julilili42/papers huggingface dataset:
The secretome of the working human skeletal muscle—A promising opportunity to combat the metabolic disaster?
2013-12-24

Recent years have provided clear evidence for the skeletal muscle as an endocrine organ. Muscle contraction during physical activity has emerged as an important activator of the release of the proteins and peptides called “myokines." Diverse proteomic profiling approaches were applied to rodent and human skeletal muscle cells to characterize the complete secretome, to study the regulation of the secretome during cell differentiation or the release of myokines upon contractile activity of myotubes. Several of the exercise‐regulated factors have the potency to mediate an interorgan crosstalk. The paracrine function of the secreted peptides and proteins to regulate muscle regeneration, tissue remodeling, and trainability can have direct effects on whole‐body glucose disposal and oxygen consumption. The overall composition and dynamic of the myokinome are still incompletely characterized. Recent advantages in metabolomics and lipidomics will add metabolites and lipids with autocrine, paracrine, or endocrine function to the contraction‐induced secretome of the skeletal muscle. The identification of these metabolites will lead to a more comprehensive view described by a new myo(metabo)kinome consisting of peptides, proteins, and metabolites.
Genome‐wide association study in musician's dystonia: A risk variant at the arylsulfatase G locus?
2013-12-26

ABSTRACT Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2‐stage genome‐wide association study in whites. Genotypes at 557,620 single‐nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed P &lt; 10 −5 and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome‐wide significant SNP ( P &lt; 5 × 10 −8 ) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome‐wide significance with MD was observed for an intronic variant in the arylsulfatase G ( ARSG ) gene (rs11655081; P = 3.95 × 10 −9 ; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66‐7.05). rs11655081 was also associated with WD ( P = 2.78 × 10 −2 ) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (λ = 1.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients. © 2013 International Parkinson and Movement Disorder Society
A Trimeric Lipoprotein Assists in Trimeric Autotransporter Biogenesis in Enterobacteria
2013-12-26

Trimeric autotransporter adhesins (TAAs) are important virulence factors of many Gram-negative bacterial pathogens. TAAs form fibrous, adhesive structures on the bacterial cell surface. Their N-terminal extracellular domains are exported through a C-terminal membrane pore; the insertion of the pore domain into the bacterial outer membrane follows the rules of β-barrel transmembrane protein biogenesis and is dependent on the essential Bam complex. We have recently described the full fiber structure of SadA, a TAA of unknown function in Salmonella and other enterobacteria. In this work, we describe the structure and function of SadB, a small inner membrane lipoprotein. The sadB gene is located in an operon with sadA; orthologous operons are only found in enterobacteria, whereas other TAAs are not typically associated with lipoproteins. Strikingly, SadB is also a trimer, and its co-expression with SadA has a direct influence on SadA structural integrity. This is the first report of a specific export factor of a TAA, suggesting that at least in some cases TAA autotransport is assisted by additional periplasmic proteins.
Increasing Bone Sclerosis During Bortezomib Therapy in Multiple Myeloma Patients: Results of a Reduced-Dose Whole-Body MDCT Study
2013-12-26

Bone remineralization may occur during bortezomib-based therapy for MM in a substantial proportion of patients. The extent, location, and patterns of sclerosis differ among patients and are unpredictable. Sclerosis was documented even in patients showing suboptimal hematologic response.
Pd@SnO2 and SnO2@Pd Core@Shell Nanocomposite Sensors
2013-12-27

Pd@SnO 2 and SnO 2 @Pd core@shell nanocomposites are prepared via a microemulsion approach. Both nanocomposites exhibit high‐surface, porous matrices of SnO 2 shells (&gt;150 m 2 g −1 ) with very small SnO 2 crystallites (&lt;10 nm) and palladium (Pd) nanoparticles (&lt;10 nm) that are uniformly distributed in the porous SnO 2 matrix. Although similar by first sight, Pd@SnO 2 and SnO 2 @Pd are significantly different in view of their structure with Pd inside or outside the SnO 2 shell and in view of their sensor performance. As SMOX‐based sensors (SMOX: semiconducting metal oxide), both nanocomposites show a very good sensor performance for the detection of CO and H 2 . Especially, the Pd@SnO 2 core@shell nanocomposite is unique and shows a fast response time (τ 90 &lt; 30 s) and a very good response at low temperature (&lt;250 °C), especially under humid‐air conditions. Extraordinarily high sensor signals are observed when exposing the Pd@SnO 2 nanocomposite to CO in humid air. Under these conditions, even commercial sensors (Figaro TGS 2442, Applied Sensor MLC, E2V MICS 5521) are outperformed.
Context affects lightness at the level of surfaces
2013-12-27

