bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever
Authors: Warfield Kelly L. , Bradfute Steven B. , Wells Jay , Lofts Loreen , Cooper Meagan T. , Alves D. Anthony , Reed Daniel K. , VanTongeren Sean A. , Mech Christine A. , Bavari Sina
Published: April 2009

The lack of a mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV), and has created a bottleneck in the development of antiviral therapeutics. Primary isolates of the filoviruses, i.e., ebolavirus (EBOV) and MARV, are not lethal to immunocompetent adult mice. Previously, pathological, virologic, and immunologic evaluation of a mouse-adapted EBOV, developed by sequential passages in suckling mice, identified many similarities between this model and EBOV infections in nonhuman primates. We recently demonstrated that serially passaging virus recovered from the liver homogenates of MARV-infected immunodeficient (SCID) mice was highly successful in reducing the time to death in these mice from 50 to 70 days to 7 to 10 days after challenge with the isolate MARV-Ci67, -Musoke, or -Ravn. In this study, we extended our findings to show that further sequential passages of MARV-Ravn in immunocompetent mice caused the MARV to kill BALB/c mice. Serial sampling studies to characterize the pathology of mouse-adapted MARV-Ravn revealed that this model is similar to the guinea pig and nonhuman primate MHF models. Infection of BALB/c mice with mouse-adapted MARV-Ravn caused uncontrolled viremia and high viral titers in the liver, spleen, lymph node, and other organs; profound lymphopenia; destruction of lymphocytes within the spleen and lymph nodes; and marked liver damage and thrombocytopenia. Sequencing the mouse-adapted MARV-Ravn strain revealed differences in 16 predicted amino acids from the progenitor virus, although the exact changes required for adaptation are unclear at this time. This mouse-adapted MARV strain can now be used to develop and evaluate novel vaccines and therapeutics and may also help to provide a better understanding of the virulence factors associated with MARV.
Cleavage and Secretion of Epstein-Barr Virus Glycoprotein 42 Promote Membrane Fusion with B Lymphocytes
Authors: Sorem Jessica , Jardetzky Theodore S. , Longnecker Richard
Published: April 2009

Epstein-Barr virus (EBV) membrane glycoprotein 42 (gp42) is required for viral entry into B lymphocytes through binding to human leukocyte antigen (HLA) class II on the B-cell surface. EBV gp42 plays multiple roles during infection, including acting as a coreceptor for viral entry into B cells, binding to EBV glycoprotein H (gH) and gL during the process of membrane fusion, and blocking T-cell recognition of HLA class II-peptide complexes through steric hindrance. EBV gp42 occurs in two forms in infected cells, a full-length membrane-bound form and a soluble form generated by proteolytic cleavage that is secreted from infected cells due to loss of the N-terminal transmembrane domain. Both the full-length and the secreted gp42 forms bind to gH/gL and HLA class II, and the functional significance of gp42 cleavage is currently unclear. We found that in a virus-free cell-cell fusion assay, enhanced secretion of gp42 promoted fusion with B lymphocytes, and mutation of the site of gp42 cleavage inhibited membrane fusion activity. The site of gp42 cleavage was found to be physically distinct from the residues of gp42 necessary for binding to gH/gL. These results suggest that cleavage and secretion of gp42 are necessary for the process of membrane fusion with B lymphocytes, providing the first indicated functional difference between full-length and cleaved, secreted gp42.
A Viral Nonstructural Protein Regulates Bluetongue Virus Trafficking and Release
Authors: Celma Cristina C. P. , Roy Polly
Published: April 2009

Bluetongue virus (BTV), a nonenveloped insect-borne virus, is released from infected cells by multiple pathways. Unlike other nonenveloped viruses, in addition to cell lysis the newly synthesized virus particles also appear to use a unique “budding” process. The nonstructural protein NS3, the only membrane protein encoded by BTV in infected cells, has been implicated in this process, since it appears to interact not only with the outermost viral capsid protein VP2 but also with a component of the cellular ESCRT pathway. However, to date it had not been possible to obtain direct evidence for the involvement of NS3 in BTV morphogenesis due to the lack of a genetic system that would allow introducing the targeted mutation in NS3 gene. In this study, we have used the recently developed T7 transcript-based reverse genetics system for BTV to introduce mutations in the sequence of NS3 into the viral genome and have investigated the effect of these mutations in the context of a replicating virus. While certain NS3 mutations exhibited drastic effects on newly synthesized virus release, others had less pronounced effects. In particular, mutations of two residues in the Tsg101 binding motif, the putative L domain of NS3, altered normal virus egress patterns and left nascent particles tethered to the cellular membrane, apparently arrested in the process of budding. In cells infected with a mutant virus that was incapable of an NS3-VP2 interaction, no budding particles were visualized. These data suggest that NS3 may act like the membrane protein of enveloped viruses and is responsible for intracellular trafficking and budding of virus particles. NS3 is thus a bridge between the maturing virion particles and cellular proteins during virus egress.
Simultaneous Cell-to-Cell Transmission of Human Immunodeficiency Virus to Multiple Targets through Polysynapses
Authors: Rudnicka Dominika , Feldmann Jérôme , Porrot Françoise , Wietgrefe Steve , Guadagnini Stéphanie , Prévost Marie-Christine , Estaquier Jérôme , Haase Ashley T. , Sol-Foulon Nathalie , Schwartz Olivier
Published: April 2009

