bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue-Specific Education of Decidual NK Cells
Authors: Sharkey Andrew M. , Xiong Shiqiu , Kennedy Philippa R. , Gardner Lucy , Farrell Lydia E. , Chazara Olympe , Ivarsson Martin A. , Hiby Susan E. , Colucci Francesco , Moffett Ashley 
Published: August 2015

Abstract
During human pregnancy, fetal trophoblast cells invade the decidua and remodel maternal spiral arteries to establish adequate nutrition during gestation. Tissue NK cells in the decidua (dNK) express inhibitory NK receptors (iNKR) that recognize allogeneic HLA-C molecules on trophoblast. Where this results in excessive dNK inhibition, the risk of pre-eclampsia or growth restriction is increased. However, the role of maternal, self–HLA-C in regulating dNK responsiveness is unknown. We investigated how the expression and function of five iNKR in dNK is influenced by maternal HLA-C. In dNK isolated from women who have HLA-C alleles that carry a C2 epitope, there is decreased expression frequency of the cognate receptor, KIR2DL1. In contrast, women with HLA-C alleles bearing a C1 epitope have increased frequency of the corresponding receptor, KIR2DL3. Maternal HLA-C had no significant effect on KIR2DL1 or KIR2DL3 in peripheral blood NK cells (pbNK). This resulted in a very different KIR repertoire for dNK capable of binding C1 or C2 epitopes compared with pbNK. We also show that, although maternal KIR2DL1 binding to C2 epitope educates dNK cells to acquire functional competence, the effects of other iNKR on dNK responsiveness are quite different from those in pbNK. This provides a basis for understanding how dNK responses to allogeneic trophoblast affect the outcome of pregnancy. Our findings suggest that the mechanisms that determine the repertoire of iNKR and the effect of self-MHC on NK education may differ in tissue NK cells compared with pbNK.
Mapping the Binding Site of a Cross-Reactive Plasmodium falciparum PfEMP1 Monoclonal Antibody Inhibitory of ICAM-1 Binding
Authors: Lennartz Frank , Bengtsson Anja , Olsen Rebecca W. , Joergensen Louise , Brown Alan , Remy Louise , Man Petr , Forest Eric , Barfod Lea K. , Adams Yvonne , Higgins Matthew K. , Jensen Anja T. R. 
Published: August 2015

Abstract
The virulence of Plasmodium falciparum is linked to the ability of infected erythrocytes (IE) to adhere to the vascular endothelium, mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1). In this article, we report the functional characterization of an mAb that recognizes a panel of PfEMP1s and inhibits ICAM-1 binding. The 24E9 mouse mAb was raised against PFD1235w DBLβ3_D4, a domain from the group A PfEMP1s associated with severe malaria. 24E9 recognizes native PfEMP1 expressed on the IE surface and shows cross-reactivity with and cross-inhibition of the ICAM-1 binding capacity of domain cassette 4 PfEMP1s. 24E9 Fab fragments bind DBLβ3_D4 with nanomolar affinity and inhibit ICAM-1 binding of domain cassette 4–expressing IE. The antigenic regions targeted by 24E9 Fab were identified by hydrogen/deuterium exchange mass spectrometry and revealed three discrete peptides that are solvent protected in the complex. When mapped onto a homology model of DBLβ3_D4, these cluster to a defined, surface-exposed region on the convex surface of DBLβ3_D4. Mutagenesis confirmed that the site most strongly protected is necessary for 24E9 binding, which is consistent with a low-resolution structure of the DBLβ3_D4::24E9 Fab complex derived from small-angle x-ray scattering. The convex surface of DBLβ3_D4 has previously been shown to contain the ICAM-1 binding site of DBLβ domains, suggesting that the mAb acts by occluding the ICAM-1 binding surface. Conserved epitopes, such as those targeted by 24E9, are promising candidates for the inclusion in a vaccine interfering with ICAM-1–specific adhesion of group A PfEMP1 expressed by P. falciparum IE during severe malaria.
Het episodisch geheugen en getuigenverhoor
Authors: Odinot Geralda , Boon Roel , Wolters Laura 
Published: August 2015

