bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferation Capacity and Cytotoxic Activity Are Mediated by Functionally and Phenotypically Distinct Virus-Specific CD8 T Cells Defined by Interleukin-7Rα (CD127) and Perforin Expression
Authors: Cellerai Cristina , Perreau Matthieu , Rozot Virginie , Enders Felicitas Bellutti , Pantaleo Giuseppe , Harari Alexandre 
Published: February 2010

ABSTRACTCytotoxicity and proliferation capacity are key functions of antiviral CD8 T cells. In the present study, we investigated a series of markers to define these functions in virus-specific CD8 T cells. We provide evidence that there is a lack of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on virus-specific CD8 T cells correlated positively with proliferation capacity and negatively with perforin expression and cytotoxicity. Influenza virus-, cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1-specific CD8 T cells were predominantly composed of CD127+perforin−/CD127−perforin+, and CD127−/perforin−CD8 T cells, respectively. CD127−/perforin−and CD127−/perforin+cells expressed significantly more PD-1 and CD57, respectively. Consistently, intracellular cytokine (gamma interferon, tumor necrosis factor alpha, and interleukin-2 [IL-2]) responses combined to perforin detection confirmed that virus-specific CD8 T cells were mostly composed of either perforin+/IL-2−or perforin−/IL-2+cells. In addition, perforin expression and IL-2 secretion were negatively correlated in virus-specific CD8 T cells (P< 0.01). As previously shown for perforin, changes in antigen exposure modulated also CD127 expression. Based on the above results, proliferating (CD127+/IL-2-secreting) and cytotoxic (perforin+) CD8 T cells were contained within phenotypically distinct T-cell populations at different stages of activation or differentiation and showed different levels of exhaustion and senescence. Furthermore, the composition of proliferating and cytotoxic CD8 T cells for a given antiviral CD8 T-cell population appeared to be influenced by antigen exposure. These results advance our understanding of the relationship between cytotoxicity, proliferation capacity, the levels of senescence and exhaustion, and antigen exposure of antiviral memory CD8 T cells.
Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus
Authors: Pistello Mauro , Bonci Francesca , Zabogli Elisa , Conti Francesca , Freer Giulia , Maggi Fabrizio , Stevenson Mario , Bendinelli Mauro 
Published: February 2010

ABSTRACT

The envelope (Env) glycoproteins of HIV and other lentiviruses possess neutralization and other protective epitopes, yet all attempts to induce protective immunity using Env as the only immunogen have either failed or afforded minimal levels of protection. In a novel prime-boost approach, specific-pathogen-free cats were primed with a plasmid expressing Env of feline immunodeficiency virus (FIV) and feline granulocyte-macrophage colony-stimulating factor and then boosted with their own T lymphocytes transduced
ex vivo
to produce the same Env and interleukin 15 (3 × 10
6
to 10 × 10
6
viable cells/cat). After the boost, the vaccinees developed elevated immune responses, including virus-neutralizing antibodies (NA). Challenge with an
ex vivo
preparation of FIV readily infected all eight control cats (four mock vaccinated and four naïve) and produced a marked decline in the proportion of peripheral CD4 T cells. In contrast, five of seven vaccinees showed little or no traces of infection, and the remaining two had reduced viral loads and underwent no changes in proportions of CD4 T cells. Interestingly, the viral loads of the vaccinees were inversely correlated to the titers of NA. The findings support the concept that Env is a valuable immunogen but needs to be administered in a way that permits the expression of its full protective potential.
Are patients receiving enough information about healthcare rationing? A qualitative study: Table 1
Authors: Owen-Smith Amanda , Coast Joanna , Donovan Jenny 
Published: February 2010

