julilili42/papers huggingface dataset:
Multiple reciprocal adaptations and rapid genetic change upon experimental coevolution of an animal host and its microbial parasite
2010-04-05

The coevolution between hosts and parasites is predicted to have complex evolutionary consequences for both antagonists, often within short time periods. To date, conclusive experimental support for the predictions is available mainly for microbial host systems, but for only a few multicellular host taxa. We here introduce a model system of experimental coevolution that consists of the multicellular nematode host Caenorhabditis elegans and the microbial parasite Bacillus thuringiensis . We demonstrate that 48 host generations of experimental coevolution under controlled laboratory conditions led to multiple changes in both parasite and host. These changes included increases in the traits of direct relevance to the interaction such as parasite virulence (i.e., host killing rate) and host resistance (i.e., the ability to survive pathogens). Importantly, our results provide evidence of reciprocal effects for several other central predictions of the coevolutionary dynamics, including ( i ) possible adaptation costs (i.e., reductions in traits related to the reproductive rate, measured in the absence of the antagonist), ( ii ) rapid genetic changes, and ( iii ) an overall increase in genetic diversity across time. Possible underlying mechanisms for the genetic effects were found to include increased rates of genetic exchange in the parasite and elevated mutation rates in the host. Taken together, our data provide comprehensive experimental evidence of the consequences of host–parasite coevolution, and thus emphasize the pace and complexity of reciprocal adaptations associated with these antagonistic interactions.
Prospective Isolation of Mesenchymal Stem Cells from Multiple Mammalian Species Using Cross-Reacting Anti-Human Monoclonal Antibodies
2010-04-05

Mesenchymal stem cells (MSCs) of human and nonhuman mammalian species are often studied for various applications in regenerative medicine research. These MSCs can be derived from human bone marrow (BM) and identified by their ability to form fibroblast-like colony forming units that develop into stromal like cells when expanded in culture. These cells are characterized by their spindle-shaped morphology, their characteristic phenotype (CD73+, CD90+, CD105+, CD45-, and CD34-), and their ability to differentiate into cells of the osteogenic, adipogenic, and chondrogenic lineages. However, the identification and purification of MSCs from nonhuman mammalian species is hampered by the lack of suitable monoclonal antibodies (mAb). In this report, primary BM and cultured BM-derived MSCs of human and monkey, goat, sheep, dog, and pig were screened for cross-reactivity using a panel of 43mAb, of which 22 react with either human BM mononuclear cells or cultured human MSCs. We found 7mAb with specificity for CD271, MSCA-1 (W8B2 antigen), W4A5, CD56, W3C4 (CD349), W5C4, and 58B1, which showed interspecies cross-reactivity. These mAb proved to be useful for prospective sorting of MSCs from the BM of the 6 mammalian species studied as well as for the characterization of their cultured offspring. Flow sorting with the cross-reacting mAb resulted in up to 2400-fold enrichment of the clonogenic cell fraction (fibroblast-like colony forming units). This study provides an important contribution for the comparative prospective isolation of primary BM-MSCs and the characterization of cultured MSCs from multiple mammalian species for preclinical research.
Cationic surfactants-modified natural zeolites: improvement of the excipients functionality
2010-04-05

In vitro release profiles of the drugs from the zeolite-surfactant-drug composites revealed that sustained drug release could be attained over a period of 8 hours. The presented results for drug uptake by surfactant-zeolite composites and the afterward drug release demonstrated the potential use of investigated modified natural zeolite as excipients for advanced excipients in drug formulations.
The third generation of gravitational wave observatories and their science reach
2010-04-06

Large gravitational wave interferometric detectors, like Virgo and LIGO, demonstrated the capability to reach their design sensitivity, but to transform these machines into an effective observational instrument for gravitational wave astronomy a large improvement in sensitivity is required. Advanced detectors in the near future and third-generation observatories in more than one decade will open the possibility to perform gravitational wave astronomical observations from the Earth. An overview of the possible science reaches and the technological progress needed to realize a third-generation observatory are discussed in this paper. The status of the project Einstein Telescope (ET), a design study of a third-generation gravitational wave observatory, will be reported.
Impact of IDH1 R132 Mutations and an IDH1 Single Nucleotide Polymorphism in Cytogenetically Normal Acute Myeloid Leukemia: SNP rs11554137 Is an Adverse Prognostic Factor
2010-04-06

