bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on clinical proteomics in Alzheimer’s research
Authors: Korolainen Minna A. , Nyman Tuula A. , Aittokallio Tero , Pirttilä Tuula
Published: December 2009

J. Neurochem. (2010) 112, 1386–1414.

Alzheimer’s disease (AD) is a pathologically complex and aetiologically multifactorial dementing disorder affecting millions of people worldwide. The pathological brain changes are assumed to occur decades prior to the onset of clinical symptoms. The diagnosis of early AD remains problematic and is mainly based on clinical and neuropsychological findings after the onset of symptoms. Currently available drugs are able to delay the symptom progression of the disease but not to attenuate the progression of pathological brain changes. Many studies exploring AD proteomes have been conducted as the middle of 1990s as a consequence of recent advances in the development of both gel‐based and gel‐free proteomics approaches. It is hoped that proteomics can contribute to improving the understanding, diagnosis, and follow‐up of the progression of AD. In this review, we summarise the present status of proteome alterations, with emphasis on quantitative approaches, in AD brain, CSF and blood, and their relevance to dementia research.
P2Y receptors and atherosclerosis in apolipoprotein E‐deficient mice
Authors: Guns Pieter‐Jan DF , Hendrickx Jan , Van Assche Tim , Fransen Paul , Bult Hidde
Published: December 2009

Background and purpose:  P2Y nucleotide receptors are involved in the regulation of vascular tone, smooth muscle cell (SMC) proliferation and inflammatory responses. The present study investigated whether they are involved in atherosclerosis.

Experimental approach:  mRNA of P2Y receptors was quantified (RT‐PCR) in atherosclerotic and plaque‐free aorta segments of apolipoprotein E‐deficient (apoE–/–) mice. Macrophage activation was assessed in J774 macrophages, and effects of non‐selective purinoceptor antagonists on atherosclerosis were evaluated in cholesterol‐fed apoE–/– mice.

Key results:  P2Y6 receptor mRNA was consistently elevated in segments with atherosclerosis, whereas P2Y2 receptor expression remained unchanged. Expression of P2Y1 or P2Y4 receptor mRNA was low or undetectable, and not influenced by atherosclerosis. P2Y6 mRNA expression was higher in cultured J774 macrophages than in cultured aortic SMCs. Furthermore, immunohistochemical staining of plaques demonstrated P2Y6‐positive macrophages, but few SMCs, suggesting that macrophage recruitment accounted for the increase in P2Y6 receptor mRNA during atherosclerosis. In contrast to ATP, the P2Y6‐selective agonist UDP increased mRNA expression and activity of inducible nitric oxide synthase and interleukin‐6 in J774 macrophages; this effect was blocked by suramin (100–300 µM) or pyridoxal‐phosphate‐6‐azophenyl‐2′‐4′‐disulphonic acid (PPADS, 10–30 µM). Finally, 4‐week treatment of cholesterol‐fed apoE–/– mice with suramin or PPADS (50 and 25 mg·kg−1·day−1 respectively) reduced plaque size, without changing plaque composition (relative SMC and macrophage content) or cell replication.

Conclusions and implications:  These results suggest involvement of nucleotide receptors, particularly P2Y6 receptors, during atherosclerosis, and warrant further research with selective purinoceptor antagonists or P2Y6 receptor‐deficient mice.
The Rituals of Public Meetings
Authors: McComas Katherine , Besley John C. , Black Laura W.
Published: December 2009

Public meetings are often referred to as “rituals” to denote a largely symbolic activity with little concrete meaning. This essay explores how public meeting rituals may produce very real impacts on participants and pragmatic outcomes. Whereas tangible outputs of rituals are not always evident, ritual theory suggests that participants can derive latent meaning and significant comfort from their application. Although rituals serve to reify certain norms or control behaviors, they may also reaffirm civic values and encourage group cohesion. A deeper appreciation of public meeting rituals will enable participants and officials to respond more effectively to restructured or nontraditional formats as well as better deal with the challenges of maintaining participation when rituals lose their meaning.
Virological Surveillance and Preliminary Antigenic Characterization of Influenza Viruses in Pigs in Five European Countries from 2006 to 2008
Authors: Kyriakis C. S. , Brown I. H. , Foni E. , Kuntz‐Simon G. , Maldonado J. , Madec F. , Essen S. C. , Chiapponi C. , Van Reeth K.
Published: December 2009

This study presents the results of the virological surveillance for swine influenza viruses (SIVs) in Belgium, UK, Italy, France and Spain from 2006 to 2008. Our major aims were to clarify the occurrence of the three SIV subtypes – H1N1, H3N2 and H1N2 – at regional levels, to identify novel reassortant viruses and to antigenically compare SIVs with human H1N1 and H3N2 influenza viruses. Lung tissue and/or nasal swabs from outbreaks of acute respiratory disease in pigs were investigated by virus isolation. The hemagglutinin (HA) and neuraminidase (NA) subtypes were determined using standard methods. Of the total 169 viruses, 81 were classified as ‘avian‐like’ H1N1, 36 as human‐like H3N2 and 47 as human‐like H1N2. Only five novel reassortant viruses were identified: two H1N1 viruses had a human‐like HA and three H1N2 viruses an avian‐like HA. All three SIV subtypes were detected in Belgium, Italy and Spain, while only H1N1 and H1N2 viruses were found in UK and Northwestern France. Cross‐hemagglutination inhibition (HI) tests with hyperimmune sera against selected older and recent human influenza viruses showed a strong antigenic relationship between human H1N1 and H3N2 viruses from the 1980s and H1N2 and H3N2 human‐like SIVs, confirming their common origin. However, antisera against human viruses isolated during the last decade did not react with currently circulating H1 or H3 SIVs, suggesting that especially young people may be, to some degree, susceptible to SIV infections.
Genotyping of Giardia duodenalis Among Children and Dogs in a Closed Socially Deprived Community From Italy
Authors: Marangi M. , Berrilli F. , Otranto D. , Giangaspero A.
Published: December 2009

