julilili42/papers huggingface dataset:
Transcellular migration of neutrophil granulocytes through the blood-cerebrospinal fluid barrier after infection with Streptococcus suis
2011-05-18

Abstract Background A critical point during the course of bacterial meningitis is the excessive influx of polymorphnuclear neutrophils (PMNs) from the blood into the brain. Both paracellular and transcellular routes of leukocyte transmigration through the blood-brain barrier have been described in CNS diseases so far. Thus, we investigated the mechanism of PMN transmigration through the blood-CSF barrier under inflammatory conditions. Methods In an "inverted" Transwell culture model of the blood-CSF barrier, the zoonotic agent Streptococcus suis ( S. suis ) was used to stimulate porcine choroid plexus epithelial cells (PCPECs) specifically from the physiologically relevant basolateral side. Barrier function was analyzed by measuring TEER and TR-dextran-flux, and tight junction morphology was investigated by immunofluorescence. Route and mechanism of PMN transmigration were determined by immunofluorescence, electron microscopy and FACS analysis. Quantitative real time-PCR was used to determine expression levels of ICAM-1 and VCAM-1. Results Here, we show that the transmigration of PMNs through PCPECs was significantly higher after stimulation with TNFα or infection with S. suis strain 10 compared to its non-encapsulated mutant. Barrier function was not significantly affected by PMN migration alone, but in combination with S. suis infection. Tight junction and cytoskeletal actin reorganisation were also observed after stimulation with S. suis or TNFα. Most strikingly, PMNs preferentially migrated across PCPECs via the transcellular route. Extensive sequential analyses of the PMN transmigration process with Apotome ® -imaging and electron microscopy revealed that paracellular migrating PMNs stop just before tight junctions. Interestingly, PMNs subsequently appeared to proceed by transcellular migration via funnel-like structures developing from the apical membrane. It is noteworthy that some PMNs contained bacteria during the transmigration process. Flow cytometric and transmigration inhibition studies with integrin-specific antibodies showed that PMN traversal is dependent on CD11b/CD18. Analysis of cell adhesion molecules in PCPECs revealed a significant increase of ICAM-1 and VCAM-1 expression after TNFα and S. suis stimulation. Conclusion Our data underline the relevance of the blood-CSF barrier as a gate for leukocyte entry into the CNS and suggest a novel transcellular migration step during the pathogenesis of bacterial meningitis.
The four-population model: a new classification scheme for pre-planetesimal collisions
2011-05-18

Within the collision growth scenario for planetesimal formation, the growth\\nstep from centimetre sized pre-planetesimals to kilometre sized planetesimals\\nis still unclear. The formation of larger objects from the highly porous\\npre-planetesimals may be halted by a combination of fragmentation in disruptive\\ncollisions and mutual rebound with compaction. However, the right amount of\\nfragmentation is necessary to explain the observed dust features in late T\\nTauri discs. Therefore, detailed data on the outcome of pre-planetesimal\\ncollisions is required and has to be presented in a suitable and precise\\nformat. We propose and apply a new classification scheme for pre-planetesimal\\ncollisions based on the quantitative aspects of four fragment populations: the\\nlargest and second largest fragment, a power-law population, and a\\nsub-resolution population. For the simulations of pre-planetesimal collisions,\\nwe adopt the SPH numerical scheme with extensions for the simulation of porous\\nsolid bodies. By means of laboratory benchmark experiments, this model was\\npreviously calibrated and tested for the correct simulation of the compaction,\\nbouncing, and fragmentation behaviour of macroscopic highly porous silica dust\\naggregates. It is shown that previous attempts to map collision data were much\\ntoo oriented on qualitatively categorising into sticking, bouncing, and\\nfragmentation events. We show that the four-populations model encompasses all\\nprevious categorisations and in addition allows for transitions. This is\\nbecause it is based on quantitative characteristic attributes of each\\npopulation such as the mass, kinetic energy, and filling factor. As a\\ndemonstration of the applicability and the power of the four-populations model,\\nwe utilise it to present the results of a study on the influence of collision\\nvelocity in head-on collisions of intermediate porosity aggregates.\\n
Discovery and Biological Evaluation of a Novel Class of Dual Microsomal Prostaglandin E2Synthase-1/5-lipoxygenase Inhibitors Based on 2-[(4,6-Diphenethoxypyrimidin-2-yl)thio]hexanoic Acid
2011-05-18