Purpose We assessed the prognostic impact of IDH1 R132 mutations and a known single nucleotide polymorphism (SNP) located in the same exon of the IDH1 gene in patients with cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other prognostic markers. Patients and Methods IDH1 exon four was directly sequenced in 275 CN-AML patients from two subsequent AML multicenter treatment trials and 120 healthy volunteers. Moreover, mutations in NPM1, FLT3, CEBPA, and WT1 were analyzed, and mRNA expression of IDH1 was quantified. Results IDH1 R132 mutations were found in 10.9% of CN-AML patients. IDH1 SNP rs11554137 was found in 12% of CN-AML patients and 11.7% of healthy volunteers. IDH1 R132 mutations had no impact on prognosis. In contrast, IDH1 SNP rs11554137 was an adverse prognostic factor for overall survival in univariate and multivariate analysis. Other significant factors were age, NPM1/FLT3 mutational status, WT1 SNP rs16754, and platelet count. The impact of IDH1 SNP rs11554137 was most pronounced in the NPM1/FLT3 high-risk patients (either NPM1 wild-type or FLT3–internal tandem duplication positive). Patients with IDH1 SNP rs11554137 had a higher expression of IDH1 mRNA than patients with two wild-type alleles. Conclusion IDH1 SNP rs11554137 but not IDH1 R132 mutations are associated with an inferior outcome in CN-AML.
Mutations in MEF2C from the 5q14.3q15 microdeletion syndrome region are a frequent cause of severe mental retardation and diminish MECP2 and CDKL5 expression
2010-04-06

The etiology of mental retardation remains elusive in the majority of cases. Microdeletions within chromosomal bands 5q14.3q15 were recently identified as a recurrent cause of severe mental retardation, epilepsy, muscular hypotonia, and variable minor anomalies. By molecular karyotyping we identified two novel 2.4- and 1.5-Mb microdeletions of this region in patients with a similar phenotype. Both deletions contained the MEF2C gene, which is located proximally to the previously defined smallest region of overlap. Nevertheless, due to its known role in neurogenesis, we considered MEF2C as a phenocritical candidate gene for the 5q14.3q15 microdeletion phenotype. We therefore performed mutational analysis in 362 patients with severe mental retardation and found two truncating and two missense de novo mutations in MEF2C, establishing defects in this transcription factor as a novel relatively frequent autosomal dominant cause of severe mental retardation accounting for as much as 1.1% of patients. In these patients we found diminished MECP2 and CDKL5 expression in vivo, and transcriptional reporter assays indicated that MEF2C mutations diminish synergistic transactivation of E-box promoters including that of MECP2 and CDKL5. We therefore conclude that the phenotypic overlap of patients with MEF2C mutations and atypical Rett syndrome is due to the involvement of a common pathway.
Regulatory Adaptation of Staphylococcus aureus during Nasal Colonization of Humans
2010-04-06

The nasopharynx is the main ecological niche of the human pathogen Staphylococcus aureus. Although colonization of the nares is asymptomatic, nasal carriage is a known risk factor for endogenous staphylococcal infection. We quantified S. aureus mRNA levels in nose swabs of persistent carriers to gain insight into the regulatory adaptation of the bacterium to the nasal environment. We could elucidate a general response of the pathogen to the surrounding milieu independent of the strain background or the human host. Colonizing bacteria preferentially express molecules necessary for tissue adherence or immune-evasion whereas toxins are down regulated. From the analysis of regulatory loci we found evidence for a predominate role of the essential two-component system WalKR of S. aureus. The results suggest that during persistent colonization the bacteria are metabolically active with a high cell surface turnover. The increased understanding of bacterial factors that maintain the colonization state can open new therapeutic options to control nasal carriage and subsequent infections.
Importance of CXC Chemokine Receptor 2 in Alveolar Neutrophil and Exudate Macrophage Recruitment in Response to Pneumococcal Lung Infection
2010-04-06