Human immunodeficiency virus type 1 (HIV-1) efficiently propagates through cell-to-cell contacts, which include virological synapses (VS), filopodia, and nanotubes. Here, we quantified and characterized further these diverse modes of contact in lymphocytes. We report that viral transmission mainly occurs across VS and through “polysynapses,” a rosette-like structure formed between one infected cell and multiple adjacent recipients. Polysynapses are characterized by simultaneous HIV clustering and transfer at multiple membrane regions. HIV Gag proteins often adopt a ring-like supramolecular organization at sites of intercellular contacts and colocalize with CD63 tetraspanin and raft components GM1, Thy-1, and CD59. In donor cells engaged in polysynapses, there is no preferential accumulation of Gag proteins at contact sites facing the microtubule organizing center. The LFA-1 adhesion molecule, known to facilitate viral replication, enhances formation of polysynapses. Altogether, our results reveal an underestimated mode of viral transfer through polysynapses. In HIV-infected individuals, these structures, by promoting concomitant infection of multiple targets in the vicinity of infected cells, may facilitate exponential viral growth and escape from immune responses.
RuvB-Like Protein 2 Is a Suppressor of Influenza A Virus Polymerases
Authors: Kakugawa Satoshi , Shimojima Masayuki , Neumann Gabriele , Goto Hideo , Kawaoka Yoshihiro
Published: April 2009

In pro- and eukaryotic cells, RuvB-like protein 2 (RBL2) resolves Holliday junction recombination intermediates. Here, we identified RBL2 as a suppressor of influenza A virus replication. Human RBL2 appears to interfere with the oligomerization of the viral nucleoprotein, a critical step in the assembly of viral replication complexes.
In Vivo Retargeting of Adenovirus Type 5 to αvβ6 Integrin Results in Reduced Hepatotoxicity and Improved Tumor Uptake following Systemic Delivery
Authors: Coughlan Lynda , Vallath Sabari , Saha Antonio , Flak Magdalena , McNeish Iain A. , Vassaux Georges , Marshall John F. , Hart Ian R. , Thomas Gareth J.
Published: April 2009

A key impediment to successful cancer therapy with adenoviral vectors is the inefficient transduction of malignant tissue in vivo. Compounding this problem is the lack of cancer-specific targets, coupled with a shortage of corresponding high-efficiency ligands, permitting selective retargeting. The epithelial cell-specific integrin αvβ6 represents an attractive target for directed therapy since it is generally not expressed on normal epithelium but is upregulated in numerous carcinomas, where it plays a role in tumor progression. We previously have characterized a high-affinity, αvβ6-selective peptide (A20FMDV2) derived from VP1 of foot-and-mouth disease virus. We generated recombinant adenovirus type 5 (Ad5) fiber knob, incorporating A20FMDV2 in the HI loop, for which we validated the selectivity of binding and functional inhibition of αvβ6. The corresponding αvβ6-retargeted virus Ad5-EGFPA20exhibited up to 50-fold increases in coxsackievirus- and-adenovirus-receptor-independent transduction and up to 480-fold-increased cytotoxicity on a panel of αvβ6-positive human carcinoma lines compared with Ad5-EGFPWT. Using an αvβ6-positive (DX3-β6) xenograft model, we observed a ∼2-fold enhancement in tumor uptake over Ad5-EGFPWTfollowing systemic delivery. Furthermore, ∼5-fold-fewer Ad5-EGFPA20genomes were detected in the liver (P= 0.0002), correlating with reduced serum transaminase levels and E1A expression. Warfarin pretreatment, to deplete coagulation factors, did not improve tumor uptake significantly with either virus but did significantly reduce liver sequestration and hepatic toxicity. The ability of Ad5-EGFPA20to improve delivery to αvβ6, combined with its reduced hepatic tropism and toxicity, highlights its potential as a prototype virus for future clinical investigation.
Disulfide Bond Formation at the C Termini of Vaccinia Virus A26 and A27 Proteins Does Not Require Viral Redox Enzymes and Suppresses Glycosaminoglycan-Mediated Cell Fusion
Authors: Ching Yao-Cheng , Chung Che-Sheng , Huang Cheng-Yen , Hsia Yu , Tang Yin-Liang , Chang Wen
Published: April 2009

Vaccinia virus A26 protein is an envelope protein of the intracellular mature virus (IMV) of vaccinia virus. A mutant A26 protein with a truncation of the 74 C-terminal amino acids was expressed in infected cells but failed to be incorporated into IMV (W. L. Chiu, C. L. Lin, M. H. Yang, D. L. Tzou, and W. Chang, J. Virol
81:
2149-2157, 2007). Here, we demonstrate that A27 protein formed a protein complex with the full-length form but not with the truncated form of A26 protein in infected cells as well as in IMV. The formation of the A26-A27 protein complex occurred prior to virion assembly and did not require another A27-binding protein, A17 protein, in the infected cells. A26 protein contains six cysteine residues, and in vitro mutagenesis showed that Cys441 and Cys442 mediated intermolecular disulfide bonds with Cys71 and Cys72 of viral A27 protein, whereas Cys43 and Cys342 mediated intramolecular disulfide bonds. A26 and A27 proteins formed disulfide-linked complexes in transfected 293T cells, showing that the intermolecular disulfide bond formation did not depend on viral redox pathways. Finally, using cell fusion from within and fusion from without, we demonstrate that cell surface glycosaminoglycan is important for virus-cell fusion and that A26 protein, by forming complexes with A27 protein, partially suppresses fusion.
Plant Geminivirus Rep Protein Induces Rereplication in Fission Yeast
Authors: Kittelmann Katharina , Rau Peter , Gronenborn Bruno , Jeske Holger
Published: April 2009

