bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Structure and Assembly Dynamics of Plasmid Actin AlfA Imply a Novel Mechanism of DNA Segregation
Authors: Polka Jessica K. , Kollman Justin M. , Agard David A. , Mullins R. Dyche 
Published: August 2009

ABSTRACT

Bacterial cytoskeletal proteins participate in a variety of processes, including cell division and DNA segregation. Polymerization of one plasmid-encoded, actin-like protein, ParM, segregates DNA by pushing two plasmids in opposite directions and forms the current paradigm for understanding active plasmid segregation. An essential feature of ParM assembly is its dynamically instability, the stochastic switching between growth and disassembly. It is unclear whether dynamic instability is an essential feature of all actin-like protein-based segregation mechanisms or whether bacterial filaments can segregate plasmids by different mechanisms. We expressed and purified AlfA, a plasmid-segregating actin-like protein from
Bacillus subtilis
, and found that it forms filaments with a unique structure and biochemistry; AlfA nucleates rapidly, polymerizes in the presence of ATP or GTP, and forms highly twisted, ribbon-like, helical filaments with a left-handed pitch and protomer nucleotide binding pockets rotated away from the filament axis. Intriguingly, AlfA filaments spontaneously associate to form uniformly sized, mixed-polarity bundles. Most surprisingly, our biochemical characterization revealed that AlfA does not display dynamic instability and is relatively stable in the presence of diphosphate nucleotides. These results (i) show that there is remarkable structural diversity among bacterial actin filaments and (ii) indicate that AlfA filaments partition DNA by a novel mechanism.
Cyclogenesis Simulation of Typhoon Prapiroon (2000) Associated with Rossby Wave Energy Dispersion*
Authors: Ge Xuyang , Li Tim , Peng Melinda S. 
Published: August 2009

Abstract
The genesis of Typhoon Prapiroon (2000), in the western North Pacific, is simulated to understand the role of Rossby wave energy dispersion of a preexisting tropical cyclone (TC) in the subsequent genesis event. Two experiments are conducted. In the control experiment (CTL), the authors retain both the previous typhoon, Typhoon Bilis, and its wave train in the initial condition. In the sensitivity experiment (EXP), the circulation of Typhoon Bilis was removed based on a spatial filtering technique of Kurihara et al., while the wave train in the wake is kept. The comparison between these two numerical simulations demonstrates that the preexisting TC impacts the subsequent TC genesis through both a direct and an indirect process. The direct process is through the conventional barotropic Rossby wave energy dispersion, which enhances the low-level wave train, the boundary layer convergence, and the convection–circulation feedback. The indirect process is through the upper-level outflow jet. The asymmetric outflow jet induces a secondary circulation with a strong divergence tendency to the left-exit side of the outflow jet. The upper-level divergence boosts large-scale ascending motion and promotes favorable environmental conditions for a TC-scale vortex development. In addition, the outflow jet induces a well-organized cyclonic eddy angular momentum flux, which acts as a momentum forcing that enhances the upper-level outflow and low-level inflow and favors the growth of the new TC.
Hesperidin attenuates benzo[α] pyrene-induced testicular toxicity in rats via regulation of oxidant/antioxidant balance
Authors: Arafa HMM , Aly HAA , Abd-Ellah MF , El-Refaey HM 
Published: August 2009

