bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Antagonism of Rhesus Macaque and Chimpanzee BST-2 by HIV-1 Vpu Is Mediated by Cytoplasmic Domain Interactions
Authors: Yoshida Takeshi , Koyanagi Yoshio , Strebel Klaus 
Published: October 2013

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) Vpu enhances the release of viral particles from infected cells by interfering with the function of BST-2/tetherin, a cellular protein inhibiting virus release. The Vpu protein encoded by NL4-3, a widely used HIV-1 laboratory strain, antagonizes human BST-2 but not monkey or murine BST-2, leading to the conclusion that BST-2 antagonism by Vpu is species specific. In contrast, we recently identified several primary Vpu isolates, such as Vpu of HIV-1
DH12
, capable of antagonizing both human and rhesus BST-2. Here we report that while Vpu interacts with human BST-2 primarily through their respective transmembrane domains, antagonism of rhesus BST-2 by Vpu involved an interaction of their cytoplasmic domains. Importantly, a Vpu mutant carrying two mutations in its transmembrane domain (A
14
L and W
22
A), rendering it incompetent for interaction with human BST-2, was able to interact with human BST-2 carrying the rhesus BST-2 cytoplasmic domain and partially neutralized the ability of this BST-2 variant to inhibit viral release. Bimolecular fluorescence complementation analysis to detect Vpu–BST-2 interactions suggested that the physical interaction of Vpu with rhesus or chimpanzee BST-2 involves a 5-residue motif in the cytoplasmic domain of BST-2 previously identified as important for the antagonism of monkey and great ape BST-2 by simian immunodeficiency virus (SIV) Nef. Thus, our study identifies a novel mechanism of antagonism of monkey and great ape BST-2 by Vpu that targets the same motif in BST-2 used by SIV Nef and might explain the expanded host range observed for Vpu isolates in our previous study.
Evolution of a Self-Inducible Cytolethal Distending Toxin Type V-Encoding Bacteriophage from Escherichia coli O157:H7 to Shigella sonnei
Authors: Allué-Guardia Anna , Imamovic Lejla , Muniesa Maite 
Published: October 2013

ABSTRACT

Some
cdt
genes are located within the genome of inducible or cryptic bacteriophages, but there is little information about the mechanisms of
cdt
transfer because of the reduced number of inducible Cdt phages described. In this study, a new self-inducible
Myoviridae
Cdt phage (ΦAA91) was isolated from a nonclinical O157:H7 Shiga toxin-producing
Escherichia coli
strain and was used to lysogenize a
cdt
-negative strain of
Shigella sonnei
. We found that the phage induced from
S. sonnei
(ΦAA91-ss) was not identical to the original phage. ΦAA91-ss was used to infect a collection of 57 bacterial strains, was infectious in 59.6% of the strains, and was able to lysogenize 22.8% of them. The complete sequence of ΦAA91-ss showed a 33,628-bp genome with characteristics of a P2-like phage with the
cdt
operon located near the
cosR
site. We found an IS
21
element composed of two open reading frames inserted within the
cox
gene of the phage, causing gene truncation. Truncation of
cox
does not affect lytic induction but could contribute to phage recombination and generation of lysogens. The IS
21
element was not present in the ΦAA91 phage from
E. coli
, but it was incorporated into the phage genome after its transduction in
Shigella
. This study shows empirically the evolution of temperate bacteriophages carrying virulence genes after infecting a new host and the generation of a phage population with better lysogenic abilities that would ultimately lead to the emergence of new pathogenic strains.
Efficiency of Cell-Free and Cell-Associated Virus in Mucosal Transmission of Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus
Authors: Kolodkin-Gal Dror , Hulot Sandrine L. , Korioth-Schmitz Birgit , Gombos Randi B. , Zheng Yi , Owuor Joshua , Lifton Michelle A. , Ayeni Christian , Najarian Robert M. , Yeh Wendy W. , Asmal Mohammed , Zamir Gideon , Letvin Norman L. 
Published: October 2013

