bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased ID4 expression, accompanied by mutant p53 accumulation and loss of BRCA1/2 proteins in triple‐negative breast cancer, adversely affects survival
Authors: Thike Aye A. , Tan Puay H. , Ikeda Murasaki , Iqbal Jabed 
Published: August 2015

AimsBreast cancer 1 (BRCA1) expression is down‐regulated in a significant proportion of non‐hereditary breast cancers, in the absence of any mutation. This phenomenon is more pronounced in oestrogen (ER)‐negative tumours. Recent studies have suggested that inhibitor of DNA binding 4 (ID4), as well as p53, participate in the transcriptional regulation of BRCA1.MethodsImmunohistochemical expression of ID4, BRCA1, BRCA2 and p53 in 699 women with triple‐negative breast cancer was investigated using tissue microarrays. The prognostic role of these biomarkers was also evaluated. Survival outcomes were estimated with the Kaplan–Meier method and compared between groups with log‐rank statistics.ResultsLoss of BRCA1 and BRCA2 expression and overexpression of ID4 and p53 was observed in 75%, 90%, 95% and 66% of tumours, respectively. ID4 expression was increased in higher tumour grade (P < 0.001) and was associated significantly with basal‐like subtype (P < 0.001), BRCA2 down‐regulation (P = 0.037) and p53 accumulation (P < 0.001). Patients with strong ID4 expression displayed worse disease‐free survival in both triple‐negative breast cancers (P = 0.041) and basal‐like triple‐negative breast cancers (P = 0.026).ConclusionThere is frequent ID4 expression and concomitant loss of BRCA proteins in triple‐negative breast cancer. We hypothesize that strong ID4 expression could be useful as a prognostic marker in triple‐negative breast cancer, predicting early tumour recurrence.
The phylogeography of the rodent genus Malacomys suggests multiple Afrotropical Pleistocene lowland forest refugia
Authors: Bohoussou Kouakou Hilaire , Cornette Raphael , Akpatou Bertin , Colyn Marc , Kerbis Peterhans Julian , Kennis Jan , Šumbera Radim , Verheyen Erik , N'Goran Eliézer , Katuala Pionus , Nicolas Violaine 
Published: August 2015

AbstractAimThis study aims to reconstruct the evolutionary history of the African rodent genus Malacomys and to identify factors driving diversification within this genus.LocationAfrican tropical lowland forest.MethodsAnalyses were based on sampling representatives from most of the known geographical range of the genus. We assessed genetic structure and historical biogeography using a combination of mitochondrial and nuclear markers. Morphological differences between lineages were analysed using a geometric morphometric approach.ResultsThree species of Malacomys are recognized within the genus. Two are endemic to West Africa, and one is endemic to Central Africa. Our analyses reveal a strong phylogeographical structure with 13 lineages, most of them allopatric or parapatric. A complex biogeographical history, including dispersal–vicariance events, explains the current genetic structure of Malacomys. Discrete divergence events within the genus are dated to the mid‐Pliocene (3.7 Ma, 95% range: 2.4–5.2 Ma) and the Pleistocene (less than 1.9 Ma, with most events less than 1 Ma). Morphological variation is partly congruent with genetic structure and may indicate local adaptations.Main conclusionsClimatic oscillations, which led to periodic fragmentation of the forest habitat, seem to be the major driver of diversification within this genus. Our results support the existence of multiple small, rather than a few large, forest refugia during glacial maxima. Rivers have played a significant role in shaping boundaries of several regional haplogroups, either by promoting diversification or by preventing secondary contact between previously isolated lineages.
Tph2 gene deletion enhances amphetamine‐induced hypermotility: effect of 5‐HT restoration and role of striatal noradrenaline release
Authors: Carli Mirjana , Kostoula Chrysaugi , Sacchetti Giuseppina , Mainolfi Pierangela , Anastasia Alessia , Villani Claudia , Invernizzi Roberto William 
Published: August 2015

