bluuebunny/crossref_metadata_2025_split huggingface dataset:
Requirements for Mouse Mammary Tumor Virus Rem Signal Peptide Processing and Function
Authors: Byun Hyewon , Halani Nimita , Gou Yongqiang , Nash Andrea K. , Lozano Mary M. , Dudley Jaquelin P. 
Published: November 2011

ABSTRACT
Mouse mammary tumor virus (MMTV) encodes a Rev-like protein, Rem, which is involved in the nuclear export and expression of viral RNA. Previous data have shown that all Rev-like functions are localized to the 98-amino-acid signal peptide (SP) at the N terminus of MMTV Rem or envelope proteins. MMTV-SP uses endoplasmic reticulum-associated degradation (ERAD) for protein trafficking. Rem cleavage by signal peptidase in the ER is necessary for MMTV-SP function in a reporter assay, but many requirements for trafficking are not known. To allow detection and localization of both MMTV-SP and the C-terminal cleavage product, we prepared plasmids expressing green fluorescent protein (GFP) tags. N-terminal Rem tagging led to protein accumulation relative to untagged Rem and allowed signal peptidase cleavage but reduced its specific activity. C-terminal tagging also led to Rem accumulation yet dramatically reduced cleavage, GFP fluorescence, and activity relative to N-terminally tagged Rem (GFPRem). Substitutions of an invariant leucine at position 71 between the known RNA-binding and nuclear export sequences interfered with GFPRem accumulation and activity but not cleavage. Similarly, deletion of 100 or 150 C-terminal amino acids from GFPRem dramatically reduced both Rem and MMTV-SP levels and function. Removal of the entire C terminus (203 amino acids) restored both protein levels and activity of MMTV-SP. Only C-terminal GFP tagging, and not other modifications, appeared to trap Rem in the ER membrane. Thus, Rem conformation in both the ER lumen and cytoplasm determines cleavage, retrotranslocation, and MMTV-SP function. These mutants further characterize intermediates in Rem trafficking and have implications for all proteins affected by ERAD.
Adenovirus Serotype 5 Neutralizing Antibodies Target both Hexon and Fiber following Vaccination and Natural Infection
Authors: Bradley Ritu R. , Lynch Diana M. , Iampietro Mark J. , Borducchi Erica N. , Barouch Dan H. 
Published: November 2011

ABSTRACT

The immunogenicity of adenovirus serotype 5 (Ad5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against the hexon hypervariable regions (HVRs). However, the role of NAbs directed against other capsid components, particularly the adenovirus fiber, remains unclear. Here we show that Ad5 NAbs target both hexon and fiber following vaccination and natural infection. Utilizing neutralization assays with capsid chimeric vectors, we observed that NAb responses to hexon appeared dominant and NAb responses against fiber were subdominant in sera from vaccinated mice, vaccinated humans, and naturally exposed humans. A novel chimeric Ad5 vector in which both the hexon HVRs and the fiber knob were exchanged nearly completely evaded Ad5-specific NAbs both
in vitro
and
in vivo
.
HIV Latency in the Humanized BLT Mouse
Authors: Marsden Matthew D. , Kovochich Michael , Suree Nuttee , Shimizu Saki , Mehta Roshni , Cortado Ruth , Bristol Gregory , An Dong Sung , Zack Jerome A. 
Published: November 2011

ABSTRACT

Even after extended treatment with powerful antiretroviral drugs, HIV is not completely eliminated from infected individuals. Latently infected CD4
+
T cells constitute one reservoir of replication-competent HIV that needs to be eliminated to completely purge virus from antiretroviral drug-treated patients. However, a major limitation in the development of therapies to eliminate this latent reservoir is the lack of relevant
in vivo
models that can be used to test purging strategies. Here, we show that the humanized BLT (bone marrow-liver-thymus) mouse can be used as both an abundant source of primary latently infected cells for
ex vivo
latency analysis and also as an
in vivo
system for the study of latency. We demonstrate that over 2% of human cells recovered from the spleens of HIV-infected BLT mice can be latently infected and that this virus is integrated, activation inducible, and replication competent. The non-tumor-inducing phorbol esters prostratin and 12-deoxyphorbol-13-phenylacetate can each induce HIV
ex vivo
from these latently infected cells, indicating that this model can be used as a source of primary cells for testing latency activators. Finally, we show activation-inducible virus is still present following suppression of plasma viral loads to undetectable levels by using the antiretroviral drugs zidovudine, indinavir sulfate, and didanosine, demonstrating that this model can also be used to assess the
in vivo
efficacy of latency-purging strategies. Therefore, the HIV-infected BLT mouse should provide a useful model for assessment of HIV latency activators and approaches to eliminate persistent
in vivo
HIV reservoirs.
Increased secretion of Gas6 by smooth muscle cells in human atherosclerotic carotid plaques
Authors: Meilhac Olivier , Bièche Ivan , Raynal Pierre , Bruneval Patrick , Michel Jean-Baptiste , Borgel Delphine , Clauser Sylvain 
Published: November 2011