BackgroundThere is broad international agreement from clinicians and academics that healthcare rationing should be undertaken as explicitly as possible, and the BMA have publicly supported the call for more accountable priority setting for some time. However, studies in the UK and elsewhere suggest that clinicians experience a number of barriers to rationing openly, and the information needs of patients at the point of provision are largely unknown.MethodologyIn-depth interviews were undertaken with NHS professionals working at the community level of provision, and with patients and professionals receiving or providing treatment for morbid obesity and breast cancer (n=52).ResultsNearly all patients wanted to know about healthcare rationing and had high expectations of their clinical professionals to provide all relevant information about treatment options. However, professionals did not always understand these information requirements, and cases of implicit rationing were common. The existence of relevant national guidance was not always known about, meaning that patients were often reliant on other sources of information about treatment options, which included the popular media, the internet, patient advocacy groups and informal networks of support.DiscussionClinical professionals need to understand patients' need for detailed information when it comes to rationing, and to understand that they are the main gateway for this to be provided. However, disclosure could be distressing for both patients and professionals, and thus the most sensitive and acceptable ways to make this information available requires further investigation.
Low-molecular-weight heparin from Cu2+ and Fe2+ Fenton type depolymerisation processes
Authors: Pierini Monica , Liverani Lino , Lima Marcelo , Guerrini Marco , Torri Giangiacomo , Vismara Elena , Mascellani Giuseppe 
Published: February 2010

SummaryHydrogen peroxide (H2O2) and Cu(OAc)2 or FeSO4 (Fenton type reagents) perform heparin (Hep) depolymerisation to low-molecular-weight heparin (LMWH) following a radical chain mechanism. Hydroxyl (OH) radicals which are initially generated from H2O2 reduction by transition metal ions abstract hydrogen atoms on the heparin chain providing carbon centred radicals whose decay leads to the depolymerisation process. The main depolymerisation mechanism involves Hep radical intermediates that cleave the glycosidic linkage at unsulphated uronic acids followed by a 6-O-nonsulphated glucosamine, thus largely preserving the pentasaccharide sequence responsible for the binding to antithrombin III (AT). Both the transition metal ions influence the overall efficiency of the radical chain processes: Fe2+ acting as a catalyst, while Cu2+ acts as a reagent. LMWHs, especially those afforded by Cu2+, are somewhat unstable to the usual basic workup. However, this lack of stability can be eliminated by a previous NaBH4 reduction. Furthermore, with Cu2+, the process is much more reproducible than with Fe2+. Therefore, for the process of Fenton type depolymerisation of heparin, the use of Cu(OAc)2 is clearly preferable to the more “classical” FeSO4. The resulting activities and characteristics of these LMWHs are peculiar to these oxidative radical processes. In addition, LMWH provided by H2O2/Cu(OAc)2 in optimised conditions was found to posses anti-Xa and anti-IIa activities comparable to those of LMWHs currently in clinical use.Footnote: Dedicated to Prof. Pietro Bianchini.
Impaired NK-cell migration in WAS/XLT patients: role of Cdc42/WASp pathway in the control of chemokine-induced β2 integrin high-affinity state
Authors: Stabile Helena , Carlino Claudia , Mazza Cinzia , Giliani Silvia , Morrone Stefania , Notarangelo Lucia D. , Notarangelo Luigi D. , Santoni Angela , Gismondi Angela 
Published: February 2010

AbstractWe analyzed the involvement of Wiskott-Aldrich syndrome protein (WASp), a critical regulator of actin cytoskeleton remodeling, in the control of natural killer (NK)–cell migration. NK cells derived from patients with Wiskott-Aldrich syndrome/X-linked thrombocytopenia (WAS/XLT), carrying different mutations in the WASP coding gene, displayed reduced migration through intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), or endothelial cells in response to CXCL12/stromal cell–derived factor-1 and CX3CL1/fractalkine. Inhibition of WAS/XLT NK-cell migration was associated with reduced ability of these cells to up-regulate the expression of CD18 activation neoepitope and to adhere to ICAM-1 or VCAM-1 following chemokine stimulation. Moreover, chemokine receptor or β1 or β2 integrin engagement on NK cells rapidly resulted in Cdc42 activation and WASp tyrosine phosphorylation as well as in WASp association with Fyn and Pyk-2 tyrosine kinases. NK-cell pretreatment with wiskostatin, to prevent Cdc42/WASp association, impaired chemokine-induced NK-cell migration through ICAM-1 and β2 integrin activation-dependent neoepitope expression. These results show that the Cdc42/WASp pathway plays a crucial role in the regulation of NK-cell migration by acting as a critical component of the chemokine-induced inside-out signaling that regulates lymphocyte function–associated antigen-1 function and suggest that after integrin or chemokine receptor engagement WASp function is regulated by the coordinate action of both Cdc42 and tyrosine kinases.
Whole-genome sequencing of a laboratory-evolved yeast strain
Authors: Araya Carlos L , Payen Celia , Dunham Maitreya J , Fields Stanley 
Published: February 2010

