julilili42/papers huggingface dataset:
Glioma tropism of lentivirally transduced hematopoietic progenitor cells
2010-04-21

Experimental gliomas attract hematopoietic progenitor cells (HPC) in vivo. HPC are therefore promising candidates for a cell-based delivery of therapeutic molecules to experimental gliomas. A therapeutic application requires efficient genetic manipulation of the cellular vector and a lack of tumorigenicity. Here, we studied the impact of lenti-viral transduction on the glioma tropism of human or murine HPC. Transduction of human or murine HPC with a GFP lentivirus (lenti-GFP) did not interfere with the glioma-mediated attraction of HPC. Bone marrow reconstitution of C57Bl/6 mice with syngeneic GFP-transgenic lineage-depleted bone marrow cells (lin- BM) was as efficient as reconstitution with syngeneic lin- BM transduced ex vivo with lenti-GFP. SMA-560 gliomas growing orthotopically in lenti-GFP-reconstituted VM/Dk mice recruited GFP-positive bone marrow-derived cells. Thus, lentiviral transduction did not interfere with the attraction of exogenously injected HPC or endogenous bone marrow-derived cells by experimental gliomas. Lenti-GFP-HPC implanted directly into tumor-free brains were not tumorigenic. The intravenous injection of lenti-GFP-HPC in glioma-bearing mice did not alter the survival of otherwise untreated animals and had no impact on the survival benefit conferred by cerebral irradiation. Taken together, genetic manipulation of HPC with lenti-GFP neither made these cells tumorigenic nor interfered with their glioma tropism.
Arabidopsis thaliana Pattern Recognition Receptors for Bacterial Elongation Factor Tu and Flagellin Can Be Combined to Form Functional Chimeric Receptors
2010-04-22

The receptor kinase EFR of Arabidopsis thaliana detects the microbe-associated molecular pattern elf18, a peptide that represents the N terminus of bacterial elongation factor Tu. Here, we tested subdomains of EFR for their importance in receptor function. Transient expression of tagged versions of EFR and EFR lacking its cytoplasmic domain in leaves of Nicotiana benthamiana resulted in functional binding sites for elf18. No binding of ligand was found with the ectodomain lacking the transmembrane domain or with EFR lacking the first 5 of its 21 leucine-rich repeats (LRRs). EFR is structurally related to the receptor kinase flagellin-sensing 2 (FLS2) that detects bacterial flagellin. Chimeric receptors with subdomains of FLS2 substituting for corresponding parts of EFR were tested for functionality in ligand binding and receptor activation assays. Substituting the transmembrane domain and the cytoplasmic domain resulted in a fully functional receptor for elf18. Replacing also the outer juxtamembrane domain with that of FLS2 led to a receptor with full affinity for elf18 but with a lower efficiency in response activation. Extending the substitution to encompass also the last two of the LRRs abolished binding and receptor activation. Substitution of the N terminus by the first six LRRs from FLS2 reduced binding affinity and strongly affected receptor activation. In summary, chimeric receptors allow mapping of subdomains relevant for ligand binding and receptor activation. The results also show that modular assembly of chimeras from different receptors can be used to form functional receptors.
“Beauty lies in the eye of the beholder”? Aspects of beauty and attractiveness
2010-04-22

Summary Discussing aesthetic issues and their management with patients is a growing area of dermatologic practice. Sometimes treatment options within one's own discipline are rapidly discussed, without a clear idea of the various aspects of the face which all combine to produce beauty and attractiveness. We review various features leading to the impression of beauty and attractiveness. Familiarity with these concepts should facilitate a broader discussion with the patient on the aspects of beauty and attractiveness beyond the borders of one's own discipline and also lead to multidisciplinary treatment options. We also examine the question how much the personality of the beholder himself is involved in the perception of attractiveness and beauty (of the person sitting opposite to him). The “ideal” face has an average profile with slightly protrusive and full lips. Attractiveness increases with average features and symmetry. Moreover, particular features such as the scheme of childlike characteristics combined with aspects of maturity and expression make a female face appear especially beautiful. Which attributes contribute to attractiveness of a man's face are controversial. Clear male signals such as a strong chin are likely not to increase attractiveness.
Equity versus Efficiency? Evidence from Three-Person Generosity Experiments
2010-04-22

