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Previous studies have shown that economic and political experiences influence the level of satisfaction with democracy; however, they fail to explain whether these experiences have the same effect for everyone, whether there is interindividual variance and where these differences might be rooted. In this article, we investigate these roots of interindividual variance and base our argument on the observation that early experiences in school are formative and influence the effect of economic and political experiences on satisfaction with democracy. We analyze an original representative dataset on the German population to test how school experiences, more precisely equal treatment in school, interact with economic and political experiences in later life and thereby influence satisfaction with democracy. We find that school experiences play a significant role here. Voting for the governing parties especially increases satisfaction with democracy if respondents were treated equally in school. Similarly, past experiences of unemployment in particular decrease people’s levels of satisfaction with the political system if they were not treated equally in school. The findings highlight that early experiences made in school can have a relevant influence on satisfaction with democracy in later life.

Les techniques d’ablathermie percutanée sont efficaces pour le contrôle des tumeurs hépatiques. Réputées sûres avec moins de 5 % de complications majeures, elles exposent cependant au risque de blessure thermique des organes de voisinage pouvant aller jusqu’à la perforation digestive dont l’issue est potentiellement fatale. Historiquement la présence d’un organe vulnérable à moins d’un centimètre de la zone d’ablation constituait une contre-indication à la réalisation d’une ablation percutanée. Afin de minimiser ces risques, de nombreuses techniques de protections, telle la création d’une ascite artificielle ont été développées. L’efficacité de ces dernières reste limitée pour la protection de l’estomac en raison de la dissipation rapide des fluides au sein de la cavité péritonéale. Notre travail consiste en une analyse rétrospective de deux cas de dissection involontaire du ligament hépatogastrique lors de la réalisation d’une ascite artificielle. L’analyse des images scanographiques peropératoires a mis en évidence une accumulation du CO2 et du soluté contrasté injectés le long de la petite courbure gastrique, silhouettant l’artère gastrique gauche, au lieu de sa libre distribution attendue au sein de la cavité péritonéale.

Hematopoietic stem cell transplantation is routinely performed for the treatment of various malignant and non‐malignant hematological diseases. Successful transplantation depends on the number and fitness of donor stem and progenitor cells, whose quality is substantially influenced by the sampling procedure, sample handling, and cryopreservation. BCL‐2 proteins are central to the survival and maintenance of stem and progenitor cells under both, physiological and stress conditions. Transplantation‐associated apoptosis of donor cells is mediated by the pro‐apoptotic BCL‐2 proteins BIM and BMF and prevented by overexpression of their antagonists, BCL‐2 and BCL‐XL. We have previously reported that deletion of BIM or BMF stabilizes donor stem cell numbers during transplantation and improves cellular fitness and transplantation outcomes, albeit posing a risk for lymphoma and autoimmunity in recipient mice. Short‐term apoptosis inhibition in donor cells appears equally effective in improving the outcome of transplantation, but in contrast does not cause pathology. In this review, we discuss the role of BCL‐2 proteins in the context of factors that negatively impact donor stem and progenitor cell fitness and viability. Finally, we suggest approaches to improve graft quality and transplantation procedures with an emphasis on the inhibition of BCL‐2 regulated apoptosis. Stem Cells2018;36:1646–1654 Despite major advances in knowledge during the last decades, hematopoietic stem cell transplantation (HSCT) is still associated with a risk of significantly delayed engraftment or graft failure. Harvest of stem and progenitor cells from the donor's bone marrow, their freezing and thawing and transport to the recipient as well as transplantation into the damaged recipient niche, all pose threat to the survival of donor cells. Most transplantation‐related apoptosis is caused by the pro‐apoptotic BCL‐2 proteins, BIM and BMF, and their short‐term inhibition can result in significantly improved HSCT outcome without side effects.

AbstractStrains belonging to Bacillus cereusGroup include six different species, among which are Bacillus thuringiensis, Bacillus weihenstephanensis,and Bacillus cereus sensu stricto,a causative agent of food poisoning. Sequence of the panC-housekeeping gene is used for B. cereusGroup affiliation to seven major phylogenetic groups (I–VII) with different ecological niches and variations in thermal growth range and spore heat resistance of B. cereusGroup microorganisms varies among phylogenetic groups. We assigned a selection of B. cereus sensu strictostrains related to food poisoning from the Spanish cultivar Collection (Valencia) to Group IV strains based on panCgene sequence. Thermal inactivation assays revealed variability of spore heat resistance within these Group IV strains. Adequate food sanitizing treatments therefore require fast and reliable identification of particular strains. In the present study, feasibility of genotyping via high-resolution melting (HRM) analysis was examined. HRM analysis of amplified polymorphic 16S-23 intergenic spacer region (ISR) region proved to be discriminatory for B. cereus sensu strictostrain typing, while two other polymorphic regions within the bacterial rRNA operon allowed differentiation between Bacillusspecies, demonstrating its applicability for discrimination on the species and strain level within B. cereusGroup.