Molecular characterization of Giardia duodenalis cysts from humans and animals living in well‐defined contexts is useful to study the circulation of isolates and represents a tool to evaluate zoonotic infection risk. The presence of giardiasis in children living in a disadvantaged and socially deprived small Rom community, as well in dogs roaming freely in the same context was carried out by microscopic analysis and beta‐giardin gene amplification. Five out of 14 children were found positive at microscopic examination for G. duodenalis and six positive at PCR, while eight out of 14 dogs tested both microscopically and molecularly positive for G. duodenalis. Moreover, most of the children and dogs were symptomatic. Molecular characterization of Giardia positive samples from children and dogs showed 99.5% identity with Giardia Assemblage A1. The dog‐specific genotypes C and D were not found. The findings of this survey provide the first European evidence to support the possible role of dogs in zoonotic transmission involving children and stray dogs in a closed context with very low standards of hygiene (i.e. Rom community), and these results show the need to monitor the health of marginal populations to safeguard ethnic minority groups.
Evaluation of Mass Vaccination Campaign Coverage Against Rabies in Dogs in Tunisia
Authors: Touihri L. , Zaouia I. , Elhili K. , Dellagi K. , Bahloul C.
Published: December 2009

In Tunisia, rabies continues to be considered as a serious public health concern. Very costly mass vaccination of dogs against rabies and expensive post‐exposure prophylaxis are prerequisites to maintain a low level of human rabies cases. In Tunisia, the implementation of mass vaccination campaigns at the national level has undoubtedly contributed to the drop of rabies endemicity, but the overall outcome is rather suboptimal. In this investigation, we wanted to estimate the extent of the vaccination coverage in dogs in three Governorates (Manouba, Kassrine and Mednine), by collecting data through questionnaires and interviews relevant to 1470 owned dogs. When the campaign is correctly applied, as in Manouba, almost all the targeted dog population can be reached by parenteral vaccination and an almost elimination of the disease can be evidenced. However, in Kasserine and especially in Medenine, where the vaccination coverage is lower than 31%, a reservoir for the disease can be maintained. To match the official figures of vaccination coverage, we should update the statistics of the size of dog population which seems to be bigger than what is assumed. In addition, we wanted to assess the level of involvement of the local population with the vaccination campaigns by marking vaccinated dogs with necklaces and establishing later on the vaccination coverage accordingly. The highest levels of vaccination coverage can be reached in the rural regions. Therefore, the low vaccination coverage in rural areas, reported at the national level, is more attributable to the lack of human and financial resources to reach remote regions. We think that rabies control programmes in Tunisia can be successful if vaccination coverage can reach 70% in all parts of the country. The achieved vaccination coverage should be estimated after random visits in many parts of the country and by checking valid vaccination certificates.
Comparison of Restriction Fragment Length Polymorphism with the Polymorphic Guanine-Cytosine-Rich Sequence and Spoligotyping for Differentiation of
Mycobacterium tuberculosis
Isolates with Five or Fewer Copies of IS
6110
Authors: Flores Laura , Jarlsberg Leah G. , Kim Elizabeth Y. , Osmond Dennis , Grinsdale Jennifer , Kawamura Masae , Desmond Ed , Hopewell Philip C. , Kato-Maeda Midori
Published: December 2009

The use of IS
6110
as a marker for molecular epidemiological studies is limited when a
Mycobacterium tuberculosis
isolate has five or fewer copies of
IS6110
. Restriction fragment length polymorphism analysis with a highly polymorphic GC-rich repetitive sequence located in the plasmid pTBN12 (PGRS RFLP) and spoligotyping (based on the polymorphism of the DR region) are two frequently used secondary typing methods. The aim of this study was to compare the performance of these two methods in a population-based study in San Francisco. We included all patients with culture-positive tuberculosis from 1999 to 2007 with IS
6110
RFLP results presenting five or fewer bands. PGRS RFLP and spoligotyping were performed using standardized methods. We determined the concordance between the two methods regarding cluster status and the risk factors for an isolate to be in a cluster with each of the methods. Our data indicate that both methods had similar discriminatory power and that the risk factors associated with clustering by either method were the same. Although the cluster/unique status was concordant in 84% of the isolates, patients were clustered differently depending on the method. Therefore, the methods are not interchangeable, and the same method should be used for longitudinal studies.
Sequestration of Free Tubulin Molecules by the Viral Protein NSP2 Induces Microtubule Depolymerization during Rotavirus Infection
Authors: Martin Davy , Duarte Mariela , Lepault Jean , Poncet Didier
Published: December 2009

