julilili42/papers huggingface dataset:
Induction but not inhibition of COX-2 confers human lung cancer cell apoptosis by celecoxib
2013-08-14

The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Among different structurally related COX-2 inhibitors, only celecoxib was found to cause apoptosis and cell death of human lung cancer cells (IC50 values of 19.96 μM [A549], 12.48 μM [H460], and 41.39 μM [H358]) that was paralleled by a time- and concentration-dependent upregulation of COX-2 and peroxisome proliferator-activated receptor γ (PPARγ) at mRNA and protein levels. Apoptotic death of celecoxib-treated cancer cells was suppressed by the PPARγ antagonist GW9662 and by siRNA targeting PPARγ and, surprisingly, also by the selective COX-2 inhibitor NS-398 and siRNA targeting COX-2. NS-398 (1 μM) was shown to suppress celecoxib-induced COX-2 activity. Among the COX-2-dependent prostaglandins (PG) induced upon celecoxib treatment, PGD2 and 15-deoxy-Δ12,14-PGJ2 were found to induce a cytosol-to-nucleus translocation of PPARγ as well as a PPARγ-dependent apoptosis. Celecoxib-elicited PPARγ translocation was inhibited by NS-398. Finally, a COX-2- and PPARγ-dependent cytotoxic action of celecoxib was proven for primary human lung tumor cells. Together, our data demonstrate a proapoptotic mechanism of celecoxib involving initial upregulation of COX-2 and PPARγ and a subsequent nuclear translocation of PPARγ by COX-2-dependent PGs.
Non‐traded Goods, Globalization and Union Influence
2013-08-14

We study how globalization affects sector‐specific wages, employment levels and welfare in a model of general oligopolistic equilibrium with partly unionized labour markets. Globalization is modelled as either reducing trade costs in open sectors or opening up shielded sectors to trade. Both forms of globalization increase union coverage and lead to lower union wage premia in shielded sectors. Trade cost reductions furthermore lead to higher union wage premia in open sectors and to lower aggregate welfare, while an increased number of open sectors lowers the union wage premium in open sectors, and may increase welfare.
Wildlife Ecotoxicology of Pesticides: Can We Track Effects to the Population Level and Beyond?
2013-08-15

During the past 50 years, the human population has more than doubled and global agricultural production has similarly risen. However, the productive arable area has increased by just 10%; thus the increased use of pesticides has been a consequence of the demands of human population growth, and its impact has reached global significance. Although we often know a pesticide′s mode of action in the target species, we still largely do not understand the full impact of unintended side effects on wildlife, particularly at higher levels of biological organization: populations, communities, and ecosystems. In these times of regional and global species declines, we are challenged with the task of causally linking knowledge about the molecular actions of pesticides to their possible interference with biological processes, in order to develop reliable predictions about the consequences of pesticide use, and misuse, in a rapidly changing world.
Incision into the Eastern Andean Plateau During Pliocene Cooling
2013-08-15

Bringing Down the Andes Mountain ranges, like the Andes in South America, have a number of forces acting on them that control their elevation. High rates of precipitation can induce rapid incision of canyons, but tectonic forces from deep within the mountain range may balance or even exceed the rate of erosion. Lease and Ehlers (p. 774 ) examined the exhumation histories of the northeastern Andean Plateau. The erosion of sediments older than ∼10 million years was controlled largely by tectonic processes. However, more recent sediments suggest that a shift to cooler temperatures increased precipitation 3 to 4 million years ago.
Helminthic Infections Rates and Malaria in HIV-Infected Pregnant Women on Anti-Retroviral Therapy in Rwanda
2013-08-15

HIV-positive pregnant women would benefit from the scaling up of de-worming programs alongside health education and hygiene interventions. The differential effect of certain ART combinations (as observed here most strongly with AZT-3TC-NVP) possibly protecting against helminth infection warrants further investigation.
Co-infection of human parvovirus B19 with Plasmodium falciparum contributes to malaria disease severity in Gabonese patients
2013-08-15