Various inflammatory diseases are associated with the excessive formation of leukotrienes (LTs) and prostaglandins (PGs). Herein, we present a novel class of dual inhibitors of 5-lipoxygenase (5-LO) and microsomal prostaglandin E(2) synthase-1 (mPGES-1), key enzymes in the formation of LTs and PGE(2), respectively. On the basis of the structure of 2-[(4,6-diphenethoxypyrimidin-2-yl)thio]hexanoic acid (1), we performed a detailed SAR analysis, and mechanistic studies were carried out to elucidate the mode of 5-LO inhibition. Interestingly, the pyrimidine ring including the thioether of 1 could be replaced by a simple benzyl or a benzylidene moiety yielding a novel series of bioactive 2-benzylidene- and 2-benzylhexanoic acids exemplified by 2-(2,3-diphenethoxybenzylidene)hexanoic acid, 29 (IC(50) 5-LO = 0.8 μM; mPGES-1 = 1.1 μM). Importantly, none of the novel bioactive derivatives strongly inhibited cyclooxygenase activities. Together, we provide novel promising lead compounds for the treatment of inflammatory diseases valuable for further investigations in vivo.
Cobalt, Rhodium, Iridium, and Ruthenium Carbonyl Complexes with Stanna-closo-dodecaborate:103Rh NMR,119Sn Mössbauer Spectroscopy, and Solid-State119Sn NMR
2011-05-18

Depending on the stoichiometry stanna-closo-dodecaborate [SnB11H11]2– reacts with the dimeric carbonyl complex [Rh(CO)2Cl]2 to give a dinuclear rhodium coordination compound with bridging tin ligands, [Et3MeN]6[Rh2(CO)4(SnB11H11)4] (1), or a pentagonal-bipyramidal complex, [Et4N]5[Rh(CO)2(SnB11H11)3] (2), with the carbonyl ligands in axial position. The analogous iridium and cobalt complexes [Et4N]5[Ir(CO)2(SnB11H11)3] (3) and [Me4N]5[Co(CO)2(SnB11H11)3] (4) exhibit a pentacoordinated structure with the tin ligands in axial positions. The dimeric ruthenium chlorocarbonyl complex [Ru(CO)3Cl2]2 reacts with four equivalents of the tin nucleophile to give the octahedrally coordinated ruthenium complex [Et3MeN]4[Ru-cis-(CO)2-cis-Cl2-trans-(SnB11H11)2] (5). The synthesized coordination compounds were characterized by X-ray crystal structure analysis, by 103Rh, 119Sn, and 11B NMR spectroscopy in solution, and in the case of the rhodium complexes 1 and 2 by 119Sn solid-state NMR and 119Sn Mössbauer spectroscopy.
Iliopsoas Cyst Causing Persistent Pain After Total Hip Arthroplasty
2011-05-18

Persistent pain after total hip arthroplasty (THA) has many potential causes. The most common are aseptic loosening, infection, and heterotopic ossification. Irritation of the iliopsoas tendon due to the acetabular component is an underestimated cause of persistent groin pain and functional disability after THA with rare incidence. Pain specific to iliopsoas tendonitis includes activities such as hyperextension of the hip, forced flexion, and activities of daily living (eg, ascending stairs). This article presents a case of a 50-year old man with clinical and radiological signs of osteoarthritis of the right hip joint. A THA was performed. After a symptom-free interval of several weeks postoperatively, the patient reported pain projecting from the right groin and radiating ventromedially along the leg. Magnetic resonance imaging of the hip showed a fluid-filled cyst in anatomical proximity to the femoral nerve causing an iliopsoas tendonitis. The patient underwent surgical resection of the cyst was performed by an anterior approach; a conjunction to the hip joint was not present. The implanted components of the prosthesis showed good osseointegration with no signs of loosening. The cyst was removed and the iliopsoas tendon was released. A few weeks after the operation, the patient was pain free. At 17-month follow-up, no problems were reported. In cases such as this, finding the correct diagnosis may be difficult and misleading. Conservative and operative therapeutic options are discussed and compared with divergent findings in the literature.
Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium
2011-05-19

