Representation Matters: The Impact of Descriptive Women's Representation on the Political Involvement of Women

In a cross-country comparison of 33 European countries, we tested whether a high degree of female representation attenuates the assumed negative impact of gender on political involvement. Our multilevel analyses show positive interactive effects of female representation: the degree to which the representation of women in a given country's national parliament was descriptively adequate was positively related to women's ratings of the importance of politics and self-reported political interest. With respect to political participation, the findings are mixed.

The equine DNAH3 gene: SNP discovery and exclusion of an involvement in recurrent airway obstruction (RAO) in European Warmblood horses

Recurrent airway obstruction is one of the most common airway diseases affecting mature horses. Increased bronchoalveolar mucus, neutrophil accumulation in airways, and airway obstruction are the main features of this disease. Mucociliary clearance is a key component of pulmonary defense mechanisms. Cilia are the motile part of this system and a complex linear array of dynein motors is responsible for their motility by moving along the microtubules in the axonemes of cilia and flagella. We previously detected a QTL for RAO on ECA 13 in a half-sib family of European Warmblood horses. The gene encoding DNAH3 is located in the peak of the detected QTL and encodes a dynein subunit. Therefore, we analysed this gene as a positional and functional candidate gene for RAO. In a mutation analysis of all 62 exons we detected 53 new polymorphisms including 7 non-synonymous variants. We performed an association study using 38 polymorphisms in a cohort of 422 animals. However, after correction for multiple testing we did not detect a significant association of any of these polymorphisms with RAO (P>0.05). Therefore, it seems unlikely that variants at the DNAH3 gene are responsible for the RAO QTL in European Warmblood horses.

The involvement of miRNA Dysregulation in Amyotrophic Lateral Sclerosis

ALS is a neurodegenerative disease that specifically affects upper and lower motor neurons leading to progressive paralysis and death. There is currently no effective treatment. Thus, identification of the signaling pathways and cellular mediators of ALS remains a major challenge in the search for novel therapeutic approaches. Recent studies have shown that non-coding RNAs have a significant impact on normal CNS development and onset and progression of neurological disorders. Based on this evidence we specifically test the hypothesis that misregulation of miRNA expression is a common feature in familiar ALS. Hence, we are exploiting human neuroblastoma cell lines either expressing the SOD1(G93A) mutation or depleted from Fused in Sarcoma (FUS) as tools to investigate the role of miRNAs in familiar ALS. To this end we performed a genome-wide scale miRNA expression on these cells, using whole-genome small RNA deep-sequencing followed by quantitative real time validation (qPCR). This strategy allowed us to find a group of dysregulated miRNAs, which are predicted to play a role in the motorneurons physiology and pathology. We verified our data on cDNA derived from SOD1-ALS mice models at early stage of the disease and on cDNA derived from lymphocytes from a small group of ALS patients. In the future, we plan to define the mechanisms responsible for the miRNA dysregulation, by silencing or stimulating the signal transduction pathways putatively involved in miRNA expression and regulation.

Systemic light-chain amyloidosis revealed by progressive nail involvement, diffuse alopecia and sicca syndrome: report of an unusual case with a review of the literature.

Immunoglobulin light-chain (AL) amyloidosis is a form of systemic amyloidosis in which the fibrils are derived from monoclonal light chains. We report a case of a 66-year-old woman presenting with nail changes, parchment-like hand changes, progressive alopecia and sicca syndrome. Histopathological studies of biopsy specimens of the scalp, the nail, minor labial salivary glands and abdominal skin revealed deposits of AL κ-type amyloid. Urine protein electrophoresis exhibited a weak band of κ-type light chains. Based on this striking case, we here review the characteristic nail and hair manifestations associated with systemic amyloidosis. Knowledge of these signs is important for an early diagnosis of systemic amyloidosis, identification of the underlying disease and patient management.

Characterization of choline uptake in Trypanosoma brucei and involvement of a mitochondrial carrier in resistance to choline analogs

Choline is an essential nutrient for eukaryotic cells, where it is used as precursor for the synthesis of choline-­containing phospholipids, such as phosphatidylcholine (PC). Our experiments showed – for the first time – that Trypanosoma brucei, the causative agent of human African sleeping sickness, is able to take up choline from the culture medium to use for PC synthesis, indicating that trypanosomes express a transporter for choline at the plasma membrane. Further characterization in procyclic and bloodstream forms revealed that choline uptake is saturable and can be inhibited by HC-3, a known inhibitor of choline uptake in mammalian cells. To obtain additional insights on choline uptake and metabolism, we investigated the effects of choline-analogs that were previously shown to be toxic for T. brucei parasites in culture. Interestingly, we found that all analogs tested effectively inhibited choline uptake into both bloodstream and procyclic form parasites. Subsequently, selected compounds were used to search for possible candidate genes encoding choline transporters in T. brucei, using an RNAi library in bloodstream forms. We identified a protein belonging to the mitochondrial carrier family, previously annotated as TbMCP14, as prime candidate. Down‐regulation of TbMCP14 by RNAi prevented drug-­induced loss of mitochondrial membrane potential and conferred 8­‐fold resistance of T. brucei bloodstream forms to choline analogs. Conversely, over‐expression of the carrier increased parasite susceptibility more than 13-­fold. However, subsequent experiments demonstrated that TbMCP14 was not involved in metabolism of choline. Instead, growth curves in glucose‐depleted medium using RNAi or knock‐out parasites suggested that TbMCP14 is involved in metabolism of amino acids for energy production. Together, our data demonstrate that the identified member of the mitochondrial carrier family is involved in drug uptake into the mitochondrion and has a vital function in energy production in T. brucei.

