julilili42/papers huggingface dataset:
Icariin Ameliorates Neuropathological Changes, TGF-β1 Accumulation and Behavioral Deficits in a Mouse Model of Cerebral Amyloidosis
2014-08-07

Icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum, exhibits multiple biological properties, including anti-inflammatory, neuroregulatory and neuroprotective activities. Therefore, Icariin might be applied in treatment of neurodegenerative disorders, including Alzheimer's disease (AD), which is neuropathologically characterized by β-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Potential therapeutic effects of Icariin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mouse. Icariin was suspended in carboxymethylcellulose and given orally to APP/PS1 mice. Therapeutic effects were monitored by behavioral tests, namely nesting assay, before and during the experimental treatment. Following an oral treatment of 10 days, Icariin significantly attenuated Aβ deposition, microglial activation and TGF-β1 immunoreactivity at amyloid plaques in cortex and hippocampus of transgenic mice 5 months of age, and restored impaired nesting ability. Our results suggest that Icariin might be considered a promising therapeutic option for human AD.
Cytokine Responses to Schistosoma mansoni and Schistosoma haematobium in Relation to Infection in a Co-endemic Focus in Northern Senegal
2014-08-07

This study is the first to compare S. mansoni and S. haematobium cytokine responses in one population residing in a co-endemic area. These findings are in line with previous epidemiological studies that also suggested S. haematobium egg and worm stages to be more immunogenic than those of S. mansoni.
What’s at Stake in Securitising Climate Change? Towards a Differentiated Approach
2014-08-08

Climate change has been successfully represented as a security concern to such an extent that it is firmly established on the political agenda, even though the implementation of concrete policies is disputed. In this paper, we develop an analytical framework to better trace the process of securitising climate change and assess its normative implications. We establish a typology of six climate security discourses on the basis of two dimensions: three levels of referent objects and two logics of securitisation, one that corresponds to the original Copenhagen School framework and one where the threat takes the form of the invocation of risk. We find that there are significant differences in the relative importance of the resulting climate security discourses in Germany and the US, but that normatively, all discourses come with their own problems, which calls for more detailed scrutiny and assessment of climate security discourses and their political effects.
Extreme localized exhumation at syntaxes initiated by subduction geometry
2014-08-08

Abstract Some of the highest and most localized rates of lithospheric deformation in the world are observed at the transition between adjacent plate boundary subduction segments. The initiating perturbation of this deformation has long been attributed to vigorous erosional processes as observed at Nanga Parbat and Namche Barwa in the Himalaya and at Mount St. Elias in Alaska. However, an erosion‐dominated mechanism ignores the 3‐D geometry of curved subducting plates. Here we present an alternative explanation for rapid exhumation at these locations based on the 3‐D thermomechanical evolution of collisions between plates with nonplanar geometries. Comparison of model predictions with existing data reproduces the defining characteristics of these mountains and offers an explanation for their spatial correlation with arc termini. These results demonstrate a “bottom‐up” tectonic rather than “top‐down” erosional initiation of feedbacks between erosion and tectonic deformation; hence, the importance of 3‐D subduction geometry.
Characterization of a Mouse Model With Complete RPE Loss and Its Use for RPE Cell Transplantation
2014-08-08

Systemic injection of sodium iodate has considerable effects on RPE, photoreceptors, and inner nuclear layer neurons, and provides a model to assay reconstitution and maturation of RPE cell transplants. The availability of an RPE-free Bruch's membrane in this model likely allows the unprecedented formation of extensive polarized cell monolayers from donor hESC-derived RPE cell suspensions.
Sustained Reduction of Seizures in Patients with Intractable Epilepsy after Self-Regulation Training of Slow Cortical Potentials â€“ 10 Years After
2014-08-08