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10(-18)), rs3803662 (16q12) (P = 3.7 × 10(-5)), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10(-6) and P = 4.1 × 10(-4), respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ≤ 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.
Involvement of Adenosine A2A Receptors in Engulfment-Dependent Apoptotic Cell Suppression of Inflammation
2011-05-19

Abstract Efficient execution of apoptotic cell death followed by efficient clearance mediated by professional macrophages is a key mechanism in maintaining tissue homeostasis. Removal of apoptotic cells usually involves three central elements: 1) attraction of phagocytes via soluble “find me” signals, 2) recognition and phagocytosis via cell surface-presenting “eat me” signals, and 3) suppression or initiation of inflammatory responses depending on additional innate immune stimuli. Suppression of inflammation involves both direct inhibition of proinflammatory cytokine production and release of anti-inflammatory factors, which all contribute to the resolution of inflammation. In the current study, using wild-type and adenosine A2A receptor (A2AR) null mice, we investigated whether A2ARs, known to mediate anti-inflammatory signals in macrophages, participate in the apoptotic cell-mediated immunosuppression. We found that macrophages engulfing apoptotic cells release adenosine in sufficient amount to trigger A2ARs, and simultaneously increase the expression of A2ARs, as a result of possible activation of liver X receptor and peroxisome proliferators activated receptor δ. In macrophages engulfing apoptotic cells, stimulation of A2ARs suppresses the NO-dependent formation of neutrophil migration factors, such as macrophage inflammatory protein-2, using the adenylate cyclase/protein kinase A pathway. As a result, loss of A2ARs results in elevated chemoattractant secretion. This was evident as pronounced neutrophil migration upon exposure of macrophages to apoptotic cells in an in vivo peritonitis model. Altogether, our data indicate that adenosine is one of the soluble mediators released by macrophages that mediate engulfment-dependent apoptotic cell suppression of inflammation.
Design of clinically useful macromolecular iron chelators
2011-05-19

Abstract Objectives In recent years, macromolecular iron chelators have received increasing attention as human therapeutic agents. The objectives of this article are: one, to discuss the factors which should be considered when designing iron binding macromolecules as human therapeutic agents, and two, to report recent achievements in the design and synthesis of appropriate macromolecular chelators that have resulted in the production of a number of agents with therapeutic potential. Key findings Macromolecular drugs exhibit unique pharmaceutical properties that are fundamentally different from their traditional small-molecule counterparts. By virtue of their high-molecular-weight characteristics, many are confined to extracellular compartments, for instance, the serum and the gastrointestinal tract. In addition, they have potential for topical administration. Consequently, these macromolecular drugs are free from many of the toxic effects that are associated with their low-molecular-weight analogues. Summary The design and synthesis of macromolecular iron chelators provides a novel aspect to chelation therapy. 3-Hydroxypyridin-4-one hexadentate-based macromolecular chelators have considerable potential for the development of new treatments for iron overload and for topical treatment of infection.
Successful Treatment of Chronic Pseudophakic Macular Edema (Irvine-Gass Syndrome) with Interferon Alpha: A Report of Three Cases
2011-05-19

IFN alpha has been demonstrated to be a successful and well-tolerated treatment option for resistant chronic pseudophakic CME. Further studies are necessary to evaluate the role of IFN alpha in Irvine-Gass syndrome.
Regulation of the Na+/K+ ATPase by Klotho
2011-05-19

Klotho-hypomorphic (Klotho(hm)) mice suffer from renal salt wasting and hypovolemia despite hyperaldosteronism. The present study explored the effect of Klotho on renal Na(+)/K(+) ATPase activity. According to immunohistochemistry and confocal microscopy Na(+)/K(+) ATPase protein abundance in isolated collecting ducts was lower in Klotho(hm) mice than in their wild type littermates (Klotho(+/+)). Analysis with dual electrode voltage clamp recording showed that expression of Klotho in Xenopus oocytes increased the Na(+)/K(+) ATPase pump current. Treatment of Xenopus oocytes with Klotho protein similarly increased the pump current. In conclusion, Klotho increases the membrane abundance and activity of the Na(+)/K(+) ATPase. Decreased Na(+)/K(+) ATPase activity could thus contribute to the volume-depletion of klotho(hm) mice.
Inhibition of suicidal erythrocyte death by blebbistatin
2011-05-19

