julilili42/papers huggingface dataset:
Evaluation of intermittent preventive treatment of malaria against group B Streptococcus colonization in pregnant women: a nested analysis of a randomized controlled clinical trial of sulfadoxine/pyrimethamine versus mefloquine
2015-02-25

Abstract Objectives Streptococcus agalactiae constitutes an important cause of neonatal infections in sub-Saharan Africa. Sulfadoxine/pyrimethamine—the current intermittent preventive treatment of malaria in pregnancy (IPTp)—has proven in vitro activity against group B Streptococcus (GBS). Because of specific drug resistance to sulfadoxine/pyrimethamine, mefloquine—an antimalarial without in vitro activity against GBS—was evaluated as a potential alternative. This study assessed the potential of sulfadoxine/pyrimethamine-IPTp to reduce the prevalence of GBS colonization in pregnant women in Gabon when compared with the inactive control mefloquine-IPTp. Methods Pregnant women participating in a randomized controlled clinical trial evaluating mefloquine-IPTp versus sulfadoxine/pyrimethamine-IPTp were invited to participate and recto-vaginal swabs were collected at delivery for detection of GBS colonization. Prevalence of recto-vaginal GBS colonization was compared between IPTp regimens and risk factor and birth outcome analyses were computed. Results Among 549 participants, 106 were positive for GBS colonization at delivery (19%; 95% CI = 16%–23%). Prevalence of maternal GBS colonization showed no significant difference between the two IPTp regimens (mefloquine-IPTp: 67 of 366 women = 18%; 95% CI = 14%–22%; sulfadoxine/pyrimethamine-IPTp: 39 of 183 women = 21%; 95% CI = 15%–27%). Risk factor analysis for GBS colonization demonstrated a significant association with illiteracy (adjusted OR = 2.03; 95% CI = 1.25–3.30). GBS colonization had no impact on birth outcome, anaemia at delivery, gestational age and birth weight. Conclusions Sulfadoxine/pyrimethamine did not reduce colonization rates when used as the IPTp drug during pregnancy. Illiteracy was associated with GBS colonization.
A revised global biogeography of turtles
2015-02-25

Background. Over the course of the last decades, much effort has gone into unraveling the biogeographic history of turtles, but while much progress has been achieved in resolving post- Jurassic dispersal events, traditional phylogenetic hypotheses have yielded incongruous results in regards to the early history of the group. Methods. We re-evaluate the fossil record of turtles in context of recent phylogenetic analyses and fossil finds, including the extensive record of fragmentary but diagnostic remains. Given that near-coastal and marine turtles readily disperse across aquatic barriers, a broad set of neritic to pelagic groups were disregarded from consideration. Significant disagreement still exists among current phylogenetic hypotheses and we therefore place much effort into tracing the fossil record of unambiguously monophyletic groups. We finally employed molecular backbone constraints, given that the molecular phylogenies are more consistent with the fossil record than current, morphological phylogenies. Results. Among derived, aquatic turtles, we recognize four clades that can be traced back to discrete biogeographic centers: Paracryptodira in North America and Europe, Pan- Cryptodira in Asia, Pan-Pelomedusoides in northern Gondwanan landmasses and Pan- Chelidae in southern Gondwanan landmasses. This pattern is partially mirrored by three clades of primarily terrestrial, basal turtles: Solemydidae in North American and Europe, Sichuanchelyidae in Asia, and Meiolaniformes sensu stricto in southern Gondwanan landmasses. Although the exact interrelationships of these clades remain unclear, most can be traced back to the Middle Jurassic. Discussion. The conclusion that the two primary lineages of pleurodires and paracryptodires can be traced back to mutually exclusive land masses is not novel, but the realization that the early history of pan-cryptodires is restricted to Asia has not been realized previously, because traditional phylogenies implied an early, global presence of pan-cryptodires. The timing of the origin of the three primary clades of derived turtles (i.e., Pan-Pleurodira, Pan-Cryptodira, and Paracryptodira) correlates with the opening of the central Atlantic and the formation of the Turgai Strait in the Middle Jurassic, somewhat later than predicted by molecular calibration studies. The primary diversity of extant turtles therefore appears to have been driven by vicariance. A similar hypothesis could also be formulated for the three clades of basal turtles that survive at least into the Late Cretaceous, but given that their combined monophyly remains uncertain, it is unclear if their diversity was also driven by vicariance, or if they emulate a vicariance-like pattern. Although most groups remained within their primary geographic range throughout their evolutionary history, the dominant vicariance signal was thoroughly obfuscated by rich dispersal from littoral to marine turtles and crown cryptodires.
State-dependencies of learning across brain scales
2015-02-26

