julilili42/papers huggingface dataset:
A draft genome of Yersinia pestis from victims of the Black Death
2011-10-11

Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.
Clinical and brain imaging characteristics in leucine‐rich repeat kinase 2–associated PD and asymptomatic mutation carriers
2011-10-11

Abstract The objective of this research was to evaluate a possible endophenotype in leucine‐rich repeat kinase 2 (LRRK2)‐associated Parkinson's disease (PD). Ten symptomatic LRRK2 patients, 24 sporadic Parkinson's disease patients as well as 10 asymptomatic LRRK2 mutation carriers and 29 matched healthy controls underwent comprehensive clinical assessments with respect to motor and non‐motor symptoms. Transcranial sonography and magnetic resonance imaging (voxel‐based morphometry [VBM]) were assessed to evaluate morphological imaging characteristics. LRRK2 patients had an earlier onset of motor symptoms and a more benign phenotype of motor and non‐motor characteristics compared to sporadic Parkinson's disease patients. However, depression scores were higher in LRRK2 patients. No clinical differences were found regarding motor and non‐motor symptoms in asymptomatic LRRK2 mutation carriers in comparison to controls. Transcranial sonography showed hyperechogenicity of the substantia nigra in both patients' cohorts as well as in asymptomatic LRRK2 mutation carriers. Voxel‐based morphometry revealed increased gray matter volume of the cerebellum and precentral gyrus in LRRK2 patients and of the cuneus in asymptomatic LRRK2 mutation carriers. In contrast, we found decreased basal ganglia gray matter volume in LRRK2 patients compared to controls. Increased gray matter volume of different anatomical structures associated with motor loops in LRRK2 patients and asymptomatic LRRK2 mutation carriers compared to age‐matched sporadic Parkinson's disease patients and controls might indicate compensatory mechanism in LRRK2 mutation carriers due to motor network plasticity not only in the symptomatic stage of the disease but even in the premotor phase. Substantia nigra hyperechogenicity in yet unaffected LRRK2 mutation carriers indicates morphologic alterations in an asymptomatic stage of disease. © 2011 Movement Disorder Society
Ephrin-A5 Suppresses Neurotrophin Evoked Neuronal Motility, ERK Activation and Gene Expression
2011-10-11

During brain development, growth cones respond to attractive and repulsive axon guidance cues. How growth cones integrate guidance instructions is poorly understood. Here, we demonstrate a link between BDNF (brain derived neurotrophic factor), promoting axonal branching and ephrin-A5, mediating axonal repulsion via Eph receptor tyrosine kinase activation. BDNF enhanced growth cone filopodial dynamics and neurite branching of primary neurons. We show that ephrin-A5 antagonized this BDNF-evoked neuronal motility. BDNF increased ERK phosphorylation (P-ERK) and nuclear ERK entry. Ephrin-A5 suppressed BDNF-induced ERK activity and might sequester P-ERK in the cytoplasm. Neurotrophins are well established stimulators of a neuronal immediate early gene (IEG) response. This is confirmed in this study by e.g. c-fos, Egr1 and Arc upregulation upon BDNF application. This BDNF-evoked IEG response required the transcription factor SRF (serum response factor). Notably, ephrin-A5 suppressed a BDNF-evoked neuronal IEG response, suggesting a role of Eph receptors in modulating gene expression. In opposite to IEGs, long-term ephrin-A5 application induced cytoskeletal gene expression of tropomyosin and actinin. To uncover specific Eph receptors mediating ephrin-As impact on neurotrophin signaling, EphA7 deficient mice were analyzed. In EphA7 deficient neurons alterations in growth cone morphology were observed. However, ephrin-A5 still counteracted neurotrophin signaling suggesting that EphA7 is not required for ephrin and BDNF crosstalk. In sum, our data suggest an interaction of ephrin-As and neurotrophin signaling pathways converging at ERK signaling and nuclear gene activity. As ephrins are involved in development and function of many organs, such modulation of receptor tyrosine kinase signaling and gene expression by Ephs might not be limited to the nervous system.
Innate immune sensing 2.0 – from linear activation pathways to fine tuned and regulated innate immune networks
2011-10-11

Abstract: The innate immune system is based on pathogen recognition receptors that bind conserved microbial molecular structures, so called pathogen‐associated molecular patterns (PAMPs). The characterization of the innate immune system was long based on a linear step‐wise concept of recognition, activation pathways and effector defense mechanisms. Only more recently it was recognized that the innate immune system needs regulatory elements, sideways and crosstalks that allows it to fine tune and adapt its response. Thus, it is an emerging field within innate immunity research to try to understand how the immune outcome of innate immune sensing is regulated and why immune responses can be substantially different, even though the same PAMPs may have been ‘sensed’ at the surface organs such as the skin. Only the expansion of the innate immune system from ‘pure’ linear activation pathways to fine tuned and regulated innate immune networks allows us to integrate the generation of gradually accentuated and qualitatively different effector and tolerogenic immune responses. This article provides a review of the basic concepts and players of the innate immune system and will present some of the newer data defining the innate immune networks effectively regulating the immune homoeostasis and immune effector mechanisms with special focus on the skin as one of the organs involved in regulating the immune interface between the environment and the organism.
A new species of Antherospora supports the systematic placement of its host plant
2011-10-11

