bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-Chain
N
-Acyl Amino Acid Synthases Are Linked to the Putative PEP-CTERM/Exosortase Protein-Sorting System in Gram-Negative Bacteria
Authors: Craig Jeffrey W. , Cherry Marisa A. , Brady Sean F. 
Published: August 2011

ABSTRACT

Clones that encode the biosynthesis of long-chain
N
-acyl amino acids are frequently recovered from activity-based screens of soil metagenomic libraries. Members of a diverse set of enzymes referred to as
N
-acyl amino acid synthases are responsible for the production of all metagenome-derived
N
-acyl amino acids characterized to date. Based on the frequency at which
N
-acyl amino acid synthase genes have been identified from metagenomic samples, related genes are expected to be common throughout the global bacterial metagenome. Homologs of metagenome-derived
N
-acyl amino acid synthase genes are scarce, however, within the sequenced genomes of cultured bacterial species. Toward the goal of understanding the role(s) played by
N
-acyl amino acids in environmental bacteria, we looked for conserved genetic features that are positionally linked to metagenome-derived
N
-acyl amino acid synthase genes. This analysis revealed that
N
-acyl amino acid synthase genes are frequently found adjacent to genes predicted to encode PEP-CTERM motif-containing proteins and, in some cases, other conserved elements of the PEP-CTERM/exosortase system. Although relatively little is known about the PEP-CTERM/exosortase system, its core components are believed to represent the putative Gram-negative equivalent of the LPXTG/sortase protein-sorting system of Gram-positive bacteria. During the course of this investigation, we were able to provide evidence that an uncharacterized family of hypothetical acyltransferases, which had previously been linked to the PEP-CTERM/exosortase system by bioinformatics, is a new family of
N
-acyl amino acid synthases that is widely distributed among the PEP-CTERM/exosortase system-containing
Proteobacteria
.
Evidence-Based Annotation of Transcripts and Proteins in the Sulfate-Reducing Bacterium Desulfovibrio vulgaris Hildenborough
Authors: Price Morgan N. , Deutschbauer Adam M. , Kuehl Jennifer V. , Liu Haichuan , Witkowska H. Ewa , Arkin Adam P. 
Published: August 2011

ABSTRACTWe used high-resolution tiling microarrays and 5′ RNA sequencing to identify transcripts inDesulfovibrio vulgarisHildenborough, a model sulfate-reducing bacterium. We identified the first nucleotide position for 1,124 transcripts, including 54 proteins with leaderless transcripts and another 72 genes for which a major transcript initiates within the upstream protein-coding gene, which confounds measurements of the upstream gene's expression. Sequence analysis of these promoters showed thatD. vulgarisprefers −10 and −35 boxes different from those preferred byEscherichia coli. A total of 549 transcripts ended at intrinsic (rho-independent) terminators, but most of the other transcripts seemed to have variable ends. We found low-level antisense expression of most genes, and the 5′ ends of these transcripts mapped to promoter-like sequences. Because antisense expression was reduced for highly expressed genes, we suspect that elongation of nonspecific antisense transcripts is suppressed by transcription of the sense strand. Finally, we combined the transcript results with comparative analysis and proteomics data to make 505 revisions to the original annotation of 3,531 proteins: we removed 255 (7.5%) proteins, changed 123 (3.6%) start codons, and added 127 (3.7%) proteins that had been missed. Tiling data had higher coverage than shotgun proteomics and hence led to most of the corrections, but many errors probably remain. Our data are available athttp://genomics.lbl.gov/supplemental/DvHtranscripts2011/.
Effect of school-based interventions on physical activity and fitness in children and adolescents: a review of reviews and systematic update
Authors: Kriemler S , Meyer U , Martin E , van Sluijs E M F , Andersen L B , Martin B W 
Published: August 2011

