts revealed particularly low DAPK2 mRNA levels in APL. DAPK2 levels were restored in APL patients undergoing ATRA therapy. PML-RARA is the predominant lesion in APL causing transcriptional repression of genes important for neutrophil differentiation. We found binding of PML-RARA and PU.1, a myeloid master regulator, to RARA and PU.1 binding sites in the DAPK2 promoter. Ectopic expression of PML-RARA in non-APL, as well as knocking down PU.1 in APL cells, resulted in a significant reduction of DAPK2 expression. Restoring DAPK2 expression in PU.1 knockdown APL cells partially rescued neutrophil differentiation, thereby identifying DAPK2 as a relevant PU.1 downstream effector. Moreover, low DAPK2 expression is also associated with C/EBPα-mutated AML patients, and we found C/EBPα-dependent regulation of DAPK2 during APL differentiation. In conclusion, we identified first inhibitory mechanisms responsible for the low DAPK2 expression in particular AML subtypes, and the regulation of DAPK2 by two myeloid transcription factors underlines its importance in neutrophil development.
Cost-effectiveness of injectable opioid treatmentv. oral methadone for chronic heroin addiction
Authors: Byford Sarah , Barrett Barbara , Metrebian Nicola , Groshkova Teodora , Cary Maria , Charles Vikki , Lintzeris Nicholas , Strang John 
Published: September 2013

BackgroundDespite evidence of the effectiveness of injectable opioid treatment compared with oral methadone for chronic heroin addiction, the additional cost of injectable treatment is considerable, and cost-effectiveness uncertain.AimsTo compare the cost-effectiveness of supervised injectable heroin and injectable methadone with optimised oral methadone for chronic refractory heroin addiction.MethodMultisite, open-label, randomised controlled trial. Outcomes were assessed in terms of quality-adjusted life-years (QALYs). Economic perspective included health, social services and criminal justice resources.ResultsIntervention costs over 26 weeks were significantly higher for injectable heroin (mean £8995 v. £4674 injectable methadone and £2596 oral methadone;P<0.0001). Costs overall were highest for oral methadone (mean £15805 v. £13410 injectable heroin and £10945 injectable methadone;P=n.s.) due to higher costs of criminal activity. In cost-effectiveness analysis, oral methadone was dominated by injectable heroin and injectable methadone (more expensive and less effective). At willingness to pay of £30 000 per QALY, there is a higher probability of injectable methadone being more cost-effective (80%) than injectable heroin.ConclusionsInjectable opioid treatments are more cost-effective than optimised oral methadone for chronic refractory heroin addiction. The choice between supervised injectable heroin and injectable methadone is less clear. There is currently evidence to suggest superior effectiveness of injectable heroin but at a cost that policy makers may find unacceptable. Future research should consider the use of decision analytic techniques to model expected costs and benefits of the treatments over the longer term.
Stimulated Thyroglobulin at Recombinant Human TSH-Aided Ablation Predicts Disease-free Status One Year Later
Authors: Melo Miguel , Costa Gracinda , Ribeiro Cristina , Carrilho Francisco , Martins Maria João , da Rocha Adriana Gaspar , Sobrinho-Simões Manuel , Carvalheiro Manuela , Soares Paula 
Published: September 2013

Context:Thyroglobulin (Tg) levels measured at the time of remnant ablation after thyroid hormone withdrawal (THW) were shown to have prognostic value in predicting disease-free status.Objectives:Our objectives were to determine whether stimulated Tg levels, measured at the time of remnant ablation performed under recombinant human TSH (rhTSH) stimulation, has value in predicting absence of detectable disease 1 year after radioiodine therapy and to compare the results obtained with this approach with a cohort of patients submitted to ablation after THW.Design:This was a prospective observational study.Setting and Patients:The study included 293 consecutive patients treated for a differentiated thyroid carcinoma with no initial evidence of distant metastasis. All patients were submitted to a total or near-total thyroidectomy, followed by ablation either under rhTSH (n = 151) or endogenous TSH stimulation (n = 142). Patients with positive Tg antibodies were excluded.Main Outcome Measures:The predictive value of Tg at ablation was assessed by receiver operating characteristic curve analysis.Results:In the rhTSH group, 96 patients (73.3%) were considered disease-free at 1 year. Stimulated Tg at ablation after rhTSH was found to be an independent prognostic indicator of disease persistence 12 months later. The highest-accuracy cutoff value for absence of detectable disease was defined as 7.2 ng/mL, with a negative predictive value of 90%. In the THW group, Tg at ablation also proved to have independent predictive value. Using the same threshold (7.2 ng/mL), the negative predictive value of Tg was 95% in the THW group.Conclusions:When rhTSH was used, stimulated Tg at ablation had independent predictive value for disease-free status 1 year later. A low stimulated Tg at rhTSH-aided ablation may be considered a favorable prognosis factor.
Reduced Serum Concentrations of Carboxylated and Undercarboxylated Osteocalcin Are Associated With Risk of Developing Type 2 Diabetes Mellitus in a High Cardiovascular Risk Population: A Nested Case-Control Study
Authors: Díaz-López Andrés , Bulló Mònica , Juanola-Falgarona Marti , Martínez-González Miguel A. , Estruch Ramón , Covas Maria-Isabel , Arós Fernando , Salas-Salvadó Jordi 
Published: September 2013

