bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell death pathways differ in several mouse models with motoneurone disease: analysis of pure motoneurone populations at a presymptomatic age
Authors: Perrin Florence E. , Boisset Gaelle , Lathuilière Aurélien , Kato Ann C. 
Published: July 2006

AbstractTo identify candidate genes that are responsible for motoneurone degeneration, we combined laser capture microdissection with microarray technology. We analysed gene expression in pure motoneurones from two mouse mutants that develop motoneurone degeneration, progressive motor neuronopathy and wobbler. At a presymptomatic age, there was a significant differential expression of a restricted number of genes (25 and 72 in progressive motor neuronopathy and wobbler respectively, of 22 600 transcripts screened). We compared these results to our previous analyses in the copper–zinc superoxide dismutase mutant mouse (SOD1G93A) in which we observed a de‐regulation of 27 genes. Some of these genes were de‐regulated uniquely in one mouse mutant and some have already been identified in cell death pathways implicated in amyotrophic lateral sclerosis and animal models of motoneurone degeneration (i.e. de‐regulation of intermediate filaments, axonal transport, the ubiquitin–proteasome system and excitotoxicity). One gene, vimentin, was differentially up‐regulated in all mouse mutants; this main candidate gene has been confirmed by in situ hybridization and immunohistochemistry to be expressed in motoneurones in all mouse mutants. Furthermore, vimentin expression correlated with the state of motoneurone degeneration. These results identify early molecular changes that may be involved in the pathogenesis of motoneurones leading to cell death and favour a complex multipathway induction of the disease; surprisingly, there was no important modification in cell death‐associated genes. This is the first study to show a clear difference in the genes that are de‐regulated at an early stage in three different mouse models of motoneurone disease.
Microsatellite markers for the Sydney rock oyster, Saccostrea glomerata, a commercially important bivalve in southeastern Australia
Authors: BANKS S. C. , PIGGOTT M. P. , RAFTOS D. A. , BEHEREGARAY L. B. 
Published: July 2006

AbstractThe Sydney rock oyster (Saccostrea glomerata) is a commercially important bivalve in southeastern Australian. We describe the isolation and characterization of nine microsatellite markers for S. glomerata. The loci are highly polymorphic, with between five and 20 alleles identified among 30 individuals. Expected heterozygosity levels ranged from 0.608 to 0.936. The markers will be used to study natural dispersal, translocations and population structure. We will also use the microsatellites to test the genetic effects of QX disease on oyster populations. This infectious parasitic disease has decimated S. glomerata productivity in a number of areas over the past few decades.
Mycobacterial spindle cell pseudotumor of the skin
Authors: Shiomi Tatsushi , Yamamoto Tetsurou , Manabe Toshiaki 
Published: July 2006

Background:  Mycobacterial spindle cell pseudotumor is a rare tumor‐like lesion characterized by the proliferation of spindle cells engorged with mycobacterial microorganisms. To our knowledge, only a few cases of cutaneous lesions have been described in the literature.Case report:  A 58‐year‐old Japanese woman presented with a nodule in her left forearm. She had systemic lupus erythematosus and interstitial pneumonia for 17 years, treated with prednisolone and azathioprine. She was also receiving insulin treatment for diabetes mellitus.Results:  Histologically, the lesion was located in the deep dermis with extension into the subcutaneous fat tissue and was composed mainly of spindle cells focally showing a vaguely storiform pattern. In limited focal areas, foam cells, epithelioid histiocytes, and multinucleated giant cells were seen sparsely. Ziehl–Neelsen staining showed numerous acid‐fast bacilli within the spindle cells and epithelioid histiocytes. The acid‐fast bacilli were determined by culture and polymerase chain reaction to be Mycobacterium intracellulare.Conclusions:  We emphasize that mycobacterial spindle cell pseudotumor should be included in the differential diagnoses of a spindle cell lesion in the skin, especially in immunosuppressed patients.
Melanoma associated with a dermatofibroma
Authors: Kovach Bradley T. , Boyd Alan S. 
Published: July 2006