BackgroundSchool-based interventions are thought to be the most universally applicable and effective way to counteract low physical activity (PA) and fitness although there is controversy about the optimal strategy to intervene.Objectives The objective of this review was to summarise recent reviews that aimed to increase PA or fitness in youth and carry out a systematic review of new intervention studies.MethodsRelevant systematic reviews and original controlled and randomised controlled school-based trials with a PA or fitness outcome measure, a duration of ≥12 weeks, a sufficient quality and involvement of a healthy population aged 6–18 years that were published from 2007 to 2010 were included.ResultsIn these reviews, 47–65% of trials were found to be effective. The effect was mostly seen in school-related PA while effects outside school were often not observed or assessed.ConclusionsThe school-based application of multicomponent intervention strategies was the most consistent, promising strategy, while controversy existed regarding the effectiveness of family involvement, focus on healthy populations at increased risk or duration and intensity of the intervention. All 20 trials in the review update showed a positive effect on in-school, out-of-school or overall PA, and 6 of 11 studies showed an increase in fitness. Taking into consideration both assessment quality and public health relevance, multicomponent approaches in children including family components showed the highest level of evidence for increasing overall PA. This review confirms the public health potential of high quality, school-based PA interventions for increasing PA and possibly fitness in healthy youth.
Hollow spheroids beyond the invasive margin indicate the malignant potential of colorectal cancer
Authors: Tamura Koichi , Yokoyama Shozo , Ieda Junji , Takifuji Katsunari , Hotta Tsukasa , Matsuda Kenji , Oku Yoshimasa , Watanabe Takashi , Nasu Toru , Kiriyama Shigehisa , Yamamoto Naoyuki , Nakamura Yasushi , Shively John E , Yamaue Hiroki 
Published: August 2011

ObjectiveTumour budding formed by histologically undifferentiated cancer cells beyond the border of the tumour margin is associated with lymph node metastasis. However, hollow tumour nests, a possible histologically advanced phenotype of tumour budding, have not been discussed. We examined whether hollow spheroids exist beyond the border of the invasive margin and are associated with metastasis and prognosis. Moreover, we suggest that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) isoform balance is associated with hollow spheroid formation.MethodsImmunohistochemical analyses with CEACAM1 and M30 as an apoptosis marker were performed to examine the importance of hollow spheroid CEACAM1 expression and central cell apoptosis in hollow spheroid formation. The correlations between the presence of hollow spheroids beyond the invasive margin and the clinicopathological characteristics of 314 patients with colorectal cancer were retrospectively evaluated. A 3D culture with colorectal cancer cells transfected with CEACAM1 cDNA or shRNA was used to determine whether CEACAM1 isoform balance controls colorectal hollow spheroid formation.ResultsHollow spheroid formation accompanying central cell apoptosis was confirmed by M30 staining and serial section with CEACAM1 staining. Of the 314 patients, 96 (30.4%) were classified as having hollow spheroids. The presence of hollow spheroids is an independent risk factor for metastases and shorter survival. In 3D culture, CEACAM1 isoform balance modulated hollow spheroid formation of colorectal cancer cells.ConclusionsHollow spheroid formation beyond the border of the tumour margin in colorectal cancer is more important than tumour budding for the prediction of malignant potential.
HER2 gene amplification in patients with breast cancer with equivocal IHC results
Authors: Meijer Sybren L , Wesseling Jelle , Smit Vincent T , Nederlof Petra M , Hooijer Gerrit K J , Ruijter Henrique , Arends Jan Willem , Kliffen Mike , van Gorp Joost M , Sterk Lotus , van de Vijver Marc J 
Published: August 2011

AimsEquivocal human epidermal growth factor receptor 2 protein (HER2) (2+) immunohistochemistry (IHC) is subject to significant interobserver variation and poses a challenge in obtaining a definitive positive or negative test result. This equivocal test result group accounts for approximately 15% of all tumours, and for optimal guidance of HER2 targeted therapy, a further analysis of quantification of gene copy number and amplification status is needed for patients with early or metastatic breast cancer.Methods553 breast-cancer specimens with equivocal HER2 IHC(2+) test results were collected and subsequently centrally retested by chromogenic in situ hybridisation (CISH), and HER2 gene copy numbers per tumour cell nucleus were determined.ResultsUsing CISH, 77 of 553 equivocal HER2 IHC(2+) test result cases (13.9% of total) showed high levels of HER2 gene amplification (≥10.0 gene copies per nucleus), and 41 of 553 (7.4% of total) showed low-level HER2 gene amplification (6.0–9.9 gene copies per nucleus). In 73.6% of cases, no amplification of the HER2 gene was shown, and in only 4.9% of cases was an equivocal test result by CISH observed (4.0–5.9 gene copies per nucleus).ConclusionsTesting by CISH of all equivocal HER2 IHC(2+) test result provides a definitive guidance in HER2 targeted therapy in 95.1% of cases. A significant proportion (21.3%) of patients with equivocal IHC(2+) test results show amplification of the HER2 gene.
Abnormal spiral artery remodelling in the decidual segment during pregnancy: from histology to clinical correlation
Authors: Avagliano Laura , Bulfamante Gaetano Pietro , Morabito Alberto , Marconi Anna Maria 
Published: August 2011