ABSTRACT

Effective strategies are needed to block mucosal transmission of human immunodeficiency virus type 1 (HIV-1). Here, we address a crucial question in HIV-1 pathogenesis: whether infected donor mononuclear cells or cell-free virus plays the more important role in initiating mucosal infection by HIV-1. This distinction is critical, as effective strategies for blocking cell-free and cell-associated virus transmission may be different. We describe a novel
ex vivo
model system that utilizes sealed human colonic mucosa explants and demonstrate in both the
ex vivo
model and
in vivo
using the rectal challenge model in rhesus monkeys that HIV-1-infected lymphocytes can transmit infection across the mucosa more efficiently than cell-free virus. These findings may have significant implications for our understanding of the pathogenesis of mucosal transmission of HIV-1 and for the development of strategies to prevent HIV-1 transmission.
Endovascular treatment of intracranial aneurysms with detachable coils: correlation between aneurysm volume, packing, and angiographic recurrence
Authors: Leng Bing , Zheng Yongtao , Ren Jinma , Xu Qiang , Tian Yanlong , Xu Feng 
Published: October 2013

Background and purposeThe relationship between dense packing and incidence of angiographic recurrence after endovascular treatment of intracranial aneurysms has been shown but remains controversial. We retrospectively analyzed intracranial aneurysms treated with detachable coils to determine the relation between aneurysm volume, packing, and recurrence.MethodsWe reviewed 221 aneurysms in 199 patients who underwent endovascular coiling using detachable coils from November 2009 to December 2011. Aneurysm volumes were determined using three-dimensional images obtained from rotational angiography. Aneurysm packing was defined as the ratio between the volume of coils inserted and the volume of aneurysm. At follow-up, angiographic results were dichotomized into presence or absence of recurrence. The relationship between aneurysm volume to fill, packing, and angiographic recurrence was determined by multivariable logistic regression.ResultsFollow-up angiography (mean follow-up 8.8 months) revealed recurrence in 14.5% of the aneurysms studied in our series. Recurrent aneurysms had a mean packing of 15.1% while stable aneurysms (non-recurrent) had a mean packing of 23.7%. Multivariable logistic regression analysis showed that aneurysm volume and packing were significantly associated with angiographic recurrence. Large volume aneurysms (>600 mm3) were found to have a higher incidence of recurrence than those with small volumes (OR=30.49, p<0.001). Compared with those with high packing (≥20%), the less packed aneurysms (<20%) had a higher incidence of recurrence (OR=29.01, p=0.002). There was no significant difference between aneurysm location, clinical presentation, stent assistance, duration of follow-up, and recurrence.ConclusionsCoiling large volume (>600 mm3) intracranial aneurysms are more likely to have a recurrence than small ones. High packing (≥20%) provides better protection against recurrence of the aneurysm.
Selective Disruption of Rb–Raf-1 Kinase Interaction Inhibits Pancreatic Adenocarcinoma Growth Irrespective of Gemcitabine Sensitivity
Authors: Treviño José G. , Verma Monika , Singh Sandeep , Pillai Smitha , Zhang Dongyu , Pernazza Daniele , Sebti Said M. , Lawrence Nicholas J. , Centeno Barbara A. , Chellappan Srikumar P. 
Published: October 2013

Abstract
Inactivation of the retinoblastoma (Rb) tumor suppressor protein is widespread in human cancers. Inactivation of Rb is thought to be initiated by association with Raf-1 (C-Raf) kinase, and here we determined how RRD-251, a disruptor of the Rb–Raf-1 interaction, affects pancreatic tumor progression. Assessment of phospho-Rb levels in resected human pancreatic tumor specimens by immunohistochemistry (n = 95) showed that increased Rb phosphorylation correlated with increasing grade of resected human pancreatic adenocarcinomas (P = 0.0272), which correlated with reduced overall patient survival (P = 0.0186). To define the antitumor effects of RRD-251 (50 μmol/L), cell-cycle analyses, senescence, cell viability, cell migration, anchorage-independent growth, angiogenic tubule formation and invasion assays were conducted on gemcitabine-sensitive and -resistant pancreatic cancer cells. RRD-251 prevented S-phase entry, induced senescence and apoptosis, and inhibited anchorage-independent growth and invasion (P &lt; 0.01). Drug efficacy on subcutaneous and orthotopic xenograft models was tested by intraperitoneal injections of RRD-251 (50 mg/kg) alone or in combination with gemcitabine (250 mg/kg). RRD-251 significantly reduced tumor growth in vivo accompanied by reduced Rb phosphorylation and lymph node and liver metastasis (P &lt; 0.01). Combination of RRD-251 with gemcitabine showed cooperative effect on tumor growth (P &lt; 0.01). In conclusion, disruption of the Rb–Raf-1 interaction significantly reduces the malignant properties of pancreatic cancer cells irrespective of their gemcitabine sensitivity. Selective targeting of Rb–Raf-1 interaction might be a promising strategy targeting pancreatic cancer. Mol Cancer Ther; 12(12); 2722–34. ©2013 AACR.
Microtubule Dynamics Control Tail Retraction in Migrating Vascular Endothelial Cells
Authors: Ganguly Anutosh , Yang Hailing , Zhang Hong , Cabral Fernando , Patel Kamala D. 
Published: October 2013