Background:  Dermatofibromas are common benign cutaneous fibrohistiocytic neoplasms, whereas melanomas are potentially aggressive malignancies. Differentiating these two entities can occasionally be difficult.Methods:  We report the case of a 56‐year‐old female presenting with a firm pink papule on the left thigh.Results:  Histopathology revealed atypical melanocytes in the epidermis and papillary dermis with numerous mitotic figures and intraepidermal pagetoid spread. Within the dermis was a poorly demarcated collection of epithelioid and spindled cells with intermixed keloidal collagen. The atypical melanocytes stained for MART‐1 and S‐100, whereas the underlying fibrohistiocytic tumor took up factor XIIIa immunostain, confirming the diagnosis of invasive malignant melanoma occurring in association with a dermatofibroma.Conclusions:  This case emphasizes the role of immunohistochemical stains in correctly diagnosing melanocytic and histiocytic neoplasms.
Simian immunodeficiency viruses replication dynamics in African non‐human primate hosts: common patterns and species‐specific differences
Authors: Pandrea Ivona , Silvestri Guido , Onanga Richard , Veazey Ronald S. , Marx Preston A. , Hirsch Vanessa , Apetrei Cristian 
Published: July 2006

AbstractMethods  To define potential common features of simian immunodeficiency virus (SIV) infections in different naturally infected host species, we compared the dynamics of viral replication in 31 African green monkeys (10 sabeus, 15 vervets and seven Caribbean AGMs), 14 mandrills and three sooty mangabeys (SMs) that were experimentally infected with their species‐specific viruses.Results  After infection, these SIVs replicated rapidly reaching viral loads (VLs) of 105–109 copies/ml of plasma between days 9–14 post‐infection (p.i). Set point viremia was established between days 42 and 60 p.i., with levels of approximately 105–106 copies/ml in SM and mandrills, and lower levels (103–105 copies/ml) in AGMs. VL during the chronic phase did not correlate with viral genome structure: SIVmnd‐2 (a vpx‐containing virus) and SIVmnd‐1 (which does not contain vpu or vpx) replicated to similar levels in mandrills. VL was dependent on virus strain: vervets infected with three different viral strains showed different patterns of viral replication. The pattern of viral replication of SIVagm.sab, which uses both CCR5 and CXCR4 co‐receptors was similar to those of the other viruses.Conclusions  Our results show a common pattern of SIV replication in naturally and experimentally infected hosts. This is similar overall to that observed in pathogenic SIV infection of macaques. This result indicates that differences in clinical outcome between pathogenic and non‐pathogenic infections rely on host responses rather than the characteristics of the virus itself.
Repetitive exposures with simian/human immunodeficiency viruses: strategy to study HIV pre‐clinical interventions in non‐human primates
Authors: Kim Caryn N. , Adams Debra R. , Bashirian Sheila , Butera Sal , Folks Thomas M. , Otten Ron A. 
Published: July 2006

AbstractBackground  Non‐human primate models for human immunodeficiency virus (HIV) infection represent a valuable pre‐clinical tool to evaluate interventions (e.g., topical microbicides, vaccines, and chemoprophylaxis) designed to prevent transmission or slow disease progression after infection. Standard transmission models use a single‐dose exposure with high, non‐physiologic levels of virus to approach 100% infection rates of control animals. These single‐exposure models do not represent the circumstances of mucosal HIV transmission in humans and may result in misleading data with regard to intervention efficacy. Therefore, we have developed a repetitive mucosal exposure model using doses of virus that better reflects human exposures.Methods  The virus used for these evaluations was simian‐human immunodeficiency virus [SHIVSF162P3 (R5‐using, subtype B HIV‐1 envelope)] and the virus dose used (approximately 105–106 viral particle equivalents or approximately 10 tissue culture infectious doses per exposure) approximates viral loads observed in the semen during acute HIV‐1 infection. Using the repeated mucosal exposure approach, we have evaluated a candidate vaginal microbicide (cellulose acetate phthalate, CAP) given 15 minutes prior to each weekly virus exposure. Pig‐tailed macaques were exposed weekly by vaginal inoculations with and without microbicide until systemic viral RNA was detected.Results  Groups of naïve control monkeys were infected after an average of three to four exposures for the vaginal route of inoculation. Data from the first application of this monkey model to evaluate the topical microbicide CAP suggested that protection from SHIV infection was possible with three of four CAP‐treated monkeys remaining uninfected after 12 exposures (P = 0.015). CAP efficacy was markedly improved from 66% in a previous single‐dose virus exposure study to 92% in this repeated exposure system.Conclusion  Our experience with using repetitive virus exposures to study topical microbicides and the findings to date from this study provides a basis to refine monkey models to more closely resemble human exposure during HIV transmission. This model may be highly relevant to pre‐clinical evaluation for a variety of therapeutic interventions which is discussed here.
Foamy virus infection in primates
Authors: Murray S.M. , Linial M.L. 
Published: July 2006