The replication-associated protein (Rep) of geminiviruses, single-stranded DNA viruses of higher plants, is essential for virus replication. Since these viruses do not encode their own polymerases, Rep induces differentiated plant cells to reenter the cell cycle by interacting with the plant homologues of retinoblastoma proteins in order to activate the host DNA synthesis machinery. We have used fission yeast (
Schizosaccharomyces pombe
) as a model organism to analyze the impact of ectopically expressed African cassava mosaic virus Rep protein on the cell division cycle in closer detail. Upon expression, Rep showed its characteristic DNA cleavage activity, and about 10% of the cells exhibited morphological changes. They were elongated threefold, on average, and possessed a single but enlarged and less compact nucleus in comparison to noninduced or vector-only control cells. Flow cytometry of Rep-expressing cultures revealed a distinct subpopulation of Rep protein-containing cells with aberrant morphology. The other 90% of the cells were indistinguishable from control cells, and no Rep was detectable. Rep-expressing cells exhibited DNA contents beyond 2C, indicating ongoing replication without intervening mitosis. Because a second open reading frame (ORF), AC4, is present within the Rep gene, the role of AC4 was examined by destroying its start codon within the AC1 ORF. The results confirmed that Rep is necessary and sufficient to induce rereplication in fission yeast. The unique potential of this well-investigated model for dissecting the cell cycle control by geminiviral proteins is discussed.
NFX1-123 Increases hTERT Expression and Telomerase Activity Posttranscriptionally in Human Papillomavirus Type 16 E6 Keratinocytes
Authors: Katzenellenbogen Rachel A. , Vliet-Gregg Portia , Xu Mei , Galloway Denise A.
Published: April 2009

High-risk human papillomavirus (HPV) E6 protein induces telomerase activity through transcriptional activation of hTERT, the catalytic subunit of telomerase. HPV type 16 (HPV16) E6 interacts with two splice variants of NFX1 to increase hTERT expression. NFX1-91 is a transcriptional repressor of hTERT that is polyubiquitinated and targeted for degradation by HPV16 E6 in concert with E6-associated protein. We previously showed that NFX1-123 augments hTERT expression through binding to cytoplasmic poly(A) binding proteins (PABPCs). In this study, we determined that unlike NFX1-91, NFX1-123 is a cytoplasmic protein that colocalized with PABPCs but does not shuttle with PABPCs between the nucleus and cytoplasm. NFX1-123 requires both its PAM2 motif, with which it binds PABPCs, and its R3H domain, which has putative nucleic acid binding capabilities, to increase hTERT mRNA levels and telomerase activity in keratinocytes expressing HPV16 E6. In keratinocytes expressing HPV16 E6 and overexpressing NFX1-123, there was increased protein expression from in vitro-transcribed RNA fused with the 5′ untranslated region (5′ UTR) of hTERT. This posttranscriptional increase in expression required the PAM2 motif and R3H domain of NFX1-123 as well as the coexpression of HPV16 E6. NFX1-123 bound endogenous hTERT mRNA and increased its stability in HPV16 E6-expressing human foreskin keratinocytes, and NFX1-123 increased the stability of in vitro-transcribed RNA fused with the 5′ UTR of hTERT. Together, these studies describe the first evidence of posttranscriptional regulation of hTERT, through the direct interaction of the cytoplasmic protein NFX1-123 with hTERT mRNA, in HPV16 E6-expressing keratinocytes.
The Hepatitis E Virus Open Reading Frame 3 Product Interacts with Microtubules and Interferes with Their Dynamics
Authors: Kannan Harilakshmi , Fan Sumin , Patel Deendayal , Bossis Ioannis , Zhang Yan-Jin
Published: April 2009

Hepatitis E virus (HEV) is the causative agent of hepatitis E, a major form of viral hepatitis in developing countries. The open reading frame 3 (ORF3) of HEV encodes a phosphoprotein with a molecular mass of approximately 13 kDa (hereinafter called vp13). vp13 is essential for establishing HEV infections in animals, yet its exact functions are still obscure. Our current study found evidence showing interaction between vp13 and microtubules. Live-cell confocal fluorescence microscopy revealed both filamentous and punctate distribution patterns of vp13 in cells transfected with recombinant ORF3 reporter plasmids. The filamentous pattern of vp13 was altered by a microtubule-destabilizing drug. The vp13 expression led to elevation of acetylated α-tubulin, indicating increased microtubule stability. Its association with microtubules was further supported by its presence in microtubule-containing pellets in microtubule isolation assays. Exposure of these pellets to a high-salt buffer caused release of the vp13 to the supernatant, suggesting an electrostatic interaction. Inclusion of ATP and GTP in the lysis buffer during microtubule isolation also disrupted the interaction, indicating its sensitivity to the nucleotides. Further assays showed that motor proteins are needed for the vp13 association with the microtubules because disruption of dynein function abolished the vp13 filamentous pattern. Analysis of ORF3 deletion constructs found that both of the N-terminal hydrophobic domains of vp13 are needed for the interaction. Thus, our findings suggest that the vp13 interaction with microtubules might be needed for establishment of an HEV infection.
West Nile Virus Capsid Degradation of Claudin Proteins Disrupts Epithelial Barrier Function
Authors: Medigeshi Guruprasad R. , Hirsch Alec J. , Brien James D. , Uhrlaub Jennifer L. , Mason Peter W. , Wiley Clayton , Nikolich-Zugich Janko , Nelson Jay A.
Published: April 2009