In two-person generosity games, the proposer’s agreement payoff is exogenously given, whereas that of the responder is endogenously determined by the proposer’s choice of the pie size. In three-person generosity games, equal agreement payoffs for two of the players are either exogenously excluded or imposed. We predict that the latter crowds out - or at least weakens - efficiency seeking. Our treatments rely on a 2x3 factorial design, differing in whether the responder or the third (dummy) player is the residual claimant and whether the proposer’s agreement payoff is larger, equal, or smaller than the other exogenously given agreement payoff.
Meta‐analysis of individual patient data to assess the risk of hypoglycaemia in people with type 2 diabetes using NPH insulin or insulin glargine
2010-04-23

Aim: To estimate absolute and relative incidence rates of hypoglycaemia when using once‐daily evening or morning regimens of insulin glargine (glargine) versus once‐daily evening NPH insulin (NPH) using individual patient data (IPD). Materials and methods: Randomized controlled trials with accessible IPD and including white European people with type 2 diabetes (T2DM) using glargine or NPH once‐daily (with oral glucose‐lowering drugs) were identified. Two study pools were analysed: evening glargine versus evening NPH (pool 1); and morning glargine versus evening NPH (pool 2). The number‐needed‐to‐treat to avoid hypoglycaemia was calculated for glargine versus NPH. Results: In study pool 1 (n = 2711), the risk of nocturnal hypoglycaemia was approximately halved with glargine compared with NPH [odds ratios (OR): 0.44–0.52, p &lt; 0.001–0.047]. This led to a significant reduction in anytime risk of symptomatic hypoglycaemia [plasma glucose (PG) &lt;3.9 mmol/l, OR: 0.64, p = 0.018; PG &lt;2.0 mmol/l, OR: 0.51, p &lt; 0.001]. In study pool 2 (n = 470), although a strong numerical reduction in all types of nocturnal hypoglycaemia was observed (OR: 0.16–0.64), statistical significance was reached only for symptomatic hypoglycaemia with PG &lt;3.9 mmol/l (p &lt; 0.001). Eight (pool 1) or five (pool 2) people with T2DM needed to use glargine rather than NPH to avoid one person from experiencing a nocturnal symptomatic hypoglycaemic event within a median of about 25 weeks of starting insulin. Conclusions: This meta‐analysis of open‐label studies provides confidence that reductions of around 50% of risk for nocturnal hypoglycaemia can be achieved with using glargine instead of NPH.
SOUTHEAST ASIA'S FIRST ISOTOPICALLY DEFINED PREHISTORIC COPPER PRODUCTION SYSTEM: WHEN DID EXTRACTIVE METALLURGY BEGIN IN THE KHAO WONG PRACHAN VALLEY OF CENTRAL THAILAND?
2010-04-23

Southeast Asian metallurgical developments have been a focus of international academic interest since Solheim (1968) and Bayard (1972) first published bronze artefacts in claimed early/middle third millennium bce contexts from northeastern Thailand, igniting a regional 'origins' of metallurgy debate that has smouldered for 40 years (e.g., White and Hamilton 2009, Higham in press). In this paper, we present the results of a lead isotope pilot study centred on the Khao Wong Prachan Valley of central Thailand—currently Southeast Asia's only documented prehistoric copper smelting locale. These preliminary data indicate that our ongoing regional metal exchange research programme may be able to elucidate interaction networks between copper-producing and -consuming societies within and beyond Southeast Asia from c. 2000 bce to c. 500 ce. Furthermore, we are able to offer tentative evidence relevant to White and Hamilton's (2009) 'Rapid Eurasian Technological Expansion Model' for the Sino-Siberian derivation of regional metal technologies around the turn of the third/second millennium bce.
Rare‐Earth Metal Phenyl(trimethylsilyl)amide Complexes
2010-04-23

Abstract The reactions of common rare‐earth metal chloride, borohydride, and triflate precursors – LnCl 3 (thf) x , Ln(BH 4 ) 3 (thf) 3 , and La(OTf) 3 – with alkali metal amide complexes M[N(SiMe 3 )(C 6 H 3 i Pr 2 ‐2,6)] (M[NRR′]; M = Li, K) were investigated in thf or hexane as a solvent. A diverse range of products was obtained comprising alkali metal‐free mono(rare‐earth metal) complexes Y[NRR′]Cl 2 (thf) 3 and Ln[NRR′] 2 (BH 4 )(thf) (Ln = Nd, La), as well as the mononeodymium ate complex {Nd[NRR′] 2 (BH 4 ) 2 }{Li(thf) 4 } and polymeric ate complexes {La[NRR′] 2 (thf)(μ‐Cl)K(thf) 2 (μ‐Cl)} n and {Nd[NRR′] 2 (μ‐BH 4 )Li(thf) 2 (μ‐BH 4 )} n . All compounds were characterized by NMR ( 1 H and 13 C) and FTIR spectroscopy, elemental and X‐ray structure analyses. The lithium salts Li[NRR′](thf) 3 and Li 4 (OTf) 4 (thf) 6 were isolated as side products and structurally characterized. The homoleptic complex La[NRR′] 3 was prepared following two synthesis protocols in hexane, either by reacting Ln[NRR′] 2 (BH 4 )(thf) with 1 equiv. of K[NRR′] or treatment of LaCl 3 (thf) 1.25 with 3 equiv. of K[NRR′].
Formation and Attachment of the Deoxysugar Moiety and Assembly of the Gene Cluster for Caprazamycin Biosynthesis
2010-04-24

