julilili42/papers huggingface dataset:
Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12
2012-01-09

Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative conditions. They are characterized by progressive spastic paralysis of the legs as a result of selective, length-dependent degeneration of the axons of the corticospinal tract. Mutations in 3 genes encoding proteins that work together to shape the ER into sheets and tubules - receptor accessory protein 1 (REEP1), atlastin-1 (ATL1), and spastin (SPAST) - have been found to underlie many cases of HSP in Northern Europe and North America. Applying Sanger and exome sequencing, we have now identified 3 mutations in reticulon 2 (RTN2), which encodes a member of the reticulon family of prototypic ER-shaping proteins, in families with spastic paraplegia 12 (SPG12). These autosomal dominant mutations included a complete deletion of RTN2 and a frameshift mutation predicted to produce a highly truncated protein. Wild-type reticulon 2, but not the truncated protein potentially encoded by the frameshift allele, localized to the ER. RTN2 interacted with spastin, and this interaction required a hydrophobic region in spastin that is involved in ER localization and that is predicted to form a curvature-inducing/sensing hairpin loop domain. Our results directly implicate a reticulon protein in axonopathy, show that this protein participates in a network of interactions among HSP proteins involved in ER shaping, and further support the hypothesis that abnormal ER morphogenesis is a pathogenic mechanism in HSP.
Specificity of jumping to conclusions and attributional biases: A comparison between patients with schizophrenia, depression, and anorexia nervosa
2012-01-09

We found evidence for the specificity of an externalising bias for paranoid schizophrenia. Concerning JTC bias the evidence was less clear. Whether the modification of those biases through psychological interventions would have an effect on psychopathology should be investigated in the context of clinical trials.
The Alzheimer’s Disease Related Tau Protein as a New Target for Chemical Protein Engineering
2012-01-09

Site-specifically phosphorylated tau: A semisynthetic strategy has been applied for the first time to generate a phosphorylated and biotinylated fully functional tau protein (see figure). The presented methodology allows for an unambiguous verification of individual phosphorylation sites on tau and significantly improves its purification. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cell Wall Antibiotics Provoke Accumulation of Anchored mCherry in the Cross Wall of Staphylococcus aureus
2012-01-10

A fluorescence microscopy method to directly follow the localization of defined proteins in Staphylococcus was hampered by the unstable fluorescence of fluorescent proteins. Here, we constructed plasmid (pCX) encoded red fluorescence (RF) mCherry (mCh) hybrids, namely mCh-cyto (no signal peptide and no sorting sequence), mCh-sec (with signal peptide), and mCh-cw (with signal peptide and cell wall sorting sequence). The S. aureus clones targeted mCh-fusion proteins into the cytosol, the supernatant and the cell envelope respectively; in all cases mCherry exhibited bright fluorescence. In staphylococci two types of signal peptides (SP) can be distinguished: the +YSIRK motif SP(lip) and the -YSIRK motif SP(sasF). mCh-hybrids supplied with the +YSIRK motif SP(lip) were always expressed higher than those with -YSIRK motif SP(sasF). To study the location of the anchoring process and also the influence of SP type, mCh-cw was supplied on the one hand with +YSIRK motif (mCh-cw1) and the other hand with -YSIRK motif (mCh-cw2). MCh-cw1 preferentially localized at the cross wall, while mCh-cw2 preferentially localized at the peripheral wall. Interestingly, when treated with sub-lethal concentrations of penicillin or moenomycin, both mCh-cw1 and mCh-cw2 were concentrated at the cross wall. The shift from the peripheral wall to the cross wall required Sortase A (SrtA), as in the srtA mutant this effect was blunted. The effect is most likely due to antibiotic mediated increase of free anchoring sites (Lipid II) at the cross wall, the substrate of SrtA, leading to a preferential incorporation of anchored proteins at the cross wall.
Pneumonectomy: calculable or non-tolerable risk factor in trimodal therapy for Stage III non-small-cell lung cancer?
2012-01-10

Pneumonectomy in neoadjuvant trimodal approach for Stage III NSCLC can be done safe with acceptable mortality rate. Patients should not withhold from operation because of necessitating pneumonectomy. Not the procedure but the selection, response rate and R0-resection are crucial for survival after trimodal therapy in experienced centres.
Contaminant Mass Transfer from NAPLs to Water Studied in a Continuously Stirred Flow-Through Reactor
2012-01-10

