julilili42/papers huggingface dataset:
Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage
2013-09-05

Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone.
Prospective randomized double‐blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE ( AUO‐AB 31/05)
2013-09-05

Objective To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine‐kinase inhibitor, compared with chemotherapy alone as first‐line treatment in advanced urothelial cancer. Patients and Methods The study was a randomized phase II trial. Its primary aim was to show an improvement in progression‐free survival ( PFS ) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate ( ORR ), overall survival ( OS ) and toxicity. The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract. Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double‐blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3–21. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles. Results Between O ctober 2006 and O ctober 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm. There were no significant differences between the two arms concerning ORR (sorafenib: complete response [ CR ] 12.5%, partial response [ PR ] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months). Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand‐foot syndrome occurred only in the sorafenib arm. The study was closed prematurely because of slow recruitment. Conclusion Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS .
Insight into structure‐function relationship in phenol‐soluble modulins using an alanine screen of the phenol‐soluble modulin (PSM) α3 peptide
2013-09-05

Phenol‐soluble modulins (PSMs) are a family of peptides with multiple functions in staphylococcal pathogenesis. To gain insight into the structural features affecting PSM functions, we analyzed an alanine substitution library of PSMα3, a strongly cytolytic and proinflammatory PSM of Staphylococcus aureus with a significant contribution to S. aureus virulence. Lysine residues were essential for both receptor‐dependent proinflammatory and receptor‐independent cytolytic activities. Both phenotypes also required additional structural features, with the C terminus being crucial for receptor activation. Biofilm formation was affected mostly by hydrophobic amino acid positions, suggesting that the capacity to disrupt hydrophobic interactions is responsible for the effect of PSMs on biofilm structure. Antimicrobial activity, absent from natural PSMα3, could be created by the exchange of large hydrophobic side chains, indicating that PSMα3 has evolved to exhibit cytolytic rather than antimicrobial activity. In addition to gaining insight into the structure‐function relationship in PSMs, our study identifies nontoxic PSMα3 derivatives for active vaccination strategies and lays the foundation for future efforts aimed to understand the biological role of PSM recognition by innate host defense.—Cheung, G. Y., Kretschmer, D., Queck, S. Y., Joo, H.‐S., Wang, R., Duong, A. C., Nguyen, T. H., Bach, T.‐H., Porter, A. R., DeLeo, F. R., Peschel, A., Otto, M. Insight into structure‐function relationship in phenol‐soluble modulins using an alanine screen of the phenol‐soluble modulin (PSM) α3 peptide. FASEB J . 28, 153–161 (2014). www.fasebj.org
Oridonin ameliorates neuropathological changes and behavioural deficits in a mouse model of cerebral amyloidosis
2013-09-05

Abstract Alzheimer's disease ( AD ) is the most common form of neurodegeneration and the major cause of dementia. This multifactorial disorder is clinically defined by progressive behavioural and cognitive deficits, and neuropathologically characterized by β‐amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia rubescens, has multiple biological properties, especially anti‐inflammatory and neuroregulatory activities. Potential therapeutic effects of Oridonin were investigated in an animal model of cerebral amyloidosis for AD , transgenic APP / PS 1 mice. Oridonin was suspended in carboxymethylcellulose or loaded with a nanostructured emulsion, and was orally administrated or injected. Before, during and following the experimental treatments, behavioural tests were performed with these transgenic mice and their naive littermates. Following relatively short‐term treatments of 10 days, brain tissue of mice were removed for immunohistochemical assays. The results indicate that both oral treatment and injection of Oridonin significantly attenuated β‐amyloid deposition, plaque‐associated APP expression and microglial activation in brain of transgenic mice. Furthermore, injection of Oridonin‐nanoemulsion ameliorated deficits in nesting, an important affiliative behaviour, and in social interaction. Additional in vitro studies indicated that Oridonin effectively attenuated inflammatory reaction of macrophage and microglial cell lines. Our results suggest that Oridonin might be considered a promising therapeutic option for human AD or other neurodegenerative diseases.
Tensile and shear strength of porous dust agglomerates
2013-09-05