Abstract Background High seroprevalence of parvovirus B19 (B19V) coinfection with Plasmodium falciparum has been previously reported. However, the impact of B19V-infection on the clinical course of malaria is still elusive. In this study, we investigated the prevalence and clinical significance of B19V co-infection in Gabonese children with malaria. Methods B19V prevalence was analyzed in serum samples of 197 Gabonese children with P. falciparum malaria and 85 healthy controls using polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and direct DNA-sequencing. Results B19V was detected in 29/282 (10.28%) of Gabonese children. B19V was observed more frequently in P. falciparum malaria patients (14.21%) in comparison to healthy individuals (1.17%) ( P&lt; 0.001). Notably, the mild-malaria group revealed significantly lower hematocrit levels in B19V/ P. falciparum co-infection than in P. falciparum mono-infection ( P&lt; 0.05). Genetic analysis revealed a predominance of B19V genotype-1 (71.43%) in the studied population. However, B19V-genotype 2 was observed significantly more often in children with severe-malaria than in mild-malaria ( P= 0.04). Conclusion Our findings reveal that B19V-infection is frequent in Gabonese children with P. falciparum malaria and signifies a possible contribution of B19V on the clinical course of malaria in a genotype-dependent manner. B19V co-infection should be considered as a additional diagnostic measure in malaria patients with life threatening anemia.
Homeostatic and injury‐induced microglia behavior in the aging brain
2013-08-16

Summary Microglia cells are essential for brain homeostasis and have essential roles in neurodegenerative diseases. Aging is the main risk factor for most neurodegenerative diseases, and age‐related changes in microglia may contribute to the susceptibility of the aging brain to dysfunction and neurodegeneration. We have analyzed morphology and dynamic behavior of neocortical microglia in their physiological environment in young adult (3‐month‐old), adult (11‐ to 12‐month‐old), and aged (26‐ to 27‐month‐old) C57BL/6J‐Iba1‐ eGFP mice using in vivo 2‐photon microscopy. Results show that surveying microglial cells in the neocortex exhibit age‐related soma volume increase, shortening of processes, and loss of homogeneous tissue distribution. Furthermore, microglial process speed significantly decreased with age. While only a small population of microglia showed soma movement in adult mice, the microglia population with soma movement was increased in aged mice. However, in response to tissue injury, the dynamic microglial response was age‐dependently diminished. These results provide novel insights into microglial behavior and indicate that microglial dysfunction in the aging brain may contribute to age‐related cognitive decline and neurodegenerative diseases.
The evolution of the f-mode instability and gravitational wave detection prospectives
2013-08-16

We study the dynamical evolution of the gravitational-wave driven instability of the f-mode in rapidly rotating relativistic stars with a polytropic equation of state. We use linear perturbation theory to describe the evolution of the mode amplitude and follow the trajectory of a newborn neutron star through its instability window. An unstable f-mode with a saturation energy of about 10−6M⊙c2 may generate a gravitational-wave signal which can be detected by the Einstein Telescope detector from the Virgo cluster. The effects of the magnetic field on the evolution and the detectability of the gravitational radiation are relevant when its strength is higher than 1012 G, while an unstable r-mode becomes dominant it reaches the maximum saturation value allowed by non-linear mode couplings. From the thermal evolution we find also that the heat generated by shear viscosity during the saturation phase completely balances the neutrinos' cooling and prevents the star from entering the regime of mutual friction. The evolution time of the instability is therefore longer and the star loses significantly larger amounts of angular momentum via gravitational waves.
A Newtonian problem as an insightful tool for the behavior of gravitational-wave sources
2013-08-16

We present the intriguing mathematical and physical similarities arising from the study of the Kerr metric and the Euler's problem of two fixed gravitational centers. We show how one could extend these similarities to physical problems that emerge from the above integrable problems, when both are slightly perturbed.
AEROSOL VARIABILITY OBSERVED WITH RPAS
2013-08-16