AbstractVariants of tryptophan hydroxylase‐2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5‐HT), have been associated with neuropsychiatric disorders, substance abuse and addiction. This study assessed the effect of Tph2 gene deletion on motor behavior and found that motor activity induced by 2.5 and 5 mg/kg amphetamine was enhanced in Tph2−/− mice. Using the in vivo microdialysis technique we found that the ability of amphetamine to stimulate noradrenaline (NA) release in the striatum was reduced by about 50% in Tph2−/− mice while the release of dopamine (DA) was not affected. Tph2 deletion did not affect the release of NA and DA in the prefrontal cortex. The role of endogenous 5‐HT in enhancing the effect of amphetamine was confirmed showing that treatment with the 5‐HT precursor 5‐hydroxytryptophan (10 mg/kg) restored tissue and extracellular levels of brain 5‐HT and the effects of amphetamine on striatal NA release and motor activity in Tph2−/− mice. Treatment with the NA precursor dihydroxyphenylserine (400 mg/kg) was sufficient to restore the effect of amphetamine on striatal NA release and motor activity in Tph2−/− mice. These findings indicate that amphetamine‐induced hyperactivity is attenuated by endogenous 5‐HT through the inhibition of striatal NA release. Tph2−/− mice may be a useful preclinical model to assess the role of 5‐HT‐dependent mechanisms in the action of psychostimulants.
image
Acute sensitivity to the motor effects of amphetamine has been associated to increased risk of psychostimulant abuse. Here, we show that deletion of Tph2, the gene responsible for brain 5‐HT synthesis, enhances the motor effect of amphetamine in mice through the inhibition of striatal NA release. This suggests that Tph2−/− mice is a useful preclinical model to assess the role of 5‐HT‐dependent mechanisms in psychostimulants action. Tph2, tryptophan hydroxylase‐2.
Functional and homeostatic defects of regulatory T cells in patients with coronary artery disease
Authors: Hasib L. , Lundberg A. K. , Zachrisson H. , Ernerudh J. , Jonasson L. 
Published: August 2015

AbstractObjectiveRegulatory T cells (Tregs) are considered atheroprotective, and low levels have been associated with the acute coronary syndrome (ACS), particularly non‐ST elevation (NSTE)‐ACS. However, the functional properties as well as homeostasis of Tregs are mainly unknown in coronary artery disease (CAD). Here, we investigated the composition and functional properties of naïve (n) and memory (m)Tregs in patients with NSTE‐ACS and in patients 6–12 months post‐ACS.MethodsBased on the expression of CD25, FOXP3, CD127, CD45RA, CD39 and CTLA‐4, Treg subsets were defined by flow cytometry in whole blood or isolated CD4+ T cells. The functional properties of nTregs and mTregs were examined in terms of proliferative capacity and modulation of cytokine secretion. To understand the potential consequences of Treg defects, we also investigated correlations with lipopolysaccharide (LPS)‐induced cytokine secretion and ultrasound‐defined carotid atherosclerosis.ResultsBoth NSTE‐ACS and post‐ACS patients exhibited reduced levels of nTregs (P < 0.001) compared with healthy control subjects, but without compensatory increases in mTregs. Both nTregs and mTregs from patients showed significantly lower replicative rates and impaired capacity to modulate T‐cell proliferation and secretion of interferon‐gamma and IL‐10. The Treg defect was also associated with LPS‐induced cytokine secretion and increased burden of carotid atherosclerosis.ConclusionOur results demonstrate a functional and homeostatic Treg defect in patients with NSTE‐ACS and also in stabilized patients 6–12 months after ACS. Moreover, this defect was associated with a subclinical proinflammatory and atherogenic state. We believe that the failure to preserve Treg function and homeostasis reflects a need for immune‐restoring strategies in CAD.
Alligator osteoderms as a source of labile calcium for eggshell formation
Authors: Dacke C. G. , Elsey R. M. , Trosclair P. L. , Sugiyama T. , Nevarez J. G. , Schweitzer M. H. 
Published: August 2015

