julilili42/papers huggingface dataset:
Role of smooth muscle protein SM22α in glomerular epithelial cell injury
2011-02-03

Podocytes are considered terminally differentiated cells in the mature kidney under normal conditions. In the face of injury, podocytes may proceed along several possible pathways, including dedifferentiation and proliferation, persistent cell cycle arrest, hypertrophy, apoptosis, or necrosis. There is mounting evidence that transdifferentiation into a dysregulated phenotype may also be a potential cell fate. We have previously reported that the transcript of SM22α, an actin-binding protein considered one of the earliest markers of smooth muscle differentiation, is upregulated nearly 70-fold in glomeruli of rats with passive Heymann nephritis (PHN). In contrast, the SM22α transcript is absent in normal adult rat glomeruli. The purpose of this study was to define SM22α's expression during kidney development and its role in glomerular diseases characterized by podocyte injury and proteinuria. During glomerulogenesis and podocyte differentiation, SM22α was expressed in glomeruli. This expression disappeared with glomerular maturation. Along with SM22α induction in PHN, confirmed at both mRNA and protein levels, SM22α was also induced across a broad range of proteinuric diseases, including experimental animal models (puromycin aminonucleoside nephropathy, adriamycin nephropathy, passive nephrotoxic nephritis, and diet-induced obesity) and human diseases (collapsing glomerulopathy, diabetic nephropathy, classic focal segmental glomerulosclerosis, IgA nephropathy, minimal-change disease, membranous nephropathy, and membranoproliferative glomerulonephritis). Crescentic glomerulonephritis was induced in SM22α +/+ and SM22α −/− mice by intraperitoneal injection of sheep anti-rabbit glomeruli antibody 12.5 mg/20 g body wt × 2 doses ( n = 12–15/group), with mice euthanized at 7 and 14 days. Compared with SM22α −/− mice, SM22α +/+ mice demonstrated worse disease by histopathological parameters. In addition, there was greater apoptosis (cleaved caspase-3 immunostaining), fewer podocytes (Wilms' tumor-1 immunostaining), and less proliferation (Ki-67 immunostaining) in diseased SM22α +/+ mice. Furthermore, there was decreased activation of Erk1/2 in diseased SM22α +/+ mice. We conclude that the de novo expression of SM22α in glomerular epithelial cells affects the course of crescentic glomerulonephritis.
Generalized parton distributions in AdS/QCD
2011-02-04

The nucleon helicity-independent generalized parton distributions (GPDs) of quarks are calculated in the zero skewness case, in the framework of the AdS/QCD model. The present approach is based on a matching procedure of sum rules relating the electromagnetic form factors to GPDs and AdS modes.
Effect of the oxLDL Binding Protein Fc-CD68 on Plaque Extension and Vulnerability in Atherosclerosis
2011-02-04

Rationale: There is strong evidence that oxidative modification of low-density lipoprotein (oxLDL) plays a critical role in atherogenesis and that oxLDL may profoundly influence the mechanical stability of atherosclerotic plaques. Objective: To block oxLDL, we designed, expressed, and tested Fc-CD68, a soluble oxLDL binding protein consisting of human Fc and the extracellular domain of the human oxLDL-binding receptor CD68. Methods and Results: Fc-CD68 bound with high specific affinity to oxLDL and strongly bound and colocalized with oxLDL in plaques. To study the effects of repeated administrations of Fc-CD68 on the progression of atherosclerosis and plaque vulnerability, 12- and 16-week old cholesterol-fed ApoE −/− mice received either Fc-CD68 (n=6) or Fc control protein (n=6 to 8) thrice weekly for 4 weeks. Macroscopic and histological analysis of Sudan red lipid staining showed strong and significant reduction of plaque extension in the aorta and in the aortic root, respectively. Histological analysis of pentachrome- and Sirius-stained sections of the brachiocephalic arteries of 20 week-old ApoE −/− mice revealed that Fc-CD68 significantly reduced the occurrence of spontaneous ruptures of established plaques by ≈20%, compared with Fc and drastically increased the collagen content of plaques. Furthermore, in immunostained sections of the brachiocephalic artery and the aortic root, Fc-CD68 reduced the infiltration of plaques with T lymphocytes, and macrophages by ≈50% and 30%, respectively. Conclusions: The oxLDL binding protein Fc-CD68 attenuates atherosclerosis and strengthens the stability of atherosclerotic plaques.
Short-Term Treadmill Running as a Model for Studying Cell-Free DNA Kinetics In Vivo
2011-02-05