The aim of this prospective study was to determine whether this test changes patient diagnosis, provides new information, or alters patient care.

Esophageal manometry (EM) is performed to evaluate symptoms of chest pain and dysphagia, although its clinical utility is not known. The aim of this study was to evaluate the clinical utility of EM by determining whether EM provides new information, changes diagnoses, or alters patient management.

Growth of lateral organs is a complex mechanism that starts with formation of lateral primordia. Basal developmental programs like polarity, organ identity and environmental cues influence the final organ size achieved via coordinated cell division and expansion. Recent evidence shows that the precise balance between these two processes, known as compensation mechanisms, seems to be influenced by the identity of the organ. Furthermore, studies of mutants affected in floral organ size suggest the existence of developmental compartments within different floral whorls that show distinct compensation behaviors.

OBJECTIVE To examine the joint effects of movie smoking exposure and team sports participation on established smoking. DESIGN Longitudinal study. SETTING School- and telephone-based surveys in New Hampshire and Vermont between September 1999 through November 1999 and February 2006 through February 2007. PARTICIPANTS A total of 2048 youths aged 16 to 21 years at follow-up. MAIN EXPOSURES Baseline movie smoking exposure categorized in quartiles assessed when respondents were aged 9 to 14 years and team sports participation assessed when respondents were aged 16 to 21 years. MAIN OUTCOME MEASURE Established smoking (having smoked ≥100 cigarettes in one's lifetime) at follow-up. RESULTS At follow-up, 353 respondents (17.2%) were established smokers. Exposure to the highest quartile of movie smoking compared with the lowest increased the likelihood of established smoking (odds ratio = 1.63; 95% confidence interval, 1.03-2.57), and team sports nonparticipants compared with participants were twice as likely to be established smokers (odds ratio = 2.01; 95% confidence interval, 1.47-2.74). The joint effects of movie smoking exposure and team sports participation revealed that at each quartile of movie smoking exposure, the odds of established smoking were greater for team sports nonparticipants than for participants. We saw a dose-response relationship of movie smoking exposure for established smoking only among team sports participants. CONCLUSIONS Team sports participation clearly plays a protective role against established smoking, even in the face of exposure to movie smoking. However, movie smoking exposure increases the risk of established smoking among both team sports participants and nonparticipants. Parents, teachers, coaches, and clinicians should be aware that encouraging team sports participation in tandem with minimizing early exposure to movie smoking may offer the greatest likelihood of preventing youth smoking.Arch Pediatr Adolesc Med. 2009;163(7):638-643--

To prospectively evaluate the tolerability and clinical utility of the Bravo pH capsule in children.

Abstract: Objectives: Evaluate known breast cancer risk factors in relation to breast density. Methods: We examined factors in relation to breast density in 144,018 New Hampshire (NH) women with at least one mammogram recorded in a statewide mammography registry. Mammographic breast density was measured by radiologists using the BI-RADS classification; risk factors of interest were obtained from patient intake forms and questionnaires. Results: Initial analyses showed a strong inverse influence of age and body mass index (BMI) on breast density. In addition, women with late age at menarche, late age at first birth, premenopausal women, and those currently using hormone therapy (HT) tended to have higher breast density, while those with greater parity tended to have less dense breasts. Analyses stratified on age and BMI suggested interactions, which were formally assessed in a multivariable model. The impact of current HT use, relative to nonuse, differed across age groups, with an inverse association in younger women, and a positive association in older women (p < 0.0001 for the interaction). The positive effects of age at menarche and age at first birth, and the inverse influence of parity were less apparent in women with low BMI than in those with high BMI (p = 0.04, p < 0.0001 and p = 0.01, respectively, for the interactions). We also noted stronger positive effects for age at first birth in postmenopausal women (p = 0.004 for the interaction). The multivariable model indicated a slight positive influence of family history of breast cancer. Conclusions: The influence of age at menarche and reproductive factors on breast density is less evident in women with high BMI. Density is reduced in young women using HT, but increased in HT users of age 50 or more.