The aim of this study was to determine whether the reduction of seizures in patients with intractable epilepsy after self-regulation of slow cortical potentials (SCPs) was maintained almost 10 years after the end of treatment. Originally, 41 patients received training with SCP-neurofeedback. A control group of 12 patients received respiratory feedback while another group of 11 patients had their anticonvulsant medications reviewed. Nineteen patients in the experimental group participated at least in parts of the long-term follow-up, but only two patients from each control group agreed to do so. The follow-up participants completed the same seizure diaries as in the original study. Patients of the experimental group also took part in three SCP-training sessions at the follow-up evaluation. Due to the small sample size, the results of participants in the control groups were not considered in the analysis. A significant decrease in seizure frequency was found about 10 years after the end of SCP treatment. The clinical significance of this result is considered medium to high. All patients were still able to self-regulate their SCPs during the feedback condition. This success was achieved without booster sessions. This is the longest follow-up evaluation of the outcome of a psychophysiological treatment in patients with epilepsy ever reported. Reduced seizure frequency may be the result of patients continued ability to self-regulate their SCPs. Given such a long follow-up period, the possible impact of confounding variables should be taken into account. The small number of patients participating in this follow-up evaluation diminishes the ability to make causal inferences. However, the consistency and duration of improvement for patients who received SCP-feedback training suggests that such treatment may be considered as a treatment for patients with intractable epilepsy and as an adjunct to conventional therapies.
Multidrug Resistance Proteins of the ABCC Subfamily
2014-08-08

Members of three ABC subfamilies play a key role in drug efflux from cells, that is, the MDR1/P-glycoprotein of ABCB subfamily, the breast cancer resistance protein of ABCG subfamily, and the multidrug resistance proteins (MRPs) of ABCC subfamily. This chapter summarizes the molecular properties of the ABCC/MRP efflux transporters, their functional characteristics and tissue distribution. Currently available data on the functional and clinical consequences of naturally occurring sequence variants are also discussed. Aspects of regulatory factors influencing transporter expression such as transcriptional regulation by nuclear receptors, posttranslational modifications, and developmental stage have been summarized in recent reviews. Genetic variants may account for interindividual variability in multidrug resistance, drug disposition, and drug response because they may affect the quantity and functional characteristics of the ABCC transporters. The ABCC/MRP transporters differ in amino acid sequence and substrate specificity from MDR1/P-glycoprotein, which is the first identified mammalian ATP-dependent drug efflux pump.
Drought stress variability in ancient Near Eastern agricultural systems evidenced by δ 13 C in barley grain
2014-08-11

Significance Collapse and resilience of ancient Near Eastern societies is intrinsically tied to agricultural production. Despite intensive palaeoclimate research, the role of environmental conditions in ancient agricultural production is little understood. Stable carbon isotope analysis on cereal grains from archaeological sites provides a direct evidence for drought stress. This paper demonstrates that drought stress correlated with major climatic fluctuations and affected many agricultural settlements in the ancient Near East but that its regional impact was diverse and influenced by geographic factors and human technology. The results lead to a better understanding of how ancient agricultural societies performed under fluctuating climate and regionally diverse environmental conditions.
Malaria: an update on current chemotherapy
2014-08-11

Malaria chemotherapy remains a dynamic field, with novel drugs and drug combinations continuing to emerge in order to outpace the development of large-scale drug resistance against the currently most important drug class, the artemisinin derivatives. More randomized controlled studies are urgently needed especially for the treatment of malaria in first trimester pregnant women. ACTs should be used for the treatment of imported malaria more consequently. Gaining sufficient efficacy and safety information on ACT use for non-falciparum species including Plasmodium ovale and malariae should be a research priority. Continuous investment into malaria drug development is a vital factor to combat artemisinin resistance and successfully improve malaria control toward the ultimate goal of elimination.
Evaporative cooling of cold atoms at surfaces
2014-08-11