What specialist police interviewers know about eyewitness memory
In this study, we examined what police interviewers know about factors that affect the reliability of eyewitness testimony. We asked 143 specialist investigative interviewers from the Dutch police to complete a questionnaire about eyewitness memory. The results indicate that the police interviewers have limited knowledge of episodic memory and accompanying interviewing issues. In addition, we analyzed the interview manual from the Dutch Police Academy on coverage of the topics in our questionnaire. The poor level of knowledge of the police interviewers was correlated with lack of knowledge in the manual. Results are discussed in relation to education in police interviewing in the Netherlands.
‘Onze kinderen zijn geen terroristen’
Authors: van San Marion 
Published: August 2015

‘Our kids are not terrorists.’ The families of Belgian and Dutch jihadists on their loved ones’ departure for Syria
Since March 2013 a sizeable number of Belgian and Dutch youngsters have joined the armed conflict in Syria. According to recent estimates, Belgium has 438 foreign fighters in Syria, the Netherlands 160. Very little is known about who these people are and what made them decide to join the armed struggle. There is also a lack of information regarding their families. The research on which this article is based comprised interviews with twenty families with at least one member who has left for Syria. In addition, former teachers of these youngsters were asked to reflect on their students’ actions. The central questions of this article concern the views of family members on the youngsters’ decision to join the armed struggle, whether or not there were signs of radicalization prior to their leaving, and whether all of them actually did go through a process of radicalization.
Relationship Between the Size of Metastatic Lymph Nodes and Positron Emission Tomographic/Computer Tomographic Findings in Patients with Esophageal Squamous Cell Carcinoma
Authors: Park Seong Yong , Kim Dae Joon , Jung Hee Suk , Yun Mi Jin , Lee Jeong Won , Park Cheol Keun 
Published: August 2015

AbstractBackgroundWe measured the sizes of metastatic lymph nodes and the relationships thereof by 18F‐fluorodeoxyglucose positron emission tomography/computer tomography (PET/CT). We identified risk factors for nodal upstaging in patients with esophageal squamous cell carcinoma (ESCC).MethodsEighty‐five patients with ESCC who underwent esophagectomy with extensive mediastinal lymphadenectomy were assessed. Two radiologists blinded to pathology data reviewed PET/CT scans, evaluating both primary tumors and lymph node involvement. A pathologist examined all metastatic lymph nodes in terms of maximal diameter (LNmax), the size of the metastatic focus (Fmax), and the metastasis occupation ratio (MOR = Fmax/LNmax).
ResultsThe maximal tumor length averaged 2.9 ± 0.2 cm and the mean SUVmax of the primary lesion 5.3 ± 0.5. On PET/CT scans, 26 (30.6 %) patients exhibited nodal metastasis and 59 (69.4 %) did not. Pathology grades of pN0, pN1, pN2, and pN3 were assigned to 45 (52.9 %), 24 (28.2 %), 13 (15.3 %), and 3 (3.5 %) patients, respectively. Nodal upstaging was evident in 29 (34.1 %) cases. In 123 metastatic nodes of 4212 nodes dissected, the LNmax was 6.60 ± 0.39 mm, the Fmax 4.47 ± 0.35 mm, and the MOR 0.68 ± 0.03. Of 123 nodes, 85 (69.1 %) were retrieved from PET‐negative stations, and the LNmax and Fmax values of these nodes were 5.88 ± 0.42 and 3.75 ± 0.31 mm, respectively. Upon multivariate analysis, tumor length (OR 1.666, p = 0.019) and lymphovascular invasion (OR 41.038, p < 0.001) were risk factors for nodal upstaging.
ConclusionA significant proportion of nodal metastases were too small to detect via PET/CT imaging. Therefore, meticulous lymph node dissection might be helpful in ESCC patients.
Counselees’ Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence
Authors: Albada Akke , van Dulmen Sandra , Dijkstra Henrietta , Wieffer Ivette , Witkamp Arjen , Ausems Margreet G. E. M. 
Published: August 2015