Abstract. To observe the origin, vertical and horizontal distribution and variability of aerosol particles, and especially ultrafine particles recently formed, we plan to employ the remotely piloted aircraft system (RPAS) Carolo-P360 "ALADINA" of TU Braunschweig. The goal of the presented project is to investigate the vertical and horizontal distribution, transport and small-scale variability of aerosol particles in the atmospheric boundary layer using RPAS. Two additional RPAS of type MASC of Tübingen University equipped with turbulence instrumentation add the opportunity to study the interaction of the aerosol concentration with turbulent transport and exchange processes of the surface and the atmosphere. The combination of different flight patterns of the three RPAS allows new insights in atmospheric boundary layer processes. Currently, the different aerosol sensors are miniaturized at the Leibniz Institute for Tropospheric Research, Leipzig and together with the TU Braunschweig adapted to fit into the RPAS. Moreover, an additional meteorological payload for measuring temperature, humidity and turbulence properties is constructed by Tübingen University. Two condensation particle counters determine the total aerosol number with a different lower detection threshold in order to investigate the horizontal and vertical aerosol variability and new particle formation (aerosol particles of some nm diameter). Further the aerosol size distribution in the range from about 0.300 to ~5 μm is given by an optical particle counter.
Thermodynamic phase structure of charged anti-de Sitter scalar-tensor black holes
2013-08-16

When electromagnetic field with nonlinear lagrangian acts as a source of gravity the no-scalar-hair theorems can be eluded and black holes with non-trivial scalar field can be found in scalar tensor theories [1]. Black holes with secondary scalar hair exist also when a cosmological constant is added in the theory. The thermodynamics of black holes in anti-de Sitter (AdS) space-time has attracted considerable interest due to the AdS/CFT conjecture. A natural question that arises is whether the non-trivial scalar field would alter the black-hole thermodynamical phase structure. In the current work we present the phase structure of charged hairy black holes coupled to nonlinear Born-Infeld electrodynamics in canonical ensemble which is naturally related to AdS space-time. In certain regions of the parameter space we find the existence of a first-order phase transition between small and very large black holes. An unexpected result is that for a small subinterval of charge values two phase transitions are observed – one of zeroth and one of first order.
Liver stiffness in HCV and ALD: Fibrosis-related cut-off values depend on degree and location of inflammation
2013-08-16

Introduction: Liver stiffness (LS) can also be drastically elevated during liver inflammation making it difficult to separate fibrosis- from inflammation-induced LS. We here performed a multicenter study both on a portal-tract pronounced (hepatitis C virus infection; HCV) and a predominantly lobular disease (alcoholic liver disease; ALD). The major aim was, first, to learn whether portal and lobular inflammation differently translate into LS elevation and, second, to calculate adapted cut-off values for concomitant inflammation.
Emergence of Daptomycin Resistance in Daptomycin-Naïve Rabbits with Methicillin-Resistant Staphylococcus aureus Prosthetic Joint Infection Is Associated with Resistance to Host Defense Cationic Peptides and mprF Polymorphisms
2013-08-19

THESE RESULTS SUGGEST: i) DAP MIC increases may occur in the absence of DAP exposures in vivo and may be triggered by organism exposure to endogenous HDPs: and ii) gain-in-function SNPs in mprF may contribute to such HDP-DAP cross-resistance phenotypes, although the mechanism of this relationship remains to be defined.
Transcranial cortex stimulation as a novel approach for probing the neurobiology of dreams: Clinical and neuroethical implications
2013-08-19

In the last two decades considerable progress in brain imaging techniques have led to increasing interest into the neurobiology of sleep stages and dream contents. However, this fascinating research field poses several methodological challenges. The aim of this article is to discuss these challenges and to suggest novel approaches for probing the neurobiology of dream contents. Most of all, I suggest (i) to overcome the correlative limitations of neuroimaging techniques by applying transcranial direct current stimulation (tDCS) during different sleep stages in order to provide causal evidence for the role of specific brain regions in different dream contents, (ii) to control for possible perceptual and cognitive biases in dream reports such as hindsight bias, (iii) to combine computer assisted qualitative data analyses of dream reports with quantitative psychometric scales by applying logistic regression analyses and (iv) to consider possible implications for psychotherapy and neuroethics.
The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein
2013-08-20

