julilili42/papers huggingface dataset:
Selective Breeding for Susceptibility to Myopia Reveals a Gene–Environment Interaction
2011-03-25

Purpose. To test whether the interanimal variability in susceptibility to visually induced myopia is genetically determined. Methods. Monocular deprivation of sharp vision (DSV) was induced in outbred White Leghorn chicks aged 4 days. After 4 days' DSV, myopia susceptibility was quantified by the relative changes in axial length and refraction. Chicks in the extreme tails of the distribution of susceptibility to DSV were kept and paired for breeding (high- and low-susceptibility lines). A second round of selection was then performed. The third generation of chicks, derived from the selected parents, was assessed after either monocular DSV (4 or 10 days) or lens wear. Results. After two rounds of selective breeding, the chicks from the high-susceptibility line developed approximately twice as much myopia in response to 4 days' DSV as did those from the low-susceptibility line (P < 0.001). All ocular component dimensions differed significantly (P < 0.001) between the two selected lines, both before treatment and in the responses of the treated eye. When DSV was conducted for 10 days, the relative changes in axial length and refractive error were still significantly different between the high and low lines (P < 0.001). The chicks bred for high or low susceptibility to DSV also showed significantly different responses to minus lens wear, but not to plus lens wear. Additive genetic effects explained ∼50% of the interanimal variability in response to DSV. Conclusions. Genes and environment interact to shape refractive development in chicks.
A new splash cup to measure the kinetic energy of rainfall
2011-03-25

Abstract Splash cups have long been successfully used for both the quantification of kinetic energy of rainfall and the detachability of soil particles by rainfall impact, the so‐called “splash erosion”. Measurements of kinetic energy, however, have been difficult to operate in the field especially in remote areas, on steep slopes, and in forests since boundary conditions need to be controlled precisely. This paper introduces a new splash cup based on Ellison's archetype that reliably and accurately measures kinetic energy as a function of sand loss under a large variety of conditions. The Tübingen splash cup (T splash cup) is relatively easy to operate under harsh field conditions, and it can be used in experimental designs with a large number of plots and replications at reasonably low costs. The cup is constructed from plastic laboratory flasks and plastic pipes from water‐supply equipments. The unit sand is held by a removable carrier system that can easily be replaced in the field. The splash cups have been calibrated in combination with a laser distrometer using a linear regression function with r 2 = 0.98. They measure kinetic energy over a wide range of rainfall intensities from 0.6 to 40 L m –2 h –1 . Kinetic energy per area varies between 10 and 250 J m –2 . Two years of field test measurements in a subtropical forest ecosystem in China proved the reliability, durability, and usability of our new splash cups and allowed detecting differences in kinetic energy between different tree species and biodiversity levels.
New Tungsten Chloride Cluster Compounds Containing Iron or Cobalt: MW2Cl10 and MW6Cl14 (M = Fe, Co)
2011-03-25

Abstract The reduction of tungsten hexachloride with iron powder or cobalt powder resulted in the formation of M W 2 Cl 10 ( M = Fe and Co) in fused silica tubes at 250 °C and 225 °C, respectively. Crystal structures of the new compounds were refined isotypically from X‐ray powder diffraction patterns [ C 2/ c , Z = 4, a = 6.1226(1) Å, b = 16.7943(1) Å, c = 12.3737(1) Å, and β = 108.99(1)° for FeW 2 Cl 10 , and a = 6.111(1) Å, b = 16.696(1) Å, c = 12.384(1) Å, and β = 108.97(1)° for CoW 2 Cl 10 ]. The structures of Fe 1/5 W 2/5 Cl 2 and Co 1/5 W 2/5 Cl 2 can be considered as a cation‐deficient CdI 2 ‐type structure, in which bioctahedral [W 2 Cl 10 ] n – anions with n ≈︁ 2 introduce significant distortions. The compounds M W 6 Cl 14 ( M = Fe and Co) were prepared following the same procedure at 475 °C. Their crystal structures were refined isotypically [ Pn3 , Z = 4, a = 12.567(1) Å for FeW 6 Cl 14 , and 12.525(1) Å for CoW 6 Cl 14 ] to the structure of PbMo 6 Cl 14 from X‐ray powder diffraction patterns.
Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans
2011-03-27