AbstractThe calcium (Ca) demand on alligators in active reproduction is significant, yet the source of this additional Ca is unclear. Three possible sources for Ca mobilization are endolymphatic deposits, as in anurans and some lizards; short‐lived skeletal medullary bone or analogous deposits, as in birds; or some other source such as the osteoderm layer of the integument or simply mobilization of structural bone. Here, we investigate possible extra‐skeletal sources for labile Ca in the reproducing alligator, including endolymphatic Ca deposits, by analogy with anuran amphibian and some reptiles and integumentary osteodermal (scale) Ca deposits. We conducted X‐ray image analyses of skulls for the presence of significant endolymphatic Ca deposits. We also examined dermal bone of scutes (osteoderm, scales) from the dorsal integument using both X‐ray and histological analyses. Tissues from reproducing females containing mature but unovulated follicles were compared with those from specimens that had nested (laid eggs) or contained eggs within the oviduct at advanced stages of calcification. A small number of immature specimens and an adult male were also compared. No clear differences were observed in endolymphatic deposits between pre‐ and post‐ovulatory specimens. Scute (osteoderm) X‐ray density was significantly greater in females with ripe ovarian follicles compared with those that had recently laid (nested) or contained heavily calcified eggs within their oviducts. The latter groups also showed histological evidence of scute resorption compared with the former, suggesting that the scutes play a role in Ca storage during egglay.
Changes in temporomandibular joint morphology in class II patients treated with fixed mandibular repositioning and evaluated through 3D imaging: a systematic review
Authors: Al‐Saleh M. A. Q. , Alsufyani N. , Flores‐Mir C. , Nebbe B. , Major P. W. 
Published: August 2015

AbstractTo estimate the effects of skeletal class II malocclusion treatment using fixed mandibular repositioning appliances on the position and morphology of the temporomandibular joint (TMJ). Two independent reviewers performed comprehensive electronic searches of MEDLINE, EMBASE, EBM reviews and Scopus (until May 5, 2015). The references of the identified articles were also manually searched. All studies investigating morphological changes of the TMJ articular disc, condyle and glenoid fossa with 3D imaging following non‐surgical fixed mandibular repositioning appliances in growing individuals with class II malocclusions were included in the analysis. Of the 269 articles initially reviewed, only 12 articles used magnetic resonance imaging and two articles used computed tomography (CT) or cone‐beam CT images. Treatment effect on condyle and glenoid fossa was discussed in eight articles. Treatment effect on TMJ articular disc position and morphology was discussed in seven articles. All articles showed a high risk of bias due to deficient methodology: inadequate consideration of confounding variables, blinding of image assessment, selection or absence of control group and outcome measurement. Reported changes in osseous remodelling, condylar and disc position were contradictory. The selected articles failed to establish conclusive evidence of the exact nature of TMJ tissue response to fixed mandibular repositioning appliances.
On the Path to Trade Liberalisation: Political Regimes in Trade Negotiations
Authors: Mölders Florian 
Published: August 2015

AbstractThe number of free trade agreements (FTA) has increased substantially since 1990 despite efforts to promote multilateral trade liberalisation. While there is evidence on the determinants of FTA formation, still little is known on the processing of trade agreements, particularly regarding the pre‐implementation duration. This paper fills the research gap by using event data on the negotiation, the signing and the implementation of trade agreements. Duration analysis is employed to examine the connection between regime types and the lengths of the negotiation and the ratification stages. The results support the claim that higher levels of democratisation are associated with shorter negotiations, while political constraints lead to delays. Moreover, the depth of an agreement matters: a higher number of WTO‐X and WTO+ provisions do not only prolong the negotiation stage, but also the subsequent ratification. Against the background of potential anticipation effects of trade agreements, these results are of interest for exporting firms that assess the timing of implementation.
International Transmission Mechanisms and Contagion in Housing Markets
Authors: Nanda Anupam , Yeh Jia‐Huey 
Published: August 2015

AbstractThis paper explores international transmission mechanism and its role in contagion effect in the housing markets across six major Asian cities. The analysis is based on the identification of house price diffusion effects through a global vector autoregressive (GVAR) model estimated using quarterly data for six major Asian cities (Hong Kong, Tokyo, Seoul, Singapore, Taipei and Bangkok) from 1991Q1 to 2011Q2. The empirical results indicate that the open economies heavily relying on international trade such as Singapore, Japan (Tokyo), Taiwan (Taipei) and Thailand (Bangkok) show positive correlations between the economy's openness and house prices, which is consistent with the Balassa–Samuelson hypothesis. Interestingly, some region‐specific conditions also appear to play important roles as determinants of house price movements, which may be driven by restrictive housing policies and demand–supply imbalances such as Singapore and Bangkok. These results are reasonably robust across several model specifications. The findings bear significant implications for formulation of investment strategy and public policies.
Evaluation of an immunochromatographic test for feline AB system blood typing
Authors: Spada Eva , Proverbio Daniela , Baggiani Luciana , Bagnagatti De Giorgi Giada , Perego Roberta , Ferro Elisabetta 
Published: August 2015