SummaryVitamin K-dependent protein Gas6 (growth-arrest specific gene 6) plays a role in vascular smooth muscle cell (VSMC) survival and migration, as well as in endothelium and leukocyte activation, and could therefore be involved in atherosclerosis. However, the study of mouse models has led to contradictory results regarding the pro- or anti-atherogenic properties of Gas6, and relatively few data are available in human pathophysiology. To better understand the implication of Gas6 in human atherosclerosis, we studied Gas6 expression and secretion in vitro in human VSMC, and analysed the effect of Gas6 on inflammatory gene expression in these cells. We show that Gas6 secretion in VSMC is strongly induced by the anti-inflammatory cytokine transforming growth factor (TGF)β, and that VSMC stimulation by recombinant Gas6 decreases the expression of inflammatory genes tumour necrosis factor (TNF)α and intracellular adhesion molecule (ICAM)-1. The study of Gas6 expression in human carotid endarterectomy samples revealed that Gas6 is mainly expressed by VSMC at all stages of human atherosclerosis, but is not detected in normal vessel wall. Analysis of plaque secretomes showed that Gas6 secretion is markedly higher in non-complicated plaques than in complicated plaques, and that TGFβ secretion pattern mirrors that of Gas6. We conclude that Gas6 is secreted in human atherosclerotic plaques by VSMC following stimulation by TGFβ, and that Gas6 secretion decreases with plaque complication. Therefore, we propose that Gas6 acts as a protective factor, in part by reducing the pro-inflammatory phenotype of VSMC.
Prognostic importance of preoperative anti-PF4/heparin antibodies in patients undergoing cardiac surgery
Authors: Warkentin Theodore E. , Arsenault Kyle A. , Whitlock Richard , Eikelboom John W. , Yusuf Arif M. 
Published: November 2011

SummaryIt was the objective of this study to obtain best estimates of the prevalence of anti-PF4/heparin antibodies in patients not suspected to have clinical heparin-induced thrombocytopenia (HIT) prior to undergoing cardiac surgery and to determine whether preoperative antibody status and antibody class is predictive of postoperative thromboembolic outcomes, non-thromboembolic outcomes, length of stay, and mortality. PubMed and EMBASE online databases were searched up to July 2011, and we included studies involving adults undergoing cardiac surgery examining the relationship between preoperative anti-PF4/heparin antibodies (ELISA) and postoperative clinical outcomes. Five studies involving a combined total of 2,332 patients met our inclusion criteria. Preoperative anti-PF4/heparin antibodies were detected in 5–22% of patients. No study demonstrated an association between preoperative anti-PF4/heparin antibodies and postoperative thromboembolic outcomes or mortality. Three studies demonstrated a statistically significant association between preoperative anti-PF4/heparin antibodies and length of stay while two showed an association with non-thromboembolic complications. In the one study that examined outcomes by anti-PF4/heparin antibody class, IgM antibodies predicted non-thromboembolic complications and length-of-stay. None of the studies reported prior heparin exposure, and most studies did not examine the relationship of the absolute value of antibody titres (ELISA OD) and risk, nor the incidence of true/clinical HIT in preoperative positive or negative patients. In conclusion, pre-formed anti-PF4/heparin antibodies are common in patients undergoing cardiac surgery, but the available literature does not support that they predict postoperative thromboembolic complications or death. There does appear to be an association between anti-PF4/heparin antibodies and non-thromboembolic adverse events, but a causal relationship is unlikely.
Neisseria meningitidis induces platelet inhibition and increases vascular endothelial permeability via nitric oxide regulated pathways
Authors: Siauw Celine , Gambaryan Stepan , Hebling Sabrina , Speer Christian , Schubert-Unkmeir Alexandra , Kobsar Anna , Eigenthaler Martin 
Published: November 2011