Context.Within the sequential accretion scenario of planet formation, planets\\nare build up through a sequence sticking collisions. The outcome of collisions\\nbetween porous dust aggregates is very important for the growth from very small\\ndust particles to planetesimals. In this work we determine the necessary\\nmaterial properties of dust aggregates as a function the porosity.\\n Aims: Continuum models such as SPH that are capable of simulating collisions\\nof macroscopic dust aggregates require a set of material parameters. Some of\\nthem such as the tensile and shear strength are difficult to obtain from\\nlaboratory experiments. The aim of this work is to determine these parameters\\nfrom ab-initio molecular dynamics simulations.\\n Methods: We simulate the behavior of porous dust aggregates using a detailed\\nmicro-physical model of the interaction of spherical grains that includes\\nadhesion forces, rolling, twisting, and sliding. Using different methods of\\npreparing the samples we study the strength behavior of our samples with\\nvarying porosity and coordination number of the material.\\n Results: For the tensile strength, we can reproduce data from laboratory\\nexperiments very well. For the shear strength, there are no experimental data\\navailable. The results from our simulations differ significantly from previous\\ntheoretical models, which indicates that the latter might not be sufficient to\\ndescribe porous dust aggregates.\\n Conclusions: We have provided functional behavior of tensile and shear\\nstrength of porous dust aggregates as a function of the porosity that can be\\ndirectly applied in continuum simulations of these objects in planet formation\\nscenarios.\\n
Flows of constant mean curvature tori in the 3-sphere: Theequivariant case
2013-09-05

Abstract We present a deformation for constant mean curvature tori in the 3-sphere. We show that the moduli space of equivariant constant mean curvature tori in the 3-sphere is connected, and we classify the minimal, the embedded, and the Alexandrov embedded tori therein.
Explanations for the heterogeneity of splenic enhancement derived from blood flow kinetic measurements using dynamic contrast-enhanced CT (DCE-CT)
2013-09-05

Background The heterogeneity of splenic computed tomography (CT) attenuation is still not fully understood. A differentiation of these enhancement patterns and other conditions such as diffuse spleen infiltration can be challenging. Purpose To understand the underlying physiological mechanisms of flow heterogeneity in normal and cirrhosis patients by quantifying perfusion parameters such as blood flow (BF), blood volume (BV), time to peak (TTP), flow extraction product (K trans ), and mean transit time (MTT) using dynamic contrast-enhanced CT (DCE-CT). Material and Methods Sixteen patients without splenic or hepatic disease and 16 patients with liver cirrhosis were retrospectively analyzed. Perfusion assessment included rapidly and slowly enhancing areas of the spleen, the entire splenic volume, as well as intra- and inter-observer reliability analysis. Results Significant differences between rapidly and slowly enhancing areas were found in controls for BF (109.8 mL/100 mL/min vs. 63.5 mL/100 mL/min), BV (37.1 mL/100 mL vs. 18.9 mL/100 mL), MTT (10.1 s vs. 13.0 s), but not for TTP (17.6 s vs. 18.6 s) and K trans (40.3 mL/100 mL/min vs. 44.7 mL/100 mL/min). In cirrhotic patients, differences proved significant for BF (90.5 mL/100 mL/min vs. 58.7 mL/100 mL/min), BV (17.5 mL/100 mL vs. 8.8 mL/100 mL), but not for K trans (60.9 mL/100 mL/min vs. 50.5 mL/100 mL/min), TTP (18.8 s vs. 20.0 s), and MTT (11.4 s vs. 14.2 s). Differences between rapidly enhancing areas in controls and cirrhotic patients reached a significant level for BV and K trans . Conclusion Preliminary results suggest that DCE-CT-based splenic perfusion measurements enable detection of different blood flow kinetics presumed to represent the complex and characteristic architecture of splenic vascular channels. It is the separate analysis of flow kinetics through the rapidly enhancing channels that allow for additional differentiation between controls and patients with portal hypertension.
Advances in the neurobiology of hearing disorders: Recent developments regarding the basis of tinnitus and hyperacusis
2013-09-06