During acute infection, West Nile virus (WNV) has been reported to infect a variety of cell types in various tissues of both experimentally and naturally infected hosts. Virus infects epithelial cells in the skin, kidney, intestine, and testes, although the importance of these findings is unclear. In the current study, we have observed that WNV infection of kidney tubules in mice coincides with the loss of expression of several members of the claudin family. Proteins of this family are often involved in epithelial barrier formation and function. WNV infection of epithelial cells in culture resulted in a decrease in the transepithelial electrical resistance, an increase in the efflux of mannitol across the monolayer, and a loss of intracellular levels of claudin-1 to -4. WNV capsid alone was sufficient for the degradation event, which was mediated through lysosomal proteases. Since epithelial cells are frequent sites of WNV infection, these observations imply a potential mechanism for virus dissemination and extraneural pathogenesis.
Genetic Analysis of Hepatitis C Virus with Defective Genome and Its Infectivity in Vitro
Authors: Sugiyama Kazuo , Suzuki Kenji , Nakazawa Takahide , Funami Kenji , Hishiki Takayuki , Ogawa Kazuya , Saito Satoru , Shimotohno Kumiko W. , Suzuki Takeshi , Shimizu Yuko , Tobita Reiri , Hijikata Makoto , Takaku Hiroshi , Shimotohno Kunitada
Published: April 2009

Replication and infectivity of hepatitis C virus (HCV) with a defective genome is ambiguous. We molecularly cloned 38 HCV isolates with defective genomes from 18 patient sera. The structural regions were widely deleted, with the 5′ untranslated, core, and NS3-NS5B regions preserved. All of the deletions were in frame, indicating that they are translatable to the authentic terminus. Phylogenetic analyses showed self-replication of the defective genomes independent of full genomes. We generated a defective genome of chimeric HCV to mimic the defective isolate in the serum. By using this, we demonstrated for the first time that the defective genome, as it is circulating in the blood, can be encapsidated as an infectious particle bytranscomplementation of the structural proteins.
A UK consensus on the management of the bladder in multiple sclerosis
Authors: Fowler C J , Panicker J N , Drake M , Harris C , Harrison S C W , Kirby M , Lucas M , Macleod N , Mangnall J , North A , Porter B , Reid S , Russell N , Watkiss K , Wells M
Published: April 2009

Bladder symptoms in multiple sclerosis (MS) are common and distressing but also highly amenable to treatment. A meeting of stakeholders involved in patients’ continence care, including neurologists, urologists, primary care, MS nurses and nursing groups was recently convened to formulate a UK consensus for management. National Institute for Health and Clinical Excellence (NICE) criteria were used for producing recommendations based on a review of the literature and expert opinion. It was agreed that in the majority of cases, successful management could be based on a simple algorithm which includes using reagent sticks to test for urine infection and measurement of the post micturition residual urine volume. This is in contrast with published guidelines from other countries which recommend cystometry. Throughout the course of their disease, patients should be offered appropriate management options for treatment of incontinence, the mainstay of which is antimuscarinic medications, in combination, if necessary, with clean intermittent self-catheterisation. The evidence for other measures, including physiotherapy, alternative strategies aimed at improving bladder emptying, other medications and detrusor injections of botulinum toxin A was reviewed. The management of urinary tract infections as well as the bladder problems as part of severe disability were discussed and recommendations agreed.
NEITHER BLACK HOLES NOR REGULAR SOLITONS: A NO-GO THEOREM
Authors: CELI ALESSIO
Published: April 2009

By studying the BPS equations for electrostatic and spherically symmetric configurations in N = 2, d = 5 gauged supergravity with vector multiplets and hypermultiplets coupled, we demonstrate that no regular supersymmetric black hole solutions of this kind exist. Furthermore, we demonstrate that it is not possible to construct supersymmetric regular solitons that have the above symmetries. As a consequence the scalar flow associated to the BPS solutions is always unbounded.
CHARACTERISTICS OF QUANTUM RADIATION OF SLOWLY VARYING NONSTATIONARY KERR–NEWMAN BLACK HOLES
Authors: HUA JIA-CHEN , HUANG YONG-CHANG
Published: April 2009

Quantum radiative characteristics of slowly varying nonstationary Kerr–Newman black holes are investigated by using the method of generalized tortoise coordinate transformation. It is shown that the temperature and the shape of the event horizon of this kind of black holes depend on the time and the angle. Further, we reveal a previously ignored relationship between thermal radiation and nonthermal radiation, which is that the chemical potential in the thermal radiation spectrum is equal to the highest energy of the negative energy state of particles in nonthermal radiation for slowly varying nonstationary Kerr–Newman black holes. Also, we show that the deduced general results can be degenerated to the known conclusion of stationary Kerr–Newman black holes.
STRUCTURAL PROPERTIES OF III-NITRIDE BINARY COMPOUNDS: A COMPREHENSIVE STUDY
Authors: AHMED RASHID , FAZAL-E-ALEEM  , RASHID HARIS , AKBARZADEH H. , HASHEMIFAR S. JAVAD
Published: April 2009