A special group of mitochondrial outer membrane proteins spans the membrane once, exposing soluble domains to both sides of the membrane. These proteins are synthesized in the cytosol and then inserted into the membrane by an unknown mechanism. To identify proteins that are involved in the biogenesis of the single-span model protein Mim1, we performed a high-throughput screen in yeast. Two interesting candidates were the cytosolic cochaperone Djp1 and the mitochondrial import receptor Tom70. Our results indeed demonstrate a direct interaction of newly synthesized Mim1 molecules with Tom70. We further observed lower steady-state levels of Mim1 in mitochondria from djp1Δ and tom70 tom71Δ cells and massive mislocalization of overexpressed GFP-Mim1 to the endoplasmic reticulum in the absence of Djp1. Importantly, these phenotypes were observed specifically for the deletion of DJP1 and were not detected in mutant cells lacking any of the other cytosolic cochaperones of the Hsp40 family. Furthermore, the djp1Δ tom70Δ tom71Δ triple deletion resulted in a severe synthetic sick/lethal growth phenotype. Taking our results together, we identified Tom70 and Djp1 as crucial players in the biogenesis of Mim1. Moreover, the involvement of Djp1 provides a unique case of specificity between a cochaperone and its substrate protein.
Can Experimental Electron‐Density Studies be Used as a Tool to Predict Biologically Relevant Properties of Low‐Molecular Weight Enzyme Ligands?
2013-08-20

Abstract The case of protease inhibitor model compounds incorporating an aziridine or epoxide ring is used to exemplify how application of experimental electron‐density techniques can be used to explain the biological properties of low‐molecular weight enzyme ligands. This is furthermore seen in the light of a comparison of crystal and enzyme environments employing QM/MM computations to elucidate to which extent the properties in the crystal can be used to predict behavior in the biological surrounding.
Plasmacytoid Dendritic Cells Are Crucial in Bifidobacterium adolescentis-Mediated Inhibition of Yersinia enterocolitica Infection
2013-08-20

In industrialized countries bacterial intestinal infections are commonly caused by enteropathogenic Enterobacteriaceae. The interaction of the microbiota with the host immune system determines the adequacy of an appropriate response against pathogens. In this study we addressed whether the probiotic Bifidobacterium adolescentis is protective during intestinal Yersinia enterocolitica infection. Female C57BL/6 mice were fed with B. adolescentis, infected with Yersinia enterocolitica, or B. adolescentis fed and subsequently infected with Yersinia enterocolitica. B. adolescentis fed and Yersinia infected mice were protected from Yersinia infection as indicated by a significantly reduced weight loss and splenic Yersinia load when compared to Yersinia infected mice. Moreover, protection from infection was associated with increased intestinal plasmacytoid dendritic cell and regulatory T-cell frequencies. Plasmacytoid dendritic cell function was investigated using depletion experiments by injecting B. adolescentis fed, Yersinia infected C57BL/6 mice with anti-mouse PDCA-1 antibody, to deplete plasmacytoid dendritic cells, or respective isotype control. The B. adolescentis-mediated protection from Yersinia dissemination to the spleen was abrogated after plasmacytoid dendritic cell depletion indicating a crucial function for pDC in control of intestinal Yersinia infection. We suggest that feeding of B. adolescentis modulates the intestinal immune system in terms of increased plasmacytoid dendritic cell and regulatory T-cell frequencies, which might account for the B. adolescentis-mediated protection from Yersinia enterocolitica infection.
The Mevalonate Auxotrophic Mutant of Staphylococcus aureus Can Adapt to Mevalonate Depletion
2013-08-20

ABSTRACT In this study, we attempted to adopt the auxotrophic mevalonate synthase mutant (Δ mvaS mutant) of Staphylococcus aureus to study whether a nongrowing but viable cell population is tolerant to bactericidal antibiotics. The mevalonate-depleted nongrowing Δ mvaS mutant was found tolerant to antibiotics. Surprisingly, after prolonged cultivation, we obtained stable Δ mvaS variants that were able to grow without mevalonate, which suggested unknown mechanisms for compensating undecaprenyl pyrophosphate production without mevalonate in S. aureus .
SDS Interferes with SaeS Signaling of Staphylococcus aureus Independently of SaePQ
2013-08-20