Abstract

Background
Experimental evolution of microbial populations provides a unique opportunity to study evolutionary adaptation in response to controlled selective pressures. However, until recently it has been difficult to identify the precise genetic changes underlying adaptation at a genome-wide scale. New DNA sequencing technologies now allow the genome of parental and evolved strains of microorganisms to be rapidly determined.

Results
We sequenced >93.5% of the genome of a laboratory-evolved strain of the yeast Saccharomyces cerevisiae and its ancestor at >28× depth. Both single nucleotide polymorphisms and copy number amplifications were found, with specific gains over array-based methodologies previously used to analyze these genomes. Applying a segmentation algorithm to quantify structural changes, we determined the approximate genomic boundaries of a 5× gene amplification. These boundaries guided the recovery of breakpoint sequences, which provide insights into the nature of a complex genomic rearrangement.

Conclusions
This study suggests that whole-genome sequencing can provide a rapid approach to uncover the genetic basis of evolutionary adaptations, with further applications in the study of laboratory selections and mutagenesis screens. In addition, we show how single-end, short read sequencing data can provide detailed information about structural rearrangements, and generate predictions about the genomic features and processes that underlie genome plasticity.
Escherichia coli genes that reduce the lethal effects of stress
Authors: Han Xiulin , Dorsey-Oresto Angella , Malik Muhammad , Wang Jian-Ying , Drlica Karl , Zhao Xilin , Lu Tao 
Published: February 2010

Abstract

Background
The continuing emergence of antimicrobial resistance requires the development of new compounds and/or enhancers of existing compounds. Genes that protect against the lethal effects of antibiotic stress are potential targets of enhancers. To distinguish such genes from those involved in drug uptake and efflux, a new susceptibility screen is required.

Results
Transposon (Tn5)-mediated mutagenesis was used to create a library of Escherichia coli mutants that was screened for hypersensitivity to the lethal action of quinolones and counter-screened to have wild-type bacteriostatic susceptibility. Mutants with this novel "hyperlethal" phenotype were found. The phenotype was transferable to other E. coli strains by P1-mediated transduction, and for a subset of the mutants the phenotype was complemented by the corresponding wild-type gene cloned into a plasmid. Thus, the inactivation of these genes was responsible for hyperlethality. Nucleotide sequence analysis identified 14 genes, mostly of unknown function, as potential factors protecting from lethal effects of stress. The 14 mutants were killed more readily than wild-type cells by mitomycin C and hydrogen peroxide; nine were also more readily killed by UV irradiation, and several exhibited increased susceptibility to killing by sodium dodecyl sulfate. No mutant was more readily killed by high temperature.

Conclusions
A new screening strategy identified a diverse set of E. coli genes involved in the response to lethal antimicrobial and environmental stress, with some genes being involved in the response to multiple stressors. The gene set, which differed from sets previously identified with bacteriostatic assays, provides an entry point for obtaining small-molecule enhancers that will affect multiple antimicrobial agents.
Effects of liquid stimuli on dual-axis swallowing accelerometry signals in a healthy population
Authors: Lee Joon , Sejdić Ervin , Steele Catriona M , Chau Tom 
Published: February 2010

Abstract

Background
Dual-axis swallowing accelerometry has recently been proposed as a tool for non-invasive analysis of swallowing function. Although swallowing is known to be physiologically modifiable by the type of food or liquid (i.e., stimuli), the effects of stimuli on dual-axis accelerometry signals have never been thoroughly investigated. Thus, the objective of this study was to investigate stimulus effects on dual-axis accelerometry signal characteristics. Signals were acquired from 17 healthy participants while swallowing 4 different stimuli: water, nectar-thick and honey-thick apple juices, and a thin-liquid barium suspension. Two swallowing tasks were examined: discrete and sequential. A variety of features were extracted in the time and time-frequency domains after swallow segmentation and pre-processing. A separate Friedman test was conducted for each feature and for each swallowing task.

