julilili42/papers huggingface dataset:
Proteome Analysis of Erythrocytes Lacking AMP-Activated Protein Kinase Reveals a Role of PAK2 Kinase in Eryptosis
2011-01-10

Activation of AMP-activated protein kinase (AMPK) upon energy depletion stimulates energy production and limits energy utilization. Erythrocytes lacking AMPK are susceptible to suicidal cell death (eryptosis). A hallmark of eryptosis is cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface, which can be identified from annexin V-binding. AMPKα1-deficient mice (ampk(-/-)) suffer from anemia due to accelerated clearance of erythrocytes from circulating blood. To determine the link between AMPK and the eryptotic phenotype, we performed a global proteome analysis of erythrocytes from ampk(-/-) mice and wild-type mice using high-accuracy mass spectrometry and label-free quantitation and measured changes of expression levels of 812 proteins. Notably, the p21-activated kinase 2 (PAK2), previously implicated in apoptosis, was detected as downregulated in erythrocytes of ampk(-/-) mice, pointing to its potential role in eryptosis. To validate this, we showed that specific inactivation of PAK2 with the inhibitor IPA3 in human and murine ampk(+/+) erythrocytes increases the binding of annexin V and augments the stimulating effect of glucose deprivation on annexin V-binding. Inhibition of PAK2 failed to significantly modify annexin V-binding in ampk(-/-) erythrocytes, showing that AMPK and PAK2 exert similar phenotypes upon inactivation in erythrocytes. This study presents the first large-scale analysis of protein expression in erythrocytes from AMPKα1-deficient mice and reveals a role of PAK2 kinase in eryptosis.
Onset of preclinical osteoarthritis: The angular spatial organization permits early diagnosis
2011-01-10

This study is the first to identify the presence of angular characteristics of spatial chondrocyte organization and species-specific remodeling processes correlating with OA onset. The appearance of distinct angular and spatial patterns between neighboring chondrocytes can identify the onset of distant OA prior to microscopically visible tissue damage and possibly before clinical onset. With further development, this novel concept may become suitable for the diagnosis and followup of patients susceptible to OA.
The role of haematuria in bladder cancer screening among men with former occupational exposure to aromatic amines
2011-01-11

Study Type – Diagnostic (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Microscopic haematuria (μH) is frequently detected in elderly adults. The American Urological Association recommends the follow‐up of subjects with μH on bladder cancer. Whereas gross haematuria is considered an important sign of the presence of bladder cancer, the disease‐predictive value of μH is less clear. No association of μH with the development of bladder tumours in a prospective screening cohort of chemical workers was observed. The positive predictive value of μH for bladder cancer was as low as 1.2%. Haematuria interfered with NMP22 but not with cytology and UroVysion TM test results. OBJECTIVE • To assess the positive predictive value (PPV) of microhaematuria (μH) and gross haematuria (GH) in bladder cancer screening and the influence of haematuria on tumour tests in a prospective study. PATIENTS AND METHODS • From September 2003 to January 2010, 1323 men took part in an annual voluntary bladder cancer screening programme for chemical workers with former exposure to aromatic amines. • In 5315 urine samples haematuria was determined with a dipstick, followed by a microscopic blood cell count in the sediment. Haematuria was categorized into traces, μH and GH. • Urinary leukocytes and other factors were investigated as potential predictors of haematuria using a generalized estimating equation model for repeated urinalysis. The risk of haematuria for positive tumour tests was analysed correspondingly. • The bladder cancer risk was estimated for the highest degree of haematuria occurring during the study with Poisson regression. RESULTS • As of July 2010, 15 bladder tumours were detected in 14 participants. • GH was found in four out of nine high‐grade tumours and associated with a rate ratio of 3.82, 95% confidence interval (CI) 0.50–29.15 for the development of bladder lesions. • The PPV of GH was 11.4%, but only 1.2% for μH. μH occurred in 18.8% of urine samples and was not associated with bladder cancer [rate ratio (RR) 0.72, 95% CI 0.11–4.78]. • Abundant urinary leukocytes were associated with μH [odds ratio (OR) 8.34, 95% CI 2.26–30.69] and even stronger with GH (OR 22.25, 95% CI 6.42–77.06). • Haematuria and leukocytes influenced NMP22 positivity (μH: OR 1.63, 95% CI 1.06–2.51, abundant leukocytes: OR 8.90, 95% CI 1.58–50.16), but not test results for urine cytology and UroVysion TM . CONCLUSION • While the PPV of μH for bladder cancer was low, there was a strong influence of haematuria and leukocytes on the protein‐based tumour test NMP22®. • Erythrocytes and leukocytes should be determined at least semi‐quantitatively for the interpretation of positive NMP22 test results. • In addition, a panel of tumour tests that includes methods not affected by the presence of erythrocytes or leukocytes such as cytology and UroVysion TM would improve bladder cancer screening.
Long-TermIn VivoImaging of β-Amyloid Plaque Appearance and Growth in a Mouse Model of Cerebral β-Amyloidosis
2011-01-12