AbstractWe studied counselees’ expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post‐counseling. Consecutive counselees were included from 2008 to 2010. Counselees with an indication for diagnostic DNA‐testing for themselves or a breast cancer affected relative were requested to complete online questionnaires before and after counseling and one year after counseling (N = 152–124). Self‐reported surveillance was compared to surveillance recommendations. Consultations were videotaped. Counselees’ reactions to the risks and recommendations were coded. Statements about the risk perception and surveillance intentions of breast cancer unaffected counselees were transcribed. Associations with outcomes were explored. Almost all breast cancer unaffected counselees (>90 %) reacted to their risk estimate with an utterance indicating understanding and this reaction was not significantly associated with their post‐visit risk perception alignment. Over one‐third (38.6 %) overestimated their risk post‐counseling. Few counselees (5.8 %) expressed surveillance intentions. One year after counseling, about three‐quarters (74.0 %) of the breast cancer unaffected counselees had adhered to the surveillance recommendation. Almost one‐quarter (23.3 %) had performed more mammograms/MRI scans than recommended, which was associated with prior mammography uptake (n = 47; X2 = 5.2; p = .02). Counselees’ post‐counseling overestimation of their risk, high levels of worry and high surveillance uptake were not reflected in their reactions to the counselor's information during the final visit.
Skeletal maturity of children with multiple osteochondromas: Is diminished stature due to a systemic influence?
Authors: Staal Heleen M. , Goud Annemarie L. , van der Woude Henk-Jan , Witlox Marianne Adhiambo , Ham S. John , Robben Simon G. F. , Dremmen Marjolein H. G. , van Rhijn Lodewijk W. 
Published: August 2015

Background Multiple ostechondromas (MO) is an autosomal dominant inherited disease caused by mutated exostosin genes. It mostly affects the long bones and can lead to growth disturbances, especially disproportionate short stature. Both the local effect on growth plates and the systemic influence of the gene disorder on growth mechanisms might explain the diminished stature. Purpose The hypothesis of this study is that the diminished stature in adults with MO is due to a systemic influence, leading to early skeletal maturation and early closure of the growth plate. Therefore, in these patients the skeletal age in adolescence is hypothesized to be higher than the calendar age. Methods Radiographs of the left hand were collected from 50 MO-affected children. The skeletal age was calculated using these radiographs according to the Greulich–Pyle bone scale and was compared to the calendar age at the time of radiography. Results Children aged 3–12 years had a significantly lower skeletal age compared to their calendar age ( p = 0.030). Children aged 12–17 years had a significantly higher skeletal age ( p = 0.019), especially boys. Skeletal maturation in children with MO therefore differs from their peers. Conclusion In this study, the skeletal age in younger children with MO is lower than their calendar age. For adolescents, particularly boys, this is reversed, suggesting an earlier or faster closure of the growth plates. These findings support a systemic influence of the gene defect on growth rate.
Outcomes of pregnancy with gestational diabetes mellitus
Authors: Srichumchit Supansa , Luewan Suchaya , Tongsong Theera 
Published: August 2015

AbstractObjectiveTo compare pregnancy outcomes between women with gestational diabetes mellitus (GDM) and those with low‐risk pregnancies during implementation of the GDM practice guideline.MethodsIn a retrospective study, data were compared between women with singleton pregnancies complicated by GDM and control women with singleton low‐risk pregnancies who delivered at Maharaj Nakorn Chiang Mai Hospital, Thailand, between January 2002 and December 2012. All pregnant women were screened and managed for GDM as recommended by the National Diabetes Data Group.ResultsDuring the study period, 1350 pregnancies with GDM and 20421 low‐risk pregnancies met the study criteria and were included in the GDM group and the control group, respectively. The incidence of fetal macrosomia—the main outcome—was significantly higher in the GDM group (n = 270, 20.0%) than in the control group (n = 2776, 3.6%; adjusted odds ratio 1.48, 95% confidence interval 1.28–1.71; P < 0.001). The incidences of cesarean delivery, cephalopelvic disproportion, pregnancy‐induced hypertension, and shoulder dystocia were also significantly higher in the GDM group (all P < 0.05).ConclusionDespite the practice guideline, adverse pregnancy outcomes including fetal macrosomia, cesarean delivery, and pregnancy‐induced hypertension, were significantly higher among women with GDM. The findings warrant an effective audit system or improved adherence to the guideline.
BS-SNPer: SNP calling in bisulfite-seq data
Authors: Gao Shengjie , Zou Dan , Mao Likai , Liu Huayu , Song Pengfei , Chen Youguo , Zhao Shancen , Gao Changduo , Li Xiangchun , Gao Zhibo , Fang Xiaodong , Yang Huanming , Ørntoft Torben F. , Sørensen Karina D. , Bolund Lars 
Published: August 2015