Abstract
Drugs that target microtubules are potent inhibitors of angiogenesis, but their mechanism of action is not well understood. To explore this, we treated human umbilical vein endothelial cells with paclitaxel, vinblastine, and colchicine and measured the effects on microtubule dynamics and cell motility. In general, lower drug concentrations suppressed microtubule dynamics and inhibited cell migration whereas higher concentrations were needed to inhibit cell division; however, surprisingly, large drug-dependent differences were seen in the relative concentrations needed to inhibit these two processes. Suppression of microtubule dynamics did not significantly affect excursions of lamellipodia away from the nucleus or prevent cells from elongating; but, it did inhibit retraction of the trailing edges that are normally enriched in dynamic microtubules, thereby limiting cell locomotion. Complete removal of microtubules with a high vinblastine concentration caused a loss of polarity that resulted in roundish, rather than elongated, cells, rapid but nondirectional membrane activity, and little cell movement. The results are consistent with a model in which more static microtubules stabilize the leading edge of migrating cells, whereas more dynamic microtubules locate to the rear where they can remodel and allow tail retraction. Suppressing microtubule dynamics interferes with tail retraction, but removal of microtubules destroys the asymmetry needed for cell elongation and directional motility. The prediction that suppressing microtubule dynamics might be sufficient to prevent angiogenesis was supported by showing that low concentrations of paclitaxel could prevent the formation of capillary-like structures in an in vitro tube formation assay. Mol Cancer Ther; 12(12); 2837–46. ©2013 AACR.
Effect of F8 B domain gene variants on synthesis, secretion, activity and stability of factor VIII protein
Authors: Pahl Saskia , Pavlova Anna , Driesen Julia , Oldenburg Johannes 
Published: October 2013

SummaryThe B domain of the coagulation factor (F)VIII comprises some unique characteristics. Though the B domain is important for processing, intracellular transport and secretion of FVIII protein, its role in the coagulation still remains unclear. This study aims to investigate the influence of 19 reported B domain variants on quantity and quality of expressed FVIII protein. F8 variants were transiently expressed in HEK293T cells. Media and cell lysates were collected after 72 hours. FVIII synthesis, relative secretion, activity and thermostability were analysed in comparison to FVIII wild-type. Eleven of 19 analysed B domain variants showed normal FVIII activity (FVIII:C), and antigen values (40–150 %). Eight variants exhibited a decreased FVIII:C, corresponding to a mild phenotype most likely due to impaired expression and secretion mechanism, reduced thermostability or combined mechanisms. One variant, p.His1066Tyr, showed markedly reduced FVIII antigen in cell lysate. The variants p.Asp845Glu, p.His998Gln, and p.Ala1610Ser revealed a significantly decreased relative secretion. Additionally, six B domain variants significantly reduced stability of FVIII. In conclusion, none of the analysed missense mutations was causative for a severe haemophilia A (HA) phenotype. Nevertheless, the mutations p.Asp845Glu, p.Pro947Arg, p.Glu1057Lys, p.His1066Tyr, p.Arg1126Trp, p.Arg1329His, p.Leu1481Pro, and p.Ala1610Ser resulted in decreased FVIII:C values that may explain mild HA phenotypes.
A novel natural mutation AαPhe98Ile in the fibrinogen coiled-coil affects fibrinogen function
Authors: Riedelová-Reicheltová Zuzana , Kotlín Roman , Suttnar Jiří , Geierová Věra , Riedel Tomáš , Májek Pavel , Dyr Jan Evangelista 
Published: October 2013