The objective of screening mammography is to identify breast carcinoma early, which requires routine screening. Although self‐report data indicate that screening utilization is high, the results of this population‐based assessment indicated that utilization is lower than reported previously.The authors compared New Hampshire population data from the 2000 Census with clinical encounter data for the corresponding time obtained from the New Hampshire Mammography Network, a mammography registry that captures approximately 90% of the mammograms performed in participating New Hampshire facilities.The results showed that approximately 36% of New Hampshire women either never had a mammogram or had not had a mammogram in > 27 months (irregular screenees), and older women (80 yrs and older) were less likely to be screened (79% unscreened/underscreened) compared with younger women (ages 40–69 yrs; 28–32% unscreened/underscreened). Of the screened women, 44% were adhering to an interval of 14 months, and 21% were adhering within 15 months and 26 months. The remaining 35% of the women had 1 or 2 mammograms and did not return within 27 months.Routine mammography screening may be occurring less often than believed when survey data alone are used. An important, compelling concern is the reason women had one or two mammograms only and then did not return for additional screening. This area deserves additional research. Cancer 2005. © 2005 American Cancer Society.

Niemeyer: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Dyskeratosis congenita (DC) belongs to the group of inherited bone marrow failure syndromes (IBMFS) and is characterized by premature telomere shortening caused by mutations in components of the telomerase or the shelterin complexes. The main cause of death in affected patients is hematopoietic failure, but there is also a 10-15% risk of malignant transformation into secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Critically short telomeres activate a DNA damage response with p53-mediated cell cycle inhibition, senescence and/or apoptosis, the latter mediated primarily by PUMA, a BCL-2 family member belonging to the group of pro-apoptotic BH3-only proteins and transcriptionally regulated by p53. Activation of p53 and expression of its target genes are critical for the exhaustion of hematopoietic stem cells (HSCs) in DC patients. Inactivation of the DNA damage checkpoint could possibly mitigate hematopoietic failure but poses a significant risk of genomic instability and leukemia. Based on our earlier mouse model of secondary leukemia (Genes Dev, 24(15):1602-7), we hypothesized that selective inhibition of p53-mediated apoptosis - while all other p53-checkpoint-induced pathways remain active - could both delay hematopoietic failure and prevent malignant transformation.

ABSTRACTRegressing tumors are usually associated with a large immune infiltrate, but the molecular and cellular interactions that govern a successful anti-tumor immunity remain elusive. Here, we have triggered type I Interferon (IFN) signaling in a breast tumor model (MMTV-PyMT) using 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a ligand of the STimulator of Interferon Genes, STING. The 2 main events rapidly triggered by DMXAA in transplanted PyMT tumors are 1) the disruption of the tumor vasculature, followed by hypoxia and cell death; 2) the release of chemokines. Both events converged to trigger the recruitment of 2 waves of immune cells: a swift, massive recruitment of neutrophils, followed by a delayed rise in monocytes and CD8 T cells in the tumor mass. Depletion experiments in vivorevealed that myeloid cell subsets and T cells need to cooperate to achieve full-blown recruitment and activation at the tumor site and to induce effective secondary cell death leading to tumor regression (Illustration 1). Altogether, our study highlights that the tumor regression induced by the STING agonist DMXAA results from a cascade of events, with an initial vessel destruction followed by several infiltration waves of immune cells which have to cooperate to amplify and sustain the initial effect. We thus provide the first global and detailed kinetic analysis of the anti-tumoral effect of DMXAA and of its different articulated steps.

Petunia hybrida is a popular bedding plant that has a long history as a genetic model system. We report the whole-genome sequencing and assembly of inbred derivatives of its two wild parents, P. axillaris N and P. inflata S6. The assemblies include 91.3% and 90.2% coverage of their diploid genomes (1.4 Gb; 2n = 14) containing 32,928 and 36,697 protein-coding genes, respectively. The genomes reveal that the Petunia lineage has experienced at least two rounds of hexaploidization: the older gamma event, which is shared with most Eudicots, and a more recent Solanaceae event that is shared with tomato and other solanaceous species. Transcription factors involved in the shift from bee to moth pollination reside in particularly dynamic regions of the genome, which may have been key to the remarkable diversity of floral colour patterns and pollination systems. The high-quality genome sequences will enhance the value of Petunia as a model system for research on unique biological phenomena such as small RNAs, symbiosis, self-incompatibility and circadian rhythms.