AbstractFoamy viruses (FV), the oldest known genus of Retroviridae, are unique among the retroviruses in having no disease association. It is not known why FV are non‐pathogenic while infection by their closest relatives can be deadly. This may be related to the estimated 60 million years of coevolution of FV and their primate hosts. We review the current state of knowledge of FV infection, including information about the sites of viral replication and host immune responses, and discuss the role these may play in establishing persistent yet non‐pathogenic infections. Whether FV has pathologic consequences in immunosuppressed hosts has not been thoroughly investigated. As most primates in HIV/SIV research are coinfected with FV, investigation into possible interactions between these viruses is of interest. The use of FV as a vector for gene therapy is also discussed.
Dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodeficiency virus identified by surface plasmon resonance
Authors: Steckbeck J.D. , Grieser H.J. , Sturgeon T. , Taber R. , Chow A. , Bruno J. , Murphy‐Corb M. , Montelaro R.C. , Cole K.S. 
Published: July 2006

AbstractBackground  Increasing evidence suggests that an effective AIDS vaccine will need to elicit broadly neutralizing antibody responses. However, the mechanisms of antibody‐mediated neutralization have not been defined. Previous studies from our lab have identified significant differences in the rates of antibody binding to trimeric SIV envelope proteins that correlate with neutralization sensitivity. Importantly, these results demonstrate differences in monoclonal antibody (MAb) binding to neutralization‐sensitive and neutralization‐resistant envelope proteins, suggesting that one mechanism for virus neutralization may be related to the stability of antibody binding. To date, little has been done to evaluate the binding properties of polyclonal serum antibodies elicited by SIV infection or vaccination.Methods  In the current study, we translate these findings with MAbs to study antibody binding properties of polyclonal serum antibody responses generated in rhesus macaques infected with attenuated SIV. Quantitative and qualitative binding properties of well‐characterized longitudinal serum samples to trimeric, recombinant SIV gp140 envelope proteins were analyzed using surface plasmon resonance (SPR) technology (Biacore).Results  Results from these studies identified two antibody populations in most of the samples analyzed; one antibody population exhibited fast association/dissociation rates (unstable) while the other population demonstrated slower association/dissociation rates (stable). Over time, the percentage of the total binding response of each antibody population evolved, demonstrating a dynamic evolution of the antibody response that was consistent with the maturation of antibody responses defined using our standard panel of serological assays. However, the current studies provided a higher resolution analysis of polyclonal antibody binding properties, particularly with respect to the early time‐points post‐infection (PI), that is not possible with standard serological assays. More importantly, the increased stability of the antibody population with time PI corresponded with potent neutralization of homologous SIV in vitro.Conclusions  These results suggest that the stability of the antibody–envelope interaction may be an important mechanism of serum antibody virus neutralization. In addition, measurements of the ‘apparent’ rates of association and dissociation may offer unique numerical descriptors to characterize the level of antibody maturation achieved by candidate vaccine strategies capable of eliciting broadly neutralizing antibody responses.
Optimization of in vitro expansion of macaque CD4+ T cells using anti‐CD3 and co‐stimulation for autotransfusion therapy
Authors: Onlamoon Nattawat , Hudson Krystal , Bryan Patsy , Mayne Ann E. , Bonyhadi Mark , Berenson Ron , Sundstrom Bruce J. , Bostik Pavel , Ansari Aftab A. , Villinger François 
Published: July 2006