We theoretically investigate the evaporative cooling of cold rubidium atoms\\nthat are brought close to a solid surface. The dynamics of the atom cloud are\\ndescribed by coupling a dissipative Gross-Pitaevskii equation for the\\ncondensate with a quantum Boltzmann description of the thermal cloud (the\\nZaremba-Nikuni-Griffin method). We have also performed experiments to allow for\\na detailed comparison with this model and find that it can capture the key\\nphysics of this system provided the full collisional dynamics of the thermal\\ncloud are included. In addition, we suggest how to optimize surface cooling to\\nobtain the purest and largest condensates.\\n
Thalassodromeus sebesensis — A new name for an old turtle. Comment on “Thalassodromeus sebesensis, an out of place and out of time Gondwanan tapejarid pterosaur”, Grellet-Tinner and Codrea (online July 2014 DOI 10.1016/j.gr.2014.06.002)
2014-08-11

The Kuh e Dena sedimentary section in Iran developed on the southwestern margin of the Neotethys Ocean. The fossil- and bioturbation-lean Early Triassic section (Late Dienerian to Early Smithian) is typified by finely laminated calcareous shales that are interbedded with laterally extending carbonate beds, which are mostly composed of calyx-shaped carbonate crystal fans. The calyxes consist of fibrous crystals that apparently formed within the subseafloor in soft, water-saturated sediment by displacive growth. Rare earth element and yttrium patterns indicate that calyx-shaped crystals precipitated from anoxic pore waters. Biomarker patterns of the carbonate beds reveal major input of lipids from prokaryotes that typically occur within layered benthic microbial mats (i.e., cyanobacteria, anoxygenic phototrophic bacteria, sulphate-reducing bacteria, and methanogenic archaea). Along their length, the fibrous crystals of the calyxes reveal a trend of increasing δ13Ccarb values (from 2.7 to 3.3‰), suggesting that archaeal methanogenesis affected the carbonate pool. Apart from the putative benthic prokaryotes, molecular fossils of halophilic, most likely planktic, archaea were detected in the carbonate beds. Low pristane to phytane ratios (≤ 0.8) and the presence of halophilic archaea are in accord with the lack of bioclasts and bioturbation, which likely reflects increased salinities. The former presence of a benthic microbial mat with cyanobacteria underlain by anoxygenic phototrophic bacteria, sulphate-reducing bacteria, and methanogenic archaea is in accordance with studies on living microbial mats in hypersaline, low-oxygen marine environments. The Early Triassic subseafloor seems to have been a sink for carbon, driven by biologically-induced formation of secondary, diagenetic carbonate.
Time-restricted activation of Protein Kinase D2 directs vasculogenesis during mouse embryonic stem cell differentiation
2014-08-11

The protein kinase D (PKD) isoenzymes PKD1, -2, and -3, are prominent downstream targets of PKCs and phospholipase D in various biological systems. Recent data from our laboratory identified PKD isoforms as novel, essential mediators of tumour cell-endothelial cell communication but also as regulators of tumour cell motility and metastasis formation. The role of PKD isoforms during vascular development remains elusive. In the current study, we aimed to dissect this contribution using mouse embryonic stem (ES) cells as bona fide tool. First, we identified Protein Kinase D2 as the predominant isoform in undifferentiated ES cells leading us to particularly focus on this isoform. Time-restricted PKD2 activation using an inducible knock-in allele in differentiating mouse ES cells prevented cardiac mesoderm but activated a vascular differentiation program as shown by gene and protein regulation. Interestingly, the proliferative capacity is strongly diminished as a consequence of forced PKD2 expression. Finally, we aimed to underpin our findings in two independent in vivo models: First, embryoid bodies were transplanted on the chorioallantois membrane (CAM) of fertilised chicken eggs, a widely used model to study pro- and anti-angiogenesis. In line, with our in vitro data pronounced vessel formation was evident in the tumour-like structures arising at day 4 of the CAM assay. Second, we used the teratoma assay and induced PKD2 in immunodeficient mice during teratoma formation. While there was no difference in teratoma weight or size, a strong increase of CD31 expression as an indicator of vasculogenesis was observed in teratoma lysates. Thus, our data obtained in ES cells demonstrate that PKD2 contributes to the regulation of vasculogenesis during early development and ascribes a vascular fate in two independent embryonic tumorgenesis models.
Overproduction of Ristomycin A by Activation of a Silent Gene Cluster in Amycolatopsis japonicum MG417-CF17
2014-08-12