SummaryDespite antibiotic therapy, infections with Neisseria meningitidis still demonstrate a high rate of morbidity and mortality even in developed countries. The fulminant septicaemic course, named Waterhouse-Friderichsen syndrome, with massive haemorrhage into the adrenal glands and widespread petechial bleeding suggest pathophysiological inhibition of platelet function. Our data show that N. meningitidis produces the important physiological platelet inhibitor and cardiovascular signalling molecule nitric oxide (NO), also known as endothelium-derived relaxing factor (EDRF). N. meningitidis-derived NO inhibited ADPinduced platelet aggregation through the activation of soluble guanylyl cyclase (sGC) followed by an increase in platelet cyclic nucleotide levels and subsequent activation of platelet cGMP- and cAMP- depend- ent protein kinases (PKG and PKA). Furthermore, direct measurement of horseradish peroxidase (HRP) passage through a vascular endothelial cell monolayer revealed that N. meningitidis significantly increased endothelial monolayer permeability. Immunfluorescence analysis demonstrated NO dependent disturbances in the structure of endothelial adherens junctions after co-incubation with N. meningitidis. In contrast to platelet inhibition, the NO effects on HBMEC were not mediated by cyclic nucleotides. Our study provides evidence that NO plays an essential role in the pathophysiology of septicaemic meningococcal infection.
The structure-function relationship of activated protein C
Authors: Wildhagen Karin , Lutgens Esther , Loubele Sarah , Cate Hugo ten , Nicolaes Gerry 
Published: November 2011

SummaryProtein C is the central enzyme of the natural anticoagulant pathway and its activated form APC (activated protein C) is able to proteolyse non-active as well as active coagulation factors V and VIII. Proteolysis renders these cofactors inactive, resulting in an attenuation of thrombin formation and overall down-regulation of coagulation. Presences of the APC cofactor, protein S, thrombomodulin, endothelial protein C receptor and a phospholipid surface are important for the expression of anticoagulant APC activity. Notably, APC also has direct cytoprotective effects on cells: APC is able to protect the endothelial barrier function and expresses anti-inflammatory and anti-apoptotic activities. Exact molecular mechanisms have thus far not been completely described but it has been shown that both the protease activated receptor 1 and EPCR are essential for the cytoprotective activity of APC. Recently it was shown that also other receptors like sphingosine 1 phosphate receptor 1, Cd11b/CD18 and tyrosine kinase with immunoglobulin-like and EGFlike domains 2 are likewise important for APC signalling. Mutagenesis studies are being performed to map the various APC functions and interactions onto its 3D structure and to dissect anticoagulant and cytoprotective properties. The results of these studies have provided a wealth of structure-function information. With this review we describe the state-of-the-art of the intricate structure-function relationships of APC, a protein that harbours several important functions for the maintenance of both humoral and tissue homeostasis.Lessons from natural and engineered mutations
The Variable Impacts of Public Housing Community Proximity on Nearby Street Robberies
Authors: Haberman Cory P. , Groff Elizabeth R. , Taylor Ralph B. 
Published: November 2011

Objectives: Use crime pattern theory to investigate the proximity effects of public housing communities on robbery crime while taking into account the presence of nearby nonresidential facilities. Method: The study uses data describing 41 Philadelphia public housing communities and their surrounds. Surrounds are defined using two increments of street block-sized buffers. Multilevel models (buffer areas nested around public housing communities) allowing the proximity effect to vary across communities and predicting its shape with public housing level predictors are estimated. Results: The multilevel models show that the shape of proximity effects varies across public housing communities and depends on community size, even after factoring in presence of nonresidential facilities. Spatially, multiple public housing communities close to one another have more intense robbery patterns. Conclusions: Labeling all public housing communities as equally criminogenic robbery exporters is unwarranted. In fact, some communities have lower robbery counts than the areas surrounding them. Consequently, effectively addressing robbery in and around public housing communities will require careful consideration of where the problem is located. Locating public housing communities more than two blocks apart may reduce robbery.
Haploinsufficiency of the genes encoding the tumor suppressor Pten predisposes zebrafish to hemangiosarcoma
Authors: Choorapoikayil Suma , Kuiper Raoul V. , de Bruin Alain , den Hertog Jeroen 
Published: November 2011