Very little information is available about the structural properties of III-nitride binary compounds in the rock-salt phase. We report/review a comprehensive theoretical study of structural properties of these compounds in rock-salt, zinc-blende and wurtzite phases. Calculations have been made using full-potential linearized augmented plane wave plus local orbitals (FP-L(APW+lo)) method as embodied in WIEN2k code framed within density functional theory (DFT). In this approach of calculations, local density approximation (LDA) [J. P. Perdew and Y. Wang, Phys. Rev. B45 (1992) 13244] and generalized gradient approximation (GGA) [J. P. Perdew, K. Burke and M. Ernzerhof, Phys. Rev. Lett.72 (1996) 3865] have been used for exchange-correlation energy and corresponding potential. Calculated results for lattice constants, bulk modulus, its pressure derivative and cohesive energy of these compounds are consistent with the experimental results. Following these calculations, besides many new results for the rock-salt and other phases, a comprehensive review of the structural properties emerges. We also list some peculiar features of these compounds.
MINIMALLY INVASIVE MANAGEMENT OF TRANS-SCAPHOID PERILUNATE FRACTURE-DISLOCATIONS
Authors: Wong Tak-Chuen , Ip Fu-Keung
Published: April 2009

This retrospective study evaluates the functional and radiological results of a series of acute trans-scaphoid dorsal perilunate fracture-dislocations treated operatively by minimally invasive technique. Twenty-one patients had surgery performed by one of three surgeons between 1994 and 2006, and all cases involved: (1) closed reduction of the carpus; (2) closed reduction and percutaneous screw fixation of the scaphoid fracture; and (3) closed reduction and multiple Kirschner wire stabilisation of the carpal dissociation. Seventeen males and four females with an average age of 29 years were evaluated. Ninety five per cent of internally fixed scaphoid healed at a mean time of 16 weeks. Radiographic alignment of the carpus was satisfactory in 17 cases. The average Mayo wrist score was 80 with three excellent and two poor results. There was one patient with asymptomatic DISI deformity. Two patients had radiographic evidence of mid-carpal arthritis. One patient with a scaphoid nonunion required surgical repair with bone grafting. The results of this study suggest that a minimally invasive technique for treating acute trans-scaphoid perilunate fracture-dislocations can be considered as an alternative to open approaches.
TREATMENT OF INTRAOSSEOUS GANGLIA AND BONE CYSTS OF THE CARPAL BONES WITH INJECTABLE CALCIUM PHOSPHATE BONE CEMENT
Authors: Yajima Hiroshi , Murata Keiichi , Kawamura Kenji , Kawate Kenji , Takakura Yoshinori
Published: April 2009

This article documents the outcome of treatment of intraosseous ganglia and simple bone cysts of the carpal bones by curettage and injectable calcium phosphate bone cement (CPC) grafting. The patients consisted of five men and three women. One had a cystic lesion in the scaphoid, one in the hamate, and five in the lunate. Curettage of the lesions was performed, and CPC was injected into the cavity. Five patients were diagnosed with a ganglion and three with a simple bone cyst. Among the five patients with wrist pain, the pain disappeared completely in four. Radiographs showed apparent partial absorption of CPC in four patients and no absorption in other four. There were no recurrence of tumours and no other complications were encountered. We conclude that calcium phosphate bone cement is a useful material for repairing bone defect after curettage of an intraosseous ganglion or bone cyst of a carpal bone.
DELAYED RUPTURE OF EXTENSOR DIGITORUM COMMUNIS TENDON FOLLOWING VOLAR PLATING OF DISTAL RADIUS FRACTURE
Authors: Hattori Yasunori , Doi Kazuteru , Sakamoto Soutetsu , Yukata Kiminori
Published: April 2009

We present a case of delayed rupture of extensor digitorum communis tendon seven years after volar plating of distal radius fracture. Drill bit penetration during surgery and prominent screw tips into the fourth extensor compartment have a potential risk to damage the tendons. Careful and accurate use of internal fixation instruments is necessary to avoid this complication.
EXTENSOR CARPI RADIALIS LONGUS AVULSION: A LITERATURE REVIEW AND CASE REPORT
Authors: Clark D. , Amirfeyz R. , McCann P. , Bhatia R.
Published: April 2009

Extensor Carpi Radialis Longus (ECRL) avulsion is a rare injury which follows resisted wrist hyperflexion. Treatment of this condition with open reduction and internal fixation is not previously described in the literature, and treatment with plaster immobilisation or k-wire fixation requires a prolonged period of immobilisation. We believe that open reduction and internal fixation of these fractures with early mobilisation will result in the best possible wrist function. We describe a sign to raise the index of suspicion for this injury: a palpable bone lump on the dorsum of the hand in the presence of wrist extensor pain or weakness after wrist hyperflexion injury is a sign of wrist extensor avulsion.
METASTASIS OF GASTRIC CANCER TO THE FIFTH METACARPAL BONE
Authors: Miyamoto Wataru , Yamamoto Soichiro , Uchio Yuji
Published: April 2009

We present a rare case of a 72-year-old woman who had a metastatic bone tumour on the fifth metacarpal of the left hand from gastric cancer. It had occurred in the patient, two years after subtotal gastrectomy and partial resection of a liver for advances gastric cancer with metastasis to the liver. A number of investigations and the needle biopsy confirmed the diagnosis of the metastatic malignant tumour of fifth metacarpal bone and an amputation was performed. Although our patient died 12 months after hand surgery, amputation was effective in providing relief from pain in the affected hand for the remainder of her life.