ABSTRACT The emergence of antibiotic-resistant pathogenic bacteria within the last decades is one reason for the urgent need for new antibacterial agents. A strategy to discover new anti-infective compounds is the evaluation of the genetic capacity of secondary metabolite producers and the activation of cryptic gene clusters (genome mining). One genus known for its potential to synthesize medically important products is Amycolatopsis . However, Amycolatopsis japonicum does not produce an antibiotic under standard laboratory conditions. In contrast to most Amycolatopsis strains, A. japonicum is genetically tractable with different methods. In order to activate a possible silent glycopeptide cluster, we introduced a gene encoding the transcriptional activator of balhimycin biosynthesis, the bbr gene from Amycolatopsis balhimycina ( bbr Aba ), into A. japonicum . This resulted in the production of an antibiotically active compound. Following whole-genome sequencing of A. japonicum , 29 cryptic gene clusters were identified by genome mining. One of these gene clusters is a putative glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin (syn. ristocetin), a type III glycopeptide, which has antibacterial activity and which is used for the diagnosis of von Willebrand disease and Bernard-Soulier syndrome, was deduced as a possible product of the gene cluster. Chemical analyses by high-performance liquid chromatography and mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy confirmed the in silico prediction that the recombinant A. japonicum /pRM4- bbr Aba synthesizes ristomycin A.
Affective coding: the emotional dimension of agency
2014-08-12

The sense of agency (SoA) (i.e., the registration that I am the initiator and controller of my actions and relevant events) is associated with several affective dimensions. This makes it surprising that the emotion factor has been largely neglected in the field of agency research. Current empirical investigations of the SoA mainly focus on sensorimotor signals (i.e., efference copy) and cognitive cues (i.e., intentions, beliefs) and on how they are integrated. Here we argue that this picture is not sufficient to explain agency experience, since agency and emotions constantly interact in our daily life by several ways. Reviewing first recent empirical evidence, we show that self-action perception is in fact modulated by the affective valence of outcomes already at the sensorimotor level. We hypothesize that the "affective coding" between agency and action outcomes plays an essential role in agency processing, i.e., the prospective, immediate or retrospective shaping of agency representations by affective components. This affective coding of agency be differentially altered in various neuropsychiatric diseases (e.g., schizophrenia vs. depression), thus helping to explain the dysfunctions and content of agency experiences in these diseases.
Antimalarial Activity of the Myxobacterial Macrolide Chlorotonil A
2014-08-12

ABSTRACT Myxobacteria are Gram-negative soil-dwelling bacteria belonging to the phylum Proteobacteria . They are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. In the course of a bioactivity screening program of secondary metabolites produced by Sorangium cellulosum strains, the macrolide chlorotonil A was found to exhibit promising antimalarial activity. Subsequently, we evaluated chlorotonil A against Plasmodium falciparum laboratory strains and clinical isolates from Gabon. Chlorotonil A was highly active, with a 50% inhibitory concentration between 4 and 32 nM; additionally, no correlations between the activities of chlorotonil A and artesunate (rho, 0.208) or chloroquine (rho, −0.046) were observed. Per os treatment of Plasmodium berghei -infected mice with four doses of as little as 36 mg of chlorotonil A per kg of body weight led to the suppression of parasitemia with no obvious signs of toxicity. Chlorotonil A acts against all stages of intraerythrocytic parasite development, including ring-stage parasites and stage IV to V gametocytes, and it requires only a very short exposure to the parasite to exert its antimalarial action. Conclusively, chlorotonil A has an exceptional and unprecedented profile of action and represents an urgently required novel antimalarial chemical scaffold. Therefore, we propose it as a lead structure for further development as an antimalarial chemotherapeutic.
The next step in modern brain lesion analysis: multivariate pattern analysis
2014-08-12