AbstractObjectiveTo determine the accuracy of an immunochromatographic cartridge (IC) test for blood typing feline type A, B, and AB blood samples.DesignProspective observational study.SettingUniversity teaching hospital.SamplesFifty‐one nonanemic and 19 anemic feline blood samples.InterventionsSamples were blood typed by both card agglutination (CA) and IC techniques. Discordant results were analyzed using a back‐typing technique for the presence of alloantibodies. Repeatability and reproducibility of the IC method were evaluated. Accuracy of the IC method was determined for feline whole blood anticoagulated with EDTA and citrate phosphate dextrose adenine (CPDA1), for feline‐packed RBCs with CPDA1 and saline adenine glucose‐mannitol, and for autoagglutinated and hemolytic samples. Accuracy of IC testing was determined for feline blood after room temperature, 4 ± 2, −20, and −80°C storage following 24, 48, 72, and 96 hours, and after 1, 2, 3, and 4 weeks of storage.Measurements and Main ResultsIn anemic and nonanemic samples the IC technique had a specificity, sensitivity, positive predictive value, and negative predictive value of 100% in detecting feline blood types A, B, and AB, outperforming a CA test. Results were repeatable and reproducible. Using IC it was possible to blood type samples anticoagulated with EDTA and CPDA1, packed RBC samples with CPDA1 and saline adenine glucose‐mannitol, autoagglutinated and hemolytic samples, and samples stored at 4 ± 2°C and at room temperature for up to 1 month.ConclusionsThe IC technique is an accurate assay for the identification of A, B, and AB blood types in anemic and nonanemic feline blood. It has a higher sensitivity and specificity than the CA test, and can be used in samples stored with common anticoagulants or preservative solutions used in feline transfusion medicine.
Systematic Review and Meta-analysis of Randomized Controlled Trials of Antibiotics and Antiseptics for Preventing Infection in People Receiving Primary Total Hip and Knee Prostheses
Authors: Voigt Jeffrey , Mosier Michael , Darouiche Rabih 
Published: August 2015

ABSTRACT
Infection rates in primary (first-time) major joint arthroplasty continue to be a significant issue. The effect of antibiotic and antiseptic prophylaxis on outcomes for this type of surgery has not been adequately reviewed. A systematic search of the main databases for randomized controlled trials (RCTs) evaluating antibiotics and antiseptics was conducted to evaluate the predetermined endpoints of infection, adverse events, costs, quality of life, and concentration levels of antibiotics. A meta-analysis using pooled effect estimates and fixed-effect and random-effect models of risk ratios (RR), calculated with 95% confidence intervals (CI), was utilized. Thirty (30) RCTs examined the effects of antibiotic and antiseptic prophylaxis on infections after primary total hip arthroplasty (THA) (total of 11,597 participants) and total knee arthroplasty (TKA) (total of 6,141 participants). For THA, preoperative systemic intravenous (i.v.) antibiotic prophylaxis may be effective in reducing the incidence of infection after THA from 6 months to ≥5 years. For TKA, there is no RCT evidence that antibiotics and/or antiseptics have any effect on infection rate. Preoperative systemic antibiotic prophylaxis in primary THA may be effective at reducing infection rate. There is no evidence that timing, route of administration, or concentration levels have an effect on reducing infections, adverse events, or costs in THA or TKA. Many of the trials included in this study were published in the 1980s and 1990s. Thus, it would be important to replicate a number of them based on current patient demographics and incidence of bacterial resistance.
Evaluation of Sulfobutylether-β-Cyclodextrin Exposure in a Critically Ill Patient Receiving Intravenous Posaconazole While Undergoing Continuous Venovenous Hemofiltration
Authors: Morris Amanda A. , Mueller Scott W. , Rower Joseph E. , Washburn Taylor , Kiser Tyree H. 
Published: August 2015