The accurate perception of object attributes such as surface lightness is vital for the successful interaction with the environment. However, it is unknown how the visual system assigns lightness values to surfaces based on the intensity distribution in the retinal image. It has been shown that the perceived lightness of an image region is influenced by its context but whether that influence involves so-called low-, mid- or high-level mechanisms is disputed. To probe the level of lightness perception psychophysically we manipulated the surface character of a target region and measured its influence on perceived lightness. We show that only when the target region was consistent with the perceptual interpretation of a surface it was subject to a subjective brightening (assimilation) effect. When the target region was consistent with a spotlight, and hence inconsistent with surface perception, there was no concomitant increase in perceived lightness. These results suggest that the effect of context on the lightness of an image region is not deterministic, but can instead be modulated by other attributes of the image region that imply a mid-level scene interpretation.
Imaging Morphology and Function of Cortical Microglia
2013-12-28

Microglial cells are the innate immune cells of the central nervous system. In the healthy adult brain "resting" ramified microglia continuously palpate their environment to monitor the integrity of and to react to any disturbance of brain homeostasis. During injury, inflammation, and in the course of neurodegenerative diseases microglia become activated, proliferate, and release a plethora of cytokines as well as reactive oxygen species. In addition to their well known role in disease, it has become increasingly clear that "resting" microglia also contribute to normal brain physiology, both during postnatal development and in the mature adult brain. Functional in vivo imaging of microglia first of all captures the morphological changes accompanying microglial transition between "resting" and activated states. In addition, intracellular Ca2+ homeostasis of microglia is believed to be altered between the two states [1–3]. So far, however, microglial Ca2+ signaling was predominantly studied in reduced preparations like brain slices or cell cultures, in which microglia are found in a rather activated state. In this chapter we describe a technique for studying microglial Ca2+ signaling in vivo. Furthermore, we discuss a new approach for visualization of morphological dynamics of microglial cells in vivo at high resolution. This approach utilizes a lectin-based staining technique and is applicable to any deliberate mouse strain at any developmental stage.
The potential additional diagnostic value of assessing for pericardial effusion on cardiac magnetic resonance imaging in patients with suspected myocarditis
2013-12-29

The finding of PE in unselected patients with suspected AMC or CMC is not specific to myocarditis. Therefore, with the currently applied criteria and methods, assessment of PE does not improve the diagnostic performance of CMR in this patient cohort.
Dynamic 18F-FET PET in Newly Diagnosed Astrocytic Low-Grade Glioma Identifies High-Risk Patients
2013-12-30

Absence of (18)F-FET uptake in newly diagnosed astrocytic low-grade glioma does not generally indicate an indolent disease course. Among the (18)F-FET-positive gliomas, decreasing time-activity curves in dynamic (18)F-FET PET constitute an unfavorable prognostic factor in astrocytic low-grade glioma and, by identifying high-risk patients, may ease treatment decisions.
Knockdown of Hsc70-5/mortalin Induces Loss of Synaptic Mitochondria in a Drosophila Parkinson’s Disease Model
2013-12-30

Mortalin is an essential component of the molecular machinery that imports nuclear-encoded proteins into mitochondria, assists in their folding, and protects against damage upon accumulation of dysfunctional, unfolded proteins in aging mitochondria. Mortalin dysfunction associated with Parkinson's disease (PD) increases the vulnerability of cultured cells to proteolytic stress and leads to changes in mitochondrial function and morphology. To date, Drosophila melanogaster has been successfully used to investigate pathogenesis following the loss of several other PD-associated genes. We generated the first loss-of-Hsc70-5/mortalin-function Drosophila model. The reduction of Mortalin expression recapitulates some of the defects observed in the existing Drosophila PD-models, which include reduced ATP levels, abnormal wing posture, shortened life span, and reduced spontaneous locomotor and climbing ability. Dopaminergic neurons seem to be more sensitive to the loss of mortalin than other neuronal sub-types and non-neuronal tissues. The loss of synaptic mitochondria is an early pathological change that might cause later degenerative events. It precedes both behavioral abnormalities and structural changes at the neuromuscular junction (NMJ) of mortalin-knockdown larvae that exhibit increased mitochondrial fragmentation. Autophagy is concomitantly up-regulated, suggesting that mitochondria are degraded via mitophagy. Ex vivo data from human fibroblasts identifies increased mitophagy as an early pathological change that precedes apoptosis. Given the specificity of the observed defects, we are confident that the loss-of-mortalin model presented in this study will be useful for further dissection of the complex network of pathways that underlie the development of mitochondrial parkinsonism.
Midtreatment Evaluation of Lymphoma Response to Chemotherapy by Volume Perfusion Computed Tomography
2013-12-30