Extracellular deposition of the amyloid-β peptide (Aβ) in the brain parenchyma is a hallmark lesion of Alzheimer's disease (AD) and a predictive marker for the progression of preclinical to symptomatic AD. Here, we used multiphoton in vivo imaging to study Aβ plaque formation in the brains of 3- to 4-month-old APPPS1 transgenic mice over a period of 6 months. A novel head fixation system provided robust and efficient long-term tracking of single plaques over time. Results revealed an estimated rate of 35 newly formed plaques per cubic millimeter of neocortical volume per week at 4–5 months of age. At later time points (i.e., in the presence of increasing cerebral β-amyloidosis), the number of newly formed plaques decreased. On average, both newly formed and existing plaques grew at a similar growth rate of 0.3 μm (radius) per week. A solid knowledge of the dynamics of cerebral β-amyloidosis in mouse models provides a powerful tool to monitor preclinical Aβ targeting therapeutic strategies and eases the interpretation of diagnostic amyloid imaging in humans.
THE SUPERSOFT X-RAY PHASE OF NOVA RS OPHIUCHI 2006
2011-01-12

Swift X-ray observations of the ~60 day super-soft phase of the recurrent\\nnova RS Ophiuchi 2006 show the progress of nuclear burning on the white dwarf\\nin exquisite detail. First seen 26 days after the optical outburst, this phase\\nstarted with extreme variability likely due to variable absorption, although\\nintrinsic white dwarf variations are not excluded. About 32 days later, a\\nsteady decline in count-rate set in. NLTE model atmosphere spectral fits during\\nthe super-soft phase show that the effective temperature of the white dwarf\\nincreases from ~65 eV to ~90 eV during the extreme variability phase, falling\\nslowly after about day 60 and more rapidly after day 80. The bolometric\\nluminosity is seen to be approximately constant and close to Eddington from day\\n45 up to day 60, the subsequent decline possibly signalling the end of\\nextensive nuclear burning. Before the decline, a multiply-periodic, ~35 s\\nmodulation of the soft X-rays was present and may be the signature of a nuclear\\nfusion driven instability. Our measurements are consistent with a white dwarf\\nmass near the Chandrasekhar limit; combined with a deduced accumulation of mass\\ntransferred from its binary companion, this leads us to suggest RS Oph is a\\nstrong candidate for a future supernova explosion. The main uncertainty now is\\nwhether the WD is the CO type necessary for a SN Ia. This may be confirmed by\\ndetailed abundance analyses of spectroscopic data from the outbursts.\\n
Hamiltonian flow in Coulomb gauge Yang-Mills theory
2011-01-12

We derive a new functional renormalization group equation for Hamiltonian\\nYang-Mills theory in Coulomb gauge. The flow equations for the static gluon and\\nghost propagators are solved under the assumption of ghost dominance within\\ndifferent diagrammatic approximations. The results are compared to those\\nobtained in the variational approach and the reliability of the approximations\\nis discussed.\\n
HCMV Spread and Cell Tropism are Determined by Distinct Virus Populations
2011-01-13