The Staphylococcus aureus regulatory saePQRS system controls the expression of numerous virulence factors, including extracellular adherence protein (Eap), which amongst others facilitates invasion of host cells. The saePQRS operon codes for 4 proteins: the histidine kinase SaeS, the response regulator SaeR, the lipoprotein SaeP and the transmembrane protein SaeQ. S. aureus strain Newman has a single amino acid substitution in the transmembrane domain of SaeS (L18P) which results in constitutive kinase activity. SDS was shown to be one of the signals interfering with SaeS activity leading to inhibition of the sae target gene eap in strains with SaeS(L) but causing activation in strains containing SaeS(P). Here, we analyzed the possible involvement of the SaeP protein and saePQ region in SDS-mediated sae/eap expression. We found that SaePQ is not needed for SDS-mediated SaeS signaling. Furthermore, we could show that SaeS activity is closely linked to the expression of Eap and the capacity to invade host cells in a number of clinical isolates. This suggests that SaeS activity might be directly modulated by structurally non-complex environmental signals, as SDS, which possibly altering its kinase/phosphatase activity.
River restoration: morphological, hydrological, biogeochemical and ecological changes and challenges
2013-08-20

Abstract. River restoration is essential as a means to enhance river dynamics, environmental heterogeneity and biodiversity. The underlying processes governing the dynamic changes need to be understood thoroughly to ensure that restoration projects meet their goals. In particular, we need to understand quantitatively how hydromorphological variability relates to ecosystem functioning and services, biodiversity and (ground)water quality in restored river corridors. Here, we provide a short overview on the literature and present a study of a restored river corridor in Switzerland combining physical, chemical, and biological observations with modeling. The results show complex spatial patterns of bank infiltration, habitat-type, biotic communities and biogeochemical processes. In particular, we found an increase in taxonomic and functional diversity for earthworms, testate amoebae and bacteria in the restored part of the river. This complexity is driven by river hydrology and morphodynamics, which are in turn actively coupled to riparian vegetation processes. Given this complexity and the multiple constraints on the uses and management of floodplains, a multi-disciplinary approach is needed to monitor the success of restoration measures and to make recommendations for future restoration projects.
Empagliflozin as Add-on to Metformin Plus Sulfonylurea in Patients With Type 2 Diabetes
2013-08-21

OBJECTIVE To investigate the efficacy and tolerability of empagliflozin as add-on to metformin and sulfonylurea in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients inadequately controlled on metformin and sulfonylurea (HbA1c ≥7 to ≤10%) were randomized and treated with once-daily empagliflozin 10 mg (n = 225), empagliflozin 25 mg (n = 216), or placebo (n = 225) for 24 weeks. The primary end point was change from baseline in HbA1c at week 24. Key secondary end points were changes from baseline in weight and mean daily glucose (MDG) at week 24. RESULTS At week 24, adjusted mean (SE) changes from baseline in HbA1c were −0.17% (0.05) for placebo vs. −0.82% (0.05) and −0.77% (0.05) for empagliflozin 10 and 25 mg, respectively (both P &amp;lt; 0.001). Empagliflozin significantly reduced MDG, weight, and systolic (but not diastolic) blood pressure versus placebo. Adverse events were reported in 62.7, 67.9, and 64.1% of patients on placebo and empagliflozin 10 and 25 mg, respectively. Events consistent with urinary tract infection were reported in 8.0, 10.3, and 8.3% of patients on placebo and empagliflozin 10 and 25 mg, respectively (females: 13.3, 18.0, and 17.5%, respectively; males: 2.7, 2.7, and 0%, respectively). Events consistent with genital infection were reported in 0.9, 2.7, and 2.3% of patients on placebo and empagliflozin 10 and 25 mg, respectively (females: 0.9, 4.5, and 3.9%, respectively; males: 0.9% in each group). CONCLUSIONS Empagliflozin 10 and 25 mg for 24 weeks as add-on to metformin plus sulfonylurea improved glycemic control, weight, and systolic blood pressure and were well tolerated.
Platelets in tissue repair: control of apoptosis and interactions with regenerative cells
2013-08-21

Abstract Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.