AbstractBackground  Our laboratory has previously shown that adoptive transfer of in vitro‐expanded autologous purified polyclonal CD4+ T cells using anti‐CD3/CD28‐coated beads induced antiviral responses capable of controlling SIV replication in vivo.Methods  As CD4+ T cells comprise several phenotypic and functional lineages, studies were carried out to optimize the in vitro culture conditions for maximal CD4+ T‐cell expansion, survival and delineate the phenotype of these expanded CD4+ T cells to be linked to maximal clinical benefit.Results and Conclusions  The results showed that whereas anti‐monkey CD3γ/ɛ was able to induce T‐cell proliferation and expansion in combination with antibodies against multiple co‐stimulatory molecules, monkey CD3ɛ cross reacting antibodies failed to induce proliferation of macaque CD4+ T cells. Among co‐stimulatory signals, anti‐CD28 stimulation was consistently superior to anti‐4‐1BB, CD27 or ICOS while the use of anti‐CD154 failed to deliver a detectable proliferation signal. Increasing the relative anti‐CD28 co‐stimulatory signal relative to anti‐CD3 provided a modest enhancement of expansion. Additional strategies for optimization included attempts to neutralize free radicals, enhancement of glucose uptake by T cells or addition of T‐cell stimulatory cytokines. However, none of these strategies provided any detectable proliferative advantage. Addition of 10 autologous irradiated feeder cells/expanding T cell provided some enhancement of expansion; however, given the high numbers of T cell needed, this approach was deemed impractical and costly, and lower ratios of feeder to expanding T cells failed to provide such benefit. The most critical parameter for efficient expansion of purified CD4+ T cells from multiple monkeys was the optimization of space and culture conditions at culture inception. Finally, anti‐CD3/28‐expanded CD4+ T cells uniformly exhibited a central memory phenotype, absence of CCR5 expression, marked CXCR4 expression in vitro, low levels of caspase 3 but also of Bcl‐2 expression.
Induction of the myofibroblastic phenotype in human gingival fibroblasts by transforming growth factor‐β1: role of RhoA‐ROCK and c‐Jun N‐terminal kinase signaling pathways
Authors: Smith Patricio C. , Cáceres Mónica , Martinez Jorge 
Published: July 2006

Background and Objectives:  Myofibroblastic differentiation is an important event in gingival wound healing and chronic inflammation. Transforming frowth factor‐β 1 (TGF‐β1) is a potent growth factor that has been implicated in this process. Gingival myofibroblasts have an increased ability to remodel the extracellular matrix and this feature has been associated with changes in the distribution of F‐actin and the expression of the myofibroblast marker α‐smooth muscle actin. In the present study we have analyzed the role of TGF‐β1 and the signaling routes activated by this factor in the cytoskeletal changes that characterize the myofibroblastic differentiation process in human gingival fibroblasts.Materials and methods:  The signalling pathways involved in myofibroblastic differentiation were studied in primary cultures of human gingival fibroblasts using several signal transduction inhibitors. RhoA activation was analyzed through a pull‐down assay. Distribution of focal adhesions and actin cytoskeleton was assessed by means of immunofluorescence and western blot. A cell adhesion assay was performed in TGF‐β1‐stimulated cells. Smooth muscle actin expression was studied through western blot and imunofluorescence. c‐Jun N‐terminal kinase phosphorylation was assessed through western blot.Results:  Our observations show that TGF‐β1 activated the GTPase RhoA, a key regulator of the actin cytoskeleton. As a consequence of this event, this growth factor stimulated the generation of actin stress fibers and the reinforcement of vinculin‐enriched focal adhesions. These responses were blocked after inhibiting ROCK, the main target of RhoA activation. TGF‐β1 also stimulated the adhesion of fibroblasts over fibronectin, an extracellular matrix molecule involved in myofibroblastic differentiation. Finally, induction of the myofibroblast marker α‐smooth muscle actin by TGF‐β1 was abolished by the c‐Jun N‐terminal protein kinase inhibitor SP600125, suggesting a role for this signaling pathway during the induction of this phenotype.Conclusions:  We propose that TGF‐β1 may promote the differentiation of myofibroblasts through the stimulation of cell spreading and adhesion, the reinforcement of focal adhesions, the maturation of the actin cytoskeleton, and the induction of α‐smooth muscle actin. Activity of RhoA‐ROCK and c‐Jun N‐terminal protein kinase signaling pathways are probably involved in these cellular events.
Litter Characteristics of Gilts Artificially Inseminated with Transforming Growth Factor‐β
Authors: Rhodes Michelle , Brendemuhl Joel H. , Hansen Peter J. 
Published: July 2006