Abstract T cell–mediated heterologous immunity to different pathogens is promising for the development of immunotherapeutic strategies. Aspergillus fumigatus and Candida albicans, the 2 most common fungal pathogens causing severe infections in immunocompromised patients, are controlled by CD4+ type 1 helper T (TH1) cells in humans and mice, making induction of fungus-specific CD4+ TH1 immunity an appealing strategy for antifungal therapy. We identified an immunogenic epitope of the A fumigatus cell wall glucanase Crf1 that can be presented by 3 common major histocompatibility complex class II alleles and that induces memory CD4+ TH1 cells with a diverse T-cell receptor repertoire that is cross-reactive to C albicans. In BALB/c mice, the Crf1 protein also elicits cross-protection against lethal infection with C albicans that is mediated by the same epitope as in humans. These data illustrate the existence of T cell–based cross-protection for the 2 distantly related clinically relevant fungal pathogens that may foster the development of immunotherapeutic strategies.
An Approach to the Core Structure of Leiodermatolide
2011-03-28

The synthesis of the 16-membered core structure of leiodermatolide 40 has been achieved in 26 linear steps starting from (R)-Roche ester. The key steps in the synthesis of 40 are a Stille cross-coupling between two main fragments 11 and 33 having roughly equal size. For the trisubstituted C4/C5 double bond a carbometalation reaction followed by a Suzuki coupling was used. A Yamaguchi macrolactonization furnished macrolactone 39.
Fine-scale community and genetic structure are tightly linked in species-rich grasslands
2011-03-28

Recent evidence indicates that grassland community structure and species diversity are influenced by genetic variation within species. We review what is known regarding the impact of intraspecific diversity on grassland community structure, using an ancient limestone pasture as a focal example. Two genotype-dependent effects appear to modify community structure in this system. First, the abundance of individual constituent species can depend upon the combined influence of direct genetic effects stemming from individuals within the population. Second, the outcome of localized interspecific interactions occurring within the community can depend on the genotypes of participating individuals (indicating indirect genetic effects). Only genotypic interactions are thought to be capable of allowing the long-term coexistence of both genotypes and species. We discuss the implications of these effects for the maintenance of diversity in grasslands. Next, we present new observations indicating that losses of genotypic diversity from each of two species can be predicted by the abundance of other coexisting species within experimental grassland communities. These results suggest genotype-specific responses to abundance in other coexisting species. We conclude that both direct and indirect genetic effects are likely to shape community structure and species coexistence in grasslands, implying tight linkage between fine-scale genetic and community structure.
Recurrent abdominal pain in children and adolescents – a survey among paediatricians
2011-03-28

Objective: Little is known about prevalence and usual treatment of childhood and adolescent recurrent abdominal pain (RAP) in outpatient paediatricians’ practice. This study’s primary objective was to acquire insights into the usual paediatricians’ treatment and their estimation of prevalence, age and gender of RAP patients. Further objectives were to assess to which extent family members of patients report similar symptoms, how paediatricians rate the strain of parents of affected children and adolescents and how paediatricians estimate the demand for psychological support. Methods: Provided by a medical register, 437 outpatient paediatricians received a questionnaire to assess their perception of several psychosomatic problems and disorders including recurrent abdominal pain. Results: According to paediatricians’ estimation, 15% of all visits are caused by patients with RAP. In 22% of these cases of RAP, at least one family member has similar problems. In about 15% of all RAP cases, parents ask for professional psychological support concerning their children’s issues, whereas 40% of paediatricians wish for psychological support considering this group of patients. Conclusions: Estimated frequencies and paediatricians’ demands show the need for evidence-based psychological interventions in RAP to support usual medical treatment.
Multiple Giant Coronary Aneurysms – Exclusion by Vein Graft Interposition
2011-03-28

Coronary artery aneurysms (CAA) in adults are rare. However, the natural history of CAA is unknown since in adults it is predominantly atherosclerotic in origin. The clinical presentation, prognosis and management of giant CAA are not well defined due to limited experience and the low incidence of CAA. We present a case of successful exclusion of multiple giant CAA with an interposed reversed saphenous vein graft.
Charging and Billing in Modern Communications Networks — A Comprehensive Survey of the State of the Art and Future Requirements
2011-03-29