SUMMARY
PTEN is an essential tumor suppressor that antagonizes Akt/PKB signaling. The zebrafish genome encodes two Pten genes, ptena and ptenb. Here, we report that zebrafish mutants that retain a single wild-type copy of ptena or ptenb (ptena+/−ptenb−/− or ptena−/−ptenb+/−) are viable and fertile. ptena+/−ptenb−/− fish develop tumors at a relatively high incidence (10.2%) and most tumors developed close to the eye (26/30). Histopathologically, the tumor masses were associated with the retrobulbar vascular network and diagnosed as hemangiosarcomas. A single tumor was identified in 42 ptena−/−ptenb+/− fish and was also diagnosed as hemangiosarcoma. Immunohistochemistry indicated that the tumor cells in ptena+/−ptenb−/− and ptena−/−ptenb+/− fish proliferated rapidly and were of endothelial origin. Akt/PKB signaling was activated in the tumors, whereas Ptena was still detected in tumor tissue from ptena+/−ptenb−/− zebrafish. We conclude that haploinsufficiency of the genes encoding Pten predisposes to hemangiosarcoma in zebrafish.
Prevalence of Borrelia Burgdorferi Infection in a Series of 98 Primary Cutaneous Lymphomas
Authors: Ponzoni Maurilio , Ferreri Andrés J. M. , Mappa Silvia , Pasini Elisa , Govi Silvia , Facchetti Fabio , Fanoni Daniele , Tucci Alessandra , Vino Arianna , Doglioni Claudio , Berti Emilio , Dolcetti Riccardo 
Published: November 2011

Abstract
Borrelia burgdorferi has been variably associated with different forms of primary cutaneous lymphoma. Differences in prevalence rates among reported studies could be a result of geographic variability or heterogeneity in the molecular approaches that have been employed. In the present study, we investigated the prevalence of Borrelia burgdorferi sensu lato DNA in diagnostic tissue samples from fresh cutaneous biopsies of 98 primary cutaneous lymphomas and 19 normal skin controls. Three different polymerase chain reaction (PCR) protocols targeting the hbb, flagellin, and Osp-A genes were used. Direct sequencing of both sense and antisense strands of purified PCR products confirmed the specificity of the amplified fragments. Sequence specificity was assessed using the Basic Local Alignment Search Tool, and MultAlin software was used to investigate the heterogeneity of target gene sequences across the different samples.
Borrelia DNA was not detected in 19 controls, 23 cases of follicular lymphoma, 31 cases of extranodal marginal zone lymphoma, or 30 cases of mycosis fungoides. A single case of 14 diffuse large B-cell lymphoma cases was positive for B. burgdorferi.
This study does not support a pathogenic role of B. burgdorferi in primary cutaneous B- and T-cell lymphomas from areas nonendemic for this microorganism and the consequent rationale for the adoption of antibiotic therapy in these patients.
Les migrations frontalières alsaciennes vers la région méridionale du Rhin supérieur
Authors: Mohr Bernhard 
Published: November 2011

The Alsacians Commuters to the « Region Su'dlicher Oberrhein » in Baden-Wurttemberg in the Federal Republic of Germany.
In 1982, approx. 37 000 Alsacians (almost 6 % of those employed in industry and trade) commuted to work in foreign countries, approx. 15 600 in the Federal Republic of Germany. A study was carried out on 5 600 commuters crossing the border into the Region Siidlicher Oberrhein in Baden Wiirttemberg. The average age was 32 years ; in comparison to German employees, they had a lower school education and were not as qualified in their professions ; and the quota of labourers was higher. Their working-places were concentrated in seven localities in Baden. The desire to have a job and a better income were the main motives. Alsacian employees were not more threatened by dismissal than their German colleagues.
« Passeur de mots, passeur d'histoires » Biographe pour personnes gravement malades. Un projet fédérateur au sein d'un service d'onco-hématologie
Authors: Patin Serpantié Anne 
Published: November 2011

Résumé Une expérience originale : dans un service d’onco-hématologie, le partenariat avec une biographe. Aux malades en situation non curative est proposé d’écrire leur récit de vie, qui leur sera ensuite remis sous la forme d’un livre, à eux ou à la personne qu’ils auront désignée. Avec le recul de quatre ans, ce projet s’apparente à un soin à destination des patients, de leurs familles, mais aussi de l’équipe. L’évocation du parcours d’une patiente, de ses rencontres avec le corps médical, des entretiens psychothérapeutiques et de l’aventure de la biographie qu’elle a voulue mener, voudrait illustrer la richesse de ce partenariat, et ses prolongements dans l’après-coup, une fois le livre transmis. Lorsqu’il n’y a plus de traitements curatifs, proposer à une personne gravement malade d’écrire son histoire, c’est ouvrir un projet de vie, et habiter cette place restée vacante dans l’abord médical de la maladie, de la transmission et du sens.
L'émotionnalité participative : corps et psychisme en interaction
Authors: Avron Ophélia 
Published: November 2011