ABSTRACT Caprazamycins are antimycobacterials produced by Streptomyces sp. MK730-62F2. Previously, cosmid cpzLK09 was shown to direct the biosynthesis of caprazamycin aglycones, but not of intact caprazamycins. Sequence analysis of cpzLK09 identified 23 genes involved in the formation of the caprazamycin aglycones and the transfer and methylation of the sugar moiety, together with genes for resistance, transport, and regulation. In this study, coexpression of cpzLK09 in Streptomyces coelicolor M512 with pRHAM, containing all the required genes for dTDP- l -rhamnose biosynthesis, led to the production of intact caprazamycins. In vitro studies showed that Cpz31 is responsible for the attachment of the l -rhamnose to the caprazamycin aglycones, generating a rare acylated deoxyhexose. An l -rhamnose gene cluster was identified elsewhere on the Streptomyces sp. MK730-62F2 genome, and its involvement in caprazamycin formation was demonstrated by insertional inactivation of cpzDIII . The l -rhamnose subcluster was assembled with cpzLK09 using Red/ET-mediated recombination. Heterologous expression of the resulting cosmid, cpzEW07, led to the production of caprazamycins, demonstrating that both sets of genes are required for caprazamycin biosynthesis. Knockouts of cpzDI and cpzDV in the l -rhamnose subcluster confirmed that four genes, cpzDII , cpzDIII , cpzDIV , and cpzDVI , are sufficient for the biosynthesis of the deoxysugar moiety. The presented recombineering strategy may provide a useful tool for the assembly of biosynthetic building blocks for heterologous production of microbial compounds.
Analyzing X-ray pulsar profiles: geometry and beam pattern of EXO 2030+375
2010-04-26

Context. The pulse profiles of the transient Be/X-ray binary EXO 2030+375 show strong dependence on energy, as well as on its luminosity state, and are asymmetric in shape. Aims. We want to identify the emission components of the two magnetic poles in the pulsed emission to understand the geometry of the neutron star and its beam pattern. Methods. We utilize a pulse-profile decomposition method that enables us to find two symmetric pulse profiles from the magnetic poles of the neutron star. The symmetry characteristics of these single-pole pulse profiles give information about the position of the magnetic poles of the neutron star relative to its rotation axis. Results. We find a possible geometry for the neutron star in EXO 2030+375 through the decomposition of the pulse profiles, which suggests that one pole gets closer to the line of sight than the other and that, during the revolution of the neutron star, both poles disappear behind the horizon for a short period of time. A considerable fraction of the emission arises from a halo while the pole is facing the observer and from the accretion stream of the other pole while it is behind the neutron star, but the gravitational line bending makes the emission visible to us.
Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia
2010-04-27

Abstract Mutations in the nicotinamide adenine dinucleotide phosphate+–dependent isocitrate dehydrogenase gene 2 (IDH2) have recently been found in patients with acute myeloid leukemia (AML) as well as in patients with leukemic transformation of myeloproliferative neoplasms. We analyzed 272 adult patients with cytogenetically normal AML (CN-AML) for the presence of IDH2 mutations in codons R140 and R172. IDH2 mutations of amino acid 140 or 172 could be identified in 12.1% of CN-AML patients, with the majority of mutations (90%) occurring at position R140. The incidence of IDH2 mutations in AML patients with aberrant karyotypes (n = 130) was significantly lower (3.8%, P = .006). IDH2 mutations were mutually exclusive with mutations in IDH1. IDH2 mutation status alone or in combination with IDH1 mutations had no impact on response to therapy, overall survival, and relapse-free survival in patients with CN-AML. In conclusion, IDH2 mutations are frequently found in CN-AML, but in our analysis these mutations did not influence treatment outcome. This study was registered at www.clinicaltrials.gov as #NCT00209833.
Safety of ProbioticEscherichia coliStrain Nissle 1917 Depends on Intestinal Microbiota and Adaptive Immunity of the Host
2010-04-27