Learning is a complex brain function operating on different time scales, from milliseconds to years, which induces enduring changes in brain dynamics. The brain also undergoes continuous "spontaneous" shifts in states, which, amongst others, are characterized by rhythmic activity of various frequencies. Besides the most obvious distinct modes of waking and sleep, wake-associated brain states comprise modulations of vigilance and attention. Recent findings show that certain brain states, particularly during sleep, are essential for learning and memory consolidation. Oscillatory activity plays a crucial role on several spatial scales, for example in plasticity at a synaptic level or in communication across brain areas. However, the underlying mechanisms and computational rules linking brain states and rhythms to learning, though relevant for our understanding of brain function and therapeutic approaches in brain disease, have not yet been elucidated. Here we review known mechanisms of how brain states mediate and modulate learning by their characteristic rhythmic signatures. To understand the critical interplay between brain states, brain rhythms, and learning processes, a wide range of experimental and theoretical work in animal models and human subjects from the single synapse to the large-scale cortical level needs to be integrated. By discussing results from experiments and theoretical approaches, we illuminate new avenues for utilizing neuronal learning mechanisms in developing tools and therapies, e.g., for stroke patients and to devise memory enhancement strategies for the elderly.
Transient X-ray pulsar V 0332+53: pulse-phase-resolved spectroscopy and the reflection model
2015-02-26

We present the results of the pulse phase- and luminosity-resolved spectroscopy of the transient X-ray pulsar V0332+53, performed for the first time in a wide luminosity range (1-40)x10^{37} erg/s during a giant outburst observed by the RXTE observatory in Dec 2004 - Feb 2005. We characterize the spectra quantitatively and built the detailed "three-dimensional" picture of spectral variations with pulse phase and throughout the outburst. We show that all spectral parameters are strongly variable with the pulse phase, and the pattern of this variability significantly changes with luminosity directly reflecting the associated changes in the structure of emission regions and their beam patterns. Obtained results are qualitatively discussed in terms of the recently developed reflection model for the formation of cyclotron lines in the spectra of X-ray pulsars.
Suppression of Early Hematogenous Dissemination of Human Breast Cancer Cells to Bone Marrow by Retinoic Acid–Induced 2
2015-02-26

Abstract Regulatory pathways that drive early hematogenous dissemination of tumor cells are insufficiently defined. Here, we used the presence of disseminated tumor cells (DTC) in the bone marrow to define patients with early disseminated breast cancer and identified low retinoic acid–induced 2 (RAI2) expression to be significantly associated with DTC status. Low RAI2 expression was also shown to be an independent poor prognostic factor in 10 different cancer datasets. Depletion of RAI2 protein in luminal breast cancer cell lines resulted in dedifferentiation marked by downregulation of ERα, FOXA1, and GATA3, together with increased invasiveness and activation of AKT signaling. Functional analysis of the previously uncharacterized RAI2 protein revealed molecular interaction with CtBP transcriptional regulators and an overlapping function in controlling the expression of a number of key target genes involved in breast cancer. These results suggest that RAI2 is a new metastasis-associated protein that sustains differentiation of luminal breast epithelial cells. Significance: We identified downregulation of RAI2 as a novel metastasis-associated genetic alteration especially associated with early occurring bone metastasis in ERα-positive breast tumors. We specified the role of the RAI2 protein to function as a transcriptional regulator that controls the expression of several key regulators of breast epithelial integrity and cancer. Cancer Discov; 5(5); 506–19. ©2015 AACR. See related commentary by Esposito and Kang, p. 466 This article is highlighted in the In This Issue feature, p. 453
Reduction in Subventricular Zone-Derived Olfactory Bulb Neurogenesis in a Rat Model of Huntington’s Disease Is Accompanied by Striatal Invasion of Neuroblasts
2015-02-26