Human cytomegalovirus (HCMV) can infect many different cell types in vivo. Two gH/gL complexes are used for entry into cells. gH/gL/pUL(128,130,131A) shows no selectivity for its host cell, whereas formation of a gH/gL/gO complex only restricts the tropism mainly to fibroblasts. Here, we describe that depending on the cell type in which virus replication takes place, virus carrying the gH/gL/pUL(128,130,131A) complex is either released or retained cell-associated. We observed that virus spread in fibroblast cultures was predominantly supernatant-driven, whereas spread in endothelial cell (EC) cultures was predominantly focal. This was due to properties of virus released from fibroblasts and EC. Fibroblasts released virus which could infect both fibroblasts and EC. In contrast, EC released virus which readily infected fibroblasts, but was barely able to infect EC. The EC infection capacities of virus released from fibroblasts or EC correlated with respectively high or low amounts of gH/gL/pUL(128,130,131A) in virus particles. Moreover, we found that focal spread in EC cultures could be attributed to EC-tropic virus tightly associated with EC and not released into the supernatant. Preincubation of fibroblast-derived virus progeny with EC or beads coated with pUL131A-specific antibodies depleted the fraction that could infect EC, and left a fraction that could predominantly infect fibroblasts. These data strongly suggest that HCMV progeny is composed of distinct virus populations. EC specifically retain the EC-tropic population, whereas fibroblasts release EC-tropic and non EC-tropic virus. Our findings offer completely new views on how HCMV spread may be controlled by its host cells.
Managing open habitats by wild ungulate browsing and grazing: A case-study in North-Eastern Germany
2011-01-13

Question: Can wild ungulates efficiently maintain and restore open habitats? Location: Brandenburg, NE Germany. Methods: The effect of wild ungulate grazing and browsing was studied in three successional stages: (1) Corynephorus canescens-dominated grassland; (2) ruderal tall forb vegetation dominated by Tanacetum vulgare; and (3) Pinus sylvestris-pioneer forest. The study was conducted over 3 yr. In each successional stage, six paired 4 m2-monitoring plots of permanently grazed versus ungrazed plots were arranged in three random blocks. Removal of grazing was introduced de novo for the study. In each plot, percentage cover of each plant and lichen species and total cover of woody plants was recorded. Results: Wild ungulates considerably affected successional pathways and species composition in open habitats but this influence became evident in alteration of abundances of only a few species. Grazing effects differed considerably between successional stages: species richness was higher in grazed versus ungrazed ruderal and pioneer forest plots, but not in the Corynephorus sites. Herbivory affected woody plant cover only in the Pioneer forest sites. Although the study period was too short to observe drastic changes in species richness and woody plant cover, notable changes in species composition were still detected in all successional stages. Conclusion: Wild ungulate browsing is a useful tool to inhibit encroachment of woody vegetation and to conserve a species-rich, open landscape.
The Ethical Differences Between Psychiatric and Neurologic DBS: Smaller Than We Think?
2011-01-13

Dunn and colleagues argue that deep brain stimulation (DBS) for treatment-resistant depression (TRD) does not require any different or additional safeguards than other innovative, higher risk thera...
Twelve-hour spikes from the Crab Pevatron
2011-01-13