Abstract
Summary: Sodium bisulfite conversion followed by sequencing (BS-Seq, such as whole genome bisulfite sequencing or reduced representation bisulfite sequencing) has become popular for studying human epigenetic profiles. Identifying single nucleotide polymorphisms (SNPs) is important for quantification of methylation levels and for study of allele-specific epigenetic events such as imprinting. However, SNP calling in such data is complex and time consuming. Here, we present an ultrafast and memory-efficient package named BS-SNPer for the exploration of SNP sites from BS-Seq data. Compared with Bis-SNP, a popular BS-Seq specific SNP caller, BS-SNPer is over 100 times faster and uses less memory. BS-SNPer also offers higher sensitivity and specificity compared with existing methods.
Availability and implementation: BS-SNPer is written in C++ and Perl, and is freely available at https://github.com/hellbelly/BS-Snper.
Contact: bolund@biomed.au.dk, kdso@clin.au.dk or orntoft@ki.au.dk
Supplementary information: Supplementary data are available at Bioinformatics online.
Development of a Novel Plasmid-Free Thymidine Producer by Reprogramming Nucleotide Metabolic Pathways
Authors: Kim Jin-Sook , Jeong Min-Kyung , Koo Bong-Seong , Lee Hyeon-Cheol 
Published: August 2015

ABSTRACT

A novel thymidine-producing strain of
Escherichia coli
was prepared by genome recombineering. Eleven genes were deleted by replacement with an expression cassette, and 7 genes were integrated into the genome. The resulting strain,
E. coli
HLT013, showed a high thymidine yield with a low deoxyuridine content. DNA microarrays were then used to compare the gene expression profiles of HLT013 and its isogenic parent strain. Based on microarray analysis, the
pyr
biosynthesis genes and 10 additional genes were selected and then expressed in HLT013 to find reasonable candidates for enhancing thymidine yield. Among these, phage shock protein A (PspA) showed positive effects on thymidine production by diminishing redox stress. Thus, we integrated
pspA
into the HLT013 genome, resulting in
E. coli
strain HLT026, which produced 13.2 g/liter thymidine for 120 h with fed-batch fermentation. Here, we also provide a basis for new testable hypotheses regarding the enhancement of thymidine productivity and the attainment of a more complete understanding of nucleotide metabolism in bacteria.
Strains of the Harmful Cyanobacterium Microcystis aeruginosa Differ in Gene Expression and Activity of Inorganic Carbon Uptake Systems at Elevated CO
2
Levels
Authors: Sandrini Giovanni , Jakupovic Dennis , Matthijs Hans C. P. , Huisman Jef 
Published: August 2015

ABSTRACT

Cyanobacteria are generally assumed to be effective competitors at low CO
2
levels because of their efficient CO
2
-concentrating mechanism (CCM), and yet how bloom-forming cyanobacteria respond to rising CO
2
concentrations is less clear. Here, we investigate changes in CCM gene expression at ambient CO
2
(400 ppm) and elevated CO
2
(1,100 ppm) in six strains of the harmful cyanobacterium
Microcystis
. All strains downregulated
cmpA
encoding the high-affinity bicarbonate uptake system BCT1, whereas both the low- and high-affinity CO
2
uptake genes were expressed constitutively. Four strains downregulated the bicarbonate uptake genes
bicA
and/or
sbtA
, whereas two strains showed constitutive expression of the
bicA
-
sbtA
operon. In one of the latter strains, a transposon insert in
bicA
caused low
bicA
and
sbtA
transcript levels, which made this strain solely dependent on BCT1 for bicarbonate uptake. Activity measurements of the inorganic carbon (C
i
) uptake systems confirmed the CCM gene expression results. Interestingly, genes encoding the RuBisCO enzyme, structural carboxysome components, and carbonic anhydrases were not regulated. Hence,
Microcystis
mainly regulates the initial uptake of inorganic carbon, which might be an effective strategy for a species experiencing strongly fluctuating C
i
concentrations. Our results show that CCM gene regulation of
Microcystis
varies among strains. The observed genetic and phenotypic variation in CCM responses may offer an important template for natural selection, leading to major changes in the genetic composition of harmful cyanobacterial blooms at elevated CO
2
.
γ-Resorcylate Catabolic-Pathway Genes in the Soil Actinomycete Rhodococcus jostii RHA1
Authors: Kasai Daisuke , Araki Naoto , Motoi Kota , Yoshikawa Shota , Iino Toju , Imai Shunsuke , Masai Eiji , Fukuda Masao 
Published: August 2015