&lt;p&gt;\\n\\tThe release of nonaqueous-phase liquids (NAPLs) from porous media to groundwater is a widespread environmental problem. The mass transfer of individual NAPL components controls both the extent of groundwater contamination and the persistence of the residual NAPL phase. In order to quantify this key process, small-scale experimental studies on NAPL-water mass transfer were performed in a dynamic system mimicking environmental conditions with &amp;quot;clean&amp;quot; water continuously flowing through the NAPL pool. To describe this process, a modified simulation method was developed and validated by the experimental data. The experimental system consisted of a custom-designed flow cell (with NAPL and water) connected to the peripheral equipment (e. g., pump, water source). This continuously stirred flow-through reactor was used to perform mass transfer experiments with simple and complex model NAPL-water systems. To simulate the experimental data (concentration versus time profiles of individual NAPL compounds), an analytical solution of a standard mass transfer model was adapted in simple model NAPL systems, and a numerical method was employed for complex multicomponent model NAPL-water systems containing phenols, heteroaromatic compounds, and polycyclic aromatic hydrocarbons (PAHs). The numerical model was developed based on a mass balance equation and a general form of Raoult&amp;#39;s law. The simulated concentration profiles of the various solutes matched well the experimental data only if the nonideal behavior of the more polar solutes was accounted for. Using the developed numerical mode simulated mass transfer coefficients for individual NAPL components compared well with previously published values if available. DOI:10.1061/(ASCE)EE.1943-7870.0000528. (C) 2012 American Society of Civil Engineers.&lt;/p&gt;
Altered miRNA expression patterns in Tff2 knock-out mice correlate with cellular pathways of neoplastic development and caloric metabolism
2012-01-10

The trefoil peptide family, consisting in mammals of three members namely TFF1, 2 and 3, plays a cytoprotective role in epithelial cells of various tissues, mainly in the digestive tract. Tff1, Tff2 or Tff3 knock-out mouse models developed various kinds of gastrointestinal impairment. microRNAs are known to be novel gene regulators. We aimed to investigate the physiological role of such miRNAs in Tff2 knock-out mice. Whole miRNome profiling and in silico analysis were performed for Tff2-KO and WT mice. Our latest data explored the role of miRNAs in the regulatory cascades and molecular processes of Tff2-/- mice. As much as 6% of the Tff2-KO mice miRNome was significantly dys-regulated. Further in silico analysis suggests that the respective dys-regulated part of the miRNome is involved in human pathological processes, including pancreatic, colorectal and basal cell cancer. Additionally, the dys-regulated miRNome targets pathways involved in carbohydrate metabolism and adipocytokine signaling. The latter links deficient caloric maintenance in Tff2 and previous observation in Tff3-KO mice with miRNAs. In summary, our proof-of-concept study indicates that miRNAs may play an important role in the regulatory processes of the trefoil peptide family, especially in the regulation of cancer-related cascades.
Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier
2012-01-11

Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens.
Nontoxic Nep1-Like Proteins of the Downy Mildew Pathogen Hyaloperonospora arabidopsidis: Repression of Necrosis-Inducing Activity by a Surface-Exposed Region
2012-01-11

The genome of the downy mildew pathogen Hyaloperonospora arabidopsidis encodes necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins (NLP). Although NLP are widely distributed in eukaryotic and prokaryotic plant pathogens, it was surprising to find these proteins in the obligate biotrophic oomycete H. arabidopsidis. Therefore, we analyzed the H. arabidopsidis NLP (HaNLP) family and identified 12 HaNLP genes and 15 pseudogenes. Most of the 27 genes form an H. arabidopsidis–specific cluster when compared with other oomycete NLP genes, suggesting this class of effectors has recently expanded in H. arabidopsidis. HaNLP transcripts were mainly detected during early infection stages. Agrobacterium tumefaciens–mediated transient expression and infiltration of recombinant NLP into tobacco and Arabidopsis leaves revealed that all HaNLP tested are noncytotoxic proteins. Even HaNLP3, which is most similar to necrosis-inducing NLP proteins of other oomycetes and which contains all amino acids that are critical for necrosis-inducing activity, did not induce necrosis. Chimeras constructed between HaNLP3 and the necrosis-inducing PsojNIP protein demonstrated that most of the HaNLP3 protein is functionally equivalent to PsojNIP, except for an exposed domain that prevents necrosis induction. The early expression and species-specific expansion of the HaNLP genes is suggestive of an alternative function of noncytolytic NLP proteins during biotrophic infection of plants.
Molecular Orientation in Polymer Films for Organic Solar Cells Studied by NEXAFS
2012-01-11