Benzo[α]pyrene (BaP) is one of the polycyclic aromatic hydrocarbons, which has shown carcinogenic, teratogenic, and mutagenic potentials. The reproductive toxicity of BaP in male was not well investigated. Thereby, we have addressed in the current study the testicular toxicity of BaP and the postulate whether or not the citrus flavonoid, hesperidin (HDN), could ameliorate such toxicity in male Swiss albino rats. In this sense, animals were challenged with BaP (50 mg/kg/day, orally) for 10 consecutive days. HDN (200 mg/kg/day, orally) was administered ahead of BaP challenge for 10 consecutive days. BaP induced testicular toxicity that was well characterized histologically and biochemically. It decreased the relative testis weight and induced pyknosis and necrobiotic changes as well as chromatolysis in the nuclei of the spermatocytes in the seminiferous tubules. It also markedly deteriorated epididymal function as shown by decreased sperm count, motility, and daily sperm production. The polyaromatic hydrocarbon also reduced the testicular activities of lactate dehydrogenase (LDH-X), superoxide dismutase (SOD), and glutathione-S-transferase (GST). Besides, it decreased the testicular reduced glutathione (GSH) but increased malondialdehyde (MDA) contents. Prior administration of HDN ahead of BaP challenge ameliorated all the histological and biochemical alterations induced by BaP. It improved the epididymal function and mitigated the injurious effects of BaP on the seminiferous tubules. In conclusion, HDN has proven protective effects in BaP-induced testicular toxicity paradigm, and this protection resides, at least in part, on its antioxidant properties.
Intravenous immunoglobulins in systemic lupus erythematosus: from the bench to the bedside
Authors: Zandman-Goddard G , Blank M , Shoenfeld Y 
Published: August 2009

This article is an update on the clinical and research data available on systemic lupus erythematosus (SLE) and intravenous immunoglobulin (IVIg) therapy that includes some studies performed under the umbrella of the European Working Party on SLE. Various mechanisms of IVIg may play a role, some synergistically, in the modulation of SLE. Recently it has been suggested that IVIg also suppresses the expansion of autoreactive B lymphocytes through signalling of the FcgRIIB, idiotype-mediated inhibition of B cell receptors and neutralisation of cytokines such as the B cell survival factors (B cell activation factor (BAFF and APRIL). In case reports and in open trials, high-dose IVIg (2 g/kg over a 5-day period) has consistently been shown to be a beneficial and safe adjunct therapeutic agent for over 20 manifestations in patients with SLE. It can be given as a first choice of therapy in some cases, for example, in neurological involvement and in those patients who refuse certain immunosuppressive agents such as cyclophosphamide, or in patients who have concomitant infections. Furthermore, IVIg may have a steroid-sparing effect although this characteristic needs further investigation. Specific IVIg (an anti-idiotype to anti-DNA, phosphorylcholine and antiphospholipids) has been shown to be effective in experimental murine models. Hence, extractable IVIg that is directed to the specific pathogenic immunoglobulins will enable the more specific therapy for patients with lupus.
Cognitive decline in multiple sclerosis: impact of topographic lesion distribution on differential cognitive deficit patterns
Authors: Tiemann L. , Penner IK , Haupts M. , Schlegel U. , Calabrese P. 
Published: August 2009

Background: Multiple sclerosis (MS) is often accompanied by cognitive dysfunction. A negative correlation between cerebral lesion load and atrophy and cognitive performance has been pointed out almost consistently. Further, the distribution of lesions might be critical for the emergence of specific patterns of cognitive deficits. Objective: The current study evaluated the significance of total lesion area (TLA) and central atrophy for the prediction of general cognitive dysfunction and tested for a correspondence between lesion topography and specific cognitive deficit patterns. Methods: Thirty-seven patients with MS underwent neuropsychological assessment and magnetic resonance imaging. Lesion burden and central atrophy were quantified. Patients were classified into three groups by means of individual lesion topography (punctiform lesions/periventricular lesions/confluencing lesions in both periventricular and extra-periventricular regions). Results: TLA was significantly related to 7 cognitive variables, whereas third ventricle width was significantly associated with 20 cognitive parameters. The three groups differed significantly in their performances on tasks concerning alertness, mental speed, and memory function. Conclusion: Third ventricle width as a straight-forward measure of central atrophy proved to be of substantial predictive value for cognitive dysfunction, whereas total lesion load played only a minor role. Periventricular located lesions were significantly related to decreased psychomotor speed, whereas equally distributed cerebral lesion load did not. These findings support the idea that periventricular lesions have a determinant impact on cognition in patients with MS.
The cytoplasmic NPM mutant induces myeloproliferation in a transgenic mouse model
Authors: Cheng Ke , Sportoletti Paolo , Ito Keisuke , Clohessy John G. , Teruya-Feldstein Julie , Kutok Jeffery L. , Pandolfi Pier Paolo 
Published: August 2009