Résumé Je situe ma recherche de « la mise en travail » psychique de l’expressivité corporelle dans le contexte économique des pulsions. Je postule deux pulsions en étayage, la pulsion sexuelle et la pulsion d’inter liaison. Cette dernière s’exprimerait à travers un processus psychique pluriel, que j’ai nommé « émotionnalité participative rythmique », qui se développerait par réactivité réciproque et réciproquement entretenue, et qui permet le rassemblement de tous les participants présents quels que soient leur nombre, leur âge et leur sexe. À travers trois exemples cliniques, j’essaie de dégager l’expressivité psycho-corporelle des affects de plaisir-déplaisir et celle de l’énergétique émotionnelle en état de réactivité réciproque entre les individus présents. Les prémisses de ces langages non-verbaux donnent des aperçus sur les parties névrotiques et psychotiques de la personnalité des patients et sur la réactivité groupale.
Écouter les corps en quête de sens : un travail groupal avec des adolescents atteints de lésions cérébrales
Authors: Toubert-Duffort Danièle 
Published: November 2011

Résumé À partir d’une expérience de groupe conduite en milieu hospitalier avec des adolescents atteints de lésions cérébrales (traumatismes crâniens sévères, tumeurs cérébrales, avc ), l’auteur analyse ce qui se métaphorise dans le corps groupal concernant le corps du sujet, et discute des enjeux du travail clinique. Cinq à huit adolescents de 15 à 20 ans constituent un groupe hebdomadaire d’une heure, qui alterne atelier photo (activité support) et groupe de parole. La façon dont le corps se mobilise dans le groupe constitue une première tentative pour signifier à autrui ce que vit le « je ». Mettre en scène son corps « troué », exhiber à autrui ses marques corporelles, fraie la voie à la figuration de ce qui, ultérieurement, s’offrira dans le groupe à l’élaboration. Il s’agit pour le sujet d’établir un lien entre corps biologique, corps érogène et événements relationnels, entre Moi-corps et corps groupal, entre affect et représentation. Cependant, le contexte particulier de ces jeunes (enjeux vitaux, handicap, traitements lourds, hospitalisation) qui agit sur le clinicien, rend plus délicate la question de l’ajustement de la distance entre le groupe et lui. Ainsi le clinicien risque-t-il de se focaliser sur les traces trop visibles de la menace que constitue l’atteinte cérébrale, ou de dénier les effets de déliaison induits par l’expérience traumatique.
Duane Retraction Syndrome: Series of 441 Cases
Authors: Kekunnaya Ramesh , Gupta Amit , Sachdeva Virender , Krishnaiah Sannapaneni , Venkateshwar Rao B. , Vashist Urvish , Ray Debajit 
Published: November 2011

Purpose:
To determine the demographic and clinical profile of various subtypes of Duane retraction syndrome (DRS).

Methods:
Retrospective case series of 441 patients.

Results:

Of the total 441 patients, 389 (88.2%) and 52 (11.8%) patients had unilateral and bilateral involvement, respectively. In both unilateral and bilateral cases, type I was the most common subtype, followed by types III and II. Mean age of presentation of type I DRS was significantly less (13.3 years) compared with types II (23 years) and III (21.9 years) (
P
< .05). Unilateral disease was significantly more common in females (57. 6%,
P
= .006), whereas there was no gender predilection in bilateral cases (
P
= .77). Type 1 DRS was significantly more common among females (57.96%,
P
= .003) compared with males, whereas there was no such gender predilection in types II and III. The left eye was more commonly involved in patients with types I and III (
P
< .05), whereas in type II there was no such predilection for any eye involvement. Esotropia was more common in patients with bilateral disease (53.8%) and exotropia was predominant ocular deviation in patients with types II and III (70% and 66.67%,
P
= .03). There was no difference in the type of deviation in patients with type I (
P
> .05). Upshoots and downshoots were more common in unilateral disease and types I and III compared with type II.

Conclusion:
Unilateral and bilateral DRS show considerable differences in gender distribution, associated ocular deviation, overshoots, and ocular and systemic associations.