Results
Significant main stimulus effects were found on 6 out of 30 features for the discrete task and on 5 out of 30 features for the sequential task. Analysis of the features with significant stimulus effects suggested that the changes in the signals revealed slower and more pronounced swallowing patterns with increasing bolus viscosity.

Conclusions
We conclude that stimulus type does affect specific characteristics of dual-axis swallowing accelerometry signals, suggesting that associated clinical screening protocols may need to be stimulus specific.
Endoplasmic reticulum protein 29 (ERp29), a protein related to sperm maturation is involved in sperm-oocyte fusion in mouse
Authors: Ying Xiaoqian , Liu Yue , Guo Qiangsu , Qu Fei , Guo Wei , Zhu Yemin , Ding Zhide 
Published: February 2010

Abstract

Background
Sperm-oocyte fusion is a critical step in fertilization, which requires a series of proteins from both spermatozoa and oocyte to mediate membrane adhesion and subsequent fusion. A rat spermatozoa membrane protein is endoplasmic reticulum protein 29 (ERp29), which significantly increases on the sperm surface as well as in the cytoplasm of epididymal epithelia from caput to cauda as the sperm undergo epididymal maturation. Moreover, ERp29 facilitates viral infection via mediating membrane penetration. We determined if in addition to promoting sperm maturation ERp29 may also play a role in facilitating gamete fusion during the fertilization process.

Methods
Laser scanning confocal microscopy (LSCM) and Western blot analysis were employed to probe for ERp29 protein in BALB/c mouse epididymal and acrosome-reacted spermatozoa. We prepared rabbit polyclonal antibodies against mouse recombinant ERp29 (rERp29) to characterize: 1) fertilization rate (FR); 2) fertilization index (FI); 3) sperm motility and 4) acrosome reaction (AR).

Results
Confocal microscopy indicated that ERp29 was partially localized at the sperm head of the epididymal caput as well as over the whole head and part of the principal piece of the tail region from the epididymal cauda. However, when the acrosome reacted, ERp29 remained in the equatorial and post-acrosomal regions of the sperm head, which is the initial site of sperm-oocyte membrane fusion. Such localization changes were confirmed based on the results of Western blot analysis. Furthermore, the antibodies against mouse rERp29 inhibited the spermatozoa from penetrating into the zona pellucida (ZP)-free oocytes. The functional blocking antibodies reduced both mouse sperm-oocyte FR and FI at concentrations of 100 and 200 micro g/ml compared with pre-immunized rabbit IgG or with anti-mouse recombinant bactericidal/permeability-increasing protein (BPI, a sperm surface protein unrelated to sperm-oocyte fusion) antibodies (100 micro g/ml), but they had no effect on sperm motility and AR.

Conclusion
This study demonstrates that ERp29 on mouse spermatozoa membrane changes during epididymal transit and AR. Accordingly, in mice this protein may be one of the important factors involved in sperm fertilization by facilitating sperm-oocyte membrane fusion.
Hematopoietic stem cells and retroviral infection
Authors: Banerjee Prabal , Crawford Lindsey , Samuelson Elizabeth , Feuer Gerold 
Published: February 2010