ABSTRACT Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury. CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. Whether or not the abundant neutrophil recruitment observed in severe pneumonia is essential for protective immunity against Streptococcus pneumoniae infections is incompletely defined. Here we show that CXCR2 deficiency severely perturbs the recruitment of both neutrophils and exudate macrophages associated with a massive bacterial outgrowth in distal airspaces after infection with S. pneumoniae , resulting in 100% mortality in knockout (KO) mice within 3 days. Moreover, irradiated wild-type mice reconstituted with increasing amounts of CXCR2 KO bone marrow (10, 25, 50, and 75% KO) have correspondingly decreased numbers of both neutrophils and exudate macrophages, which is associated with a stepwise increase in bacterial burden and a reciprocal stepwise decrease in survival in S. pneumoniae -induced pulmonary infection. Finally, application of the CXCR2 antagonist SB-225002 resulted in decreased alveolar neutrophil and exudate macrophage recruitment in mice along with increased lung bacterial loads after infection with S. pneumoniae . Together, these data show that CXC chemokine receptor 2 serves a previously unrecognized nonredundant role in the regulation of both neutrophil and exudate macrophage recruitment to the lung in response to S. pneumoniae infection. In addition, we demonstrate that a threshold level of 10 to 25% of reduced neutrophil recruitment is sufficient to cause increased mortality in mice infected with S. pneumoniae .
Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles
2010-04-06

In our study an innovative labeling protocol for tracking MSCs by MRI using SPIO in combination with magnetic fields was established. Both, SPIO and the static magnetic field were identified as independent factors which affect the functional biology of human MSCs. Further in vivo investigations are needed to elucidate the molecular mechanisms of the interaction of magnetic fields with stem cell biology.
Epoetin Alfa in Patients With Advanced-Stage Hodgkin's Lymphoma: Results of the Randomized Placebo-Controlled GHSG HD15EPO Trial
2010-04-06

Purpose To determine whether epoetin alfa reduces anemia-related fatigue, improves other aspects of health-related patient-recorded outcomes (PROs), reduces the number of RBC transfusions, and has an impact on freedom from treatment failure (FFTF) and overall survival (OS) in patients with advanced-stage Hodgkin's lymphoma (HL). Patients and Methods The prospectively randomized HD15EPO study performed by the German Hodgkin Study Group investigated epoetin alfa administered at doses of 40,000 U weekly during and after chemotherapy (six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [BEACOPP]) in a double-blind, placebo-controlled setting. The study accrued 1,379 patients, of whom 1,328 were assessable for safety, 1,303 were assessable for clinical outcome, and 930 were assessable for PROs. Results PROs were not different in patients receiving placebo or epoetin alfa, both after the end of chemotherapy and 6 months thereafter. There was no difference between patients treated with epoetin alfa or placebo with respect to FFTF and OS. There were also no differences in the numbers of deaths, progressions, relapses, and thromboembolic events. The median number of RBC transfusions was reduced from four per patient in the placebo group to two per patient in the epoetin alfa group (P &lt; .001), with 27.4% of patients needing no RBC transfusion in the placebo group compared with 36.7% of patients in the epoetin alfa group (P &lt; .001). Conclusion Epoetin alfa administered at 40,000 U weekly parallel to BEACOPP chemotherapy was safe in patients with advanced-stage HL and reduced the number of RBC transfusions but had no impact on fatigue and other PRO domains.
Hemolysis Is Associated with Low Reticulocyte Production Index and Predicts Blood Transfusion in Severe Malarial Anemia
2010-04-06