BACKGROUND Increased plasma concentrations of cell-free DNA (cf-DNA) are considered a hallmark of various clinical conditions. Despite intensive research in this field, limited data are available concerning the time course of release and clearance of cf-DNA in vivo. METHODS We extracted cf-DNA from plasma samples taken before and immediately after a 10-km cross-country run, and from samples taken before, immediately after, and 30 min after exhaustive short-term treadmill exercise. The contribution of nuclear (nDNA) and mitochondrial DNA (mtDNA) was measured by quantitative real-time PCR. The incremental treadmill exercise setup was exploited to delineate the precise sequencing and timing of cf-nDNA, lactate, and high-mobility group box 1 protein (HMGB1) release during the exercise and recovery phases. RESULTS Postexercise plasma cf-nDNA concentrations in cross-country and treadmill runners were significantly increased, by 7.6-fold and 9.9-fold, respectively (P &amp;lt; 0.001). cf-nDNA concentrations were not correlated with age, sex, or body mass index. Plasma concentrations of cf-nDNA and HMGB1 in postexercise samples of treadmill runners were significantly correlated (r = 0.84; P = 0.004). cf-mtDNA concentrations were not affected by treadmill exercise. Time-course analyses demonstrated that cf-nDNA is released within minutes after the onset of exercise and is rapidly cleared from the circulation after the cessation of exercise. Nearly congruent kinetics for cf-nDNA, lactate, and HMGB1 were observed during the exercise phase. CONCLUSIONS A single bout of exhaustive short-term treadmill exercise constitutes a versatile model system suitable for addressing basic questions about cf-DNA biology.
Dissecting work commitment: the role of Machiavellianism
2011-02-05

Purpose The aim of this paper is to refine the concept of work commitment by proposing a dissociation between self‐related work commitment (namely, employees' career commitment) and other‐related work commitment (pertaining more strongly to others such as team members or supervisors). The dissociation is demonstrated empirically through the differential predictive validity of Machiavellianism, which holds when the influence of broad personality dimensions is controlled for. Design/methodology/approach Personality characteristics (Machiavellianism and the six factors of the HEXACO model of personality) as well as organizational, supervisor, team, and career commitment of 154 employees were assessed via self‐reports. Findings Results support the hypotheses that Machiavellianism is related positively to self‐related work commitment (career commitment) and negatively to other‐related work commitment (organizational, supervisor, and team commitment), and explains unique variance in all criteria above the six broad dimensions of personality. Originality/value Although meta‐analyses have indicated strong overlaps between diverse work commitment foci, it is argued and shown that there are core differences between self‐related career commitment and other‐related commitment foci. Additionally, Machiavellianism as well as the HEXACO dimensions are investigated as predictors of work commitment foci for the first time.
Immunoinhibitory Adapter Protein Src Homology Domain 3 Lymphocyte Protein 2 (SLy2) Regulates Actin Dynamics and B Cell Spreading
2011-02-05

Appropriate B cell activation is essential for adaptive immunity. In contrast to the molecular mechanisms that regulate positive signaling in immune responses, the counterbalancing negative regulatory pathways remain insufficiently understood. The Src homology domain 3 (SH3)-containing adapter protein SH3 lymphocyte protein 2 (SLy2, also known as hematopoietic adapter-containing SH3 and sterile α-motif (SAM) domains 1; HACS1) is strongly up-regulated upon B cell activation and functions as an endogenous immunoinhibitor in vivo, but the underlying molecular mechanisms of SLy2 function have been elusive. We have generated transgenic mice overexpressing SLy2 in B and T cells and have studied the biological effects of elevated SLy2 levels in Jurkat and HeLa cells. Our results demonstrate that SLy2 induces Rac1-dependent membrane ruffle formation and regulates cell spreading and polarization and that the SLy2 SH3 domain is essential for these effects. Using immunoprecipitation and confocal microscopy, we provide evidence that the actin nucleation-promoting factor cortactin is an SH3 domain-directed interaction partner of SLy2. Consistent with an important role of SLy2 for actin cytoskeletal reorganization, we further show that SLy2-transgenic B cells are severely defective in cell spreading. Together, our findings extend our mechanistic understanding of the immunoinhibitory roles of SLy2 in vivo and suggest that the physiological up-regulation of SLy2 observed upon B cell activation functions to counteract excessive B cell spreading.
A Systematic Review of Propensity Score Methods in the Social Sciences
2011-02-07

The use of propensity scores in psychological and educational research has been steadily increasing in the last 2 to 3 years. However, there are some common misconceptions about the use of different estimation techniques and conditioning choices in the context of propensity score analysis. In addition, reporting practices for propensity score analyses often lack important details that allow other researchers to confidently judge the appropriateness of reported analyses and potentially to replicate published findings. In this article we conduct a systematic literature review of a large number of published articles in major areas of social science that used propensity scores up until the fall of 2009. We identify common errors in estimation, conditioning, and reporting of propensity score analyses and suggest possible solutions.
Opportunity Mars Rover mission: Overview and selected results from Purgatory ripple to traverses to Endeavour crater
2011-02-07

Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony‐iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional‐scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour&amp;rsquo;s rim that will be markedly different from anything examined to date.
Glossary of terms used in biomolecular screening (IUPAC Recommendations 2011)
2011-02-07

Biomolecular screening is now a crucial component of the drug discovery process, and this glossary will be of use to practitioners in the field of screening and to those who interact with the screening community. The glossary contains definitions related to various aspects of the screening process such as assay types, data handling, and relevant technologies. Many of the terms used in this discipline are not covered by existing glossaries, and where they are, the definitions are often not appropriate for this field. Where appropriate, this document provides new or modified definitions to better reflect the new context. The field of biomolecular screening is multidisciplinary in nature, and this glossary, containing authoritative definitions, will be useful not only for regular practitioners, but also for those who make use of data generated during the screening process.
Regulation of PINK1-Parkin-mediated mitophagy
2011-02-08

Parkinson disease (PD) is a devastating disorder of the nervous system for which no cure exists. Although the exact mechanisms involved in the pathogenesis of PD are unclear, very recently, a novel cellular process has been identified that promises great future potential. Two PD-associated genes have been found to converge on the emerging mitophagy pathway that links the two major cellular dysfunctions implicated in the pathogenesis of PD. Thereby, PINK1 and Parkin physically associate and functionally cooperate to identify and label damaged mitochondria for selective degradation via autophagy. PD-associated mutations in both genes disrupt mitophagy although through different mechanisms, revealing a sequential multistep process. Further key players that tie into this process have been identified and provide the framework for future research aiming at a complete dissection of this neuroprotective pathway. This may not only yield novel targets for therapeutic intervention in PD, but possibly for other neurodegenerative disorders as well.
Volitional Interventions within Cardiac Exercise Therapy (VIN‐CET): Long‐Term Effects on Physical Activity and Health‐Related Quality of Life
2011-02-08

Objectives : The present study tested the effectiveness of a theory‐based intervention (VIN‐CET) aimed to promote physical activity and to improve health‐related quality of life in cardiac rehabilitation. Design : Program effectiveness was evaluated by means of a quasi‐experiment with a longitudinal sample of 485 individuals with cardiovascular diseases participating in a 3‐week inpatient rehabilitation program (phase II). The VIN‐CET intervention was integrated into the exercise therapy of the standard program ( n = 300). Standard program participants were used as comparison group ( n = 185). Follow‐ups were conducted at 3 and 12 months after the intervention. Method : Physical exercise and leisure‐time physical activity were assessed by standardised self‐report measures. Physical and mental health status was measured with the SF‐12 and physical functioning was assessed with a sub‐scale of the SF‐36. Results : One year after the intervention, group comparisons showed small intervention effects ( p s &lt; .05) for physical exercise (Standardised Mean Difference, SMD = 0.22), physical health status (SMD = 0.20) and physical functioning (SMD = 0.17). Conclusion : The VIN‐CET intervention seems to be an effective and efficient way of promoting physical exercise in cardiac rehabilitation. Practical significance is reinforced by effects on physical aspects of health‐related quality of life.
‘Immunogenetics of Aging’: report on the activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop
2011-02-08

‘Immunogenetics of Aging’ is a component that was first included in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th Workshop. The aim of this component was to assess the impact of human leukocyte antigen (HLA) genes, cytokine genes, and some innate immunity genes such as killer‐cell immunoglobulin‐like receptors (KIRs) and mannose‐binding lectin 2 (MBL2) in successful aging and their contribution to the better understanding of immune dysfunction in old age. Within the 15th IHIWS new populations were included in the analysis. Additional cytokine gene polymorphisms were assessed and innate immunity genes were analyzed for possible relevance in longevity. The results showed that longevity might be associated with anti‐inflammatory cytokine gene profiles, decreased frequency of interleukin‐10 (IL‐10) and transforming growth factor‐B1 haplotypes associated with a low level of gene expression, and increased frequency of haplotypes determining a high level of expression. Extended tumor necrosis factor‐A and IL‐12B genotypes were also likely relevant to longevity. Data also showed that innate immunity genes are associated with susceptibility to infections in the elderly and showed that these genes might be an important genetic marker in aging. Decreased frequencies of KIR2DS5 and A1B10 haplotypes, and an increased proportion of MBL2‐deficient haplotypes were found in the group with higher cytomegalovirus‐specific IgG antibody levels. Together, these studies emphasize the relevance of genes regulating immune functions in maintaining human longevity and stress the importance of further clarifying their impact on successful aging.
Determination of the PSI/PSII ratio in living plant cells at room temperature by spectrally resolved fluorescence spectroscopy
2011-02-08