Huntington's disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.
Phase-dependent modulation as a novel approach for therapeutic brain stimulation
2015-02-26

Closed-loop paradigms provide us with the opportunity to optimize stimulation protocols for perturbation of pathological oscillatory activity in brain-related disorders. In this vein, spiking activity of motor cortex neurons and beta activity of local field potentials in the subthalamic nucleus have both been used independently of each other as neuronal signals to trigger deep brain stimulation for alleviating Parkinsonism. These approaches were superior to the standard continuous high-frequency stimulation protocols used in daily practice. However, they achieved their effects by bursts of stimulation that were applied at high-frequency as well, i.e., independent of the phase information in the stimulated region. In this context, we propose that, by timing stimulation pulses relative to the ongoing oscillation, an alternative approach, namely the targeted perturbation of pathological rhythms, could be obtained. In this modeling study, we first captured the underlying dynamics of neuronal oscillations in the human subthalamic nucleus by phased coupled neuronal oscillators. We then quantified the nature of the interaction between these coupled oscillators by obtaining a physiologically informed phase response curve from local field potentials. Reconstruction of the phase response curve predicted the sensitivity of the phase oscillator to external stimuli, revealing phase intervals that optimally maximized the degree of perturbation. We conclude that our specifically timed intervention based on the coupled oscillator concept will enable us to identify personalized ways of delivering stimulation pulses in closed-loop paradigms triggered by the phase of pathological oscillations. This will pave the way for novel physiological insights and substantial clinical benefits. In addition, this precisely phased modulation may be capable of modifying the effective interactions between oscillators in an entirely new manner.
Correction to Tetra-Substituted Pyridinylimidazoles As Dual Inhibitors of p38α Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase 3 for Potential Treatment of Neurodegenerative Diseases
2015-02-26

Tetra-substituted imidazoles were designed as dual inhibitors of c-Jun N-terminal kinase (JNK) 3 and p38α mitogen-activated protein (MAP) kinase. A library of 45 derivatives was prepared and evaluated in a kinase activity assay for their ability to inhibit both kinases, JNK3 and p38α MAP kinase. Dual inhibitors with IC50 values down to the low double-digit nanomolar range at both enzymes were identified. The best balanced dual JNK3/p38α MAP kinase inhibitors are 6m (IC50: JNK3, 18 nM; p38α, 30 nM) and 14d (IC50: JNK3, 26 nM; p38α, 34 nM) featuring both excellent solubility and metabolic stability. They may serve as useful tool compounds for preclinical proof-of-principle studies in order to validate the synergistic role of both kinases in the progression of Huntington's disease.
Noninvasive Prenatal Testing and Fetal Sonographic Screening
2015-02-26

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Simultaneous Resection of High-risk Liver Tumors and Pulmonary Metastases in Children
2015-02-26

Urla, Cristian MD; Seitz, Guido MD, PhD; Tsiflikas, Ilias MD; Handgretinger, Rupert MD, PhD; Fideler, Frank MD; Neunhoeffer, Felix MD; Warmann, Steven W. MD, PhD; Fuchs, Jörg MD, PhD Author Information
Visibly Counter Languages and Constant Depth Circuits
2015-02-26

We examine visibly counter languages, which are languages recognized by visibly counter automata (a.k.a. input driven counter automata). We are able to effectively characterize the visibly counter languages in AC^0 and show that they are contained in FO[+].
Rare variants in γ‐aminobutyric acid type A receptor genes in rolandic epilepsy and related syndromes
2015-02-27