Crop-plant-yield safety is jeopardized by temperature stress caused by the global climate change. To take countermeasures by breeding and/or transgenic approaches it is essential to understand the mechanisms underlying plant acclimation to heat stress. To this end proteomics approaches are most promising, as acclimation is largely mediated by proteins. Accordingly, several proteomics studies, mainly based on two-dimensional gel-tandem MS approaches, were conducted in the past. However, results often were inconsistent, presumably attributable to artifacts inherent to the display of complex proteomes via two-dimensional-gels. We describe here a new approach to monitor proteome dynamics in time course experiments. This approach involves full 15N metabolic labeling and mass spectrometry based quantitative shotgun proteomics using a uniform 15N standard over all time points. It comprises a software framework, IOMIQS, that features batch job mediated automated peptide identification by four parallelized search engines, peptide quantification and data assembly for the processing of large numbers of samples. We have applied this approach to monitor proteome dynamics in a heat stress time course using the unicellular green alga Chlamydomonas reinhardtii as model system. We were able to identify 3433 Chlamydomonas proteins, of which 1116 were quantified in at least three of five time points of the time course. Statistical analyses revealed that levels of 38 proteins significantly increased, whereas levels of 206 proteins significantly decreased during heat stress. The increasing proteins comprise 25 (co-)chaperones and 13 proteins involved in chromatin remodeling, signal transduction, apoptosis, photosynthetic light reactions, and yet unknown functions. Proteins decreasing during heat stress were significantly enriched in functional categories that mediate carbon flux from CO2and external acetate into protein biosynthesis, which also correlated with a rapid, but fully reversible cell cycle arrest after onset of stress. Our approach opens up new perspectives for plant systems biology and provides novel insights into plant stress acclimation.

Crop-plant-yield safety is jeopardized by temperature stress caused by the global climate change. To take countermeasures by breeding and/or transgenic approaches it is essential to understand the mechanisms underlying plant acclimation to heat stress. To this end proteomics approaches are most promising, as acclimation is largely mediated by proteins. Accordingly, several proteomics studies, mainly based on two-dimensional gel-tandem MS approaches, were conducted in the past. However, results often were inconsistent, presumably attributable to artifacts inherent to the display of complex proteomes via two-dimensional-gels. We describe here a new approach to monitor proteome dynamics in time course experiments. This approach involves full 15N metabolic labeling and mass spectrometry based quantitative shotgun proteomics using a uniform 15N standard over all time points. It comprises a software framework, IOMIQS, that features batch job mediated automated peptide identification by four parallelized search engines, peptide quantification and data assembly for the processing of large numbers of samples. We have applied this approach to monitor proteome dynamics in a heat stress time course using the unicellular green alga Chlamydomonas reinhardtiias model system. We were able to identify 3433 Chlamydomonasproteins, of which 1116 were quantified in at least three of five time points of the time course. Statistical analyses revealed that levels of 38 proteins significantly increased, whereas levels of 206 proteins significantly decreased during heat stress. The increasing proteins comprise 25 (co-)chaperones and 13 proteins involved in chromatin remodeling, signal transduction, apoptosis, photosynthetic light reactions, and yet unknown functions. Proteins decreasing during heat stress were significantly enriched in functional categories that mediate carbon flux from CO2and external acetate into protein biosynthesis, which also correlated with a rapid, but fully reversible cell cycle arrest after onset of stress. Our approach opens up new perspectives for plant systems biology and provides novel insights into plant stress acclimation.

