bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shift in Monocyte Apoptosis with Increasing Viral Load and Change in Apoptosis-Related ISG/Bcl2 Family Gene Expression in Chronically HIV-1-Infected Subjects
Authors: Patro Sean C. , Pal Sharmistha , Bi Yingtao , Lynn Kenneth , Mounzer Karam C. , Kostman Jay R. , Davuluri Ramana V. , Montaner Luis J. 
Published: October 2014

ABSTRACT

Although monocytes and macrophages are targets of HIV-1-mediated immunopathology, the impact of high viremia on activation-induced monocyte apoptosis relative to monocyte and macrophage activation changes remains undetermined. In this study, we determined constitutive and oxidative stress-induced monocyte apoptosis in uninfected and HIV
+
individuals across a spectrum of viral loads (
n =
35; range, 2,243 to 1,355,998 HIV-1 RNA copies/ml) and CD4 counts (range, 26 to 801 cells/mm
3
). Both constitutive apoptosis and oxidative stress-induced apoptosis were positively associated with viral load and negatively associated with CD4, with an elevation in apoptosis occurring in patients with more than 40,000 (4.6 log) copies/ml. As expected, expression of Rb1 and interferon-stimulated genes (ISGs), plasma soluble CD163 (sCD163) concentration, and the proportion of CD14
++
CD16
+
intermediate monocytes were elevated in viremic patients compared to those in uninfected controls. Although CD14
++
CD16
+
frequencies, sCD14, sCD163, and most ISG expression were not directly associated with a change in apoptosis, sCD14 and ISG expression showed an association with increasing viral load. Multivariable analysis of clinical values and monocyte gene expression identified changes in IFI27, IFITM2, Rb1, and Bcl2 expression as determinants of constitutive apoptosis (
P
= 3.77 × 10
−5
; adjusted
R
2
= 0.5983), while changes in viral load, IFITM2, Rb1, and Bax expression were determinants of oxidative stress-induced apoptosis (
P
= 5.59 × 10
−5
; adjusted
R
2
= 0.5996). Our data demonstrate differential activation states in monocytes between levels of viremia in association with differences in apoptosis that may contribute to greater monocyte turnover with high viremia.

IMPORTANCE
This study characterized differential monocyte activation, apoptosis, and apoptosis-related gene expression in low- versus high-level viremic HIV-1 patients, suggesting a shift in apoptosis regulation that may be associated with disease state. Using single and multivariable analysis of monocyte activation parameters and gene expression, we supported the hypothesis that monocyte apoptosis in HIV disease is a reflection of viremia and activation state with contributions from gene expression changes within the ISG and Bcl2 gene families. Understanding monocyte apoptosis response may inform HIV immunopathogenesis, retention of infected macrophages, and monocyte turnover in low- or high-viral-load states.
APOBEC3A Functions as a Restriction Factor of Human Papillomavirus
Authors: Warren Cody J. , Xu Tao , Guo Kejun , Griffin Laura M. , Westrich Joseph A. , Lee Denis , Lambert Paul F. , Santiago Mario L. , Pyeon Dohun 
Published: October 2014

ABSTRACT
Human papillomaviruses (HPVs) are small DNA viruses causally associated with benign warts and multiple cancers, including cervical and head-and-neck cancers. While the vast majority of people are exposed to HPV, most instances of infection are cleared naturally. However, the intrinsic host defense mechanisms that block the early establishment of HPV infections remain mysterious. Several antiviral cytidine deaminases of the human APOBEC3 (hA3) family have been identified as potent viral DNA mutators. While editing of HPV genomes in benign and premalignant cervical lesions has been demonstrated, it remains unclear whether hA3 proteins can directly inhibit HPV infection. Interestingly, recent studies revealed that HPV-positive cervical and head-and-neck cancers exhibited higher rates of hA3 mutation signatures than most HPV-negative cancers. Here, we report that hA3A and hA3B expression levels are highly upregulated in HPV-positive keratinocytes and cervical tissues in early stages of cancer progression, potentially through a mechanism involving the HPV E7 oncoprotein. HPV16 virions assembled in the presence of hA3A, but not in the presence of hA3B or hA3C, have significantly decreased infectivity compared to HPV virions assembled without hA3A or with a catalytically inactive mutant, hA3A/E72Q. Importantly, hA3A knockdown in human keratinocytes results in a significant increase in HPV infectivity. Collectively, our findings suggest that hA3A acts as a restriction factor against HPV infection, but the induction of this restriction mechanism by HPV may come at a cost to the host by promoting cancer mutagenesis.