Blebbistatin, a myosin II inhibitor, interferes with myosin-actin interaction and microtubule assembly. By influencing cytoskeletal dynamics blebbistatin counteracts apoptosis of several types of nucleated cells. Even though lacking nuclei and mitochondria, erythrocytes may undergo suicidal cell death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include energy depletion and osmotic shock, which enhance cytosolic Ca 2+ activity with subsequent Ca 2+ -sensitive cell shrinkage and cell membrane scrambling. The present study explored the effect of blebbistatin on eryptosis. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, cell volume from forward scatter in fluorescence-activated cell sorting analysis and cytosolic Ca 2+ concentration from Fluo3 fluorescence. Exposure to blebbistatin on its own (1–50 μM) did not significantly modify cytosolic Ca 2+ concentration, forward scatter, or annexin V binding. Glucose depletion (48 h) was followed by a significant increase of Fluo3 fluorescence and annexin V binding, effects significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 10 μM). Osmotic shock (addition of 550 mM sucrose) again significantly increased Fluo3 fluorescence and annexin binding, effects again significantly blunted by blebbistatin (Fluo3 fluorescence ≥ 25 μM, annexin V binding ≥ 25 μM). The present observations disclose a novel effect of blebbistatin, i.e., an influence on Ca 2+ entry and suicidal erythrocyte death following energy depletion and osmotic shock.
Cavity-Controlled Collective Scattering at the Recoil Limit
2011-05-20

We study collective scattering with Bose-Einstein condensates interacting with a high-finesse ring cavity. The condensate scatters the light of a transverse pump beam superradiantly into modes which, in contrast to previous experiments, are not determined by the geometrical shape of the condensate, but specified by a resonant cavity mode. Moreover, since the recoil-shifted frequency of the scattered light depends on the initial momentum of the scattered fraction of the condensate, we show that it is possible to employ the good resolution of the cavity as a filter selecting particular quantized momentum states.
Anti-malarial effect of gum arabic
2011-05-20

Abstract Background Gum Arabic (GA), a nonabsorbable nutrient from the exudate of Acacia senegal , exerts a powerful immunomodulatory effect on dendritic cells, antigen-presenting cells involved in the initiation of both innate and adaptive immunity. On the other hand GA degradation delivers short chain fatty acids, which in turn have been shown to foster the expression of foetal haemoglobin in erythrocytes. Increased levels of erythrocyte foetal haemoglobin are known to impede the intraerythrocytic growth of Plasmodium and thus confer some protection against malaria. The present study tested whether gum arabic may influence the clinical course of malaria. Methods Human erythrocytes were in vitro infected with Plasmodium falciparum in the absence and presence of butyrate and mice were in vivo infected with Plasmodium berghei ANKA by injecting parasitized murine erythrocytes (1 × 10 6 ) intraperitoneally. Half of the mice received gum arabic (10% in drinking water starting 10 days before the day of infection). Results According to the in vitro experiments butyrate significantly blunted parasitaemia only at concentrations much higher (3 mM) than those encountered in vivo following GA ingestion (&lt;1 μM). According to the in vivo experiments the administration of gum arabic slightly but significantly decreased the parasitaemia and significantly extended the life span of infected mice. Discussion GA moderately influences the parasitaemia and survival of Plasmodium- infected mice. The underlying mechanism remained, however, elusive. Conclusions Gum arabic favourably influences the course of murine malaria.
Spin of ground state baryons
2011-05-20

We calculate the quark spin contribution to the total angular momentum of flavor octet and flavor decuplet ground state baryons using a spin-flavor symmetry based parametrization method of quantum chromodynamics. We find that third order SU(6) symmetry breaking three-quark operators are necessary to explain the experimental result Sigma_1=0.32(10). For spin 3/2 decuplet baryons we predict that the quark spin contribution is Sigma_3=3.93(22), i.e. considerably larger than their total angular momentum.
A novel anti-GD2 monoclonal antibody (mAb), hu14.18K322A, in children with refractory or recurrent neuroblastoma: Early-phase evaluation.
2011-05-20