ABSTRACT Probiotics are viable microorganisms that are increasingly used for treatment of a variety of diseases. Occasionally, however, probiotics may have adverse clinical effects, including septicemia. Here we examined the role of the intestinal microbiota and the adaptive immune system in preventing translocation of probiotics (e.g., Escherichia coli Nissle). We challenged C57BL/6J mice raised under germfree conditions (GF-raised C57BL/6J mice) and Rag1 −/− mice raised under germfree conditions (GF-raised Rag1 −/− mice) and under specific-pathogen-free conditions (SPF-raised Rag1 −/− mice) with probiotic E. coli strain Nissle 1917, strain Nissle 1917 mutants, the commensal strain E. coli mpk, or Bacteroides vulgatus mpk. Additionally, we reconstituted Rag1 −/− mice with CD4 + T cells. E. coli translocation and dissemination and the mortality of mice were assessed. In GF-raised Rag1 −/− mice, but not in SPF-raised Rag1 −/− mice or GF-raised C57BL/6J mice, oral challenge with E. coli strain Nissle 1917, but not oral challenge with E. coli mpk, resulted in translocation and dissemination. The mortality rate was significantly higher for E. coli strain Nissle 1917-challenged GF-raised Rag1 −/− mice (100%; P &lt; 0.001) than for E. coli strain Nissle 1917-challenged SPF-raised Rag1 −/ − mice (0%) and GF-raised C57BL/6J mice (0%). Translocation of and mortality due to strain E. coli Nissle 1917 in GF-raised Rag1 −/− mice were prevented when mice were reconstituted with T cells prior to strain E. coli Nissle 1917 challenge, but not when mice were reconstituted with T cells after E. coli strain Nissle 1917 challenge. Cocolonization experiments revealed that E. coli mpk could not prevent translocation of strain E. coli Nissle 1917. Moreover, we demonstrated that neither lipopolysaccharide structure nor flagella play a role in E. coli strain Nissle 1917 translocation and dissemination. Our results suggest that if both the microbiota and adaptive immunity are defective, translocation across the intestinal epithelium and dissemination of the probiotic E. coli strain Nissle 1917 may occur and have potentially severe adverse effects. Future work should define the possibly related molecular factors that promote probiotic functions, fitness, and facultative pathogenicity.
Transcranial Electrocortical Stimulation to Monitor the Facial Nerve Motor Function During Cerebellopontine Angle Surgery
2010-04-27

FMEPs can be obtained reliably by using TES with 3 to 5 train pulses. Stable intraoperative FMEPs can predict a good postoperative outcome of facial function. However, further refinements of this technique are necessary to minimize artifacts and to make this method more reliable.
Holocene soils and sediments around Ma’rib Oasis, Yemen: Further Sabaean treasures?
2010-04-27

The ancient cultures of Southern Arabia are increasingly recognised as playing as major a role in the heritage of mankind as the early cultures of Egypt, Mesopotamia or the Indus Valley. The beginning of the widely known Sabaean culture dates back to the end of the second millennium BC. Whereas, undoubtedly, its wealth came mainly from the trade along the Incense Road, the backbone of its economy was irrigated agriculture. Since agriculture is based on soil and water resources and, hence, land availability, the buried soils and sediments of the area surrounding the Ma’rib Oasis have been investigated, both as an archive of Holocene soil development in Pre-Sabaean times and as ‘natural treasures’, as, for example, ores or alabaster are defined. The natural buried Holocene soils around Ma’rib are rich in phosphate, organic material and volcanic ashes. In a few places they demonstrate cultivation before the Great Dam of Ma’rib was built in the first millennium BC. Most important are those soils that formed during the Neolithic between 8000 and 3000 BC, a time before the permanent settlement of humans in the Bronze Age, and before the arrival of those of the early Sabaean period at the Ar-Rub’ Al-Khali desert margin. Since the area surrounding the oasis shows a huge variety of landscapes, such as dune belts, volcanic fields with archaeological structures and different soils, it is worth accentuating the significance of Holocene soils as an important record or archive of land use. As well as classical soil analysis, AMS- 14 C-datings, the results of phytolith analysis and geochemistry, including XRF data, have been taken into consideration.
CLC-b-Mediated NOFormula/H+ Exchange Across the Tonoplast of Arabidopsis Vacuoles
2010-04-28