Problem  Semen is a rich source of transforming growth factor‐β (TGF‐β) and it has been proposed that this molecule promotes embryonic survival by modifying immune responses to promote tolerance toward paternal antigens and by inducing release of cytokines that promote embryonic development. The role of TGF‐β was tested using pigs by evaluating whether its addition to washed sperm improves conceptus survival and fetal growth.Methods of study  At estrus, gilts were artificially inseminated twice at 12‐hr intervals with 100 mL of either washed semen resuspended in a commercial semen extender supplemented with 2 mg/mL of gelatin or washed semen in the same extender containing 65 ng/mL of TGF‐β1. Three boars were used as semen donors. At day 80 (±4 days) of gestation, gilts were sacrificed and reproductive tracts harvested.Results  Treatment had no effect (P > 0.10) on total or live fetuses per litter, implantation rate, fetal survival or percentage of corpora lutea resulting in live fetuses at day 80. Insemination with TGF‐β1 also did not affect total or average fetal weight or total placental weight. There was a tendency (P = 0.09) for average placental weight of live fetuses to be lower for pregnancies established in gilts treated with TGF‐β1. Also, placental efficiency (mass of fetus/mass of placenta) was greater (P < 0.05) for pregnancies established in gilts treated with TGF‐β1. The high fertility in control gilts (80% implantation rate and 11.5 live fetuses per litter) is indicative that soluble seminal factors are not necessary for the establishment of pregnancy.Conclusions  Within the ranges tested, concentration of TGF‐β in the fluid phase of the inseminate is not an important determinant of conceptus survival or fetal and placental growth to day 80 of gestation in the pig.
Yeh1 Constitutes the Major Steryl Ester Hydrolase under Heme-Deficient Conditions in
Saccharomyces cerevisiae
Authors: Köffel René , Schneiter Roger 
Published: July 2006

ABSTRACT

Steryl esters are stored in intracellular lipid droplets from which they are mobilized upon demand and hydrolyzed to yield free sterols and fatty acids. The mechanisms that control steryl ester mobilization are not well understood. We have previously identified a family of three lipases of
Saccharomyces cerevisiae
that are required for efficient steryl ester hydrolysis, Yeh1, Yeh2, and Tgl1 (R. Köffel, R. Tiwari, L. Falquet, and R. Schneiter, Mol. Cell. Biol. 25:1655-1668, 2005). Both Yeh1 and Tgl1 localize to lipid droplets, whereas Yeh2 is localized to the plasma membrane. To characterize the precise function of these three partially redundant lipases, we examined steryl ester mobilization under heme-deficient conditions.
S. cerevisiae
is a facultative anaerobic organism that becomes auxotrophic for sterols and unsaturated fatty acids in the absence of molecular oxygen. Anaerobic conditions can be mimicked in cells that are deficient for heme synthesis. We here report that Yeh1 is the sole active steryl ester hydrolase under such heme-deficient conditions, indicating that Yeh1 is activated whereas Yeh2 and Tgl1 are inactivated by the lack of heme. The heme-dependent activation of Yeh1 is mediated at least in part by an increase in steady-state levels of Yeh1 at the expense of Yeh2 and Tgl1 in exponentially growing cells. This increase in steady-state levels of Yeh1 requires Rox3, a component of the mediator complex that regulates transcription by RNA polymerase II. These data thus provide the first link between fat degradation and the transcriptional control of lipase activity in yeast.