Objective To test whether mutations in γ‐aminobutyric acid type A receptor (GABA A ‐R) subunit genes contribute to the etiology of rolandic epilepsy (RE) or its atypical variants (ARE). Methods We performed exome sequencing to compare the frequency of variants in 18 GABA A ‐R genes in 204 European patients with RE/ARE versus 728 platform‐matched controls. Identified GABRG2 variants were functionally assessed for protein stability, trafficking, postsynaptic clustering, and receptor function. Results Of 18 screened GABA A ‐R genes, we detected an enrichment of rare variants in the GABRG2 gene in RE/ARE patients (5 of 204, 2.45%) in comparison to controls (1 of 723, 0.14%; odds ratio = 18.07, 95% confidence interval = 2.01–855.07, p = 0.0024, p corr = 0.043). We identified a GABRG2 splice variant (c.549‐3T&gt;G) in 2 unrelated patients as well as 3 nonsynonymous variations in this gene (p.G257R, p.R323Q, p.I389V). Functional assessment showed reduced surface expression of p.G257R and decreased GABA‐evoked currents for p.R323Q. The p.G257R mutation displayed diminished levels of palmitoylation, a post‐translational modification crucial for trafficking of proteins to the cell membrane. Enzymatically raised palmitoylation levels restored the surface expression of the p.G257R variant γ2 subunit. Interpretation The statistical association and the functional evidence suggest that mutations of the GABRG2 gene may increase the risk of RE/ARE. Restoring the impaired membrane trafficking of some GABRG2 mutations by enhancing palmitoylation might be an interesting therapeutic approach to reverse the pathogenic effect of such mutants. Ann Neurol 2015;77:972–986
Peptide length and folding state govern the capacity of staphylococcal β-type phenol-soluble modulins to activate human formyl-peptide receptors 1 or 2
2015-02-27

Abstract Most staphylococci produce short α-type PSMs and about twice as long β-type PSMs that are potent leukocyte attractants and toxins. PSMs are usually secreted with the N-terminal formyl group but are only weak agonists for the leukocyte FPR1. Instead, the FPR1-related FPR2 senses PSMs efficiently and is crucial for leukocyte recruitment in infection. Which structural features distinguish FPR1 from FPR2 ligands has remained elusive. To analyze which peptide properties may govern the capacities of β-type PSMs to activate FPRs, full-length and truncated variants of such peptides from Staphylococcus aureus, Staphylococcus epidermidis, and Staphylococcus lugdunensis were synthesized. FPR2 activation was observed even for short N- or C-terminal β-type PSM variants once they were longer than 18 aa, and this activity increased with length. In contrast, the shortest tested peptides were potent FPR1 agonists, and this property declined with increasing peptide length. Whereas full-length β-type PSMs formed α-helices and exhibited no FPR1-specific activity, the truncated peptides had less-stable secondary structures, were weak agonists for FPR1, and required N-terminal formyl-methionine residues to be FPR2 agonists. Together, these data suggest that FPR1 and FPR2 have opposed ligand preferences. Short, flexible PSM structures may favor FPR1 but not FPR2 activation, whereas longer peptides with α-helical, amphipathic properties are strong FPR2 but only weak FPR1 agonists. These findings should help to unravel the ligand specificities of 2 critical human PRRs, and they may be important for new, anti-infective and anti-inflammatory strategies.
Climate variability and its magnetic response recorded in a lacustrine sequence in Heqing basin at the SE Tibetan Plateau since 900 ka
2015-02-27