Objective The aim of this study was to search for chemotherapy-induced perfusion changes of diffuse large B-cell lymphoma, follicular lymphoma, and Hodgkin lymphoma at midtreatment versus baseline volume perfusion computed tomography (VPCT). Methods Forty-five consecutive patients with untreated diffuse large B-cell lymphoma, follicular lymphoma, and Hodgkin lymphoma received VPCT examinations of the tumor bulk at baseline and during chemotherapy (midtreatment). Blood flow (BF), blood volume (BV), and transit constant (K-trans) were determined. Treatment response was categorized according to the Cheson criteria into complete or partial remission and stable or relapsed/progressive disease. Results Midtreatment follow-up showed a reduction in BF, BV, and K-trans in all lymphoma subtypes compared with baseline. The reduction in BV was less pronounced in larger tumors. Notably, BF, BV, and K-trans decreased in the responders (complete remission/partial remission) when compared with the nonresponders (stable or relapsed/progressive disease). Less than 10% reduction in BF was shown to be the best VPCT criterion for the identification of nonresponse. Conclusions Chemotherapy-induced perfusion changes in responders are recognizable at midtreatment VPCT.
Learning is not decline
2013-12-31

As otherwise healthy adults age, their performance on cognitive tests tends to decline. This change is traditionally taken as evidence that cognitive processing is subject to significant declines in healthy aging. We examine this claim, showing current theories over-estimate the evidence in support of it, and demonstrating that when properly evaluated, the empirical record often indicates that the opposite is true. To explain the disparity between the evidence and current theories, we show how the models of learning assumed in aging research are incapable of capturing even the most basic of empirical facts of “associative” learning, and lend themselves to spurious discoveries of “cognitive decline.” Once a more accurate model of learning is introduced, we demonstrate that far from declining, the accuracy of older adults lexical processing appears to improve continuously across the lifespan. We further identify other measures on which performance does not decline with age, and show how these different patterns of performance fit within an overall framework of learning. Finally, we consider the implications of our demonstrations of continuous and consistent learning performance throughout adulthood for our understanding of the changes in underlying brain morphology that occur during the course of cognitive development across the lifespan.
Identification and Quantification of Protein Adducts Formed by Metabolites of 1-Methoxy-3-indolylmethyl Glucosinolate in Vitro and in Mouse Models
2013-12-31

1-Methoxy-3-indolylmethyl (1-MIM) glucosinolate (GLS) occurring in cabbage, broccoli, and other cruciferous plants is a potent mutagen requiring metabolic activation by myrosinase present in plant cells and intestinal bacteria. We previously reported that 1-MIM-GLS and its alcoholic breakdown product 1-MIM-OH, which requires additional activation by sulfotransferases, form DNA adducts in mice. In the present study, the formation of protein adducts was investigated. First, two major adducts obtained after incubation of individual amino acids, serum albumin, or hemoglobin with 1-MIM-GLS in the presence of myrosinase were identified as τN-(1-MIM)-His and πN-(1-MIM)-His using MS and NMR spectroscopy. After the development of a specific detection method using isotope-dilution UPLC-ESI-MS/MS, adduct formation was confirmed in mice after oral treatment with 1-MIM-GLS. Adduct levels were highest in the cecum and colon, somewhat lower in serum albumin and the liver, and also readily detectable in the lung and hemoglobin. On the contrary, oral treatment with 1-MIM-OH produced the highest adduct levels in the liver. The higher ratio of albumin to hemoglobin adducts in 1-MIM-OH- compared to 1-MIM-GLS-treated animals (8.1 versus 3.5) suggests that in 1-MIM-OH-treated animals albumin adducts were produced mostly in the liver, the site of albumin synthesis. The formation of adducts was approximately linear over a range of single oral doses from 20 to 600 μmol/kg body mass. Repeated oral administration of 1-MIM-OH (up to 40 treatments, thrice per week) led to continuous accumulation of hemoglobin adducts, whereas the level of serum albumin adducts remained rather constant, which reflects the different turnover rates of these proteins (t1/2 nearly 1.9 d for serum albumin and 25 d for hemoglobin in the mouse). Accumulation of adducts was also noticed in the lung. Adduct levels were higher, but their accumulation was weaker in the liver and kidney. The method developed will be useful to assess the exposure of humans to reactive metabolites formed from 1-MIM-GLS present in many foods.
Ramoplanin Imaging Conjugates – Synthesis and Evaluation
2013-12-31