Abstract
Although NPM1 gene mutations leading to aberrant cytoplasmic expression of nucleophosmin (NPMc+) are the most frequent genetic lesions in acute myeloid leukemia, there is yet no experimental model demonstrating their oncogenicity in vivo. We report the generation and characterization of a transgenic mouse model expressing the most frequent human NPMc+ mutation driven by the myeloid-specific human MRP8 promoter (hMRP8-NPMc+). In parallel, we generated a similar wild-type NPM trans-genic model (hMRP8-NPM). Interestingly, hMRP8-NPMc+ transgenic mice developed myeloproliferation in bone marrow and spleen, whereas nontransgenic littermates and hMRP8-NPM transgenic mice remained disease free. These findings provide the first in vivo evidence indicating that NPMc+ confers a proliferative advantage in the myeloid lineage. No spontaneous acute myeloid leukemia was found in hMPR8-NPMc+ or hMRP8-NPM mice. This model will also aid in the development of therapeutic regimens that specifically target NPMc+.
Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors
Authors: Hölig Kristina , Kramer Michael , Kroschinsky Frank , Bornhäuser Martin , Mengling Thilo , Schmidt Alexander H. , Rutt Claudia , Ehninger Gerhard 
Published: August 2009

Abstract
We present results of peripheral blood stem cell (PBSC) mobilization, collection, and follow-up from 3928 consecutive unrelated stem cell donors. Assessments were performed prospectively at baseline, leukapheresis, 1 month, 6 months, and annually after PBSC donation. During follow-up, side effects were recorded by return post questionnaires. The median CD34+ cell counts on day 5 were 67.5/μL in male and 51/μL in female donors. Bone pain and headache were the most common side effects of recombinant human granulocyte-colony stimulating factor. Central venous access was required for 23 donations (0.6%). Throughout the follow-up, the absolute neutrophil counts were slightly below the initial baseline values but remained within the normal range. The majority of the donors reported good or very good health. Malignancies occurred in 12 donors (0.3%), among whom were 1 case of acute myeloid leukemia, 1 case of chronic lymphatic leukemia, and 2 cases of Hodgkin disease. Only the incidence of Hodgkin lymphoma differed significantly from an age-adjusted population. In conclusion, 7.5 μg/kg per day lenograstim proved to be safe and effective for mobilizing hematopoietic stem cells for allogeneic transplantation. Long-term monitoring of healthy PBSC donors remains important to guarantee the safety standards of PBSC mobilization and collection.
Dynamic behavior of NK cells during activation in lymph nodes
Authors: Beuneu Hélène , Deguine Jacques , Breart Béatrice , Mandelboim Ofer , Di Santo James P. , Bousso Philippe 
Published: August 2009

AbstractDuring infection, Toll-like receptor agonists induce natural killer (NK)–cell activation by stimulating dendritic cells (DCs) to produce cytokines and transpresent IL-15 to NK cells. Yet the cellular dynamics underlying NK-cell activation by DCs in secondary lymphoid organs are largely unknown. Here, we have visualized NK-cell activation using mice in which NK cells and DCs express different fluorescent proteins. In response to polyI:C or lipopolysaccharide, NK cells maintained a vigorous migratory behavior, establishing multiple short contacts with maturing DCs. Furthermore, mature antigen-loaded DCs that made long-lived interactions with T cells formed short-lived contacts with NK cells. The different behaviors of T cells and NK cells during activation was correlated with distinct calcium responses upon interaction with DCs. That NK cells become activated while remaining motile may constitute an efficient strategy for sampling local concentrations of cytokines around DCs in secondary lymphoid tissues.
A fungal phylogeny based on 82 complete genomes using the composition vector method
Authors: Wang Hao , Xu Zhao , Gao Lei , Hao Bailin 
Published: August 2009

Abstract

Background
Molecular phylogenetics and phylogenomics have greatly revised and enriched the fungal systematics in the last two decades. Most of the analyses have been performed by comparing single or multiple orthologous gene regions. Sequence alignment has always been an essential element in tree construction. These alignment-based methods (to be called the standard methods hereafter) need independent verification in order to put the fungal Tree of Life (TOL) on a secure footing. The ever-increasing number of sequenced fungal genomes and the recent success of our newly proposed alignment-free composition vector tree (CVTree, see Methods) approach have made the verification feasible.