Nitrate is frequently the major nitrogen source for plants and is generally assimilated during the day. In the absence of light, nitrate can transiently accumulate in the vacuolar lumen via tonoplast transporters. CLC-a, a member of the CLC family of anion transporters, is critically involved in this nitrate storage in the vacuole, while other CLC family members apparently have different roles in diverse cell organelles. Here, CLC-b, a close relative of CLC-a, was functionally expressed in oocytes and analyzed. CLC-b conducted strongly outwardly rectifying anionic currents that were largest in the presence of nitrate. Fluorescence ratio changes of oocytes loaded with a pH-dependent fluorescent dye suggested that NO(-)(3) transport is associated with H(+) exchange. CLC-b was localized at the tonoplast, as was CLC-c, when tagged with the green fluorescent protein. CLC-b expression was strongest in young roots, hypocotyl and cotyledons. The physiological role of CLC-b was analyzed using two independent knock-out alleles. Both lines grew as the wild type in various conditions. The total chloride and nitrate content was identical in clcb lines and the wild type, potentially suggesting that mutants were able to compensate the loss of CLC-b.
In-Situ Magnetic Susceptibility Measurements As a Tool to Follow Geomicrobiological Transformation of Fe Minerals
2010-04-28

Fe minerals sorb nutrients and pollutants and participate in microbial and abiotic redox reactions. Formation and transformation of Fe minerals is typically followed by mineral analysis at different time points. However, in lab studies the available sample amount is often limited and sampling may even influence the experimental conditions. We therefore evaluated the suitability of in situ magnetic susceptibility (MS) measurements, which do not require sampling, as an alternative tool to follow ferro(i)magnetic mineral (trans-)formation during ferrihydrite reduction by Shewanella oneidensis MR-1, and in soil microcosms. In our experiments with MR-1, a large initial increase in volume specific MS (kappa) followed by a slight decrease correlated well with the initial formation of magnetite and further reduction of magnetite to siderite as also identified by micro-XRD. The presence of humic acids retarded magnetite formation, and even inhibited magnetite formation completely, depending on their concentration. In soil microcosms, an increase in kappa accompanied by increasing concentrations of HCl-extractable Fe occurred only in microbially active set-ups, indicating a microbially induced change in soil Fe mineralogy. Based on our results, we conclude that MS measurements are suitable to follow microbial Fe mineral transformation in pure cultures as well as in complex soil samples.
Endothelin B receptor stimulation inhibits suicidal erythrocyte death
2010-04-28

ABSTRACT Endothelins (ETs), potent endothelium‐derived mediators, stimulate formation of nitric oxide, which, in turn, protects against suicidal erythrocyte death or eryptosis, characterized by phosphatidylserine exposure at the erythrocyte surface and triggered by increase in cytosolic Ca 2+ ([Ca 2+ ] i ). The present study explored whether the ET1‐receptor ETB influences suicidal erythrocyte death. To this end, [Ca 2+ ] i (Fluo3‐fluorescence) and phosphatidylserine exposure (annexin V‐binding) were determined utilizing FACS analysis. Energy depletion increased [Ca 2+ ] i and phosphatidylserine‐exposure, effects significantly blunted by ET1 (IC 50 ≈ 100 nM) and the ETB receptor‐agonist sarafotoxin 6c (IC 50 ≈ =T0 nM) but not by ET2 and ET3. ET1 and sarafotoxin significantly delayed the kinetics of suicidal erythrocyte death following energy depletion. ETB stimulation did not blunt the effect of Ca 2+ ‐ionophore ionomycin (1 μM) on phosphatidylserine exposure. The in vivo significance was tested using rescued ETB‐knockout ( etb −/− ) and wild‐type ( etb +/+ ) mice. The number of phosphatidylserine‐exposing erythrocytes, of reticulocytes and spleen size were significantly larger in etb −/− mice than in etb +/+ ‐mice. The etb −/− erythrocytes were more susceptible to the eryptotic effect of oxidative stress and more rapidly cleared from circulating blood than etb +/+ erythrocytes. Finally, the spleens from etb −/− mice were enlarged and contained markedly more phosphatidylserine‐exposing erythrocytes than spleens from etb +/+ mice. The observations disclose a novel function of ET1, i.e ., protection from suicidal erythrocyte death.— Foller, M., Mahmud, H., Qadri, S. M., Gu, S., Braun, M., Bobbala, D., Hocher, B., Lang, F. Endothelin B receptor stimulation inhibits suicidal erythrocyte death. FASEB J . 24, 3351–3359 (2010). www.fasebj.org