Our results show the multifactorial pathophysiology of SMA, whereby EVH and IVH play a particularly important role. We propose a model where removal of infected and non-infected erythrocytes of all ages (including reticulocytes) by EVH and IVH is a main mechanism of SMA. Further studies are underway to investigate the mechanism and extent of reticulocyte removal to identify possible interventions to reduce the risk of SMA development.
A novel third type of recurrent NF1 microdeletion mediated by nonallelic homologous recombination between LRRC37B-containing low-copy repeats in 17q11.2
2010-04-06

Large microdeletions encompassing the neurofibromatosis type-1 (NF1) gene and its flanking regions at 17q11.2 belong to the group of genomic disorders caused by aberrant recombination between segmental duplications. The most common NF1 microdeletions (type-1) span 1.4-Mb and have breakpoints located within NF1-REPs A and C, low-copy repeats (LCRs) containing LRRC37-core duplicons. We have identified a novel type of recurrent NF1 deletion mediated by nonallelic homologous recombination (NAHR) between the highly homologous NF1-REPs B and C. The breakpoints of these approximately 1.0-Mb ("type-3") NF1 deletions were characterized at the DNA sequence level in three unrelated patients. Recombination regions, spanning 275, 180, and 109-bp, respectively, were identified within the LRRC37B-P paralogues of NF1-REPs B and C, and were found to contain sequences capable of non-B DNA formation. Both LCRs contain LRRC37-core duplicons, abundant and highly dynamic sequences in the human genome. NAHR between LRRC37-containing LCRs at 17q21.31 is known to have mediated the 970-kb polymorphic inversions of the MAPT-locus that occurred independently in different primate species, but also underlies the syndromes associated with recurrent 17q21.31 microdeletions and reciprocal microduplications. The novel NF1 microdeletions reported here provide further evidence for the unusually high recombinogenic potential of LRRC37-containing LCRs in the human genome.
Cutaneous melanoma in the elderly: epidemiology, prognosis and treatment
2010-04-07

The incidence and mortality of cutaneous melanoma (CM) has increased over the last decades in fair-skinned populations. Incidence and mortality, as well as rates of increase, have been significantly higher in elderly people compared with younger age groups. Lower survival rates from CM among elderly are mainly the result of late diagnosis of tumors with dismal prognostic features. Expansion of current preventive strategies to include older age groups is therefore warranted. Despite differences in clinical presentation and pathological characteristics of CM in the elderly, there is no evidence that primary surgical treatment should differ from that proposed generally for melanoma. However, the rate of positive sentinel node dissection decreases with age, even though overall survival is shorter in older patients, a paradox that remains to be explained. The use of adjuvant treatment with interferon-alpha in elderly patients requires careful discussion of the risks and benefits, especially when serious illness coexists. For metastatic melanoma, complete metastasectomy is the only treatment associated with benefit for overall survival. However, careful selection of surgical oncogeriatric candidates is necessary, probably with the use of tools to provide a comprehensive geriatric assessment, to identify patients more likely to benefit from this treatment. In the absence of any effective systemic treatment for disseminated CM, new therapeutic agents are urgently needed. Practical means to improve accrual of older patients in clinical trials are necessary to provide better evidence for their treatment.
Contributions of the Ah receptor to bilirubin homeostasis and its antioxidative and atheroprotective functions
2010-04-07

Abstract The homeostasis and atheroprotective function of bilirubin could be an appealing model to investigate one of the many physiologic functions of the human aryl hydrocarbon receptor (AhR). Several clinical and epidemiological studies have been carried out on key enzymes generating and eliminating bilirubin (heme oxygenase-1 and UDP-glucuronosyltransferase UGT1A1, respectively) and their regulation by the AhR. Studies with AhR-deficient mice strongly suggest a role of the AhR in vascular biology. Atherosclerosis, a major cause of premature death, is initiated by pro-oxidative insults of the vascular endothelium. The strong antioxidant and activator of AhR bilirubin is generated in vascular endothelial cells, smooth muscles and macrophages. It acts mostly in the lipid environment, thereby complementing other antioxidants such as glutathione which act mostly on water-soluble proteins. In conclusion, the atheroprotective functions of bilirubin might not only provide models to study physiologic functions of the human AhR but also provide opportunities to improve prevention and treatment of a major life-threatening disease.
Actin-mediated gene expression in neurons: the MRTF-SRF connection
2010-04-07