ABSTRACTTheRhodococcus jostiiRHA1 gene cluster required for γ-resorcylate (GRA) catabolism was characterized. The cluster includestsdA,tsdB,tsdC,tsdD,tsdR,tsdT, andtsdX, which encode GRA decarboxylase, resorcinol 4-hydroxylase, hydroxyquinol 1,2-dioxygenase, maleylacetate reductase, an IclR-type regulator, a major facilitator superfamily transporter, and a putative hydrolase, respectively. ThetsdAgene conferred GRA decarboxylase activity onEscherichia coli. Purified TsdB oxidized NADH in the presence of resorcinol, suggesting thattsdBencodes a unique NADH-specific single-component resorcinol 4-hydroxylase. Mutations in eithertsdAortsdBresulted in growth deficiency on GRA. ThetsdCandtsdDgenes conferred hydroxyquinol 1,2-dioxygenase and maleylacetate reductase activities, respectively, onE. coli. Inactivation oftsdTsignificantly retarded the growth of RHA1 on GRA. The growth retardation was partially suppressed under acidic conditions, suggesting the involvement oftsdTin GRA uptake. Reverse transcription-PCR analysis revealed that thetsdgenes constitute three transcriptional units, thetsdBADCandtsdTXoperons andtsdR. Transcription of thetsdBADCandtsdTXoperons was induced during growth on GRA. Inactivation oftsdRderepressed transcription of thetsdBADCandtsdTXoperons in the absence of GRA, suggesting thattsdgene transcription is negatively regulated by thetsdR-encoded regulator. Binding of TsdR to thetsdR-tsdBandtsdT-tsdRintergenic regions was inhibited by the addition of GRA, indicating that GRA interacts with TsdR as an effector molecule.
A Conserved Gammaherpesvirus Cyclin Specifically Bypasses Host p18INK4cTo Promote Reactivation from Latency
Authors: Williams Lisa M. , Niemeyer Brian F. , Franklin David S. , Clambey Eric T. , van Dyk Linda F. 
Published: August 2015

ABSTRACTGammaherpesviruses (GHVs) carry homologs of cellular genes, including those encoding a viral cyclin that promotes reactivation from latent infection. The viral cyclin has reduced sensitivity to host cyclin-dependent kinase inhibitorsin vitro; however, thein vivosignificance of this is unclear. Here, we tested the genetic requirement for the viral cyclin in mice that lack the host inhibitors p27Kip1and p18INK4c, two cyclin-dependent kinase inhibitors known to be important in regulating B cell proliferation and differentiation. While the viral cyclin was essential for reactivation in wild-type mice, strikingly, it was dispensable for reactivation in mice lacking p27Kip1and p18INK4c. Further analysis revealed that genetic ablation of only p18INK4calleviated the requirement for the viral cyclin for reactivation from latency. p18INK4cregulated reactivation in a dose-dependent manner so that the viral cyclin was dispensable in p18INK4cheterozygous mice. Finally, treatment of wild-type cells with the cytokine BAFF, a known attenuator of p18INK4cfunction in B lymphocytes, was also able to bypass the requirement for the viral cyclin in reactivation. These data show that the gammaherpesvirus viral cyclin functions specifically to bypass the cyclin-dependent kinase inhibitor p18INK4c, revealing an unanticipated specificity between a GHV cyclin and a single cyclin-dependent kinase inhibitor.IMPORTANCEThe gammaherpesviruses (GHVs) cause lifelong infection and can cause chronic inflammatory diseases and cancer, especially in immunosuppressed individuals. Many GHVs encode a conserved viral cyclin that is required for infection and disease. While a common property of the viral cyclins is that they resist inhibition by normal cellular mechanisms, it remains unclear how important it is that the GHVs resist this inhibition. We used a mouse GHV that either contained or lacked a viral cyclin to test whether the viral cyclin lost importance when these inhibitory pathways were removed. These studies revealed that the viral cyclin was required for optimal function in normal mice but that it was no longer required following removal or reduced function of a single cellular inhibitor. These data define a very specific role for the viral cyclin in bypassing one cellular inhibitor and point to new methods to intervene with viral cyclins.