Results
In all, 82 fungal genomes covering 5 phyla were obtained from the relevant genome sequencing centers. An unscaled phylogenetic tree with 3 outgroup species was constructed by using the CVTree method. Overall, the resultant phylogeny infers all major groups in accordance with standard methods. Furthermore, the CVTree provides information on the placement of several currently unsettled groups. Within the sub-phylum Pezizomycotina, our phylogeny places the Dothideomycetes and Eurotiomycetes as sister taxa. Within the Sordariomycetes, it infers that Magnaporthe grisea and the Plectosphaerellaceae are closely related to the Sordariales and Hypocreales, respectively. Within the Eurotiales, it supports that Aspergillus nidulans is the early-branching species among the 8 aspergilli. Within the Onygenales, it groups Histoplasma and Paracoccidioides together, supporting that the Ajellomycetaceae is a distinct clade from Onygenaceae. Within the sub-phylum Saccharomycotina, the CVTree clearly resolves two clades: (1) species that translate CTG as serine instead of leucine (the CTG clade) and (2) species that have undergone whole-genome duplication (the WGD clade). It places Candida glabrata at the base of the WGD clade.

Conclusion
Using different input data and methodology, the CVTree approach is a good complement to the standard methods. The remarkable consistency between them has brought about more confidence to the current understanding of the fungal branch of TOL.
A physical map of the papaya genome with integrated genetic map and genome sequence
Authors: Yu Qingyi , Tong Eric , Skelton Rachel L , Bowers John E , Jones Meghan R , Murray Jan E , Hou Shaobin , Guan Peizhu , Acob Ricelle A , Luo Ming-Cheng , Moore Paul H , Alam Maqsudul , Paterson Andrew H , Ming Ray 
Published: August 2009

Abstract

Background
Papaya is a major fruit crop in tropical and subtropical regions worldwide and has primitive sex chromosomes controlling sex determination in this trioecious species. The papaya genome was recently sequenced because of its agricultural importance, unique biological features, and successful application of transgenic papaya for resistance to papaya ringspot virus. As a part of the genome sequencing project, we constructed a BAC-based physical map using a high information-content fingerprinting approach to assist whole genome shotgun sequence assembly.

Results
The physical map consists of 963 contigs, representing 9.4× genome equivalents, and was integrated with the genetic map and genome sequence using BAC end sequences and a sequence-tagged high-density genetic map. The estimated genome coverage of the physical map is about 95.8%, while 72.4% of the genome was aligned to the genetic map. A total of 1,181 high quality overgo (overlapping oligonucleotide) probes representing conserved sequences in Arabidopsis and genetically mapped loci in Brassica were anchored on the physical map, which provides a foundation for comparative genomics in the Brassicales. The integrated genetic and physical map aligned with the genome sequence revealed recombination hotspots as well as regions suppressed for recombination across the genome, particularly on the recently evolved sex chromosomes. Suppression of recombination spread to the adjacent region of the male specific region of the Y chromosome (MSY), and recombination rates were recovered gradually and then exceeded the genome average. Recombination hotspots were observed at about 10 Mb away on both sides of the MSY, showing 7-fold increase compared with the genome wide average, demonstrating the dynamics of recombination of the sex chromosomes.