Fibrinogen association with human monocytes: evidence for constitutive expression of fibrinogen receptors and for involvement of Mac-1 (CD18, CR3) in the binding

Radiolabeled fibrinogen (Fg) specifically binds to mononuclear leukocytes (MNL) and to purified monocytes, but not to nylon-nonadherent lymphocytes. The association is rapid, Ca++-dependent and reversible. MNL containing Fg-binding monocytes had not been exposed to endotoxin (less than 4 pg/mL) during the isolation and the binding test, and Fg binding was not altered by preincubation of MNL with lipopolysaccharide. The binding of Fg was inhibited by anti-Mac-1 antibodies (OKM1). Antibodies to surface-bound Fg were able to induce luminol-dependent chemiluminescence, indicating that Fg binding sites have receptor function. Emission of a signal depended on MNL exposure to Fg, on specific, divalent antibodies, but not on the antibody Fc portion. These data show that human monocytes constitutively express specific Fg receptors and suggest that Mac-1, a member of the integrin superfamily, is involved in Fg recognition.

Predictors of healthcare professionals' attitudes towards family involvement in safety-relevant behaviours: a cross-sectional factorial survey study.

OBJECTIVES To investigate predictors of healthcare professionals' (HCPs) attitudes towards family involvement in safety-relevant behaviours. DESIGN A cross-sectional fractional factorial survey that assessed HCPs' attitudes towards family involvement in two error scenarios relating to hand hygiene and medication safety. Each survey comprised two randomised vignettes that described the potential error, how the family member communicated with the HCP about the error and how the HCP responded to the family member's question. SETTING 5 teaching hospitals in London, the Midlands and York. HCPs were approached on a range of medical and surgical wards. PARTICIPANTS 160 HCPs (73 doctors; 87 nurses) aged between 21 and 65 years (mean 37) 102 were female. OUTCOME MEASURES HCP approval of family member's behaviour; HCP reaction to the family member; anticipated effects on the family member-HCP relationship; HCP support for being questioned about hand hygiene/medication; affective rating responses. RESULTS HCPs supported family member's intervening (88%) but only 41% agreed this would have positive effects on the family member/HCP relationship. Across vignettes and error scenarios the strongest predictors of attitudes were how the HCP (in the scenario) responded to the family member and whether an error actually occurred. Doctors (vs nurses) provided systematically more positive affective ratings to the vignettes. CONCLUSIONS Important predictors of HCPs' attitudes towards family members' involvement in patient safety have been highlighted. In particular, a discouraging response from HCP's decreased support for family members being involved and had strong perceived negative effects on the family member/HCP relationship.

Leader–member exchange (LMX), job autonomy, and creative work involvement

Researchers have claimed that high quality of supervisor–employee relationships (i.e., leader– member exchange; LMX) fosters creativity at work. Moreover, researchers have acknowledged that this relationship is not clear-cut but rather complex. The present study focused on the moderating role of job autonomy in the LMX-creative work involvement relationship. Longitu-dinal field survey data (N = 144) collected in a high-technology firm revealed a positive asso-ciation between LMX and creative work involvement and confirmed our assumptions on the moderating role of job autonomy. The positive relationship between LMX and creative work involvement was stronger when employees experienced greater job autonomy. Our findings point to the importance of considering the interplay of both, the leader–member relationship and job design issues for increasing employees' creative work involvement.

Retrocrural space involvement on computed tomography as a predictor of mortality and disease severity in acute pancreatitis

BACKGROUND Because computed tomography (CT) has advantages for visualizing the manifestation of necrosis and local complications, a series of scoring systems based on CT manifestations have been developed for assessing the clinical outcomes of acute pancreatitis (AP), including the CT severity index (CTSI), modified CTSI, etc. Despite the internationally accepted CTSI having been successfully used to predict the overall mortality and disease severity of AP, recent literature has revealed the limitations of the CTSI. Using the Delphi method, we establish a new scoring system based on retrocrural space involvement (RCSI), and compared its effectiveness at evaluating the mortality and severity of AP with that of the CTSI. METHODS We reviewed CT images of 257 patients with AP taken within 3-5 days of admission in 2012. The RCSI scoring system, which includes assessment of infectious conditions involving the retrocrural space and the adjacent pleural cavity, was established using the Delphi method. Two radiologists independently assessed the RCSI and CTSI scores. The predictive points of the RCSI and CTSI scoring systems in evaluating the mortality and severity of AP were estimated using receiver operating characteristic (ROC) curves. PRINCIPAL FINDINGS The RCSI score can accurately predict the mortality and disease severity. The area under the ROC curve for the RCSI versus CTSI score was 0.962±0.011 versus 0.900±0.021 for predicting the mortality, and 0.888±0.025 versus 0.904±0.020 for predicting the severity of AP. Applying ROC analysis to our data showed that a RCSI score of 4 was the best cutoff value, above which mortality could be identified. CONCLUSION The Delphi method was innovatively adopted to establish a scoring system to predict the clinical outcome of AP. The RCSI scoring system can predict the mortality of AP better than the CTSI system, and the severity of AP equally as well.