Abstract The traditional view of cellular actin is a rather autarkic cytoskeletal framework function confined to the cytoplasm. However, there is now evidence that alterations in actin dynamics are sensed by the nucleus and subsequently modulate gene expression. In communicating with the nucleus, cytoplasmic, and most likely also nucleus-resident actin, provides a further (gene) regulatory loop to cell motility. A transcription module composed of MRTF (myocardin-related transcription factor) and SRF (serum response factor) emerges as prime target of such actin signaling. Here, I focus on the nervous system, where the actin-MRTF-SRF entity governs multiple aspects of neuronal motility.
The Role of Sphingolipids and Ceramide in Pulmonary Inflammation in Cystic Fibrosis~!2009-07-23~!2009-10-21~!2010-03-30~!
2010-04-07

Sphingolipids and in particular ceramide have been shown to be critically involved in the response to many receptor-mediated, but also receptor-independent, mainly stress stimuli. Recent studies demonstrate that ceramide plays an important role in the pathogenesis of cystic fibrosis, a hereditary metabolic disorder caused by mutations of the Cystic Fibrosis Transmembrane Conductance Regulator. Patients with cystic fibrosis suffer from chronic pulmonary inflammation and microbial lung infections, in particular with Pseudomonas aeruginosa. Chronic pulmonary inflammation in these patients seems to be the initial pathophysiological event. Inflammation may finally result in the high infection susceptibility of these patients, fibrosis and loss of lung function. Recent studies demonstrated that ceramide accumulates in lungs of cystic fibrosis mice and causes age-dependent pulmonary inflammation as indicated by accumulation of neutrophils and macrophages in the lung and increased pulmonary concentrations of Interleukins 1 and 8, death of bronchial epithelial cells, deposition of DNA in bronchi and high susceptibility to Pseudomonas aeruginosa infections. Genetic or pharmacological inhibition of the acid sphingomyelinase blocks excessive ceramide production in lungs of cystic fibrosis mice and corrects pathological lung findings. First clinical studies confirm that inhibition of the acid sphingomyelinase with small molecules might be a novel strategy to treat patients with cystic fibrosis.
Faculty Opinions recommendation of Seeing gray when feeling blue? Depression can be measured in the eye of the diseased.
2010-04-07

BACKGROUND: Everyday language relates depressed mood to visual phenomena. Previous studies point to a reduced sensitivity of subjective contrast perception in depressed patients. One way to assess visual contrast perception in an objective way at the level of the retina is to measure the pattern electroretinogram (PERG). To find an objective correlate of reduced contrast perception, we measured the PERG in healthy control subjects and unmedicated and medicated patients with depression.METHODS: Forty patients with a diagnosis of major depression (20 with and 20 without medication) and 40 matched healthy subjects were studied. Visual PERGs were recorded from both eyes.RESULTS: Unmedicated and medicated depressed patients displayed dramatically lower retinal contrast gain. We found a strong and significant correlation between contrast gain and severity of depression. This marker distinguishes most patients on a single-case basis from control subjects. A receiver operating characteristic analysis revealed a specificity of 92.5% and a sensitivity of 77.5% for classifying the participants correctly.CONCLUSIONS: Because PERG recording does not depend on subjective ratings, this marker may be an objective correlate of depression in human beings. If replicated, PERG may be helpful in further animal and human research in depression.Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. PMID: 20359698
BRST symmetry versus horizon condition in Yang-Mills theories
2010-04-08

We show that in SU(2) Yang-Mills theories a simple relation exists between lattice gluon propagators in Coulomb and Landau gauge and discuss the physical implications of such result. In particular, the realization of the Gribov-Zwanziger confinement mechanism in Coulomb gauge, linked to dual-superconductivity, would imply that the standard BRST charge must be ill defined non perturbatively. As a consequence, the Kugo-Ojima confinement criterion, which relies on BRST charge conservation beyond perturbation theory, would not be fulfilled.