Microtubules, components of the cell cytoskeleton, play a central role in cellular trafficking. Here we show that rotavirus infection leads to a remodeling of the microtubule network together with the formation of tubulin granules. While most microtubules surrounding the nucleus depolymerize, others appear packed at the cell periphery. In microtubule depolymerization areas, tubulin granules are observed; they colocalize with viroplasms, viral compartments formed by interactions between rotavirus proteins NSP2 and NSP5. With purified proteins, we show that tubulin directly interactsin vitrowith NSP2 but not with NSP5. The binding of NSP2 to tubulin is independent of its phosphatase activity. The comparison of three-dimensional (3-D) reconstructions of NSP2 octamers alone or associated with tubulin reveals electron densities in the positively charged grooves of NSP2 that we attribute to tubulin. Site-directed mutagenesis of NSP2 and competition assays between RNA and tubulin for NSP2 binding confirm that tubulin binds to these charged grooves of NSP2. Although the tubulin position within NSP2 grooves cannot be precisely determined, the tubulin C-terminal H12 α-helix could be involved in the interaction. NSP2 overexpression and rotavirus infection produce similar effects on the microtubule network. NSP2 depolymerizes microtubules and leads to tubulin granule formation. Our results demonstrate that tubulin is a viroplasm component and reveal an original mechanism. Tubulin sequestration by NSP2 induces microtubule depolymerization. This depolymerization probably reroutes the cell machinery by inhibiting trafficking and functions potentially involved in defenses to viral infections.
The Latent Origin of Replication of Epstein-Barr Virus Directs Viral Genomes to Active Regions of the Nucleus
Authors: Deutsch Manuel J. , Ott Elisabeth , Papior Peer , Schepers Aloys
Published: December 2009

The Epstein-Barr virus efficiently infects human B cells. The EBV genome is maintained extrachromosomally and replicates synchronously with the host's chromosomes. The latent origin of replication (
oriP
) guarantees plasmid stability by mediating two basic functions: replication and segregation of the viral genome. While the segregation process of EBV genomes is well understood, little is known about its chromatin association and nuclear distribution during interphase. Here, we analyzed the nuclear localization of EBV genomes and the role of functional
oriP
domains FR and DS for basic functions such as the transformation of primary cells, their role in targeting EBV genomes to distinct nuclear regions, and their association with epigenetic domains. Fluorescence
in situ
hybridization visualized the localization of extrachromosomal EBV genomes in the regions adjacent to chromatin-dense territories called the perichromatin. Further, immunofluorescence experiments demonstrated a preference of the viral genome for histone 3 lysine 4-trimethylated (H3K4me3) and histone 3 lysine 9-acetylated (H3K9ac) nuclear regions. To determine the role of FR and DS for establishment and subnuclear localization of EBV genomes, we transformed primary human B lymphocytes with recombinant mini-EBV genomes containing different
oriP
mutants. The loss of DS results in a slightly increased association in H3K27me3 domains. This study demonstrates that EBV genomes or
oriP
-based extrachromosomal vector systems are integrated into the higher order nuclear organization. We found that viral genomes are not randomly distributed in the nucleus. FR but not DS is crucial for the localization of EBV in perichromatic regions that are enriched for H3K4me3 and H3K9ac, which are hallmarks of transcriptionally active regions.
Identification of the CD163 Protein Domains Involved in Infection of the Porcine Reproductive and Respiratory Syndrome Virus
Authors: Van Gorp Hanne , Van Breedam Wander , Van Doorsselaere Jan , Delputte Peter L. , Nauwynck Hans J.
Published: December 2009

Scavenger receptor CD163 is a key entry mediator for porcine reproductive and respiratory syndrome virus (PRRSV). To identify the CD163 protein domains involved in PRRSV infection, deletion mutants and chimeric mutants were created. Infection experiments revealed that scavenger receptor cysteine-rich (SRCR) domain 5 (SRCR 5) is essential for PRRSV infection, while the four N-terminal SRCR domains and the cytoplasmic tail are not required. The remaining CD163 protein domains need to be present but can be replaced by corresponding SRCR domains from CD163-L1, resulting in reduced (SRCR 6 and interdomain regions) or unchanged (SRCR 7 to SRCR 9) infection efficiency. In addition, CD163-specific antibodies recognizing SRCR 5 are able to reduce PRRSV infection.
Contributions of the Avian Influenza Virus HA, NA, and M2 Surface Proteins to the Induction of Neutralizing Antibodies and Protective Immunity
Authors: Nayak Baibaswata , Kumar Sachin , DiNapoli Joshua M. , Paldurai Anandan , Perez Daniel R. , Collins Peter L. , Samal Siba K.
Published: December 2009

Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes severe disease and mortality in poultry. Increased transmission of H5N1 HPAIV from birds to humans is a serious threat to public health. We evaluated the individual contributions of each of the three HPAIV surface proteins, namely, the hemagglutinin (HA), the neuraminidase (NA), and the M2 proteins, to the induction of HPAIV-neutralizing serum antibodies and protective immunity in chickens. Using reverse genetics, three recombinant Newcastle disease viruses (rNDVs) were engineered, each expressing the HA, NA, or M2 protein of H5N1 HPAIV. Chickens were immunized with NDVs expressing a single antigen (HA, NA, and M2), two antigens (HA+NA, HA+M2, and NA+M2), or three antigens (HA+NA+M2). Immunization with HA or NA induced high titers of HPAIV-neutralizing serum antibodies, with the response to HA being greater, thus identifying HA and NA as independent neutralization antigens. M2 did not induce a detectable neutralizing serum antibody response, and inclusion of M2 with HA or NA reduced the magnitude of the response. Immunization with HA alone or in combination with NA induced complete protection against HPAIV challenge. Immunization with NA alone or in combination with M2 did not prevent death following challenge, but extended the time period before death. Immunization with M2 alone had no effect on morbidity or mortality. Thus, there was no indication that M2 is immunogenic or protective. Furthermore, inclusion of NA in addition to HA in a vaccine preparation for chickens may not enhance the high level of protection provided by HA.
A Human Cytomegalovirus gO-Null Mutant Fails To Incorporate gH/gL into the Virion Envelope and Is Unable To Enter Fibroblasts and Epithelial and Endothelial Cells
Authors: Wille Paul T. , Knoche Amber J. , Nelson Jay A. , Jarvis Michael A. , Johnson David C.
Published: December 2009

Human cytomegalovirus (HCMV) depends upon a five-protein complex, gH/gL/UL128-131, to enter epithelial and endothelial cells. A separate HCMV gH/gL-containing complex, gH/gL/gO, has been described. Our prevailing model is that gH/gL/UL128-131 is required for entry into biologically important epithelial and endothelial cells and that gH/gL/gO is required for infection of fibroblasts. Genes encoding UL128-131 are rapidly mutated during laboratory propagation of HCMV on fibroblasts, apparently related to selective pressure for the fibroblast entry pathway. Arguing against this model in the accompanying paper by B. J. Ryckman et al. (J. Virol., 84:2597-2609, 2010), we describe evidence that clinical HCMV strain TR expresses a gO molecule that acts to promote endoplasmic reticulum (ER) export of gH/gL and that gO is not stably incorporated into the virus envelope. This was different from results involving fibroblast-adapted HCMV strain AD169, which incorporates gO into the virion envelope. Here, we constructed a TR gO-null mutant, TRΔgO, that replicated to low titers, spread poorly among fibroblasts, but produced normal quantities of extracellular virus particles. TRΔgO particles released from fibroblasts failed to infect fibroblasts and epithelial and endothelial cells, but the chemical fusogen polyethylene glycol (PEG) could partially overcome defects in infection. Therefore, TRΔgO is defective for entry into all three cell types. Defects in entry were explained by observations showing that TRΔgO incorporated about 5% of the quantities of gH/gL in extracellular virus particles compared with that in wild-type virions. Although TRΔgO particles could not enter cells, cell-to-cell spread involving epithelial and endothelial cells was increased relative to TR, apparently resulting from increased quantities of gH/gL/UL128-131 in virions. Together, our data suggest that TR gO acts as a chaperone to promote ER export and the incorporation of gH/gL complexes into the HCMV envelope. Moreover, these data suggest that it is gH/gL, and not gH/gL/gO, that is present in virions and is required for infection of fibroblasts and epithelial and endothelial cells. Our observations that both gH/gL and gH/gL/UL128-131 are required for entry into epithelial/endothelial cells differ from models for other beta- and gammaherpesviruses that use one of two different gH/gL complexes to enter different cells.
CRYSTALLIZATION BEHAVIORS OF FERROELECTRIC AND PIEZOELECTRIC MATERIALS
Authors: ZHAO XU , SUN CONGTING , SI YUNFEI , LIU MEINAN , XUE DONGFENG
Published: December 2009

Crystallization represents a kind of phase transition, which can be regarded as a process related to bond formation and breaking. According to the chemical bonding characteristics of constituent atoms, the ideal morphology of LiNbO 3 crystals has been successfully predicted by using the chemical bonding theory, which consists well with our experimental results. Some observations concerning the morphology evolution of KH 2 PO 4 (KDP), NH 4 H 2 PO 4 (ADP) and ZnO crystals can also be kinetically simulated by the present theory. The obtained results indicate that the microscopic constituent chemical bonds can help us to comprehensively understand the crystallization mechanism on the basis of quantitative calculations of growth rate in different crystal faces. The chemical bonding theory builds up a link between the crystallographic structure, growth morphology and microscopic chemical bonds of crystal materials, which provides us a useful microscopic tool to quantitatively understand single crystal growth behaviors.
Expression and function of CXCL12/CXCR4 in rat urinary bladder with cyclophosphamide-induced cystitis
Authors: Arms Lauren , Girard Beatrice M. , Vizzard Margaret A.
Published: December 2009