Conclusion
A BAC-based physical map of papaya was constructed and integrated with the genetic map and genome sequence. The integrated map facilitated the draft genome assembly, and is a valuable resource for comparative genomics and map-based cloning of agronomically and economically important genes and for sex chromosome research.
Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers
Authors: Peng Xinxia , Li Yu , Walters Kathie-Anne , Rosenzweig Elizabeth R , Lederer Sharon L , Aicher Lauri D , Proll Sean , Katze Michael G 
Published: August 2009

Abstract

Background
Hepatitis C virus (HCV) is a major cause of chronic liver disease by infecting over 170 million people worldwide. Recent studies have shown that microRNAs (miRNAs), a class of small non-coding regulatory RNAs, are involved in the regulation of HCV infection, but their functions have not been systematically studied. We propose an integrative strategy for identifying the miRNA-mRNA regulatory modules that are associated with HCV infection. This strategy combines paired expression profiles of miRNAs and mRNAs and computational target predictions. A miRNA-mRNA regulatory module consists of a set of miRNAs and their targets, in which the miRNAs are predicted to coordinately regulate the level of the target mRNA.

Results
We simultaneously profiled the expression of cellular miRNAs and mRNAs across 30 HCV positive or negative human liver biopsy samples using microarray technology. We constructed a miRNA-mRNA regulatory network, and using a graph theoretical approach, identified 38 miRNA-mRNA regulatory modules in the network that were associated with HCV infection. We evaluated the direct miRNA regulation of the mRNA levels of targets in regulatory modules using previously published miRNA transfection data. We analyzed the functional roles of individual modules at the systems level by integrating a large-scale protein interaction network. We found that various biological processes, including some HCV infection related canonical pathways, were regulated at the miRNA level during HCV infection.

Conclusion
Our regulatory modules provide a framework for future experimental analyses. This report demonstrates the utility of our approach to obtain new insights into post-transcriptional gene regulation at the miRNA level in complex human diseases.
Modulations of cell cycle checkpoints during HCV associated disease
Authors: Sarfraz Saira , Hamid Saeed , Ali Syed , Jafri Wasim , Siddiqui Anwar A 
Published: August 2009

Abstract

Background
Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC). This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection.

Methods
Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1) with significant changes in mRNA levels (> 2-fold, p-value < 0.05) were selected, and their protein expressions were examined in the liver biopsies of 38 chronic hepatitis C patients.

Results
In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease.

Conclusion
Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development.
Down-regulation of the pro-apoptotic XIAP associated factor-1 (XAF1) during progression of clear-cell renal cancer
Authors: Kempkensteffen Carsten , Fritzsche Florian Rudolf , Johannsen Manfred , Weikert Steffen , Hinz Stefan , Dietel Manfred , Riener Marc-Oliver , Moch Holger , Jung Klaus , Krause Hans , Miller Kurt , Kristiansen Glen 
Published: August 2009

Abstract

Background
Decreased expression of the interferon-stimulated, putative tumour suppressor gene XAF1 has been shown to play a role during the onset, progression and treatment failure in various malignancies. However, little is yet known about its potential implication in the tumour biology of clear-cell renal cell cancer (ccRCC).

Methods
This study assessed the expression of XAF1 protein in tumour tissue obtained from 291 ccRCC patients and 68 normal renal tissue samples, utilizing immunohistochemistry on a tissue-micro-array. XAF1 expression was correlated to clinico-pathological tumour features and prognosis.

Results
Nuclear XAF1 expression was commonly detected in normal renal- (94.1%) and ccRCC (91.8%) samples, without significant differences of expression levels. Low XAF1 expression in ccRCC tissue, however, was associated with progression of tumour stage (p = 0.040) and grade (p < 0.001). Low XAF1 tumour levels were also prognostic of significantly shortened overall survival times in univariate analysis (p = 0.018), but did not provide independent prognostic information.

Conclusion
These data suggest down-regulation of XAF1 expression to be implicated in ccRCC progression and implies that its re-induction may provide a therapeutic approach. Although the prognostic value of XAF1 in ccRCC appears to be limited, its predictive value remains to be determined, especially in patients with metastatic disease undergoing novel combination therapies of targeted agents with Interferon-alpha.