IntroductionModification of the spiral arteries with loss of the muscular vascular wall, invaded by the trophoblasts, represents the goal of the physiological vascular adaptation during human implantation. When physiological vascular changes do not occur, an unfavourable evolution of gestation may develop as suggested by uterine biopsies studies.AimsTo evaluate the prevalence of the abnormal spiral arteries modification (ASAM) through the routine examination of placentas, to identify maternal predisposing factors and to examine the correlations between the histological lesion and pregnancy outcome.Methods1534 consecutive singleton pregnancies were retrospectively analysed. An extensive histological and clinical investigation was performed.ResultsASAM was present in 5.8% pregnancies. When compared with cases without ASAM, cases with ASAM exhibited a higher prevalence of pre-eclampsia (10% vs 2%), placental abruption (5.5% vs 0.3%), preterm premature rupture of membranes (7% vs 1.3%) and intrauterine fetal death (18% vs 2.2%). Multivariate analysis showed that the maternal body mass index represents the major maternal pregestational factor that can influence the prevalence of ASAM (OR=1.8, 95% CI 1.1 to 3 in cases with BMI>30 kg/m2).ConclusionThe abnormal modification of the decidual segment of the spiral arteries is identifiable at the time of the conventional histopathological placental evaluation and is associated with adverse pregnancy outcome. The identification of the cause of the unfavourable evolution of pregnancy is fundamental for parents, both for counselling and for prevention; the identification of ASAM in such pregnancies might provide additional valuable information.
Measuring interobserver variation in a pathology EQA scheme using weighted κ for multiple readers
Authors: Wright Karen C , Melia Jane , Moss Sue , Berney Dan M , Coleman Derek , Harnden Patricia 
Published: August 2011

BackgroundA Urological Pathology External Quality Assurance (EQA) Scheme in the UK has reported observer variation in the diagnosis and grading of adenocarcinoma in prostatic biopsies using basic κ statistics, which rate all disagreements equally.AimThe aim of this study is to use customised weighting schemes to report κ statistics that reflect the closeness of interobserver agreement in the prostate EQA scheme.MethodsA total of 83, 114 and 116 pathologists took part, respectively, in three web-based circulations and were classified as either expert or other readers. For analyses of diagnosis, there were 10, 8 and 8 cases in the three circulations, respectively. For analyses of Gleason Sum Score, only invasive cases were included, leaving 5, 5 and 6 cases, respectively. Analyses were conducted using customised weighting schemes with ‘pairwise-weighted’ κ for multiple readers.ResultsAnalysis of diagnosis for all circulations and all readers gave a composite κ value of 0.86 and pairwise-weighted κ (κp–w) value of 0.91, both regarded as ‘almost perfect’ agreement. This was due to the high proportion of responses that showed partial agreement. Analysis of Gleason Sum Score gaveκ=0.38 andκp–w=0.58 over all circulations and all readers, indicating that discrepancies occur at the boundary between adjacent grades and may not be as clinically significant as suggested by composite κ.ConclusionWeighted κ show higher levels of agreement than previously reported as they have the advantage of applying weighting, which reflects the relative importance of different types of discordance in diagnosis or grading. Agreement on grading remained low.
HIV testing in colposcopy and termination of pregnancy services: a missed opportunity?
Authors: Briggs Aparna , Partridge David G , Bates Sylvia 
Published: August 2011