It is necessary to consider rare acrometastasis to the hand if a patient complains of swelling and pain of the hand without a trigger if there is a history of malignancy, including gastric cancer.
Synthesis of new glycoporphyrin derivatives through carbohydrate-substituted α-diazoacetates
Authors: Gomes Ana T. P. C. , Leão Raquel A. C. , da Silva Fernando C. , Neves Maria G. P. M. S. , Faustino Maria A. F. , Tomé Augusto C. , Silva Artur M. S. , Pinheiro Sérgio , de Souza Maria C. B. V. , Ferreira Vítor F. , Cavaleiro José A. S.
Published: April 2009

The reaction of carbohydrate-substituted α-diazoacetates with meso-tetrakis(pentafluorophenyl)porphyrinatozin(II) allows the synthesis of new glyco-hydroporphyrin derivatives.
Genetic Algorithm File Fitter (GAFFitter)
Authors: Augusto Douglas A.
Published: April 2009

Genetic Algorithm File Fitter,
GAFFitter
for short, is a tool based on a genetic algorithm (GA) that tries to fit a collection of items into as few volumes of specific size as possible. For example, the items might be files and the volumes might be CDs or DVDs.
Solving complex problems in human genetics using GP
Authors: Greene Casey S. , Moore Jason H.
Published: April 2009

The development of rapid data-collection technologies is changing the biomedical and biological sciences. In human genetics chip-based methods facilitate the measurement of thousands of DNA sequence variations from across the human genome. The collection of genetic data is no longer a major rate limiting step. Instead the new challenges are the analysis and interpretation of these high dimensional and frequently noisy datasets. The specific challenge we are interested in is the identification of combinations of interacting DNA sequence variations predictive of common human diseases. Specifically, we wish to detect epistasis or gene-gene interactions. Here we focus solely on the situation where there is an epistatic effect but no detectable main effect. The challenge for applying search algorithms to this problem is that the accuracy of a model is not indicative of the quality of the attributes within the model. Instead we use pre-processing of the dataset to provide building blocks which enable our evolutionary computation strategy to discover an optimal model.
A camera obscura for ants
Authors: Fernandes Carlos M.
Published: April 2009

Pherographiais a drawing procedure that arises from an artificial life model and addresses the hypothetical relationship between photography and the so-called cognitive maps created by the model. The theme is discussed within the emergent research field calledArtificial Artand recent theoretical advances that link Swarm Intelligence and cognitive sciences are also addressed. The system and its equations are given and their outcome is shown in its different forms. Finally, the drawings and other potentialities of the system as a creative tool are discussed within an image-processing framework.
Switching Social Contexts: The Effects of Housing Mobility and School Choice Programs on Youth Outcomes
Authors: DeLuca Stefanie , Dayton Elizabeth
Published: April 2009

Despite years of research, methodological and practical obstacles make it difficult to conclude whether policies aimed at improving schools and communities are effective for improving youth outcomes. To complement existing work, we assess research on the educational and social outcomes for comparable youth who change school and neighborhood settings through unique housing policy and school voucher programs. Research shows that housing programs have helped poor families move to much safer, less disadvantaged, and less segregated neighborhoods. Some housing programs have also provided early educational benefits for young people who relocated to less poor and less segregated neighborhoods, but these gains were not maintained in the long run. School voucher programs have helped disadvantaged youth attend higher-performing private schools in less segregated environments with more middle-class peers. Although some voucher programs have shown small positive effects, the results of others are less certain owing to methodological weaknesses. Future research should directly examine families’ selection processes and be cautious with quantitative research that uses naturally occurring variation to model the effects of potential social programs. Researchers should also recognize the family processes that interact with social policy to determine how youth development can be improved, alongside the structural and political processes that condition how programs work at a larger scale.
Taming Prometheus: Talk About Safety and Culture
Authors: Silbey Susan S.
Published: April 2009

Talk of safety culture has emerged as a common trope in contemporary scholarship and popular media as an explanation for accidents and as a recipe for improvement in complex sociotechnical systems. Three conceptions of culture appear in talk about safety: culture as causal attitude, culture as engineered organization, and culture as emergent and indeterminate. If we understand culture as sociologists and anthropologists theorize as an indissoluble dialectic of system and practice, as both the product and context of social action, the first two perspectives deploying standard causal logics fail to provide persuasive accounts. Displaying affinities with individualist and reductionist epistemologies, safety culture is frequently operationalized in terms of the attitudes and behaviors of individual actors, often the lowest-level actors, with the least authority, in the organizational hierarchy. Sociological critiques claim that culture is emergent and indeterminate and cannot be instrumentalized to prevent technological accidents. Research should explore the features of complex systems that have been elided in the talk of safety culture: normative heterogeneity and conflict, inequalities in power and authority, and competing sets of legitimate interests within organizations.
Gonadotropin-releasing hormone-regulated chemokine expression in human placentation
Authors: Cavanagh P. Craig , Dunk Caroline , Pampillo Macarena , Szereszewski Jacob M. , Taylor Jay E. , Kahiri Caroline , Han Victor , Lye Stephen , Bhattacharya Moshmi , Babwah Andy V.
Published: April 2009