In a previous study we found that fluorescence-marked vancomycin--a glycopeptide antibiotic--is taken up into human tumor cells. To expand on these investigations we now used the lipoglycodepsipeptide antibiotic ramoplanin. Compared to vancomycin it is not only a bigger molecule, but it also has two potential binding sites for coupling to the imaging agents. Three different ramoplanin imaging conjugates were synthesized, two used for fluorescence imaging and one for magnetic resonance imaging. The two fluorescent dyes used in confocal laser scanning microscopy (CLSM) and fluorescence activated cell sorting (FACS) were fluorescein isothiocyanate (FITC) and rhodamine isothiocyanate (RITC). The third was the magnetic resonance imaging (MRI) contrast agent gadolinium-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (GdDOTA). The uptake of ramoplanin conjugates, their specificity for different cell lines and the accessibility of the conjugates by imaging methods were evaluated on 8 human cell lines (two benign, six malignant) by CLSM, FACS and MRI experiments. Cytotoxicity of the ramoplanin conjugates was determined in the FACS experiments with the propidium iodide and Annexin-V-Fluos indicating any disruption in the cell membranes. Cytoplasmic uptake of the ramoplanin conjugates was observed in confocal laser scanning images and was measured using FACS and MRI experiments. Compared to the vancomycin conjugates the ramoplanin conjugates showed much weaker and slower uptake. Additionally, uptake of the ramoplanin conjugates led to strong membrane disruption and cell death.
Jan Grzegorzewski’s Karaite materials in the archive of the Polish Academy of Sciences in Kraków
2013-12-31

The article focuses on the survey of Jan Grzegorzewski’s Karaite-related materials kept in the archive of the Polish Academy of Sciences in Kraków. The article also analyzes the biography and contribution to the field of Karaite studies of Jan Grzegorzewski (1846/9-1922), one of the earliest students of the Karaim language in Europe. Quite an eccentric person, Grzegorzewski was at the same time traveller, litterateur, Slavicist, and Orientalist. Although some academicians (e.g. T. Kowalski) have expressed their scepticism about Grzegorzewski’s scholarly activity, there is no doubt that his Karaitica articles remain highly significant contribution to the field of the history of the Karaim language and folklore. Jan Grzegorzewski’s archival collection contains varied materials such as ethnographic and linguistic data, fairy-tales, proverbs, poetry, letters, drafts of articles, statistics, and official documents. Some interesting documents from Grzegorzewski’s collection are published as appendices at the end of the article.
Distributional Evidence and Beyond: the Success and Limitations of Machine Learning in Chinese Word Segmentation
2013-12-31

In this paper, we argue that the key to the success of the current state-of-art statistical learning algorithms for Chinese word segmentation (CWS) mostly lies in their optimal weighting of non-overlapping distributional evidence in the corpora.The utilization of distributional evidence is more essential than the learning algorithm.We further analyze the characteristics of distributional evidence for CWS, under the framework of Zipf's law and summarize the limitation of statistical learning in CWS as the feature absence problem, which may be apparent yet usually neglected.Making a connection between theoretical/empirical linguistics and CWS, we suggest that the study and development of a generative word formation system may be beneficial for both the science and engineering of CWS.We wrap up the discussion after reviewing some recent works that are already on this line.
Diffusive protofilament switching of kinesin-8 investigated with optical tweezers
2013-12-31

The budding yeast Kinesin-8 Kip3 is a highly processive motor protein that walks to the end of microtubules and shortens them in a collective manner [1].Microtubules usually consist of 12 to 15 circularly-arranged tubulin polymer chains, called protofilaments.Left-handed rotations of microtubules in Kip3 gliding assays indicate sideward motion of Kip3 perpendicular to the microtubule axis [2], i.e. a switching between single protofilaments.Here, we used a high-resolution optical tweezers setup in a force feedback mode to apply sideward loads on single motor proteins.Our studies show that Kip3 steps sideward in both directions under alternating sideward loads.In control experiments with immobilized Kip3 and not protofilament switching kinesin-1, we measured no effective sideward motion.Statistical analysis and comparison with simulations propose a diffusive motion of Kip3 on the microtubule lattice with a preference to the left with respect to the direction of forward motion.This is consistent with the gliding assays.Protofilament switching has implications for the suggested mechanical signaling role of Kinesin-8 in budding yeast with respect to its ability to bypass obstacles.
The Principle A Problem
2013-12-31

The presence or absence of Principle A of the Binding Theory can be explained by a requirement at the syntax semantics interface. Principle A effects surface in the presence of unmodified self, where there is a requirement for the subject and object to be identical; this requirement triggers self-incorporation into the predicate. In contrast, modified self -incorporation is blocked in the syntax, giving rise to an asymmetric part-of relation. Given that self-incorporation is absent, we predict that Principle A effects do not surface, and this is exactly what we find.