The application of new polymer materials for organic solar cells requires a detailed understanding of the orientation and the electronic properties of the system because these have a dramatic effect on the device performance and efficiency. The films were prepared by doctor blade casting, a simple preparation route from solution. We study the orientation of the low band gap polymers poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b:3,4-b′]dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT) and poly-[2,6-(4,4-bis(2-ethyl)-4H-cyclopenta[2,1-b:3,4-b′]dithiophene)-alt-5,8-(2,3-dioctylquinoxaline)] (PCPDTQ) as well as of the state of the art polymer poly(3-hexyl-thiophene) (P3HT) using near-edge X-ray absorption fine structure spectroscopy (NEXAFS). Clear angular dependence in the NEXAFS spectra is observed for P3HT and PCPDTBT pointing to well-orientated films.
Current status of molecular markers for prognostication and outcome in invasive bladder cancer
2012-01-11

What's known on the subject? and What does the study add? Currently, prognostication of patients with invasive BC is hampered owing to the inadequacy of standard clinicopathological risk factors to predict accurately individual treatment outcomes. This review provides a comprehensive albeit brief overview on current studies elucidating the potential role of different molecular markers to close this gap of evidence. It focusses on biostatistical considerations in the interpretation of study results which are essential to provide meaningful clinical conclusions for an individual patient. OBJECTIVE To improve prognostication and the management of patients with invasive bladder cancer (BC). METHODS Standard clinicopathological risk factors are not reliably enough to accurately predict outcomes in patients after radical treatment and guide clinicians for recommending selectively the use of adjuvant therapies. With detailed insights into the molecular pathology of BC, biomarkers have come to the fore of researchers as a potential tool to close this gap of evidence. However, their definitive role in the diagnostic and therapeutic management of patients with invasive BC has not clearly been addressed so far. RESULTS Invasive BC are an extremely heterogenenous group of malignancies which are characterized by multiple genetic alterations involved in the carcinogenesis and development of metastatic spread. Thus, it is questionable whether any single marker will provide superior prognostication compared with a combination of markers. Current studies evaluating the predictive value of a multitude of markers have used high‐throughput technologies and investigated the gain in predictive accuracy within new nomograms which encompass well‐established clinicopathological and novel putative molecular parameters. p53 overexpression was found to be associated with increased risk of recurrence in urothelial and non‐urothelial cancer. In pT1 disease, the combination of p53, p21 and p16 as well as epigenetic alterations of myopodin expression has been shown to provide improved prognostication, and this might help to advocate more selectively the use of early radical treatment. After the bladder‐sparing approach, p53 and p21 overexpression indicate decreased probability of long‐term bladder preservation. Additionally, altered retinoblastoma expression is associated with improved survival after adjuvant chemotherapy. To provide meaningful conclusions for individual prognosis and the need of adjuvant treatment, biostatistical pitfalls in the analysis and interpretation of results have to be taken into account. CONCLUSIONS Different molecular markers have the potential to improve prognostication of patients with invasive BC and provide improved evidence for targeted therapy in the neoadjuvant, adjuvant and metastatic setting. However, in order to advocate their routine clinical use on a sound scientific basis prospective data are still necessary.
Haploidentical stem cell transplantation for children with high‐risk leukemia
2012-01-11

Abstract Background The Chilean population is ethnically diverse, and more than 50% of children referred for hematopoietic stem cell transplantation (HSCT) lack a suitable donor. Procedure To expand the donor pool, we assessed the feasibility, tolerance, and efficacy of using a haploidentical (HI) donor and a reduced‐intensity conditioning regimen for high‐risk pediatric leukemia. This study was facilitated by technology transfer from St. Jude Children's Research Hospital over the 2 preceding years. Results Between March 2006 and April 2009, 10 patients (median age, 9.8 years) received T cell‐depleted grafts at Calvo Mackenna Hospital in Santiago. Median cell doses were CD34+: 7.45 × 10 6 /kg (range, 4.00–20.20 × 10 6 /kg); CD3+: 0.88 × 10 5 /kg (0.11–1.35 × 10 5 /kg); and CD56+: 71.30 × 10 6 /kg (31.50–131.80 × 10 6 /kg). Nine patients experienced complete engraftment; six of the nine remain alive and clinically well 13–50 months post‐HSCT. Three patients died after bone marrow relapse, while only one died of transplant‐related causes. Virus reactivation was the main post‐transplant complication: 5/10 had positive CMV PCR but none had CMV disease. One patient developed acute GvHD &gt; grade II and only one had chronic GvHD. Conclusions HI‐HSCT is feasible in our setting, offers a rational treatment option, and expands the donor pool significantly for children with high‐risk leukemia in a developing country. This information is especially relevant to other ethnically diverse populations that are poorly represented in international donor registries. Pediatr Blood Cancer 2012; 59: 895–901. © 2012 Wiley Periodicals, Inc.
Two Distinct Coagulase-Dependent Barriers Protect Staphylococcus aureus from Neutrophils in a Three Dimensional in vitro Infection Model
2012-01-12