In mobile telecommunication networks the trend for an increasing heterogeneity of access networks, the convergence with fixed networks as well as with the Internet are apparent. The resulting future converged network with an expected wide variety of services and a possibly stiff competition between the different market participants as well as legal issues will bring about requirements for charging systems that demand for more flexibility, scalability and efficiency than is available in today's systems. This article surveys recent developments in charging and billing architectures comprising both standardisation work as well as research projects. The second main contribution of this article is a comparison of key features of these developments thus giving a list of essential charging and billing ingredients for tomorrow's communication and service environments.
Functional Neuroanatomy of Sustained Memory Encoding Performance in Healthy Aging and in Alzheimer's Disease
2011-03-29

The aim of our study was to examine brain networks involved with sustaining memory encoding performance in healthy aging and in Alzheimer's disease (AD). Since different brain regions are affected by degradation in these two conditions, it might be conceivable that different compensation mechanisms occur to keep up memory performance in aging and in AD. Using an event-related functional magnetic resonance imaging (FMRI) design and a correlation analysis, 8 patients suffering from AD and 29 elderly control subjects were scanned while they studied a list of words for a subsequent memory test. Individual performance was assessed on the basis of a subsequent recognition test, and brain regions were identified where functional activations during study correlated with memory performance. In both groups, successful memory encoding performance was significantly correlated with the activation of the right frontal cortex. Furthermore, in healthy controls, there was a significant correlation of memory performance and the activation of the left medial and lateral temporal lobe. In contrast, in AD patients, increasing memory performance goes along with increasing activation of the hippocampus and a bilateral brain network including the frontal and temporal cortices. Our data show that in healthy aging and in AD, common and distinct compensatory mechanisms are employed to keep up a certain level of memory performance. Both in healthy aging and in patients with AD, an increased level of monitoring and control processes mediated by the (right) frontal lobe seems to be necessary to maintain a certain level of memory performance. In addition, memory performance in healthy older subjects seems to rely on an increased effort in encoding item-specific semantic and contextual information in lateral areas of the (left) temporal lobe. In AD patients, on the other hand, the maintenance of memory performance is related to an increase of activation of the (left) hippocampus in conjunction with a bilateral network of cortical areas that might be involved with phonological and visual rehearsal of the incoming information.
Adenylate‐Forming Enzymes of Rubradirin Biosynthesis: RubC1 Is a Bifunctional Enzyme with Aminocoumarin Acyl Ligase and Tyrosine‐Activating Domains
2011-03-29

Abstract The biosynthesis of aminocoumarin antibiotics requires two acyladenylate‐forming enzymes: one for the activation of L ‐tyrosine as a precursor of the aminocoumarin moiety and another for the linkage of an acyl moiety to the aminocoumarin moiety. Unexpectedly, the biosynthetic gene cluster of the aminocoumarin antibiotic rubradirin was found to contain three genes for putative acyladenylate‐forming enzymes of aminocoumarin biosynthesis and conjugation. We expressed, purified, and investigated these three proteins. Orf4 (55 kDa) was shown to be an active aminocoumarin acyl ligase. RubF6 (56 kDa) was inactive, but could be converted into an active enzyme by site‐directed mutagenesis. RubC1 (138 kDa) was shown to be a unique bifunctional enzyme, comprising an aminocoumarin acyl ligase, and tyrosine‐adenylation and peptidyl‐carrier domains. This natural hybrid enzyme is unique among known proteins. A hypothesis is proposed as to how such an enzyme could offer a particularly effective machinery for aminocoumarin antibiotic biosynthesis.
Activity Levels of Tamoxifen Metabolites at the Estrogen Receptor and the Impact of Genetic Polymorphisms of Phase I and II Enzymes on Their Concentration Levels in Plasma
2011-03-30