Chemokines, otherwise known as chemotactic cytokines, are proinflammatory mediators of the immune response and have been implicated in altered sensory processing, hyperalgesia, and central sensitization following tissue injury or inflammation. To address the role of CXCL12/CXCR4 signaling in normal micturition and inflammation-induced bladder hyperreflexia, bladder inflammation in adult female Wistar rats (175–250 g) was induced by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every 3rd day for 10 days) time points. CXCL12, and its receptor, CXCR4, were examined in the whole urinary bladder of control and CYP-treated rats using enzyme-linked immunosorbent assays (ELISAs), quantitative PCR (qRT-PCR), and immunostaining techniques. ELISAs, qRT-PCR, and immunostaining experiments revealed a significant ( P ≤ 0.01) increase in CXCL12 and CXCR4 expression in the whole urinary bladder, and particularly in the urothelium, with CYP treatment. The functional role of CXCL12/CXCR4 signaling in micturition was evaluated using conscious cystometry with continuous instillation of saline and CXCR4 receptor antagonist (AMD-3100; 5 μM) administration in control and CYP (48 h)-treated rats. Receptor blockade of CXCR4 using AMD-3100 increased bladder capacity in control (no CYP) rats and reduced CYP-induced bladder hyperexcitability as demonstrated by significant ( P ≤ 0.01) increases in intercontraction interval, bladder capacity, and void volume. These results suggest a role for CXCL12/CXCR4 signaling in both normal micturition and with bladder hyperreflexia following bladder inflammation.
Safety and Function of a New Clinical Intracerebral Microinjection Instrument for Stem Cells and Therapeutics Examined in the Göttingen Minipig
Authors: Bjarkam Carsten R. , Glud Andreas N. , Margolin Lee , Reinhart Karl , Franklin Ron , Deding Dorthe , Ettrup Kåre S. , Fitting Lise M. , Nielsen Mette S. , Sørensen Jens-Christian H. , Cunningham Miles G.
Published: December 2009

Background: A new intracerebral microinjection instrument (IMI) allowing multiple electrophysiologically guided microvolume injections from a single proximal injection path in rats has been adapted to clinical use by coupling the IMI to an FHC microTargeting Manual Drive, designed to be used with standard stereotactic frame-based systems and FHC frameless microTargeting Platforms. Methods: The function and safety of the device was tested by conducting bilateral electrophysiologically guided microinjections of fluorescent microspheres in the substantia nigra of 4 Göttingen minipigs. Results: The device was easy to handle and enabled accurate electrophysiologically guided targeting of the substantia nigra with minimal local tissue damage. Conclusion: The IMI is suitable for clinical use and may prove useful for various stereotactic procedures that require high levels of precision and/or three-dimensional distribution of therapeutics within the brain.
Noncommunicating Thoracolumbar Intradural Extramedullary Arachnoid Cyst in an 8-Year-Old Boy: Intact Removal by Spontaneous Delivery
Authors: Gul Sanser , Bahadir Burak , Kalayci Murat , Acikgoz Bektas
Published: December 2009

Noncommunicating spinal intradural extramedullary arachnoid cysts are an extremely rare cause of spinal cord compression. An 8-year-old boy presented with progressive paraparesis. Magnetic resonance imaging revealed a posterior intradural extramedullary arachnoid cyst extending from T11 to L3 vertebral bodies. The multilevel noncommunicating cyst was totally removed by simple delivery without rupture through a single-level laminoplasty. To our knowledge, no such case has been reported in the literature.
Conventional and Diffusion-Weighted Magnetic Resonance Imaging Findings in a Pediatric Patient with a Posterior Fossa Brain Tumor and Papilledema
Authors: Pakzad-Vaezi Kaivon , Cochrane Doug , Sargent Michael , Singhal Ash
Published: December 2009

We present a case report of a 21-month-old female patient to highlight magnetic resonance (MR) imaging findings associated with papilledema in a pediatric patient with an intracranial tumor. The MR findings included optic disc elevation, dilated perioptic subarachnoid spaces, optic nerve tortuosity and restricted diffusion in the optic nerve heads, all of which resolved upon resolution of raised intracranial pressure (ICP) and papilledema. The case demonstrates that both conventional and diffusion-weighted MR imaging findings can detect the presence, and follow posttreatment resolution, of increased ICP and papilledema in a pediatric tumor patient. The postoperative resolution of optic disc elevation clearly indicates the intracranial tumor etiology.
Congenital Cervical Kyphosis in a Child Associated with Tetraparesis: Case Report
Authors: Van Gorp Viola , Dricot Frederic , van Berlaer Gerlant , Van Rompaey Katrijn , Hachimi-Idrissi Said
Published: December 2009

Congenital cervical kyphosis is a rare clinical condition. We describe an infant presenting with tetraparesis, rapidly progressing to phrenic paralysis and fatal respiratory insufficiency. Therapeutic options remain challenging. Surgical arthrodesis is technically difficult, and one report of a therapeutic thermoplastic body splint is described. Final outcome, however, is dismal. No long-term survivors have been described.
Effect of Follicular Fluid Oxidative Stress on Meiotic Spindle Formation in Infertile Women with Polycystic Ovarian Syndrome
Authors: Chattopadhayay R. , Ganesh A. , Samanta J. , Jana S.K. , Chakravarty B.N. , Chaudhury K.
Published: December 2009

Background: The effect of follicular fluid (FF) oxidative stress (OS) on meiotic spindle (MS) formation in oocytes and subsequent outcome in women with polycystic ovarian syndrome (PCOS) are evaluated in this study. Methods: 326 oocytes from 35 PCOS women (group A) and 208 oocytes from 32 women with tubal infertility (group B) were visualized for MS using PolScope. FF was analyzed for OS markers including reactive oxygen species (ROS), lipid peroxidation and total antioxidant capacity (TAC). Group A was further classified into groups A1 and A2, and group B into groups B1 and B2 depending upon the presence or absence of MS, respectively. Results: MS formation was absent in a significantly higher number of oocytes in group A compared to group B (p ≤ 0.05). OS markers were significantly higher in group A compared to group B (p ≤ 0.05). Fertilization rate, number of good quality embryos and clinical pregnancy rates were higher in group B compared to group A, though not statistically significant. FF ROS was significantly higher and TAC significantly lower in groups A2 and B2 compared to groups A1 and B1 (p < 0.001). Conclusion: The presence of MS and oocyte maturation in PCOS women showed a positive correlation with low levels of OS.
Which Role for Rituximab in Hairy Cell Leukemia? Reflections on Six Cases
Authors: Malfuson J.V. , Fagot T. , Konopacki J. , Souleau B. , Cremades S. , de Revel T.
Published: December 2009