The morphology and phylogeny of anther smut specimens on Tractema verna collected in the United Kingdom were investigated using light microscopy, scanning electron microscopy and partial rDNA sequence analyses. The anther smut of Tractema verna shows similarity to Antherospora eucomis, A. scillae, A. tourneuxii, A. urgineae, A. vaillantii, and A. vindobonensis but differs in spore size range, spore wall thickness, host plant genera and considerable divergences of ITS and LSU sequences. Consequently, the smut is described here as a new species, Antherospora tractemae. The host plant was formerly included in the genus Scilla (S. verna), but recently moved to a distinct genus Tractema. Molecular phylogenetic analyses reveal that Antherospora tractemae is sister to the lineage of Muscari-parasitizing Antherospora and only distantly related to the Scilla-parasitizing Antherospora species. Thus, the phylogenetic placement of the smut fungus supports the systematic placement of its host plant.
Combined STN/SNr-DBS for the treatment of refractory gait disturbances in Parkinson's disease: study protocol for a randomized controlled trial
2011-10-11

Abstract Background Severe gait disturbances in idiopathic Parkinson's disease (PD) are observed in up to 80% of all patients in advanced disease stages with important impact on quality of life. There is an unmet need for further symptomatic therapeutic strategies, particularly as gait disturbances generally respond unfavourably to dopaminergic medication and conventional deep brain stimulation of the subthalamic nucleus in advanced disease stages. Recent pathophysiological research pointed to nigro-pontine networks entrained to locomotor integration. Stimulation of the pedunculopontine nucleus is currently under investigation, however, hitherto remains controversial. The substantia nigra pars reticulata (SNr) - entrained into integrative locomotor networks - is pathologically overactive in PD. High-frequent stimulation of the substantia nigra pars reticulata preferentially modulated axial symptoms and therefore is suggested as a novel therapeutic candidate target for neuromodulation of refractory gait disturbances in PD. Methods 12 patients with idiopathic Parkinson's disease and refractory gait disturbances under best individual subthalamic nucleus stimulation and dopaminergic medication will be enroled into this double-blind 2 × 2 cross-over clinical trial. The treatment consists of two different stimulation settings using (i) conventional stimulation of the subthalamic nucleus [STNmono] and (ii) combined stimulation of distant electrode contacts located in the subthalamic nucleus and caudal border zone of STN and substantia nigra pars reticulata [STN+SNr]. The primary outcome measure is the change of the cumulative 'axial score' (UPDRS II items '13-15' and UPRDS III items '27-31') at three weeks of constant stimulation in either condition. Secondary outcome measures include specific scores on freezing of gait, balance function, quality of life, non-motor symptoms, and neuropsychiatric symptoms. The aim of the present trial is to investigate the efficacy and safety of a three week constant combined stimulation on [STN+SNr] compared to [STNmono]. The results will clarify, whether stimulation on nigral contacts additional to subthalamic stimulation will improve therapeutic response of otherwise refractory gait disturbances in PD. Trial registration The trial was registered with the clinical trials register of http://www.clinicaltrials.gov ( NCT01355835 )
On the Elusiveness of Clusters
2011-10-11

Rooted phylogenetic networks are often used to represent conflicting phylogenetic signals. Given a set of clusters, a network is said to represent these clusters in the softwired sense if, for each cluster, at least one tree embedded in the network contains it. Motivated by parsimony we might wish to construct such a network using as few reticulations as possible, or minimizing the level of the network, i.e. the maximum number of reticulations used in any "tangled" region of the network. Although these are NP-hard problems, here we prove that, for every fixed k &#x2265; 0, it is polynomial-time solvable to construct a phylogenetic network with level equal to k representing a cluster set, or to determine that no such network exists. However, this algorithm does not lend itself to a practical implementation. We also prove that the comparatively efficient CASS algorithm correctly solves this problem (and also minimizes the reticulation number) when input clusters are obtained from two not necessarily binary gene trees on the same set of taxa but does not always minimize level for general cluster sets. Finally, we describe a new algorithm which generates in polynomial-time all binary phylogenetic networks with exactly r reticulations representing a set of input clusters (for every fixed r &#x2265; 0).
No apparent accretion mode changes detected in Centaurus X-3
2011-10-11