Placental expression of gonadotropin-releasing hormone (GnRH)-I and II, as well as their cognate receptor, coincides with a period of extensive remodeling of the maternal-fetal interface, near the end of the first trimester of pregnancy. To further define the role of GnRH in human placentation, we performed a microarray screen of HTR-8/SVneo trophoblasts to identify GnRH-regulated genes and their roles in placentation. This screen revealed that GnRH regulates the expression of four angiogenic chemokines: CXCL2, CXCL3, CXCL6, and CXCL8. The microarray data were subsequently confirmed by an extensive Q-PCR time-course analysis. CXCL8, a representative chemokine, was selected for further analysis and shown to be strongly expressed by trophoblasts at the maternal-fetal interface of the human placenta, as well as to accumulate in a GnRH-dependent manner in trophoblast-conditioned media in culture. Trophoblasts were subsequently shown to recruit lymphocytes (Jurkat T cells and primary peripheral blood T and uterine natural killer cells) in chemotaxis assays and this was shown to be GnRH dependent. Furthermore, this recruitment was shown to occur via the release of CXCR1/CXCR2 interacting chemokines, such as the CXCLs investigated in this study. This novel regulation of chemokines by GnRH signaling demonstrates the role of GnRH in regulating the recruitment of lymphocytes to the decidua and the possibility of a direct effect on spiral artery remodeling via the release of proangiogenic chemokines and secondary effects via release of angiogenic factors by recruited lymphocytes.
Nhe1 is a luminal Na+/H+ exchanger in mouse choroid plexus and is targeted to the basolateral membrane in Ncbe/Nbcn2-null mice
Authors: Damkier Helle Hasager , Prasad Vikram , Hübner Christian Andreas , Praetorius Jeppe
Published: April 2009

The choroid plexus epithelium (CPE) secretes the major fraction of the cerebrospinal fluid (CSF). The Na+-HCO3− transporter Ncbe/Nbcn2 in the basolateral membrane of CPE cells is important for Na+-dependent pHi increases and probably for CSF secretion. In the current study, the anion transport inhibitor DIDS had no effect on the residual pHi recovery in acidified CPE from Ncbe/Nbcn2 knockout mouse by 2′,7′- bis(2-carboxyethyl)-5( 6 )-carboxyfluorescein (BCECF)-fluorescence microscopy in the presence of CO2/HCO3− (Ncbe/Nbcn2-ko+DIDS 109% of control, P = 0.76, n = 5). Thus Ncbe/Nbcn2 mediates the DIDS-sensitive Na+-dependent pHi recovery in the CPE. The Na+/H+ exchanger-1 Nhe1 is proposed to mediate similar functions as Ncbe/Nbcn2 in CPE. Here, we immunolocalize the Nhe1 protein to the luminal membrane domain in mouse and human CPE. The Na+-dependent pHi recovery of Nhe1 wild-type (Nhe1-wt) mice in the absence of CO2/HCO3− was abolished in the Nhe1 knockout CPE (Nhe1-ko 0.37% of Nhe1-wt, P = 0.0007, n = 5). In Ncbe/Nbcn2-ko mice, Nhe1 was targeted to the basolateral membrane. Nevertheless, the luminal Na+-dependent pHi recovery was increased in Ncbe/Nbcn2-ko compared with wild-type littermates (Nhe1-ko 146% of Nhe1-wt, P = 0.007, n = 5). Whereas the luminal Nhe activity was inhibited by the Nhe blocker EIPA (10 μM) in the Ncbe/Nbcn2-wt, it was insensitive to the inhibitor in Ncbe/Nbcn2-ko (Ncbe/Nbcn2-ko+EIPA 100% of control, P = 0.98, n = 5). This indicates that a luminal EIPA-insensitive Nhe was induced in Ncbe/Nbcn2-ko CPE and that EIPA-sensitive Nhe activity was basolateral. The Nhe1 translocation in Ncbe/Nbcn2-ko CPE may reflect a compensatory response, which provides the cells with better means of regulating pHi or transporting Na+ after Ncbe/Nbcn2 disruption.
Differential epigenetic modifications of histones at the myosin heavy chain genes in fast and slow skeletal muscle fibers and in response to muscle unloading
Authors: Pandorf Clay E. , Haddad Fadia , Wright Carola , Bodell Paul W. , Baldwin Kenneth M.
Published: April 2009

Recent advances in chromatin biology have enhanced our understanding of gene regulation. It is now widely appreciated that gene regulation is dependent upon post-translational modifications to the histones which package genes in the nucleus of cells. Active genes are known to be associated with acetylation of histones (H3ac) and trimethylation of lysine 4 in histone H3 (H3K4me3). Using chromatin immunoprecipitation (ChIP), we examined histone modifications at the myosin heavy chain (MHC) genes expressed in fast vs. slow fiber-type skeletal muscle, and in a model of muscle unloading, which results in a shift to fast MHC gene expression in slow muscles. Both H3ac and H3K4me3 varied directly with the transcriptional activity of the MHC genes in fast fiber-type plantaris and slow fiber-type soleus. During MHC transitions with muscle unloading, histone H3 at the type I MHC becomes de-acetylated in correspondence with down-regulation of that gene, while upregulation of the fast type IIx and IIb MHCs occurs in conjunction with enhanced H3ac in those MHCs. Enrichment of H3K4me3 is also increased at the type IIx and IIb MHCs when these genes are induced with muscle unloading. Downregulation of IIa MHC, however, was not associated with corresponding loss of H3ac or H3K4me3. These observations demonstrate the feasibility of using the ChIP assay to understand the native chromatin environment in adult skeletal muscle, and also suggest that the transcriptional state of types I, IIx and IIb MHC genes are sensitive to histone modifications both in different muscle fiber-types and in response to altered loading states.
Mechanical stimulus alters conformation of type 1 parathyroid hormone receptor in bone cells
Authors: Zhang Yan-Liang , Frangos John A. , Chachisvilis Mirianas
Published: April 2009