ABSTRACT
We present a 31-year-old female who had undergone an allogeneic bone marrow transplantation and who was started on intravenous posaconazole for pulmonary mycosis while undergoing continuous venovenous hemofiltration (CVVH). We performed steady-state pharmacokinetic evaluations for both posaconazole and sulfobutylether-β-cyclodextrin (SBECD). SBECD was effectively removed by CVVH, with observed exposure similar to that for patients with moderate renal impairment. Intravenous posaconazole at standard doses may be utilized in critically ill patients undergoing CVVH without significant risk of SBECD accumulation.
Primary Structural Variation in Anaplasma marginale Msp2 Efficiently Generates Immune Escape Variants
Authors: Graça Telmo , Paradiso Lydia , Broschat Shira L. , Noh Susan M. , Palmer Guy H. 
Published: August 2015

ABSTRACT

Antigenic variation allows microbial pathogens to evade immune clearance and establish persistent infection.
Anaplasma marginale
utilizes gene conversion of a repertoire of silent
msp2
alleles into a single active expression site to encode unique Msp2 variants. As the genomic complement of
msp2
alleles alone is insufficient to generate the number of variants required for persistence,
A. marginale
uses segmental gene conversion, in which oligonucleotide segments from multiple alleles are recombined into the expression site to generate a novel
msp2
mosaic not represented elsewhere in the genome. Whether these segmental changes are sufficient to evade a broad antibody response is unknown. We addressed this question by identifying Msp2 variants that differed in primary structure within the immunogenic hypervariable region microdomains and tested whether they represented true antigenic variants. The minimal primary structural difference between variants was a single amino acid resulting from a codon insertion, and overall, the amino acid identity among paired microdomains ranged from 18 to 92%. Collectively, 89% of the expressed structural variants were also antigenic variants across all biological replicates, independent of a specific host major histocompatibility complex haplotype. Biological relevance is supported by the following: (i) all structural variants were expressed during infection of a natural host, (ii) the structural variation observed in the microdomains corresponded to the mean length of variants generated by segmental gene conversion, and (iii) antigenic variants were identified using a broad antibody response that developed during infection of a natural host. The findings demonstrate that segmental gene conversion efficiently generates Msp2 antigenic variants.
Positive Effect of Carbon Sources on Natural Transformation in Escherichia coli: Role of Low-Level Cyclic AMP (cAMP)-cAMP Receptor Protein in the Derepression of
rpoS
Authors: Guo Mengyue , Wang Huanyu , Xie Nengbin , Xie Zhixiong 
Published: August 2015

ABSTRACT

Natural plasmid transformation of
Escherichia coli
is a complex process that occurs strictly on agar plates and requires the global stress response factor σ
S
. Here, we showed that additional carbon sources could significantly enhance the transformability of
E. coli
. Inactivation of phosphotransferase system genes (
ptsH
,
ptsG
, and
crr
) caused an increase in the transformation frequency, and the addition of cyclic AMP (cAMP) neutralized the promotional effect of carbon sources. This implies a negative role of cAMP in natural transformation. Further study showed that
crp
and
cyaA
mutations conferred a higher transformation frequency, suggesting that the cAMP-cAMP receptor protein (CRP) complex has an inhibitory effect on transformation. Moreover, we observed that
rpoS
is negatively regulated by cAMP-CRP in early log phase and that both
crp
and
cyaA
mutants show no transformation superiority when
rpoS
is knocked out. Therefore, it can be concluded that both the
crp
and
cyaA
mutations derepress
rpoS
expression in early log phase, whereby they aid in the promotion of natural transformation ability. We also showed that the accumulation of RpoS during early log phase can account for the enhanced transformation aroused by additional carbon sources. Our results thus demonstrated that the presence of additional carbon sources promotes competence development and natural transformation by reducing cAMP-CRP and, thus, derepressing
rpoS
expression during log phase. This finding could contribute to a better understanding of the relationship between nutrition state and competence, as well as the mechanism of natural plasmid transformation in
E. coli
.

IMPORTANCE
Escherichia coli
, which is not usually considered to be naturally transformable, was found to spontaneously take up plasmid DNA on agar plates. Researching the mechanism of natural transformation is important for understanding the role of transformation in evolution, as well as in the transfer of pathogenicity and antibiotic resistance genes. In this work, we found that carbon sources significantly improve transformation by decreasing cAMP. Then, the low level of cAMP-CRP derepresses the general stress response regulator RpoS via a biphasic regulatory pattern, thereby contributing to transformation. Thus, we demonstrate the mechanism by which carbon sources affect natural transformation, which is important for revealing information about the interplay between nutrition state and competence development in
E. coli
.