The presence of two distinct spectral states has previously been reported for\\nCen X-3 on the basis of RXTE/ASM observations. Triggered by this result, we\\ninvestigated the spectral properties of the source using the larger amount of\\nX-ray data now available with the aim to clarify and interpret the reported\\nbehavior. To check the reported results we used the same data set and followed\\nthe same analysis procedures as in the work reporting the two spectral states.\\nAdditionally, we repeated the analysis using the enlarged data sample including\\nthe newest RXTE/ASM observations as well as the data from the MAXI monitor and\\nfrom the INTEGRAL/JEM-X and ISGRI instruments. We could not confirm the\\nreported presence of the two spectral states in Cen X-3 either in\\n
Soluble Aβ Seeds Are Potent Inducers of Cerebral β-Amyloid Deposition
2011-10-12

Cerebral β-amyloidosis and associated pathologies can be exogenously induced by the intracerebral injection of small amounts of pathogenic Aβ-containing brain extract into young β-amyloid precursor protein (APP) transgenic mice. The probable β-amyloid-inducing factor in the brain extract has been identified as a species of aggregated Aβ that is generated in its most effective conformation or composition in vivo . Here we report that Aβ in the brain extract is more proteinase K (PK) resistant than is synthetic fibrillar Aβ, and that this PK-resistant fraction of the brain extract retains the capacity to induce β-amyloid deposition upon intracerebral injection in young, pre-depositing APP23 transgenic mice. After ultracentrifugation of the brain extract, &lt;0.05% of the Aβ remained in the supernatant fraction, and these soluble Aβ species were largely PK sensitive. However, upon intracerebral injection, this soluble fraction accounted for up to 30% of the β-amyloid induction observed with the unfractionated extract. Fragmentation of the Aβ seeds by extended sonication increased the seeding capacity of the brain extract. In summary, these results suggest that multiple Aβ assemblies, with various PK sensitivities, are capable of inducing β-amyloid aggregation in vivo . The finding that small and soluble Aβ seeds are potent inducers of cerebral β-amyloidosis raises the possibility that such seeds may mediate the spread of β-amyloidosis in the brain. If they can be identified in vivo , soluble Aβ seeds in bodily fluids also could serve as early biomarkers for cerebral β-amyloidogenesis and eventually Alzheimer's disease.
Prospective Biopsy-Controlled Evaluation of Cell Death Biomarkers for Prediction of Liver Fibrosis and Nonalcoholic Steatohepatitis
2011-10-12

Abstract Fibrosis and steatosis are major histopathological alterations in chronic liver diseases. Despite various shortcomings, disease severity is generally determined by liver biopsy, emphasizing the need for simple noninvasive methods for assessing disease activity. Because hepatocyte cell death is considered a crucial pathogenic factor, we prospectively evaluated the utility of serum biomarkers of cell death to predict different stages of fibrosis and steatosis in 121 patients with chronic liver disease. We compared the M30 enzyme-linked immunosorbent assay (ELISA), which detects a caspase-cleaved cytokeratin-18 (CK-18) fragment and thereby apoptotic cell death, with the M65 ELISA, which detects both caspase-cleaved and uncleaved CK-18 and thereby overall cell death. Both biomarkers significantly discriminated patients with different fibrosis stages from healthy controls. However, whereas both markers differentiated low or moderate from advanced fibrosis, only the M65 antigen could discriminate even lower stages of fibrosis. The M65 assay also performed better in distinguishing low (≤10%) and higher (&gt;10%) grades of steatosis. In a subgroup of patients, we evaluated the biomarkers for their power to predict nonalcoholic steatohepatitis (NASH). Importantly, both markers accurately differentiated healthy controls or simple steatosis from NASH. However, only serum levels of M65 antigen could differentiate simple steatosis from healthy controls. Conclusion: Cell death biomarkers are potentially useful to predict fibrosis, steatosis, or NASH. Compared with the widely used apoptosis marker M30, the M65 assay had a better diagnostic performance and even differentiated between lower fibrosis stages as well as between healthy individuals and patients with simple steatosis. (Hepatology 2012)
Relationship between anthropometric variables and nutrient intake in apparently healthy male elderly individuals: A study from Pakistan
2011-10-12

Malnutrition is common in apparently healthy elderly Pakistani men. Very few elderly have adequate nutrient intake. Obese and overweight had higher % BF as compared to normal weight elderly. Older age is associated with changes not only in anthropometrics and body composition but also in intake of key nutrients like energy and protein.
Geo-referencing of continental-scale JERS-1 SAR mosaics based on matching homologous features with a digital elevation model: theory and practice
2011-10-12