Staphylococcus aureus is a pyogenic abscess-forming facultative pathogenic microorganism expressing a large set of virulence-associated factors. Among these, secreted proteins with binding capacity to plasma proteins (e.g. fibrinogen binding proteins Eap and Emp) and prothrombin activators such as Coagulase (Coa) and vWbp are involved in abscess formation. By using a three-dimensional collagen gel (3D-CoG) supplemented with fibrinogen (Fib) we studied the growth behavior of S. aureus strain Newman and a set of mutants as well as their interaction with mouse neutrophils by real-time confocal microscopy. In 3D-CoG/Fib, S. aureus forms microcolonies which are surrounded by an inner pseudocapsule and an extended outer dense microcolony-associated meshwork (MAM) containing fibrin. Coa is involved in formation of the pseudocapsule whereas MAM formation depends on vWbp. Moreover, agr-dependent dispersal of late stage microcolonies could be observed. Furthermore, we demonstrate that the pseudocapsule and the MAM act as mechanical barriers against neutrophils attracted to the microcolony. The thrombin inhibitor argatroban is able to prevent formation of both pseudocapsule and MAM and supports access of neutrophils to staphylococci. Taken together, this model can simulate specific stages of S. aureus abscess formation by temporal dissection of bacterial growth and recruitment of immune cells. It can complement established animal infection models in the development of new treatment options.
Hydromagnetic equilibrium in non-barotropic multifluid neutron stars
2012-01-12

Traditionally, the subject of hydromagnetic equilibrium in neutron stars has been addressed in the context of standard magnetohydrodynamics, with matter obeying a barotropic equation of state. In this paper we take a step towards a more realistic treatment of the problem by considering neutron stars with interior superfluid components. In this multifluid model stratification associated with a varying matter composition (the relative proton to neutron density fraction) enters as a natural ingredient, leading to a non-barotropic system. After formulating the hydromagnetic equilibrium of superfluid/superconducting neutron stars as a perturbation problem, we focus on the particular case of a three-fluid system consisting of superfluid neutrons and normal protons and electrons. We determine the equilibrium structure of dipolar magnetic fields with a mixed poloidal-toroidal composition. We find that, with respect to barotropic models, stratification has the generic effect of leading to equilibria with a higher fraction of magnetic energy stored in the toroidal component. However, even in models with strong stratification the poloidal and toroidal components are comparable, with the former contributing the bulk of the magnetic energy.
New features of the triaxial nuclei described with a coherent state model
2012-01-12

Supplementing the Liquid Drop Model (LDM) Hamiltonian, written in the\\nintrinsic reference frame, with a sextic oscillator plus a centrifugal term in\\nthe variable and a potential in with a minimum in\\n , the Sch\\\\"{o}dinger equation is separated for the two variables\\nwhich results in having a new description for the triaxial nuclei, called\\nSextic and Mathieu Approach (SMA). SMA is applied for two non-axial nuclei,\\n Hf and W and results are compared with those yielded by the\\nCoherent State Model (CSM). As the main result of this paper we derive\\nanalytically the equations characterizing SMA from a semi-classical treatment\\nof the CSM Hamiltonian. In this manner the potentials in and \\nvariables respectively, show up in a quite natural way which contrasts their\\nad-hoc choice when SMA emerges from LDM.\\n
Banking Globalization
2012-01-12

This article provides an overview of research on the causes and effects of international bank mergers. It focuses on three main questions: First, what are the determinants and driving forces of cross-border bank mergers? Second, what are the effects of cross-border bank mergers on the efficiency and competitiveness of financial institutions and the financial system? Third, what are the implications of bank mergers for risks in banking? It begins with a brief review of the stylized facts on international bank mergers.