Splicing changes in SMA mouse motoneurons and SMN-depleted neuroblastoma cells: evidence for involvement of splicing regulatory proteins.

Spinal Muscular Atrophy (SMA) is caused by deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene. The second gene copy, SMN2, produces some, but not enough, functional SMN protein. SMN is essential to assemble small nuclear ribonucleoproteins (snRNPs) that form the spliceosome. However, it is not clear whether SMA is caused by defects in this function that could lead to splicing changes in all tissues, or by the impairment of an additional, less well characterized, but motoneuron-specific SMN function. We addressed the first possibility by exon junction microarray analysis of motoneurons (MNs) isolated by laser capture microdissection from a severe SMA mouse model. This revealed changes in multiple U2-dependent splicing events. Moreover, splicing appeared to be more strongly affected in MNs than in other cells. By testing mutiple genes in a model of progressive SMN depletion in NB2a neuroblastoma cells, we obtained evidence that U2-dependent splicing changes occur earlier than U12-dependent ones. As several of these changes affect genes coding for splicing regulators, this may acerbate the splicing response induced by low SMN levels and induce secondary waves of splicing alterations.

The effects of legal involvement on crime victims' psychological adjustment

The purpose of this chapter is to examine the effects of legal involvement of crime victims on their psychological adjustment. First, causes of possible effects are described, which may be located within the procedure or the outcome of the legal process. Then, the available evidence is reviewed, most of it suggesting that legal involvement does not strongly affect the victims' psychological adjustment, neither negatively nor positively. The chapter continues with a discussion of whether victims should be advised to report the assault to the police or not, and it describes relevant decision criteria, such as victim adjustment retributive justice, victim compensation, victim security and societal security. Finally, suggestions for future research are outlined, pointing to necessary methodological improvements in the design of future studies on legal involvement.

Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.

OBJECTIVE Short-chain enoyl-CoA hydratase (ECHS1) is a multifunctional mitochondrial matrix enzyme that is involved in the oxidation of fatty acids and essential amino acids such as valine. Here, we describe the broad phenotypic spectrum and pathobiochemistry of individuals with autosomal-recessive ECHS1 deficiency. METHODS Using exome sequencing, we identified ten unrelated individuals carrying compound heterozygous or homozygous mutations in ECHS1. Functional investigations in patient-derived fibroblast cell lines included immunoblotting, enzyme activity measurement, and a palmitate loading assay. RESULTS Patients showed a heterogeneous phenotype with disease onset in the first year of life and course ranging from neonatal death to survival into adulthood. The most prominent clinical features were encephalopathy (10/10), deafness (9/9), epilepsy (6/9), optic atrophy (6/10), and cardiomyopathy (4/10). Serum lactate was elevated and brain magnetic resonance imaging showed white matter changes or a Leigh-like pattern resembling disorders of mitochondrial energy metabolism. Analysis of patients' fibroblast cell lines (6/10) provided further evidence for the pathogenicity of the respective mutations by showing reduced ECHS1 protein levels and reduced 2-enoyl-CoA hydratase activity. While serum acylcarnitine profiles were largely normal, in vitro palmitate loading of patient fibroblasts revealed increased butyrylcarnitine, unmasking the functional defect in mitochondrial β-oxidation of short-chain fatty acids. Urinary excretion of 2-methyl-2,3-dihydroxybutyrate - a potential derivative of acryloyl-CoA in the valine catabolic pathway - was significantly increased, indicating impaired valine oxidation. INTERPRETATION In conclusion, we define the phenotypic spectrum of a new syndrome caused by ECHS1 deficiency. We speculate that both the β-oxidation defect and the block in l-valine metabolism, with accumulation of toxic methacrylyl-CoA and acryloyl-CoA, contribute to the disorder that may be amenable to metabolic treatment approaches.

Possible involvement of plant ABC transporters in cadmium detoxification: a cDNA sub-microarray approach

As a nontolerant plant to a large number of toxic compounds, Arabidopsis thaliana is a suitable model to study regulation of genes involved in response to heavy metals. Using a cDNA-microarray approach, we identified some ABC transporters that are differentially regulated after cadmium treatments, making them putative candidates for being involved in Cd sequestration and redistribution in plants. Regarding yeast and fission yeast, in which Cd is able to form complexes either with glutathione (GSH) or phytochelatins (PC) subsequently transported into vacuoles via ABC transporters, it is also very likely that some plant ABC transporters are able to transport GS2–Cd or PC–Cd complexes into subcellular compartments or outside of the cell. The characterization of such transporters is of great interest for developing molecular biology approaches in phytoremediation.