Aims. The Crab nebula displayed a large gamma-ray flare on September 18,\\n2010. To more closely understand the origin of this phenomenon, we analyze the\\nINTEGRAL (20-500 keV) and FERMI (0.1-300 GeV) data collected almost\\nsimultaneously during the flare. Methods. We divide the available data into\\nthree different sets, corresponding to the pre-flare period, the flare, and the\\nsubsequent quiescence. For each period, we perform timing and spectral analyses\\nto differentiate between the contributions of the pulsar and from the\\nsurrounding nebula to the gamma-ray luminosity. Results. No significant\\nvariations in the pulse profile and spectral characteristics are detected in\\nthe hard X-ray domain. In contrast, we identify three separate enhancements in\\nthe gamma-ray flux lasting for about 12 hours and separated by an interval of\\nabout two days from each other. The spectral analysis shows that the flux\\nenhancement, confined below ~ 1 GeV, can be modelled by a power-law with a high\\nenergy exponential cut-off, where either the cut-off energy or the model\\nnormalization increased by a factor of ~ 5 relative to the pre-flare emission.\\nWe also confirm that the gamma-ray flare is not pulsed. Conclusions. The timing\\nand spectral analysis indicate that the gamma-ray flare is due to synchrotron\\nemission from a very compact Pevatron located in the region of interaction\\nbetween the pulsar wind and the surrounding nebula. These are the highest\\nelectron energies ever measured in a cosmic accelerator. The spectral\\nproperties of the flare are interpreted in the framework of a relativistically\\nmoving emitter and/or a harder emitting electron population.\\n
Inhibition of the heterotetrameric K+channel KCNQ1/KCNE1 by the AMP-activated protein kinase
2011-01-13

The heterotetrameric K(+)-channel KCNQ1/KCNE1 is expressed in heart, skeletal muscle, liver and several epithelia including the renal proximal tubule. In the heart, it contributes to the repolarization of cardiomyocytes. The repolarization is impaired in ischemia. Ischemia stimulates the AMP-activated protein kinase (AMPK), a serine/threonine kinase, sensing energy depletion and stimulating several cellular mechanisms to enhance energy production and to limit energy utilization. AMPK has previously been shown to downregulate the epithelial Na(+) channel ENaC, an effect mediated by the ubiquitin ligase Nedd4-2. The present study explored whether AMPK regulates KCNQ1/KCNE1. To this end, cRNA encoding KCNQ1/KCNE1 was injected into Xenopus oocytes with and without additional injection of wild type AMPK (AMPKα1 + AMPKβ1 + AMPKγ1), of the constitutively active (γR70Q)AMPK (α1β1γ1(R70Q)), of the kinase dead mutant (αK45R)AMPK (α1(K45R)β1γ1), or of the ubiquitin ligase Nedd4-2. KCNQ1/KCNE1 activity was determined in two electrode voltage clamp experiments. Moreover, KCNQ1 abundance in the cell membrane was determined by immunostaining and subsequent confocal imaging. As a result, wild type and constitutively active AMPK significantly reduced KCNQ1/KCNE1-mediated currents and reduced KCNQ1 abundance in the cell membrane. Similarly, Nedd4-2 decreased KCNQ1/KCNE1-mediated currents and KCNQ1 protein abundance in the cell membrane. Activation of AMPK in isolated perfused proximal renal tubules by AICAR (10 mM) was followed by significant depolarization. In conclusion, AMPK is a potent regulator of KCNQ1/KCNE1.
Influence of a genetic variant of the neuronal growth associated protein Stathmin 1 on cognitive and affective control processes: An event‐related potential study
2011-01-13

Abstract Stathmin 1 (STMN1) is a neuronal growth associated protein (NGAP) that is involved in microtubule dynamics and plays an important role in neurite outgrowth and synaptic plasticity. It is highly expressed in the amygdala, but also in different areas of the neocortex including the frontal lobe. Based on previous findings regarding an impact of STMN1 on fear processing, the present study aimed at extending the evidence concerning its functional role to include the domain of executive (frontal lobe) functions. To this end, a group of 59 healthy volunteers stratified for the single‐nucleotide polymorphism rs182455 of the STMN1 gene was examined by means of three experimental paradigms probing different aspects of cognitive–affective functioning. Event‐related potential measures of cognitive response control, emotional interference processing, and action monitoring were analyzed. STMN1 genotype significantly affected the NoGo‐anteriorization (NGA)—a neurophysiological marker of cognitive response control associated with medial prefrontal cortex activation—as well as the modulation of the P300 by the valence of emotional Stroop stimuli. In both cases, carriers of the rs182455 C‐allele showed altered cognitive–affective processing; effects appeared to be more pronounced in females. Our findings indicate a functional impact of STMN1 on cognitive and affective control processes, thereby complementing previous evidence on its role in fear processing. Based on these results, an influence of STMN1 should be considered in studies aiming at the etiopathogenesis of a broad range of neuropsychiatric disorders with dysfunctional networking, including neurodegenerative disorders as well as schizophrenia, autism spectrum disorders, anxiety disorders, depression, and ADHD. © 2011 Wiley‐Liss, Inc.
Identification and structural elucidation of new caprazamycins from Streptomyces sp. MK730–62F2 by liquid chromatography/electrospray ionization tandem mass spectrometry
2011-01-13