Hairy cell leukemia (HCL) is a rare, chronic, B-cell, lymphoproliferative disorder. Treatment has been revolutionized by the advent of interferon (IFN)-α and purine analogs (PA). First-line therapy with PA yields complete response rates of 75–100%, with many long-lasting remissions. In the event of profound neutropenia and/or infectious complications, a short sequence of IFN-α may precede PA treatment. Because of the excellent results achieved with PA therapy, the potential role of rituximab (an anti-CD20 monoclonal antibody that is highly effective against most B-cell lymphomas) in HCL has yet to be elucidated. Six HCL cases treated with rituximab are reported herein with a view to elucidating the potential role of the drug in HCL. The indications essentially consist of relapsing or refractory disease, avoiding the cumulative toxicity of PA, consolidation therapy in order to eradicate minimal residual disease, and first-line therapy for patients with contraindications to PA and IFN-α.
Histologische Veränderungen in den unterbundenen Stümpfen der Ovarialgefässe bei präoperativer niedermolekularer Heparinprophylaxe
Authors: Slunsky R.
Published: December 2009

Fragestellung: WÄhrend einer Adnexektomie untersuchten wir thrombotische VerÄnderungen sowie GefÁsslÄsionen und resezierten die StÜmpfe der Vasa ovarica nach 30 min. Methoden: Wir spritzten 2 h vor der Operation 20 mg Lovenox® s.c. Spezielle FÄrbemethoden kamen zur Anwendung. Ergebnisse: In LigaturnÄhe fanden wir 3mal (10%) in den Arterien und 4mal (13,3%) in den Venen nur wandstÄndige Thromben, die EndothelschÄden waren reduziert. Schlussfolgerungen: Niedermolekulares Heparin bietet hÖchste Wirkung und Sicherheit in der Thromboseprophylaxe. Aufgrund der Ergebnisse haben wir defÍnitiv das «alte» Standard-Heparin in der klinischen Praxis fallengelassen.
Subclinical Myocardial Necrosis and Cardiovascular Risk in Stable Patients Undergoing Elective Cardiac Evaluation
Authors: Tang W. H. Wilson , Wu Yuping , Nicholls Stephen J. , Brennan Danielle M. , Pepoy Michael , Mann Shirley , Pratt Alan , Van Lente Frederick , Hazen Stanley L.
Published: December 2009

Objective—

The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, “troponin leak”) within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function.

Methods and Results—

Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m
2
) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (<0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. “Probable” (cTnI 0.001–0.008 ng/mL) and “definite” (cTnI 0.009–0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4–3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin;
P
<0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase;
P
<0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline associations with myeloperoxidase, a marker of leukocyte activation.

Conclusion—

In stable cardiology patients, prodromal subclinical myocardial necrosis is associated with substantially higher long-term risk for major adverse cardiovascular events. The underlying mechanisms contributing to this minimal troponin leak phenomenon warrants further investigation.
The Janus-Face of New Reproductive Technologies: Escaping the Polarized Debate
Authors: Widdows Heather
Published: December 2009

Reproduction is held by some to be a divine gift, and by others to be a matter of reproductive rights. The first can leave infertile couples feeling unfulfilled and ‘unblessed’ and the second can be seen as dehumanizing. Yet, despite these vastly divergent understandings, public theology has given little guidance on the use of reproductive technologies and little consideration to their effect on women in particular. This article will interrogate the fault line in feminist thinking—between those who view reproduction as a source of disempowerment and those who view it as empowering—and explore how the debate has developed with the introduction of New Reproductive Technologies (NRTs). It will track the original debate about reproduction in first and second wave feminism. Then, it will consider how this debate has changed with the advent of NRTs. The final section will turn to feminist theology and its surprising lack of contribution to this debate. It will conclude by seeking possible ways forward, identifying resources, in the original feminist debate and in feminist theology, that could usefully be brought into conversation with public theology in order to address this core feminist concern.
Educational Leadership and Globalization: Literacy for a Glocal Perspective
Authors: Brooks Jeffrey S. , Normore Anthony H.
Published: December 2009

This article synthesizes and presents literature in support of the argument that the preparation and practice of educational leadership must be rethought to be relevant for 21st-century schools. Specifically, the authors explore how the concept of glocalization, a meaningful integration of local and global forces, can help educational leaders inform and enhance their pedagogy and practice. They suggest that contemporary educational leaders must develop glocal literacy in nine specific knowledge domains: political literacy, economic literacy, cultural literacy, moral literacy, pedagogical literacy, information literacy, organizational literacy, spiritual and religious literacy, and temporal literacy. Furthermore, they explain that each of these domains of literacy is dynamic, interconnected, and can be influenced by the discrete agency of educational leaders.
Macrophage activation in exacerbated COPD with and without community-acquired pneumonia
Authors: Gutierrez P. , Closa D. , Piñer R. , Bulbena O. , Menéndez R. , Torres A.
Published: December 2009

In large series of nonresponding community-acquired pneumonia (CAP) patients, chronic obstructive pulmonary disease (COPD) was observed to be a protective factor for nonresponse to initial antibiotics. This intriguing fact may be linked to changes in the phenotype of inflammatory cells and, in particular, to the induction of classical-M1 or alternative-M2 activation of macrophages, which result in different inflammatory profiles.