The prevalence of hearing problems in the Western world has, due to aging of the population, doubled over the past 30 years. Thereby, noise-induced hearing loss is an important factor that worsens over time in addition to age-related hearing loss. Hearing loss is usually measured as an elevation of a person's hearing thresholds, expressed in decibel (dB). However, recent animal studies have unraveled a type of permanent cochlear damage, without an elevation of hearing thresholds. This subtle damage is linked to a permanent and progressive degeneration of auditory fibers that occurs in association with damage of the inner hair cell synapse. Afferent neuronal degeneration has been suggested to be involved in hyperacusis (over sensitivity to sound) and tinnitus (a phantom sound percept). Hyperacusis and tinnitus are potentially devastating conditions that are still incurable. The main risk factors to develop tinnitus or hyperacusis are hearing loss, social stress and age. Both tinnitus and hyperacusis have been discussed in the context of a pathological increased response gain in subcortical brain regions as a reaction to deprivation of sensory input. Novel studies confirm the involvement of peripheral deafferentation for tinnitus and hyperacusis, but suggest that the disorder results from different brain responses to different degrees of deafferentation: while tinnitus may arise as a failure of the brain to adapt to deprived peripheral input, hyperacusis may result from an 'over-adaptive' increase in response gain. Moreover, moderate and high stress levels at the time of acoustic trauma have been suggested to play a pivotal role in the vulnerability of the cochlea to acoustic damage and therefore for the development of tinnitus and hyperacusis.
Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A
2013-09-06

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10(-9), odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures.
The transient gravitational-wave sky
2013-09-06

Interferometric detectors will very soon give us an unprecedented view of the gravitational-wave sky, and in particular of the explosive and transient Universe. Now is the time to challenge our theoretical understanding of short-duration gravitational-wave signatures from cataclysmic events, their connection to more traditional electromagnetic and particle astrophysics, and the data analysis techniques that will make the observations a reality. This paper summarizes the state of the art, future science opportunities, and current challenges in understanding gravitational-wave transients.
Anti‐[2.2](1,4)pentacenophane: A Covalently Coupled Pentacene Dimer
2013-09-06

Two in a row: A pentacene dimer in which both units are covalently linked through a [2.2]paracyclophane bridge, has been synthesized. The electronic properties of the molecule were elucidated by a combination of experimental and computational methods. Such molecules could lead to materials with improved charge-transport properties.
Autonomous functions of murine thyroid hormone receptor TRα and TRβ in cochlear hair cells
2013-09-06

Thyroid hormone acts on gene transcription by binding to its nuclear receptors TRα1 and TRβ. Whereas global deletion of TRβ causes deafness, global TRα-deficient mice have normal hearing thresholds. Since the individual roles of the two receptors in cochlear hair cells are still unclear, we generated mice with a hair cell-specific mutation of TRα1 or deletion of TRβ using the Cre-loxP system. Hair cell-specific TRβ mutant mice showed normal hearing thresholds but delayed BK channel expression in inner hair cells, slightly stronger outer hair cell function, and slightly reduced amplitudes of auditory brainstem responses. In contrast, hair cell-specific TRα mutant mice showed normal timing of BK channel expression, slightly reduced outer hair cell function, and slightly enhanced amplitudes of auditory brainstem responses. Our data demonstrate that TRβ-related deafness originates outside of hair cells and that TRα and TRβ play opposing, non-redundant roles in hair cells. A role for thyroid hormone receptors in controlling key regulators that shape signal transduction during development is discussed. Thyroid hormone may act through different thyroid hormone receptor activities to permanently alter the sensitivity of auditory neurotransmission.
Peptides as triggers of plant defence
2013-09-07