Abstract The development of reliable analytic methods, capable of separating mixtures of secondary metabolites as well as providing structural information, is essential for the investigation of secondary metabolites, e.g. from Streptomyces . Here we report a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS) method using a triple quadrupole mass analyzer for the structural elucidation of caprazamycins and liposidomycins from culture extracts of the wild‐type producer strains. Comparison of the fragmentation patterns in positive as well as in negative ionization mode revealed several characteristic product ions used for identification of six new caprazamycins. Furthermore, a chromatographic method for the purification of nucleosides from cell cultures using a boronic acid gel was adapted for the partial purification of the culture extracts. Copyright © 2011 John Wiley &amp; Sons, Ltd.
Information retrieval for education: making search engines language aware
2011-01-14

Search engines have been a major factor in making the web the successful and widely used information source it is today. Generally speaking, they make it possible to retrieve web pages on a topic specified by the keywords entered by the user. Yet web searching currently does not take into account which of the search results are comprehensible for a given user – an issue of particular relevance when considering students in an educational setting. And current search engines do not support teachers in searching for language properties relevant for selecting texts appropriate for language students at different stages in the second language acquisition process. At the same time, raising language awareness is a major focus in second language acquisition research and foreign language teaching practice, and research since the 20s has tried to identify indicators predicting which texts are comprehensible for readers at a particular level of ability. For example, the military has been interested in ensuring that workers at a given level of education can understand the manuals they need to read in order to perform their job. We present a new search engine approach which makes it possible for teachers to search for texts both in terms of contents and in terms of their reading difficulty and other language properties. The implemented prototype builds on state-of-the art information retrieval technology and exemplifies how a range of readability measures can be integrated in a modular fashion.
Lumbar spinal stenosis in elderly patients: is a unilateral microsurgical approach sufficient for decompression?
2011-01-14

Object For the treatment of lumbar spinal stenosis, less invasive procedures, which preserve maximal bony and ligamentous structures, have been recommended to reduce associated morbidity. The authors examined the outcome after decompression of spinal stenosis in the elderly by comparing 3 different surgical approaches. Their focus was whether a unilateral microsurgical decompression provided sufficient outcomes in the elderly population. Methods The authors investigated 108 elderly patients (age ≥ 60 years) with lumbar spinal stenosis (mean age 71 years [range 60–93 years]) who underwent surgery between 2004 and June 2006 at the authors' institution. Three different modes of decompression were analyzed in this study: a unilateral partial hemilaminectomy, a hemilaminectomy, and a laminectomy. The outcome was assessed 12 months postoperatively using the Quebec Back Pain Disability Scale and the Hannover Functional Back Pain Questionnaire. Results The authors performed a unilateral partial hemilaminectomy in 53 patients (49%). Patients who underwent unilateral partial hemilaminectomies achieved favorable results of at least 80% as assessed using the Quebec Back Pain Disability Scale and Hannover Functional Back Pain Questionnaire. Hemilaminectomies were performed in 45 patients (41.7%), and laminectomies were performed in 10 patients (9.3%). However, there was no statistically significant difference between the various techniques regarding the postoperative results (p &lt; 0.05). Conclusions Laminectomies did not show any advantage when compared with unilateral transmedian approaches. A unilateral partial hemilaminectomy combined with a transmedian decompression sufficiently treated the stenosis. This method seemed advantageous in minimizing the procedure and associated morbidity in this elderly population. Further investigations with long-term results (&gt; 5 years) are still necessary.