AbstractRetroviral induced malignancies serve as ideal models to help us better understand the molecular mechanisms associated with the initiation and progression of leukemogenesis. Numerous retroviruses including AEV, FLV, M-MuLV and HTLV-1 have the ability to infect hematopoietic stem and progenitor cells, resulting in the deregulation of normal hematopoiesis and the development of leukemia/lymphoma. Research over the last few decades has elucidated similarities between retroviral-induced leukemogenesis, initiated by deregulation of innate hematopoietic stem cell traits, and the cancer stem cell hypothesis. Ongoing research in some of these models may provide a better understanding of the processes of normal hematopoiesis and cancer stem cells. Research on retroviral induced leukemias and lymphomas may identify the molecular events which trigger the initial cellular transformation and subsequent maintenance of hematologic malignancies, including the generation of cancer stem cells. This review focuses on the role of retroviral infection in hematopoietic stem cells and the initiation, maintenance and progression of hematological malignancies.
In vivo MRI assessment of permanent middle cerebral artery occlusion by electrocoagulation: pitfalls of procedure
Authors: Chauveau Fabien , Moucharrafie Samir , Wiart Marlène , Brisset Jean-Christophe , Berthezène Yves , Nighoghossian Norbert , Cho Tae-Hee 
Published: February 2010

Abstract
Permanent middle cerebral artery (MCA) occlusion (pMCAO) by electrocoagulation is a commonly used model but with potential traumatic lesions. Early MRI monitoring may assess pMCAO for non-specific brain damage. The surgical steps of pMCAO were evaluated for traumatic cerebral injury in 22 Swiss mice using diffusion and T2-weighted MRI (7T) performed within 1 h and 24 h after surgery. Temporal muscle cauterization without MCA occlusion produced an early T2 hyperintensity mimicking an infarct. No lesion was visible after temporal muscle incision or craniotomy. Early MRI monitoring is useful to identify non-specific brain injury that could hamper neuroprotective drugs assessment.
Transfer of the tendon of tibialis anterior in relapsed congenital clubfoot
Authors: Lampasi M. , Bettuzzi C. , Palmonari M. , Donzelli O. 
Published: February 2010

A total of 38 relapsed congenital clubfeet (16 stiff, 22 partially correctable) underwent revision of soft-tissue surgery, with or without a bony procedure, and transfer of the tendon of tibialis anterior at a mean age of 4.8 years (2.0 to 10.1). The tendon was transferred to the third cuneiform in five cases, to the base of the third metatarsal in ten and to the base of the fourth in 23. The patients were reviewed at a mean follow-up of 24.8 years (10.8 to 35.6). A total of 11 feet were regarded as failures (one a tendon failure, five with a subtalar fusion due to over-correction, and five with a triple arthrodesis due to under-correction or relapse). In the remaining feet the clinical outcome was excellent or good in 20 and fair or poor in seven. The mean Laaveg-Ponseti score was 81.6 of 100 points (52 to 92). Stiffness was mild in four feet and moderate or severe in 23. Comparison between the post-operative and follow-up radiographs showed statistically significant variations of the talo-first metatarsal angle towards abduction. Variations of the talocalcaneal angles and of the overlap ratio were not significant. Extensive surgery for relapsed clubfoot has a high rate of poor long-term results. The addition of transfer of the tendon of tibialis anterior can restore balance and may provide some improvement of forefoot adduction. However, it has a considerable complication rate, including failure of transfer, over-correction, and weakening of dorsiflexion. The procedure should be reserved for those limited cases in which muscle imbalance is a causative or contributing factor.
Migration of the humeral component of the Souter-Strathclyde elbow prosthesis
Authors: van der Lugt J. C. T. , Valstar E. R. , Witvoet-Braam S. W. , Nelissen R. G. H. H. 
Published: February 2010

Mechanical loosening which begins with early-onset migration of the prosthesis is the major reason for failure of the Souter-Strathclyde elbow replacement. In a prospective study of 18 Souter-Strathclyde replacements we evaluated the patterns of migration using roentgen stereophotogrammetric analysis. We had previously reported the short-term results after a follow-up of two years which we have now extended to a mean follow-up of 8.2 years (1 to 11.3). Migration was assessed along the co-ordinal axes and overall micromovement was expressed as the maximum total point movement. The alignment of the prosthesis and the presence of radiolucent lines were examined on conventional standardised radiographs. All the humeral components showed increased and variable patterns of migration at the extended follow-up and four humeral components were revised. The maximum total point movement at two years in the revised prostheses was 1.8 mm (sd 1.0) and in the non-revised 0.7 mm (sd 0.5, p = 0.01). Most humeral components migrated into external rotation resulting in an anterior and varus tilt. The ulnar components remained stable.