An effective method for a posteriori orthorectification of continental scale SAR mosaics using a digital elevation model (DEM) has been developed. The method is based on homologous feature matching between the DEM and a simulated SAR image. The simulated image is derived from the radar viewing geometry, topographic information and contextual information provided by the SRTM Water Bodies data set (SWBD) and GeoCover Landsat mosaics. Two large L-band SAR mosaics (the GBFM Siberia mosaic and the GRFM Africa mosaic), assembled from JERS-1 data, were accurately geo-referenced, orthorectified and radiometrically corrected for topographic effects. The accurate co-registration with the digital elevation model allows for improved classification methods based on the combination of SAR backscatter with terrain features. Comparison of the revised GBFM and GRFM mosaics with a forthcoming set of continental scale mosaics assembled from ALOS PALSAR data will offer a unique possibility for change detection studies over the Tropical and Boreal forest zones with a temporal spacing of some 10 years.
Time evolution of the radial perturbations and linear stability of solitons and black holes in a generalized Skyrme model
2011-10-12

We study the time evolution of the radial perturbation for self-gravitating\\nsoliton and black-hole solutions in a generalized Skyrme model in which a\\ndilaton is present. The background solutions were obtained recently by some of\\nthe authors. For both the solitons and the black holes two branches of\\nsolutions exist which merge at some critical value of the corresponding\\nparameter. The results show that, similar to the case without a scalar field,\\none of the branches is stable against radial perturbations and the other is\\nunstable. The conclusions for the linear stability of the black holes in the\\ngeneralized Skyrme model are also in agreement with the results from the\\nthermodynamical stability analysis based on the turning point method.\\n
Expertise modulates the neural basis of context dependent recognition of objects and their relations
2011-10-13

Abstract Recognition of objects and their relations is necessary for orienting in real life. We examined cognitive processes related to recognition of objects, their relations, and the patterns they form by using the game of chess. Chess enables us to compare experts with novices and thus gain insight in the nature of development of recognition skills. Eye movement recordings showed that experts were generally faster than novices on a task that required enumeration of relations between chess objects because their extensive knowledge enabled them to immediately focus on the objects of interest. The advantage was less pronounced on random positions where the location of chess objects, and thus typical relations between them, was randomized. Neuroimaging data related experts' superior performance to the areas along the dorsal stream—bilateral posterior temporal areas and left inferior parietal lobe were related to recognition of object and their functions. The bilateral collateral sulci, together with bilateral retrosplenial cortex, were also more sensitive to normal than random positions among experts indicating their involvement in pattern recognition. The pattern of activations suggests experts engage the same regions as novices, but also that they employ novel additional regions. Expert processing, as the final stage of development, is qualitatively different than novice processing, which can be viewed as the starting stage. Since we are all experts in real life and dealing with meaningful stimuli in typical contexts, our results underline the importance of expert‐like cognitive processing on generalization of laboratory results to everyday life. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Intentional social distance regulation alters affective responses towards victims of violence: An FMRI study
2011-10-13

Abstract We used functional magnetic resonance imaging (fMRI) to investigate brain processes underlying control of emotional responses towards a person in distress by cognitive social distance modulation. fMRI and peripheral physiological responses (startle response and electrodermal activity) were recorded from 24 women while they watched victim–offender scenes and modulated their social distance to the victim by cognitive reappraisal. We found that emotional responses, including startle eyeblink and amygdala responses, can effectively be modulated by social distance modulation. Furthermore, our data provide evidence that activity in the dorsomedial prefrontal cortex (dmPFC) and the anterior paracingulate cortex (aPCC), two brain regions that have previously been associated with brain processes related to distant and close others, is differentially modulated by intentional social distance modulation: activity in the dmPFC increased with increasing disengagement from the victim and activity in the aPCC increased with increasing engagement with the victim. We suggest that these two regions play opposing roles in cognitive modulation of social distance and affective responses towards persons in distress that enable the adaptive and flexible social behavior observed in humans. Hum Brain Mapp 33:2464–2476, 2012. © 2011 Wiley Periodicals, Inc.
Superconductor-insulator-ferromagnet-superconductor Josephson junction: From the dirty to the clean limit
2011-10-13

The proximity effect and the Josephson current in a superconductor-insulator-ferromagnet-superconductor (SIFS) junction are investigated within the framework of the quasiclassical Eilenberger equations. This investigation allows us to compare the dirty and the clean limits, to investigate an arbitrary impurity scattering, and to determine the applicability limits of the Usadel equations for such structures. The role of different types of the FS interface is analyzed. It is shown that the decay length and the spatial oscillation period of the Eilenberger function may exhibit a nonmonotonic dependence on the properties of the ferromagnetic layer such as exchange field or electron mean free path. The results of our calculations are applied to the interpretation of experimentally observed dependencies of the critical current density on the ferromagnet thickness in Josephson junctions containing a Ni layer with an arbitrary scattering.