SummaryThe aim of this study was to investigate the structure and function of fibrinogen obtained from a patient with normal coagulation times and idiopathic thrombophilia. This was done by SDS-PAGE and DNA sequence analyses, scanning electron microscopy, fibrinopeptide release, fibrin polymerisation initiated by thrombin and reptilase, fibrinolysis, and platelet aggregometry. A novel heterozygous point mutation in the fibrinogen Aα chain, Phe98 to Ile, was found and designated as fibrinogen Vizovice. The mutation, which is located in the RGDF sequence (Aα 95–98) of the fibrinogen coiled-coil region, significantly affected fibrin clot morphology. Namely, the clot formed by fibrinogen Vizovice contained thinner and curled fibrin fibers with reduced length. Lysis of the clots prepared from Vizovice plasma and isolated fibrinogen were found to be impaired. The lysis rate of Vizovice clots was almost four times slower than the lysis rate of control clots. In the presence of platelets agonists the mutant fibrinogen caused increased platelet aggregation. The data obtained show that natural mutation of Phe98 to Ile in the fibrinogen Aα chain influences lateral aggregation of fibrin protofibrils, fibrinolysis, and platelet aggregation. They also suggest that delayed fibrinolysis, together with the abnormal fibrin network morphology and increased platelet aggregation, may be the direct cause of thrombotic complications in the patient associated with pregnancy loss.
Pharmacological modulation of procoagulant microparticles improves haemodynamic dysfunction during septic shock in rats
Authors: Boisramé-Helms Julie , Delabranche Xavier , Degirmenci Su-Emmanuelle , Zobairi Fatiha , Berger Asael , Meyer Grégory , Burban Mélanie , Mostefai Hadj-Ahmed , Levy Bruno , Toti Florence , Meziani Ferhat 
Published: October 2013

SummaryCirculating microparticles play a pro-inflammatory and procoagulant detrimental role in the vascular dysfunction of septic shock. It was the objective of this study to investigate mechanisms by which a pharmacological modulation of microparticles could affect vascular dysfunction in a rat model of septic shock. Septic or sham rats were treated by activated protein C (aPC) and resuscitated during 4 hours. Their microparticles were harvested and inoculated to another set of healthy recipient rats. Haemodynamic parameters were monitored, circulating total procoagulant microparticles assessed by prothrombinase assay, and their cell origin characterised. Mesenteric resistance arteries, aorta and heart were harvested for western blotting analysis. We found that a) the amount and phenotype of circulating microparticles were altered in septic rats with an enhanced endothelial, leucocyte and platelet contribution; b) aPC treatment significantly reduced the generation of leucocyte microparticles and norepinephrine requirements to reach the mean arterial pressure target in septic rats; c) Microparticles from untreated septic rats, but not from aPC-treated ones, significantly reduced the healthy recipients’ mean arterial pressure; d) Microparticle thromboxane content and aPC activity were significantly increased in aPC-treated septic rats. In inoculated naïve recipients, microparticles from aPC-treated septic rats prompted reduced NF-κB and cyclooxygenase-2 arterial activation, blunted the generation of pro-inflammatory iNOS and secondarily increased platelet and endothelial microparticles. In conclusion, in this septic shock model, increased circulating levels of procoagulant microparticles led to negative haemodynamic outcomes. Pharmacological treatment by aPC modified the cell origin and levels of circulating microparticles, thereby limiting vascular inflammation and favouring haemodynamic improvement.
Mandatory contrast-enhanced venography to detect deep-vein thrombosis (DVT) in studies of DVT prophylaxis: upsides and downsides
Authors: Hirsh Jack , Ginsberg Jeffrey S. , Chan Noel , Guyatt Gordon , Eikelboom John W. 
Published: October 2013

SummaryThe introduction of venography into patient care was a major advance because it was the first accurate method for the diagnosis of DVT. Compression ultrasound has since become the preferred test for patients with suspected DVT because, unlike venography, it is simple, non-invasive and widely available. Venography has facilitated the development and approval of new anticoagulants and remains widely used as an efficacy outcome in trials of venous thromboembolism prevention. Most thrombi detected by screening venography are, however, small and unimportant for patients. In order to calculate the trade-off between an asymptomatic thrombus and a bleed we require an estimate of the number of asymptomatic thrombi that must be prevented to avoid a patient-important thrombus. A credible estimate of this ratio is not available. Therefore when used as a measure of efficacy in trials of thromboprophylaxis, venography has limitations for comparing the relative effects of alternative antithrombotic agents on outcomes important to patients.
Epicardial Ablation of Ventricular Tachycardia in Ischemic Heart Disease
Authors: Sarkozy Andrea , Tokuda Michifumi , Tedrow Usha B. , Sieria Juan , Michaud Gregory F. , Couper Gregory S. , John Roy , Stevenson William G. 
Published: October 2013

Background—
Epicardial approaches have increased ablation success in nonischemic cardiomyopathy, but the use for postinfarction ventricular tachycardias (VT) is less clear. We report the findings for epicardial VT ablation in postinfarct patients.