IntroductionThe 2008 National HIV testing guidelines produced jointly by the British Association of Sexual Health and HIV, British HIV Association and British Infection Society recommend HIV testing for patients attending termination of pregnancy (TOP) services and patients diagnosed with cervical intraepithelial neoplasia (CIN) Grade 2 or above. The aim is to reduce the time between acquisition and diagnosis of HIV by encouraging testing in settings where patients present with indicator diseases. Benefits of earlier HIV diagnosis include improved survival, prevention of onward transmission, and optimisation of maternal health when planning pregnancy. There is evidence that HIV reduces the effectiveness of standard treatment for CIN 2/3 and cervical cancer. The experience of antenatal screening indicates that the majority of women accept HIV screening if it is offered as part of a package of care.MethodsThis retrospective case notes review of 60 HIV-positive women, diagnosed between 1 January 2006 and 31 July 2009, collected data on age, ethnicity, length of time in the UK, timing of HIV diagnosis and possible timing of acquisition relative to attendance at colposcopy or TOP services, CD4 count and symptoms at diagnosis and cervical cytology history.ResultsThe authors found that three (5%) women were diagnosed with CIN Grade 2 or above prior to HIV diagnosis; HIV testing at the time of TOP may have resulted in earlier diagnosis for three (5%) women. There was at least one missed opportunity for earlier diagnosis in five (8%) cases.ConclusionsThe authors suggest further work should be undertaken to establish HIV prevalence in TOP and colposcopy services and that HIV testing should become standard practice in the management of CIN 2/3 and cervical cancer.
MODELING SETTLEMENT PATTERNS IN REAL TERRITORIES
Authors: CARVALHO JOAQUIM , LOPES RUI L. , TOJO JOÃO 
Published: August 2011

This paper, describes an agent based model of the spreading of a population over a territory. The models aims at reproducing a distribution of settlements with statistical and spatial characteristics similar to a historically produced pattern. The model operates on a representation of a real territory, taking into account hydrography and relief. The two main goals are to obtain a rank size distribution of the size of settlements which corresponds to a power law (also known as the Zipf Law of settlements) and to place the settlements in the territory in patterns that are close to the real ones, in zones where settlements were the result of a long historical process. The goal of the project was to demonstrate that a set of relatively simple rules could produce a complex pattern, similar to the result of a long and complex historical process. Therefore, it is an assumed reductionist approach. Our conclusions show that a simple territorial logic, taking into account the quality of land, accessibility, population growth and migration preferences could reproduce Zipf distributions and interesting patterns of agent flow among the settlements created. However, achieving spatial patterns closer to the historical record needs an extra dimension involving field of sight. The best results were achieved by creating an artifical population which chooses to create settlements in places where a wide field of view exists of quality territory.
Transplantation of β-Endorphin Neurons into the Hypothalamus Promotes Immune Function and Restricts the Growth and Metastasis of Mammary Carcinoma
Authors: Sarkar Dipak K. , Zhang Changqing , Murugan Sengottuvelan , Dokur Madhavi , Boyadjieva Nadka I. , Ortigüela Maria , Reuhl Kenneth R. , Mojtehedzadeh Sepide 
Published: August 2011

Abstract
Neurobehavioral stress has been shown to promote tumor growth and progression and dampen the immune system. In this study, we investigated whether inhibiting stress hormone production could inhibit the development of mammary carcinoma and metastasis in a rat model of breast carcinogenesis. To enhance β-endorphin (BEP), the endogenous opioid polypeptide that boosts immune activity and decreases stress, we generated BEP neurons by in vitro differentiation from fetal neuronal stem cells and transplanted them into the hypothalami of rats subjected to breast carcinogenesis. BEP-transplanted rats displayed a reduction in mammary tumor incidence, growth, malignancy rate, and metastasis compared with cortical cells–transplanted rats. BEP neuron transplants also reduced inflammation and epithelial to mesenchymal transition in the tumor tissues. In addition, BEP neuron transplants increased peripheral natural killer (NK) cell and macrophage activities, elevated plasma levels of antiinflammatory cytokines, and reduced plasma levels of inflammatory cytokines. Antimetastatic effects along with stimulation of NK cells and macrophages could be reversed by treatment with the opiate antagonist naloxone, the β-receptor agonist metaproterenol, or the nicotine acetylcholine receptor antagonist methyllycaconitine. Together, our findings establish a protective role for BEP against the growth and metastasis of mammary tumor cells by altering autonomic nervous system activities that enhance innate immune function. Cancer Res; 71(19); 6282–91. ©2011 AACR.
Mechanism of the Mesenchymal–Epithelial Transition and Its Relationship with Metastatic Tumor Formation
Authors: Yao Dianbo , Dai Chaoliu , Peng Songlin 
Published: August 2011