We evaluated the effect of sputum obtained from patients with acute exacerbation of COPD (AECOPD), CAP and COPD+CAP on the phenotypic changes in macrophages. Human THP1 cells differentiated to macrophages were incubated with sputum from patients with AECOPD, CAP or COPD+CAP, and expression of tumour necrosis factor-α, interleukin-6, mannose receptor and arginase was measured to evaluate the phenotype acquired by macrophages. We found that sputum from CAP patients induced the M1 phenotype and that from AECOPD patients induced an M2-like phenotype. Sputum from CAP+COPD patients did not present a clear M1 or M2 phenotype.

These results indicate that the microenvironment in the lung modulates the activation of macrophages, resulting in different phenotypes in AECOPD, CAP and COPD+CAP patients. This different type of activation induces different inflammatory responses and may be involved in the different outcome observed when COPD and CAP present simultaneously.
The malate synthase of Paracoccidioides brasiliensisis a linked surface protein that behaves as an anchorless adhesin
Authors: da Silva Neto Benedito Rodrigues , de Fátima da Silva Julhiany , Mendes-Giannini Maria José Soares , Lenzi Henrique Leonel , de Almeida Soares Célia Maria , Pereira Maristela
Published: December 2009

Background

The pathogenic fungus Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM). This is a pulmonary mycosis acquired by inhalation of fungal airborne propagules that can disseminate to several organs and tissues leading to a severe form of the disease. Adhesion and invasion to host cells are essential steps involved in the internalization and dissemination of pathogens. Inside the host, P. brasiliensis may use the glyoxylate cycle for intracellular survival.

Results

Here, we provide evidence that the malate synthase of P. brasiliensis (PbMLS) is located on the fungal cell surface, and is secreted. PbMLS was overexpressed in Escherichia coli, and polyclonal antibody was obtained against this protein. By using Confocal Laser Scanning Microscopy, PbMLS was detected in the cytoplasm and in the cell wall of the mother, but mainly of budding cells of the P. brasiliensis yeast phase. PbMLSr and its respective polyclonal antibody produced against this protein inhibited the interaction of P. brasiliensis with in vitro cultured epithelial cells A549.

Conclusion

These observations indicated that cell wall-associated PbMLS could be mediating the binding of fungal cells to the host, thus contributing to the adhesion of fungus to host tissues and to the dissemination of infection, behaving as an anchorless adhesin.
Quantitative mass spectrometry of TATA binding protein-containing complexes and subunit phosphorylations during the cell cycle
Authors: Pijnappel WWM Pim , Kolkman Annemieke , Baltissen Marijke PA , Heck Albert JR , Timmers HT Marc
Published: December 2009

Background

Progression through the cell cycle is accompanied by tightly controlled regulation of transcription. On one hand, a subset of genes is expressed in a cell cycle-dependent manner. On the other hand, a general inhibition of transcription occurs during mitosis.

Genetic and genome-wide studies suggest cell cycle regulation at the level of transcription initiation by protein complexes containing the common DNA-binding subunit TATA binding protein (TBP). TBP is a key player in regulating transcription by all three nuclear RNA polymerases. It forms at least four distinct protein complexes with TBP-associated factors (TAFs): SL1, B-TFIID, TFIID, and TFIIIB. Some TAFs are known to remain associated with TBP during the cell cycle. Here we analyze all TAFs and their phosphorylation status during the cell cycle using a quantitative mass spectrometry approach.

Results

TBP protein complexes present in human cells at the G2/M and G1/S transitions were analyzed by combining affinity purification with quantitative mass spectrometry using stable isotope labeling with amino acids in cell culture (SILAC). Phosphorylations were mapped and quantified after enrichment of tryptic peptides by titanium dioxide. This revealed that subunit stoichiometries of TBP complexes remained intact, but their relative abundances in nuclear extracts changed during the cell cycle. Several novel phosphorylations were detected on subunits of the TBP complexes TFIID and SL1. G2/M-specific phosphorylations were detected on TAF1, TAF4, TAF7, and TAFI41/TAF1D, and G1/S-specific dephosphorylations were detected on TAF3. Many phosphorylated residues were evolutionary conserved from human to zebrafish and/or drosophila, and were present in conserved regions suggesting important regulatory functions.