Leaf cells of living plants exhibit strong fluorescence from chloroplasts, the reaction centers of photosynthesis. Mutations in the photosystems change their structure and can, thus, be monitored by recording the fluorescence spectra of the emitted chlorophyll light. These measurements have, up to now, mostly been carried out at low temperatures (77 K), as these conditions enable the differentiation between the fluorescence of Photosystem I (PSI) and Photosystem II (PSII). In contrast, at room temperature, energy transfer processes between the various photosynthetic complexes result in very similar fluorescence emissions, which mainly consist of fluorescence photons emitted by PSII hindering a discrimination based on spectral ROIs (regions of interest). However, by statistical analysis of high resolution fluorescence spectra recorded at room temperature, it is possible to draw conclusions about the relative PSI/PSII ratio. Here, the possibility of determining the relative PSI/PSII ratio by fluorescence spectroscopy is demonstrated in living maize plants. Bundle-sheath chloroplasts of mature maize plants have a special morphologic characteristic; they are agranal, or exhibit only rudimentary grana, respectively. These chloroplasts are depleted in PSII activity and it could be shown that PSII is progressively reduced during leaf differentiation. A direct comparison of PSII activity in isolated chloroplasts is nearly impossible, since the activity of PSII in both mesophyll- and bundle-sheath chloroplasts decays with time after isolation and it takes significantly longer to isolate bundle-sheath chloroplasts. Considering this fact the measurement of PSI/PSII ratios with the 77K method, which includes taking fluorescence spectra from a diluted suspension of isolated chloroplasts at 77K, is questionable. These spectra are then used to analyze the distribution of energy between PSI and PSII. After rapid cooling to 77K secondary biochemical influences, which attenuate the fluorescence emanated from PSI, are frozen out. Due to their characteristic morphology, maize chloroplasts of mesophyll and bundle-sheath cells are an appropriate system for demonstrating the applicability of our in vivo method which, unlike the common 77K method, does not require the isolation of chloroplasts. In mesophyll chloroplasts of higher land plants, the thylakoids have a heterogenic morphology of appressed and non-appressed membrane domains, called the grana and the stroma lamellae. PSII is enriched in the grana, whereas PSI is enriched in the stroma lamellae. Changes in chloroplast membrane structure and composition, according to changes in the PSI/ PSII ratio, can be triggered by light quality and carbon source deficiency. Here, we demonstrate the applicability of statistical analysis of fluorescence spectra to detect changes in the PSI/PSII ratio resulting from structure changes in the thylakoid membrane.
LRRK2 Controls Synaptic Vesicle Storage and Mobilization within the Recycling Pool
2011-02-09

Mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are the single most common cause of inherited Parkinson's disease. Little is known about its involvement in the pathogenesis of Parkinson's disease mainly because of the lack of knowledge about the physiological role of LRRK2. To determine the function of LRRK2, we studied the impact of short hairpin RNA-mediated silencing of LRRK2 expression in cortical neurons. Paired recording indicated that LRRK2 silencing affects evoked postsynaptic currents. Furthermore, LRRK2 silencing induces at the presynaptic site a redistribution of vesicles within the bouton, altered recycling dynamics, and increased vesicle kinetics. Accordingly, LRRK2 protein is present in the synaptosomal compartment of cortical neurons in which it interacts with several proteins involved in vesicular recycling. Our results suggest that LRRK2 modulates synaptic vesicle trafficking and distribution in neurons and in consequence participates in regulating the dynamics between vesicle pools inside the presynaptic bouton.
Host–parasite local adaptation after experimental coevolution of Caenorhabditis elegans and its microparasite Bacillus thuringiensis
2011-02-09

Coevolving hosts and parasites can adapt to their local antagonist. In studies on natural populations, the observation of local adaptation patterns is thus often taken as indirect evidence for coevolution. Based on this approach, coevolution was previously inferred from an overall pattern of either parasite or host local adaptation. Many studies, however, failed to detect such a pattern. One explanation is that the studied system was not subject to coevolution. Alternatively, coevolution occurred, but remained undetected because it took different routes in different populations. In some populations, it is the host that is locally adapted, whereas in others it is the parasite, leading to the absence of an overall local adaptation pattern. Here, we test for overall as well as population-specific patterns of local adaptation using experimentally coevolved populations of the nematode Caenorhabditis elegans and its bacterial microparasite Bacillus thuringiensis . Furthermore, we assessed the importance of random interaction effects using control populations that evolved in the absence of the respective antagonist. Our results demonstrate that experimental coevolution produces distinct local adaptation patterns in different replicate populations, including host, parasite or absence of local adaptation. Our study thus provides experimental evidence of the predictions of the geographical mosaic theory of coevolution, i.e. that the interaction between parasite and host varies across populations.