The molecular mechanisms by which bone cells transduce mechanical stimuli into intracellular biochemical responses have yet to be established. There is evidence that mechanical stimulation acts synergistically with parathyroid hormone PTH(1-34) in mediating bone growth. Using picosecond time-resolved fluorescence microscopy and G protein-coupled receptor conformation-sensitive fluorescence resonance energy transfer (FRET), we investigated conformational transitions in parathyroid hormone type 1 receptor (PTH1R). 1) A genetically engineered PTH1R sensor containing an intramolecular FRET pair was constructed that enabled detection of conformational activity of PTH1R in single cells. 2) The nature of ligand-dependent conformational change of PTH1R depends on the type of ligand: stimulation with the PTH(1-34) leads to conformational transitions characterized by decrease in FRET efficiency while NH2-terminal truncated ligand PTH(3-34) stimulates conformational transitions characterized by higher FRET efficiencies. 3) Stimulation of murine preosteoblastic cells (MC3T3-E1) with fluid shear stress (FSS) leads to significant changes in conformational equilibrium of the PTH1R in MC3T3-E1 cells, suggesting that mechanical perturbation of the plasma membrane leads to ligand-independent response of the PTH1R. Conformational transitions induced by mechanical stress were characterized by an increase in FRET efficiency, similar to those induced by the NH2-terminal truncated ligand PTH(3-34). The response to the FSS stimulation was inhibited in the presence of PTH(1-34) in the flow medium. These results indicate that the FSS can modulate the action of the PTH(1-34) ligand. 4) Plasma membrane fluidization using benzyl alcohol or cholesterol extraction also leads to conformational transitions characterized by increased FRET levels. We therefore suggest that PTH1R is involved in mediating primary mechanochemical signal transduction in MC3T3-E1 cells.
Upregulation of RGS4 expression by IL-1β in colonic smooth muscle is enhanced by ERK1/2 and p38 MAPK and inhibited by the PI3K/Akt/GSK3β pathway
Authors: Hu Wenhui , Li Fang , Mahavadi Sunila , Murthy Karnam S.
Published: April 2009

Initial Ca2+-dependent contraction of intestinal smooth muscle is inhibited upon IL-1β treatment. The decrease in contraction reflects the upregulation of regulator of G protein signaling-4 (RGS4) via the canonical inhibitor of NF-κB kinase-2 (IKK2)/IκB-α/NF-κB pathway. Here, we show that the activation of various protein kinases, including ERK1/2, p38 MAPK, and phosphoinositide 3-kinase (PI3K), differentially modulates IL-1β-induced upregulation of RGS4 in rabbit colonic muscle cells. IL-1β treatment caused a transient phosphorylation of ERK1/2 and p38 MAPK. It also caused the phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β), sequential downstream effectors of PI3K. Pretreatment with PD-98059 (an ERK inhibitor) and SB-203580 (a p38 MAPK inhibitor) significantly inhibited IL-1β-induced RGS4 expression. In contrast, LY-294002 (a PI3K inhibitor) augmented, whereas GSK3β inhibitors inhibited, IL-1β-induced RGS4 expression. PD-98059 blocked IL-1β-induced phosphorylation of IKK2, degradation of IκB-α, and phosphorylation and nuclear translocation of NF-κB subunit p65, whereas SB-203580 had a marginal effect, implying that the effect of ERK1/2 is exerted on the canonical IKK2/IκB-α/p65 pathway of NF-κB activation but that the effect of p38 MAPK may not predominantly involve NF-κB signaling. The increase in RGS4 expression enhanced by LY-294002 was accompanied by an increase in the phosphorylation of IKK2/IκB-α/p65 and blocked by pretreatment with inhibitors of IKK2 (IKK2-IV) and IκB-α (MG-132). Inhibition of GSK3β abolished IL-1β-induced phosphorylation of IKK2/p65. These findings suggest that ERK1/2 and p38 MAPK enhance IL-1β-induced upregulation of RGS4; the effect of ERK1/2 reflects its ability to promote IKK2 phosphorylation and increase NF-κB activity. GSK3β acts normally to augment the activation of the canonical NF-κB signaling. The PI3K/Akt/GSK3β pathway attenuates IL-1β-induced upregulation of RGS4 expression by inhibiting NF-κB activation.
Testosterone replacement does not normalize carcass composition in chronically decerebrate male rats
Authors: Harris Ruth B. S. , Kelso Emily W. , Flatt William P. , Grill Harvey J. , Bartness Timothy J.
Published: April 2009

Chronically decerebrate (CD) rats, in which the forebrain and its descending projections are completely neurally isolated from hindbrain and rostral projections, gain substantial amounts of body fat, lose lean tissue, and have low circulating testosterone concentrations. We tested whether testosterone replacement would normalize body composition of male CD rats. Five groups of rats were used: CD placebo, CD testosterone, control placebo, castrate placebo, and castrate testosterone. Testosterone replacement was initiated at the first stage of CD surgery in both CDs and castrate controls. The second stage of CD surgery occurred 8 days later, and the study ended 15 days later. Testosterone implants produced 10-fold normal circulating concentrations. Food intake was fixed for all rats by tube feeding. CD rats had substantially more body fat and less lean tissue than neurally intact rats. Testosterone replacement did not affect adiposity of CD rats but did increase carcass water content. Energy expenditure of CD rats was significantly lower than that of control placebo and castrated rats. Testosterone lowered respiratory equivalency ratio and ameliorated a fall in energy expenditure late in the intermeal interval in CD rats. Castration increased, and testosterone decreased luteinizing hormone (LH) and follicle stimulating hormone (FSH) in neurally intact controls. LH was undetectable, and FSH was equivalent to neurally intact controls in CD rats, and neither was affected by testosterone. Collectively, low testosterone did not explain obesity or decreased lean body mass of CD rats, although CD rats exhibited abnormal levels of circulating reproductive hormones and disrupted testosterone negative feedback.