Methods and Results—

Records of 444 consecutive patients with VT because of prior infarction referred for 600 catheter ablation procedures were reviewed. Epicardial procedures were performed in the electrophysiology laboratory in 56 (13%) patients using percutaneous (43 patients) or surgical (13 patients) epicardial access. In 7 patients, epicardial ablation was performed surgically in the operating room. In the electrophysiology laboratory epicardial VT targets were identified in 38 (68%) patients and epicardial ablation abolished ≥1 VT in 27 patients (6% of the total study population); inducibility was not tested after ablation in 4, and VT remained inducible in 7 patients. No ablation was performed in 18 (32%) patients because of no accessible epicardial target or a complication. Major complications occurred in 8 (14%) of the 57 electrophysiology laboratory procedures. After the first procedure any VT recurred in 21 (54%) of 39 patients who had epicardial ablation compared with 164 (47%) of 347 endocardial-only ablation patients (
P
=0.35).

Conclusions—
Epicardial ablation is potentially useful in ≥6% of the postinfarction VT population, but the number could be substantially greater because more than two thirds of patients selected for epicardial mapping after failed ablation had an epicardial VT target. Successful epicardial ablation of a VT was not predictable from infarct location or other patient characteristics.
What’s New About Muslim Ismaili Transnationalism? Comparing Business Practices in British East Africa, Colonial Mozambique and Contemporary Angola
Authors: Trovão Susana Salvaterra , Batoréu Filomena 
Published: October 2013

Abstract
The way in which the history of colonialism might link up with the formation of postcolonial migrant identities remains insufficiently examined. Through a comparison between transnational business practices of Khoja Ismaili Muslim settled in the British and Portuguese colonial territories of East Africa and in contemporary Angola, the present paper aims to discuss the impact of colonial experiences in the configuration of postcolonial business cultures. Articulating several guiding empirical questions, we will attempt to show that the continuing centrality of the nation-states in which Ismaili transnational economic activities are embedded, the notion of a disadvantageous network closure, concomitant with the importance of face-to-face contacts, the mutual trust and understanding sustained through personal relations, and the tendency for national loyalty to prevail over religious belonging (whenever any potential conflict between the two exists) constitute crucial dimensions of an accumulated colonial knowledge which is significant in the analysis of the Ismaili competitive advantage in postcolonial Africa. This argument will be developed on the basis of a multi-sited ethnographic research. The U.K. and Portugal emerged as a strategic passage for our encounters with East African Ismailis from former British and Portuguese colonial territories. The current Angolan context, absent from the available literature, was selected as a postcolonial term of comparison.
Comparing Peer Reviews: The Universal Periodic Review of the UN Human Rights Council and the African Peer Review Mechanism
Authors: McMahon Edward R. , Busia Kojo , Ascherio Marta 
Published: October 2013

Abstract
The Universal Periodic Review Mechanism (UPR) of the UN Human Rights Council and the African Peer Review Mechanism (APRM) reflect a growing trend in international organizations to utilize peer review processes to assess and improve member state governance and human rights performance. The two mechanisms are distinct in many ways. For example, the APRM undertakes a more in-depth and rigorous examination of a broader range of issues. Both review mechanisms, however, also have similarities e.g. they emphasize follow-up and actions to be taken as a result of the reviews and are products of a consensus decision-making process based on voluntary engagement. They represent an evolutionary process by which international norms can be integrated in a national context.
The Return of the Natives: Asian Diaspora Issues and Dilemmas – The Case of India
Authors: Varshney Deepanjana 
Published: October 2013

Abstract
The research paper probes into the reverse migrants’ psychological dimensions and provides insights on their motivational dynamics. Key demographic variables are taken into consideration and the respondents’ perception towards own life cycle stage, the foreign country and the home country provides salient insights on the reverse migration literature. I have, in this empirical paper, correlated demographic variables with select reverse migration factors and have offered plausible reasons and underlying forces behind the return of Indian expatriates abroad. I present the argument in my paper that the underlying causes for return migration are the same globally irrespective of the country of present residence.