The therapeutic effect of tamoxifen depends on active metabolites, e.g., cytochrome P450 2D6 (CYP2D6) mediated formation of endoxifen. To test for additional relationships, 236 breast cancer patients were genotyped for CYP2D6, CYP2C9, CYP2B6, CYP2C19, CYP3A5, UGT1A4, UGT2B7, and UGT2B15; also, plasma concentrations of tamoxifen and 22 of its metabolites, including the (E)-, (Z)-, 3-, and 4'-hydroxymetabolites as well as their glucuronides, were quantified using liquid chromatography-tandem mass spectrometry (MS). The activity levels of the metabolites were measured using an estrogen response element reporter assay; the strongest estrogen receptor inhibition was found for (Z)-endoxifen and (Z)-4-hydroxytamoxifen (inhibitory concentration 50 (IC50) 3 and 7 nmol/l, respectively). CYP2D6 genotypes explained 39 and 9% of the variability of steady-state concentrations of (Z)-endoxifen and (Z)-4-hydroxytamoxifen, respectively. Among the poor metabolizers, 93% had (Z)-endoxifen levels below IC90 values, underscoring the role of CYP2D6 deficiency in compromised tamoxifen bioactivation. For other enzymes tested, carriers of reduced-function CYP2C9 (*2, *3) alleles had lower plasma concentrations of active metabolites (P < 0.004), pointing to the role of additional pathways.
Non-LTE models for the gaseous metal component of circumstellar discs around white dwarfs
2011-03-30

\\n Context. Gaseous metal discs around single white dwarfs have been discovered recently. They are thought to develop from disrupted planetary bodies.\\n Aims. Spectroscopic analyses will allow us to study the composition of extrasolar planetary material. We investigate in detail the first object for which a gas disc was discovered (SDSS J122859.93+104032.9).\\n Methods. We perform non-LTE modelling of viscous gas discs by computing the detailed vertical structure and line spectra. The models are composed of carbon, oxygen, magnesium, silicon, calcium, and hydrogen with chemical abundances typical for Solar System asteroids. Line asymmetries are modelled by assuming spiral-arm and eccentric disc structures as suggested by hydrodynamical simulations.\\n Results. The observed infrared Ca <sc>ii </sc>emission triplet can be modelled with a hydrogen-deficient metal gas disc located inside of the tidal disruption radius, with Teff ≈ 6000 K and a surface mass density of Σ ≈ 0.3 g/cm2. The inner radius is well constrained at about 0.64 R⊙. The line profile asymmetry can be reproduced by either a spiral-arm structure or an eccentric disc, the latter being favoured by its time variability behaviour. Such structures, reaching from 0.64 to 1.5 R⊙, contain a mass of about 3−6 × 1021 g, the latter equivalent to the mass of a 135-km diameter Solar System asteroid. \\n
Ca2+ signaling in the regulation of dendritic cell functions
2011-03-31

Dendritic cells (DCs) are highly versatile antigen-presenting cells critically involved in both innate and adaptive immunity as well as maintenance of self-tolerance. DC function is governed by Ca 2+ signaling, which directs the DC responses to diverse antigens, including Toll-like receptor ligands, intact bacteria, and microbial toxins. Ca 2+ -sensitive DC functions include DC activation, maturation, migration, and formation of immunological synapses with T cells. Moreover, alterations of cytosolic Ca 2+ trigger immune suppression or switch off DC activity. Ca 2+ signals are generated by the orchestration of Ca 2+ transport processes across plasma, endoplasmic reticulum, and inner mitochondrial membrane. These processes include active pumping of Ca 2+ , Ca 2+ /Na + antiport, and electrodiffusion through Ca 2+ -permeable channels or uniporters. Ca 2+ channels in the plasma membrane such as Ca 2+ release-activated Ca 2+ or L-type Ca 2+ channels are tightly regulated by the membrane potential which in turn depends on the activity of voltage-gated K + or Ca 2+ -activated nonselective cation channels. The rapidly growing knowledge on the function and regulation of these membrane transport proteins provides novel insight into pathophysiological mechanisms underlying dysfunction of the immune system and opens novel therapeutic opportunity to favorably influence the function of the immune system.
The DNA methyltransferase inhibitors zebularine and decitabine induce mitochondria‐mediated apoptosis and DNA damage in p53 mutant leukemic T cells
2011-03-31