Conclusions

This study provides the first quantitative proteomic analysis of human TBP containing protein complexes at the G2/M and G1/S transitions, and identifies new cell cycle-dependent phosphorylations on TAFs present in their protein complex. We speculate that phosphorylation of complex-specific subunits may be involved in regulating the activities of TBP protein complexes during the cell cycle.
Testosterone Induces Redistribution of Forkhead Box-3a and Down-Regulation of Growth and Differentiation Factor 9 Messenger Ribonucleic Acid Expression at Early Stage of Mouse Folliculogenesis
Authors: Yang Jun-Ling , Zhang Chun-Ping , Li Lei , Huang Lin , Ji Shao-Yang , Lu Cui-Ling , Fan Cui-Hong , Cai Huan , Ren Yu , Hu Zhao-Yuan , Gao Fei , Liu Yi-Xun
Published: December 2009

Increasing evidence has shown that excess androgen may be a main cause of polycystic ovary syndrome (PCOS). However, the molecular mechanism of androgen action on the ovary is unclear. To investigate the possible impacts of androgen on early follicular development, neonatal mouse ovaries mainly containing primordial follicles were cultured with testosterone. We demonstrated that the number of primary follicles was increased after 10 d culture with testosterone treatment via phosphatidylinositol 3-kinase/Akt pathway. Androgen induced Forkhead box (Foxo)-3a activation, and translocation of Foxo3a protein from oocyte nuclei to cytoplasm, which might be a key step for primordial follicle activation. Interestingly, testosterone was also capable of down-regulating growth and differentiation factor-9 expression via its receptor. In summary, we infer that intraovarian excess androgen in PCOS might result in excess early follicles by inducing oocyte Foxo3a translocation and follicular arrest by down-regulating growth and differentiation factor-9 expression.
Prolactin Exerts a Prosurvival Effect on Human Spermatozoa via Mechanisms that Involve the Stimulation of Akt Phosphorylation and Suppression of Caspase Activation and Capacitation
Authors: Pujianto Dwi Ari , Curry Benjamin J. , Aitken R. John
Published: December 2009

The purpose of this study was to examine the impact of prolactin (PRL) on human sperm function, in light of a recent proteomic analysis indicating that these cells express the PRL receptor (PRLR). Immunocytochemical analyses confirmed the presence of PRLR in human spermatozoa and localized this receptor to the postacrosomal region of the sperm head as well as the neck, midpiece, and principal piece of the sperm tail. Nested PCR analysis indicated that these cells possess four splice variants of the PRLR: the long form and three short isoforms, one of which is reported for the first time. A combination of Western blot analyses and immunocytochemistry demonstrated that PRL inhibited sperm capacitation in a dose-dependent manner, suppressing SRC kinase activation and phosphotyrosine expression, two hallmarks of this process. The suppression of sperm capacitation was accompanied by a powerful prosurvival effect, supporting the prolonged motility of these cells and preventing the formation of spontaneous DNA strand breaks via mechanisms that involved the concomitant suppression of caspase activation. Western blot analyses indicated that the prosurvival effect of PRL on human spermatozoa involved the stimulation of Akt phosphorylation, whereas inhibitors of phosphatidylinositol-3-OH kinase and Akt negated this effect, as did the direct induction of sperm capacitation with cAMP analogues. We conclude that PRL is a prosurvival factor for human spermatozoa that prevents these cells from defaulting to an intrinsic apoptotic pathway associated with cell senescence. These findings have implications for preservation of sperm integrity in vivo and in vitro.
Minireview: Posttranscriptional Regulation of the Insulin and Insulin-Like Growth Factor Systems
Authors: Lee Eun Kyung , Gorospe Myriam
Published: December 2009

Insulin and IGFs share structural similarities and regulate metabolic processes including glucose homeostasis. Acute alterations in glucose levels trigger rapid changes in insulin concentration and insulin signaling. These processes are tightly regulated by posttranscriptional mechanisms that alter the stability and translation of mRNAs encoding insulin and the insulin receptor. Long-term glucose homeostasis is also modulated by IGFs and IGF receptors, whose expression is likewise subject to changes in the stability and translation of the encoding mRNAs. The control of mRNA half-life and translation is governed by RNA-binding proteins and microRNAs that interact with target transcripts at the 3′ and 5′ untranslated regions. In this review, we describe the RNA-binding proteins and microRNAs that target the mRNAs encoding insulin, IGFs, and their receptors. We discuss how these mRNA-binding factors help to elicit timely, versatile, and tissue-specific changes in insulin and IGF function, thereby effecting critical control of energy metabolism.
Moderate Deviations for Word Counts in Biological Sequences
Authors: Behrens Sarah , Löwe Matthias
Published: December 2009

We derive a moderate deviation principle for word counts (which is extended to counts of multiple patterns) in biological sequences under different models: independent and identically distributed letters, homogeneous Markov chains of order 1 and m, and, in view of the codon structure of DNA sequences, Markov chains with three different transition matrices. This enables us to approximate P-values for the number of word occurrences in DNA and protein sequences in a new manner.
The Vanishing Discount Approach for the Average Continuous Control of Piecewise Deterministic Markov Processes
Authors: Costa O. L. V. , Dufour F.
Published: December 2009

This work is concerned with the existence of an optimal control strategy for the long-run average continuous control problem of piecewise-deterministic Markov processes (PDMPs). In Costa and Dufour (2008), sufficient conditions were derived to ensure the existence of an optimal control by using the vanishing discount approach. These conditions were mainly expressed in terms of the relative difference of the α-discount value functions. The main goal of this paper is to derive tractable conditions directly related to the primitive data of the PDMP to ensure the existence of an optimal control. The present work can be seen as a continuation of the results derived in Costa and Dufour (2008). Our main assumptions are written in terms of some integro-differential inequalities related to the so-called expected growth condition, and geometric convergence of the post-jump location kernel associated to the PDMP. An example based on the capacity expansion problem is presented, illustrating the possible applications of the results developed in the paper.