This scientific commentary refers to ‘Human brain lesion-deficit inference remapped’, by Y.-H. Mah et al. (doi: 10.1093/brain/awu164). A cardinal goal in neuroscience relates to mapping brain circuits to specific functions. Although progress towards this goal has been made using a range of measurement techniques applicable in healthy human subjects, the brain circuits that are necessary for a given function can only be ascertained by observing the behavioural consequences of brain injury (Rorden and Karnath, 2004). In the evolution of this domain, voxel-wise lesion symptom mapping (VLSM; Bates et al. , 2003) represents a tremendous step forward. This statistical approach, as well as other inferential methods (e.g. Rorden et al. , 2007), controls for regions that are not critical for the behavioural deficit under consideration; i.e. VLSM rules out regions of the brain that are simply vulnerable to damage and thus commonly damaged in stroke patients. However, a limitation of this mass univariate approach is that it typically does not consider how multiple regions interact to produce a behavioural deficit. Indeed, in cases where function is tied to a distributed network of regions, two patients with the same symptom and with damage to the same functional network may have damage to distinct parts of the network, thus appearing as statistical counter examples to each other [ cf . the ‘partial injury problem’ (Rorden and Karnath, 2004)]. To overcome this problem, Smith et al. (2013) used multivariate pattern analysis (MVPA) for lesion analysis, which uses machine learning algorithms (e.g. support vector machines) to train and then test predictive models based on the pattern of damage to multiple regions (Fig. 1). This seminal application of MVPA to lesion data addressed the multivariate patterns of damage predictive of spatial neglect. In a large sample of 140 patients with acute right brain damage, MVPA ...
Face processing regions are sensitive to distinct aspects of temporal sequence in facial dynamics
2014-08-12

Facial movement conveys important information for social interactions, yet its neural processing is poorly understood. Computational models propose that shape- and temporal sequence sensitive mechanisms interact in processing dynamic faces. While face processing regions are known to respond to facial movement, their sensitivity to particular temporal sequences has barely been studied. Here we used fMRI to examine the sensitivity of human face-processing regions to two aspects of directionality in facial movement trajectories. We presented genuine movie recordings of increasing and decreasing fear expressions, each of which were played in natural or reversed frame order. This two-by-two factorial design matched low-level visual properties, static content and motion energy within each factor, emotion-direction (increasing or decreasing emotion) and timeline (natural versus artificial). The results showed sensitivity for emotion-direction in FFA, which was timeline-dependent as it only occurred within the natural frame order, and sensitivity to timeline in the STS, which was emotion-direction-dependent as it only occurred for decreased fear. The occipital face area (OFA) was sensitive to the factor timeline. These findings reveal interacting temporal sequence sensitive mechanisms that are responsive to both ecological meaning and to prototypical unfolding of facial dynamics. These mechanisms are temporally directional, provide socially relevant information regarding emotional state or naturalness of behavior, and agree with predictions from modeling and predictive coding theory.
Contraceptive counselling and self-prescription of contraceptives of German gynaecologists: Results of a nationwide survey
2014-08-12

The contraceptives most prescribed by German gynaecologists were COCs, followed by the LNG-IUS, the vaginal ring, and POPs. The spectrum of contraceptives preferred for personal use differed in some ways from those prescribed to patients. Reasons for this discrepancy should be investigated.
Demo
2014-08-12

This demo presents a testbed for computer networking education. It leverages hardware virtualization to accommodate 6 PCs and 2 routers on a single testbed host to reduce costs, energy consumption, space requirements, and heat emission. The testbed excels by providing dedicated physical Ethernet and USB interfaces for virtual machines so that students can interconnect them with cables and switches like in a non-virtualized testbed
KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL
2014-08-13

Key Points KIR haplotype B donors and high KIR B content score confer better protection against relapse after HLA-haploidentical transplantation in pediatric acute lymphoblastic leukemia. Haploidentical donor selection criteria for childhood acute lymphoblastic leukemia should include KIR haplotype and KIR B-content score.