Abstract DNA methyltransferase (DNMT)‐inhibiting nucleoside analogs reactivate the expression of tumor suppressor genes and apoptosis‐related genes silenced by methylation, thus favoring the induction of apoptosis in tumor cells. Moreover, induction of DNA damage seems to contribute to their antitumor effect. However, the apoptotic signaling pathway induced by these demethylating drugs is not well understood. Here, we have investigated the induction of apoptosis by two nucleoside DNMT inhibitors, decitabine and zebularine, in leukemic T cells. Both inhibitors induced caspase‐dependent apoptosis in Jurkat, CEM‐6 and MOLT‐4 leukemia T cell lines, all with mutant p53, whereas resting and activated normal T lymphocytes were highly resistant to these demethylating agents. Although decitabine and zebularine showed different ability to induce apoptosis and cell cycle arrest among the three cell lines, they similarly activated the intrinsic apoptotic pathway by inducing mitochondrial alterations such as Bak activation, loss of transmembrane potential and generation of reactive oxygen species (ROS). Accordingly, Bcl‐2‐ and Bcl‐x L ‐overexpressing Jurkat cells, as well as caspase‐9‐deficient Jurkat cells, were resistant to apoptosis induced by decitabine and zebularine. Interestingly, ROS production seemed to be necessary for the induction of apoptosis. Apoptotic events, such as Bak and caspase activation, started as soon as 20 hr after treatment with either decitabine or zebularine. In addition, progression of apoptosis triggered by both DNMT inhibitors was paralleled by the induction of DNA damage. Our results suggest that the mitochondrial apoptotic pathway activated by decitabine and zebularine in p53 mutant leukemic T cells depends mainly on the induction of DNA damage.
Mediastinal gray zone lymphoma
2011-03-31

The current classification of lymphoid neoplasms is based on the integrated utilization of morphological, immunohistochemical, genetic and clinical criteria to define disease entities, which putatively have their origin in a “normal counterpart” in the immune system.[1][1] The application of
Chiral Sulfoxides as Metabolites of 2-Thioimidazole-Based p38α Mitogen-Activated Protein Kinase Inhibitors: Enantioselective Synthesis and Biological Evaluation
2011-03-31

A number of pharmaceutically important drugs contain asymmetric sulfinyl moieties, so the biological evaluation of chiral sulfoxides as human drug metabolites is important for the development of safe and effective pharmaceuticals. Asymmetric oxidation is one of the most attractive ways to prepare chiral sulfoxides. In combination with different chiral ligands, the iron- and titanium-catalyzed asymmetric oxidations of tri- and tetrasubstituted 2-thioimidazoles afford the corresponding sulfoxides with enantiomeric excesses up to 99% as novel p38α mitogen-activated protein kinase (p38α MAPK) inhibitors. The enantiomerically pure sulfoxides were evaluated on their inhibitory potency against p38α MAPK compared to the respective sulfides and sulfoxide racemates and showed differences in their affinities for the enzyme with IC(50) in the low nanomolar range. In addition, the ability to inhibit the release of tumor necrosis factor-α (TNF-α) from human whole blood (HWB) was examined. Some pyridinylimidazole derivatives showed excellent HWB activity with IC(50) as low as 52 nM.
Histone Acetylation Patterns of Typical and Atypical Pituitary Adenomas Indicate Epigenetic Shift of these Tumours
2011-03-31

Pituitary adenomas are benign endocrine tumours of the anterior pituitary that are subclassified as typical (conventional) or atypical adenomas, with uncertain prognosis based on histopathological features. Clarifying epigenetic alterations of pituitary tumours, as well as the mechanisms underlying them, will hopefully open new windows to treatment and the classification of these tumours and maybe even prediction of patient survival. In the present study, using immunohistochemistry, we investigated the acetylation pattern of histone 3 lysine 9 (H3K9), an epigenetic marker of active chromatin state and gene transcription, in typical and atypical pituitary adenomas and the normal pituitary. We observed a significant increase in H3K9 acetylation from the normal pituitary to typical and atypical pituitary adenomas, which was associated with significant hyperacetylation of H3K9 in atypical adenomas (P < 0.0001). MIB-1 (Ki-67) overexpression was also highly associated with increased acetylation of H3K9, correlating prositively with tumour severity (P < 0.0001). p53 overexpression had a contributing effect on altered global H3K9 acetylation of atypical pituitary adenomas (P < 0.05). These data suggests that H3K9 acetylation status might serve as a relevant additional biomarker of tumour severity in pituitary adenomas, and also as a proper target for epigenetic-based therapies.