Follicular Lymphomas (FL) are considered the neoplastic counterpart of germinal center (GC) B cells due to their characteristic growth pattern, composition of a mixture of centroblasts and centrocytes, a GC gene expression profile, and ongoing acquisition of somatic mutations of their immunoglobulin (Ig) genes. A minority of FL has undergone Ig class switching from IgM to IgG or IgA at diagnosis. Based on PCR-mediated cloning of Ig heavy chain (IgH) genes with a success rate of 73%, Aarts et al. (Blood, 2000) have reported from an analysis of 30 FL cases that isotype-switched FL harbor significantly more IgH mutations than IgM-expressing cases, suggesting that the somatic hypermutation (SHM) machinery remains fully active even after class switch recombination (CSR) in FL. We have readdressed this question in 38 FL cases and compared their SHM pattern to 31 lymphomas of other types. 16 of these controls expressed IgM (including 5 MCL, 4 DLCL, and 3 CLL) and 15 IgG/A (including 13 myelomas). The Ig isotype and light chain (IgL) restriction of the lymphoma cells were identified by flow cytometry, and both clonal IgH and IgL transcripts were cloned by anchored PCR. This approach has a success rate of 98% (Bertinetti et al., Eur. J. Haematol., 2006). At the DNA (Table 1 and 2) and amino acid sequence level (not shown), the SHM frequency did not differ significantly between the 23 IgM-expressing and 15 class-switched FL. IgM-expressing FL, however, had more SHM than unswitched non-FL cases. In contrast, class-switched FL did not harbor more mutations than switched non-FL tumors. Although the molecular mechanisms are not yet fully understood, activation-induced cytidine deaminase (AID) has been identifed as an essential enzyme required for both SHM and CSR and is frequently expressed by GC lymphomas. To investigate whether downregulation of AID might be responsible for cessation of SHM after CSR in FL, we measured the AID expression in the FL biopsies by a semiquantitative RT-PCR. In contrast to our hypothesis, AID transcripts were present in both IgM- and IgG/A-expressing FL, and the median AID expression was even significantly higher in switched FL (p=0.014). These data indicate that despite their arrest in the GC maturation stage, FL behave similar to normal B cells by downregulating the SHM machinery after CSR. In addition, the data are consistent with a model in which intermediate expression of AID is sufficient for SHM, but higher levels are required to initiate CSR in FL. Subsequent cessation of SHM might be attributable to subcellular relocalisation of AID or decreased activity of AID cofactors, such as single-stranded binding protein (RPA) or protein kinase A (PKA). Median (range) of VH Mutations IgM IgG/A IgM versus IgG/A Comparison of mutation frequency of the clonal VH gene between non-switched and switched FL cases and between FL and non-FL cases FL (n=38) 32 (8–106) 38 (12–58) p=0.4 Non-FL (n=31) 18 (6–57) 25 (13–65) p=0.07 FL versus non-FL p=0.006 p=0.11 Median (range) of VL Mutations IgM IgG/A IgM versus IgG/A Comparison of mutation frequency of the clonal VL gene between non-switched and switched FL cases and between FL and non-FL cases FL (n=38) 14 (0–38) 18 (5–31) p=0.36 Non-FL (n=31) 5.5 (0–25) 14 (5–53) p=0.001 FL versus non-FL p=0.002 p=0.32

Follicular Lymphomas (FL) are considered the neoplastic counterpart of germinal center (GC) B cells due to their characteristic growth pattern, composition of a mixture of centroblasts and centrocytes, a GC gene expression profile, and ongoing acquisition of somatic mutations of their immunoglobulin (Ig) genes. A minority of FL has undergone Ig class switching from IgM to IgG or IgA at diagnosis. Based on PCR-mediated cloning of Ig heavy chain (IgH) genes with a success rate of 73%, Aarts et al. (Blood, 2000) have reported from an analysis of 30 FL cases that isotype-switched FL harbor significantly more IgH mutations than IgM-expressing cases, suggesting that the somatic hypermutation (SHM) machinery remains fully active even after class switch recombination (CSR) in FL. We have readdressed this question in 38 FL cases and compared their SHM pattern to 31 lymphomas of other types. 16 of these controls expressed IgM (including 5 MCL, 4 DLCL, and 3 CLL) and 15 IgG/A (including 13 myelomas). The Ig isotype and light chain (IgL) restriction of the lymphoma cells were identified by flow cytometry, and both clonal IgH and IgL transcripts were cloned by anchored PCR. This approach has a success rate of 98% (Bertinetti et al., Eur. J. Haematol., 2006). At the DNA (Table 1 and 2) and amino acid sequence level (not shown), the SHM frequency did not differ significantly between the 23 IgM-expressing and 15 class-switched FL. IgM-expressing FL, however, had more SHM than unswitched non-FL cases. In contrast, class-switched FL did not harbor more mutations than switched non-FL tumors. Although the molecular mechanisms are not yet fully understood, activation-induced cytidine deaminase (AID) has been identifed as an essential enzyme required for both SHM and CSR and is frequently expressed by GC lymphomas. To investigate whether downregulation of AID might be responsible for cessation of SHM after CSR in FL, we measured the AID expression in the FL biopsies by a semiquantitative RT-PCR. In contrast to our hypothesis, AID transcripts were present in both IgM- and IgG/A-expressing FL, and the median AID expression was even significantly higher in switched FL (p=0.014). These data indicate that despite their arrest in the GC maturation stage, FL behave similar to normal B cells by downregulating the SHM machinery after CSR. In addition, the data are consistent with a model in which intermediate expression of AID is sufficient for SHM, but higher levels are required to initiate CSR in FL. Subsequent cessation of SHM might be attributable to subcellular relocalisation of AID or decreased activity of AID cofactors, such as single-stranded binding protein (RPA) or protein kinase A (PKA).