Abstract
Cancer metastasis consists of a sequential series of events, and the epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET) are recognized as critical events for metastasis of carcinomas. A current area of focus is the histopathological similarity between primary and metastatic tumors, and MET at sites of metastases has been postulated to be part of the process of metastatic tumor formation. Here, we summarize accumulating evidence from experimental studies that directly supports the role of MET in cancer metastasis, and we analyze the main mechanisms that regulate MET or reverse EMT in carcinomas. Given the critical role of MET in metastatic tumor formation, the potential to effectively target the MET process at sites of metastasis offers new hope for inhibiting metastatic tumor formation. Mol Cancer Res; 9(12); 1608–20. ©2011 AACR.
Dietary Vitamin D and Vitamin D Receptor Level Modulate Epithelial Cell Proliferation and Apoptosis in the Prostate
Authors: Kovalenko Pavlo L. , Zhang Zhentao , Yu Jun-Ge , Li Yan , Clinton Steven K. , Fleet James C. 
Published: August 2011

Abstract
Low vitamin D (VD) status may increase prostate cancer risk but experimental evidence for this relationship is modest. We tested whether low VD status or VD receptor (VDR) deletion influences prostate epithelial cell (PEC) biology using intact mice, castrated mice, or castrated mice treated with testosterone propionate (TP, 2.5 mg/kg BW). PEC proliferation (Ki-67 staining) and apoptosis (TUNEL method) were determined in the anterior prostate (AP). In study 1, wild-type (WT) and TgAPT121 mice (a model of prostate intraepithelial neoplasia) were fed diets with 25, 200 (reference diet), or 10,000 IU VD/kg diet (as vitamin D3) prior to castration/repletion. Serum 25 hydroxyvitamin D levels were 26, 78, and 237 nmol/L in the three diet groups, respectively. Castration reduced proliferation and increased apoptosis in the AP while TP reversed these effects. Low VD diet increased proliferation in WT (+82%) and TgAPT121 (+24%) mice while it suppressed apoptosis in WT (−29%) and TgAPT121 (−37%) mice. This diet also increased the severity of prostate intraepithelial neoplastic lesions in the AP of intact TgAPT121 mice. In study 2, mice with PEC-specific VDR deletion (PEC VDR KO) were examined after castration/repletion. TUNEL staining was 60% lower in castrated PEC VDR KO mice compared with castrated WT mice. In castrated mice given TP, Ki-67 staining was 2-fold higher in PEC VDR KO compared with WT mice. Our data show that low diet VDR or VDR deletion provide a prostate environment that is permissive to early procarcinogenic events that enhance prostate cancer risk. Cancer Prev Res; 4(10); 1617–25. ©2011 AACR.
Proteomic Signature of Thrombin-Activated Platelets After In Vivo Nitric Oxide–Donor Treatment
Authors: Peña Esther , Padro Teresa , Molins Blanca , Vilahur Gemma , Badimon Lina 
Published: August 2011

Objective—
Growing insight into the antiplatelet properties of new nitric oxide (NO) donors has expanded their potential use in cardiovascular diseases. As such, we reported that oral administration of a new exogenous NO donor (LA419) induced significant inhibition of platelet deposition on damaged vascular wall without provoking hypotension in an in vivo experimental model. Thrombin is one of the major triggers of platelet deposition and thrombosis on injured vessels; however, the effects of NO on thrombin-induced platelet activation are not fully known. Here, our aim was to investigate the inhibitory effects of exogenous NO administration on the major changes in platelet proteins induced by thrombin.

Methods and Results—

Platelets were obtained from a group of swine orally treated with LA419 (0.9 mg kg
−1
) or placebo for 8 days. Washed platelets were incubated with thrombin (0.4 NIH U/mL). Platelet proteins were then sequentially extracted based on differential solubility and studied by two-dimensional electrophoresis, mass spectrometry (matrix-assisted laser desorption ionization/time of flight), Western blot, and confocal immunofluorescence. NO treatment abrogated thrombin effects on 24 proteins involved in actin assembly, signaling, and metabolic activity. NO treatment prevented thrombin-induced translocation of gelsolin, filamin, 14-3-3ζ, phosphatidylinositol 3-kinase-γ isoform, and growth factor receptor-bound protein 2 (Grb2).

Conclusion—
Our results show that exogenous NO donor treatment renders platelets less sensitive to thrombin activation and inhibits thrombosis by interfering with the platelet shape change machinery.