9523 Background: Immunotherapy, including combination anti-GD2 mAb ch14.18 and cytokines, improves the outcome of patients with advanced neuroblastoma. Dose escalation of antibodies targeting GD2 antigen on neuroblastoma cells has been limited by toxicities which may be partially mediated by complement activation. Hu14.18K332A is a humanized anti-GD2 mAb with a single point mutation (K322A) reducing complement-dependent lysis. We report the preliminary results of a phase I trial to determine the maximum tolerated dose (MTD) and toxicity profile of hu14.18K322A. Methods: Cohorts of 3-6 eligible patients with refractory or recurrent neuroblastoma received a 4-hour daily IV infusion of escalating doses of hu14.18K322A (2, 4, 6, 10, 20, 40, 50, and 60 mg/m2/dose) for 4 consecutive days every 28 days (1 course). Patients were allowed to receive up to 4 courses in the absence of progressive disease or unacceptable toxicity. Results: A total of 32 patients (22 males, median age 6.5 years) received a total of 71 courses. Patients received a median of 2 courses. Dose-limiting grade 3 toxicities occurred in 2 of 29 evaluable patients and were characterized by cough and asthenia. The most common grade 3 or 4 toxicities were pain (65% of patients), fever (19%) and hyponatremia (13%). Pain was well managed and predominately occurred on the first day of course 1. Grade 1 or 2 ocular abnormalities were noted in 13 patients and appear to be dose related. No objective responses by RECIST have been observed; however, 9 patients completed the maximum of 4 courses allowed by protocol. Conclusions: Hu14.18K322A is well tolerated at the doses tested which exceed the dosages of similar GD2 mAbs used in other trials. MTD has not been defined and the study continues to accrue patients at higher doses.
Regulon of the N -Acetylglucosamine Utilization Regulator NagR in Bacillus subtilis
2011-05-21

ABSTRACT N -Acetylglucosamine (GlcNAc) is the most abundant carbon-nitrogen biocompound on earth and has been shown to be an important source of nutrients for both catabolic and anabolic purposes in Bacillus species. In this work we show that the GntR family regulator YvoA of Bacillus subtilis serves as a negative transcriptional regulator of GlcNAc catabolism gene expression. YvoA represses transcription by binding a 16-bp sequence upstream of nagP encoding the GlcNAc-specific EIIBC component of the sugar phosphotransferase system involved in GlcNAc transport and phosphorylation, as well as another very similar 16-bp sequence upstream of the nagAB-yvoA locus, wherein nagA codes for N -acetylglucosamine-6-phosphate deacetylase and nagB codes for the glucosamine-6-phosphate (GlcN-6-P) deaminase. In vitro experiments demonstrated that GlcN-6-P acts as an inhibitor of YvoA DNA-binding activity, as occurs for its Streptomyces ortholog, DasR. Interestingly, we observed that the expression of nag genes was still activated upon addition of GlcNAc in a Δ yvoA mutant background, suggesting the existence of an auxiliary transcriptional control instance. Initial computational prediction of the YvoA regulon showed a distribution of YvoA binding sites limited to nag genes and therefore suggests renaming YvoA to NagR, for N -acetylglucosamine utilization regulator. Whole-transcriptome studies showed significant repercussions of nagR deletion for several major B. subtilis regulators, probably indirectly due to an excess of the crucial molecules acetate, ammonia, and fructose-6-phosphate, resulting from complete hydrolysis of GlcNAc. We discuss a model deduced from NagR-mediated gene expression, which highlights clear connections with pathways for GlcNAc-containing polymer biosynthesis and adaptation to growth under oxygen limitation.
Fluorescent Chemosensors for Chromium(III) Ions and the Cr3+/Cr2+ Ratio
2011-05-21

Abstract The shielded linear trisphenanthroline 1 is utilized as a triple reassurance probe and as an ON–OFF–ON signaling unit (after addition of Cu2+) for the detection and quantification of Cr3+ ions. The analogous monophenanthroline 2 served as a ratiometric fluorescent chemosensor for analyzing the Cr3+/Cr2+ ratio.