The lacustrine deposits in Heqing basin provide an excellent archive for long-term high-resolution palaeoclimate studies in the monsoon-dominated southeastern Tibetan Plateau region. In this study, we investigate the climatic significance of magnetic parameters for analysing the variability of the past climate. For this, we performed comprehensive time-series and statistical analysis on previously published proxy data from a 168-m-long drill core (Core-HQ) that spans ∼900–30 ka, comprising mainly magnetic parameters and carbonate content (CC). Moreover, we investigated magnetic properties of modern soil in the catchment that predominantly formed on limestone bedrock. Key findings are: (1) modern soils and sediments of Core-HQ both contain a mixture of magnetite (Mt), maghemite (Mgh) and hematite (Ht), but magnetic concentration of the soils is one order higher; (2) a superparamagnetic (SP) fraction of Mt/Mgh dominates in the soils whereas in Core-HQ the SP contribution is generally very low; (3) a larger grain-size fraction of Mt/Mgh and Ht is also present in the soils. We explain variations of magnetic concentration and CC in Core-HQ by an increased wind transport of soil and a decreased surface water transport of carbonate and soil in less humid periods. Low-temperature oxidation of magnetite in the catchment is as another crucial process that reflects weathering conditions and is likely sensitive to humidity; the degree of LTO can be semi-quantified by the magnetic parameters ARM/SIRM and S-ratio. Combining CC, ARM/SIRM and S-ratio values, we derive a weathering intensity (WI). The WI index variation along Core-HQ shows strong fluctuations on a 100-kyr eccentricity scale in the lower part, especially during ∼630–380 ka, followed by a long period (∼320–80 ka) of persistently weaker weathering (drier?) conditions with low variability, and a rapid return of much stronger weathering (wetter?) conditions at ∼80 ka. We suggest that a reduced influence of the Indian summer monsoon accounts for less moisture supply to the region and lower climatic variability.
Luminescence Matching with the Sensitivity Curve of the Human Eye: Optical Ceramics Mg8–xMx(BN2)2N4 with M = Al (x = 2) and M = Si (x = 1)
2015-02-27

Abstract Compounds Mg 8– x M x (BN 2 ) 2 N 4 were prepared by solid‐state reaction of MgCl 2 , Li 3 (BN 2 ), and AlN for M = Al, and of Mg 3 N 2 , BN, and Si 3 N 4 for M = Si. Their crystal structures were refined from powder X‐ray diffraction data with the space group R m for M = Al, Si, and P2 1 / c for M = Si. The structures of Mg 8– x M x (BN 2 ) 2 N 4 are characterized by layered arrangements of wurtzite‐related block layers alternating with a layer of di‐nitridoborate ions along the c ‐axis direction. Cations in each structure are surrounded tetrahedrally by nitride and di‐nitridoborate ions. Europium(II)‐doped powders of Mg 8– x M x (BN 2 ) 2 N 4 show exceptional broad band emissions in the visible region of the spectrum, on excitation with UV radiation at λ ex = 320 nm.
Identification of peneplains by multi‐parameter assessment of digital elevation models
2015-02-28

ABSTRACT The concept of peneplains has existed since the end of the nineteenth century. Typical peneplains are elevated geomorphological features with a low relief surface on top. They may be tilted due to tectonic activity or intersected by evolving erosion. Until now neither a standardized definition for peneplains, nor an established procedure to identify and quantify well preserved peneplains as prominent landforms existed. At present the global availability of homogeneous digital elevation models (DEMs) provides an accurate characterization of the morphology of the Earth surface. In this study a new, numerical, DEM‐based fuzzy‐logic approach is presented for the delineation of peneplains solely from a morphological perspective. The approach is based on a morphometric analysis of the 90‐arcsec Shuttle Radar Topography Mission (SRTM) DEM. Four critical parameters are employed which are implemented within a geographic information system (GIS). The parameters for the correct and unambiguous description of a ‘flat top mountain’ are: (i) slope, (ii) curvature, (iii) terrain ruggedness index, and (iv) relative height. The approach was developed using a test area in the central Tibetan Plateau, which is characterized by representative and well preserved peneplains and for which additional field data were collected. In order to verify the method, peneplains were delineated in different regions with various geological settings for which potential peneplains were already described in the literature. The results from the Appalachian Mountains, Andes, Massif Central, and New Zealand confirm the robustness of the proposed approach. Copyright © 2015 John Wiley &amp; Sons, Ltd.