Plants are confronted with several biotic stresses such as microbial pathogens and other herbivores. To defend against such attackers, plants possess an array of pattern recognition receptors (PRRs) that sense the danger and consequently initiate a defence programme that prevents further damage and spreading of the pest. Characteristic pathogenic structures, so-called microbe-associated molecular patterns (MAMPs), serve as signals that allow the plant to sense invaders. Additionally, pathogens wound or damage the plant and the resulting release of damage-associated molecular patterns (DAMPs) serves as a warning signal. This review focuses on peptides that serve as triggers or amplifiers of plant defence and thus follow the definition of a MAMP or a DAMP.
IFIT2 Is an Effector Protein of Type I IFN–Mediated Amplification of Lipopolysaccharide (LPS)-Induced TNF-α Secretion and LPS-Induced Endotoxin Shock
2013-09-07

Abstract Type I IFN signaling amplifies the secretion of LPS-induced proinflammatory cytokines such as TNF-α or IL-6 and might thus contribute to the high mortality associated with Gram-negative septic shock in humans. The underlying molecular mechanism, however, is ill defined. In this study, we report the generation of mice deficient in IFN-induced protein with tetratricopeptide repeats 2 (Ifit2) and demonstrate that Ifit2 is a critical signaling intermediate for LPS-induced septic shock. Ifit2 expression was significantly upregulated in response to LPS challenge in an IFN-α receptor– and IFN regulatory factor (Irf)9–dependent manner. Also, LPS induced secretion of IL-6 and TNF-α by bone marrow–derived macrophages (BMDMs) was significantly enhanced in the presence of Ifit2. In accordance, Ifit2-deficient mice exhibited significantly reduced serum levels of IL-6 and TNF-α and reduced mortality in an endotoxin shock model. Investigation of the underlying signal transduction events revealed that Ifit2 upregulates Irf3 phosphorylation. In the absence of Irf3, reduced Ifn-β mRNA expression and Ifit2 protein expression after LPS stimulation was found. Also, Tnf-α and Il-6 secretion but not Tnf-α and Il-6 mRNA expression levels were reduced. Thus, IFN-stimulated Ifit2 via enhanced Irf3 phosphorylation upregulates the secretion of proinflammatory cytokines. It thereby amplifies LPS-induced cytokine production and critically influences the outcome of endotoxin shock.
Bladder cancer discussed on the internet: a systematic analysis of gender differences of initial posters on an online discussion board
2013-09-08

Abstract Objectives To evaluate gender differences of initial posters in threads dealing with bladder cancer on an online discussion board. Method 529 threads opened between 09/2005 and 03/2012 were screened on the largest German speaking bladder cancer online discussion board. 366 threads fulfilled the requirements for this study. Gender, age, number, status of concern and oncological situation of initiating posters as well as their motives and language style were analyzed following a standardized protocol. Results Threads were initiated in 45% (164/366) by men and in 55% (202/366) by women. Mean age of male initiating posters was 50 years and of female posters 44 years (p &lt; 0.001). Of males 80% (132/164) were concerned patients and 20% (32/164) relatives or friends. Of females they were 39% (78/202) and 61% (124/202), respectively (p &lt; 0.001). In general motives for initial posting were focused on medical information and did not differ between both genders. 81% of the posters asked for medical information or therapeutic recommendations regarding diagnosis, treatment and prognosis. However, women significantly more often expressed their wish for emotional support (p = 0.034) and in tendency wanted to share their experiences with others (p = 0.057). Language analysis revealed that women significantly more often used a tentative language style than men (p = 0.003). Conclusion Even though women are less often affected by bladder cancer, they are more active –especially for their concerned family members - on the evaluated discussion board than men. Whereas both genders equally often ask for medical information, women more often want to share their experiences and look for emotional support.