Context and Objective:
Because it has been suggested that osteocalcin (OC), an osteoblast-derived hormone, is a new link between bone and glucose metabolism, we tested whether serum carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC) levels are independently associated with the development of type 2 diabetes in subjects at high cardiovascular risk.

Design, Setting, and Participants:
A prospective, nested case-control study was conducted using data from the Prevención con Dieta Mediterránea (PREDIMED) study. We included 153 case subjects with newly diagnosed diabetes and 306 individually matched control subjects free of diabetes identified during a mean 5-year follow-up. Conditional logistic regression models were used to estimate matched odds ratios for incident diabetes according to categories of both forms of OC measured by ELISAs.

Results:
Baseline serum concentrations of both forms of OC were significantly lower in case subjects than in control subjects. In subjects with incident cases of diabetes, concentrations of cOC, but not of ucOC, were inversely and significantly associated with homeostasis model assessment of insulin resistance levels (β = −0.335) and with fasting glucose concentrations (β = −0.044) in control subjects, independent of other relevant confounders. In the conditional logistic model that took into account the matching factors, the odds ratios for diabetes incidence in the lowest vs the highest tertile of cOC and ucOC were 2.03 (95% confidence interval, 1.32–3.13) and 1.88 (1.23–2.85), respectively. Further adjustment for family history of diabetes, lifestyle, and other confounding factors did not appreciably change the magnitude of these associations.

Conclusion:
In a population at high cardiovascular risk, low concentrations of serum cOC and ucOC were strongly associated with an increased risk of incident diabetes.
Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen
Authors: Staudinger Lisa A. , Spano Stephen J. , Lee Wilson , Coelho Nuno , Rajshankar Dhaarmini , Bendeck Michelle P. , Moriarty Tara , McCulloch Christopher A. 
Published: September 2013

SummaryCollagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling.
Unique properties of Drosophila spermatocyte primary cilia
Authors: Riparbelli Maria Giovanna , Cabrera Oscar A. , Callaini Giuliano , Megraw Timothy L. 
Published: September 2013

Summary
The primary cilium is an essential organelle required for animal development and adult homeostasis that is found on most animal cells. The primary cilium contains a microtubule-based axoneme cytoskeleton that typically grows from the mother centriole in G0/G1 phase of the cell cycle as a membrane-bound compartment that protrudes from the cell surface. A unique system of bidirectional transport, intraflagellar transport (IFT), maintains the structure and function of cilia. While the axoneme is dynamic, growing and shrinking at its tip, at the same time it is very stable to the effects of microtubule-targeting drugs. The primary cilia found on Drosophila spermatocytes diverge from the general rules of primary cilium biology in several respects. Among these unique attributes, spermatocyte cilia assemble from all four centrioles in an IFT-independent manner in G2 phase, and persist continuously through two cell divisions. Here, we show that Drosophila spermatocyte primary cilia are extremely sensitive to microtubule-targeting drugs, unlike their mammalian counterparts. Spermatocyte cilia and their axonemes fail to assemble or be maintained upon nocodazole treatment, while centriole replication appears unperturbed. On the other hand, paclitaxel (Taxol), a microtubule-stabilizing drug, disrupted transition zone assembly and anchoring to the plasma membrane while causing spermatocyte primary cilia to grow extensively long during the assembly/elongation phase, but did not overtly affect the centrioles. However, once assembled to their mature length, spermatocyte cilia appeared unaffected by Taxol. The effects of these drugs on axoneme dynamics further demonstrate that spermatocyte primary cilia are endowed with unique assembly properties.