IMPORTANCE
Human papillomaviruses (HPVs) are highly prevalent and potent human pathogens that cause >5% of all human cancers, including cervical and head-and-neck cancers. While the majority of people become infected with HPV, only 10 to 20% of infections are established as persistent infections. This suggests the existence of intrinsic host defense mechanisms that inhibit viral persistence. Using a robust method to produce infectious HPV virions, we demonstrate that hA3A, but not hA3B or hA3C, can significantly inhibit HPV infectivity. Moreover, hA3A and hA3B were coordinately induced in HPV-positive clinical specimens during cancer progression, likely through an HPV E7 oncoprotein-dependent mechanism. Interestingly, HPV-positive cervical and head-and-neck cancer specimens were recently shown to harbor significant amounts of hA3 mutation signatures. Our findings raise the intriguing possibility that the induction of this host restriction mechanism by HPV may also trigger hA3A- and hA3B-induced cancer mutagenesis.
Conformational Changes in the Adenovirus Hexon Subunit Responsible for Regulating Cytoplasmic Dynein Recruitment
Authors: Scherer Julian , Vallee Richard B. 
Published: October 2014

ABSTRACT
Virus capsids provide genome protection from environmental challenges but are also poised to execute a program of compositional and conformational changes to facilitate virion entry and infection. The most abundant adenovirus serotype 5 (AdV5) capsid protein, hexon, directly recruits the motor protein cytoplasmic dynein following virion entry. Dynein recruitment is crucial for capsid transport to the nucleus and requires the transient exposure of AdV5 hexon to low pH, presumably mimicking passage through the endosomal compartment. These results suggest a pH-dependent capsid modification during early infection. The changes to hexon structure controlling this behavior have not been explored. We report that hexon remains trimeric at low pH but undergoes more subtle conformational changes. These changes are indicated by increased sensitivities to SDS-mediated dissociation and dispase proteolysis. Both effects are reversed at neutral pH, as is dynein binding by low-pH-treated hexon. Dispase cleavage, which we find maps to a specific site within hypervariable region 1 (HVR1) of AdV5 hexon, has no apparent effect on virion entry but completely inhibits its transport to the nucleus. In addition, an AdV5 mutant containing HVR1 of AdV48 is unable to bind dynein and is strongly inhibited in the postentry transport step. These results reveal that conformational changes involving hexon HVR1 are the basis for a novel viral mechanism controlling capsid transport to the nucleus.

IMPORTANCE
The adenovirus serotype 5 (AdV5) capsid protein hexon recruits the molecular motor protein cytoplasmic dynein in a pH-dependent manner, a function critical for efficient transport toward the nucleus and AdV5 infectivity. In this work, we describe how low-pH exposure induces reversible structural changes in AdV5 hexon and how these changes affect dynein binding. In addition, we identified a pH-sensitive dispase cleavage site in hexon HVR1, which depends on the same structural changes and furthermore regulates dynein recruitment and capsid redistribution in infected cells. These data provide the first evidence relating long-known but subtle pH-dependent structural changes in hexon to a more recently established essential but poorly understood role in virus transport. These results have broad implications for understanding virus infectivity in general, and our ability to block the recruitment mechanism has potential therapeutic implications as well.
Improving the accuracy and turn-around time of controlled drug prescribing for patients being discharged home for end-of-life care
Authors: Daniel Suzanne , Patel Janki , Benson Debbie 
Published: October 2014

AbstractMany patients approaching the end of their life express the preference to die at home,[1] although unfortunately the majority of people will still die in hospital.[2] For patients approaching the end of their life, it was noted anecdotally that often those who have expressed a preference to go home from hospital for end of life care may have their discharge delayed due to problems in the prescribing of common medications used to alleviate distressing symptoms at the end of life.An initial audit at Conquest Hospital showed an 89% error rate in these prescriptions, mostly related to prescribing controlled drugs such as morphine and midazolam. A single standardised dispensing chart for commonly prescribed medications at the end of life, in the form of both "Just in Case" medications and syringe driver medications, was created which addressed this problem by having the medications pre-written so as to meet all legal requirements for controlled drugs. The prescriber is able to choose and fill out an appropriate drug and dose by using flow-chart information overleaf and then sign the prescription to allow it to be dispensed. After an initial two month pilot period, a re-audit showed a significant fall in error rate down to 11%, as well as an improvement in turnaround time in dispensing the medications.
Electrochemistry and spectroelectrochemistry of 5,10,15,20-tetrakis(1,3-benzodioxole) porphyrin and its manganese and iron complexes
Authors: Ucoski Geani Maria , Nakagaki Shirley , Nunes Fábio Souza 
Published: October 2014

Cyclic voltammetry and thin-layer spectroelectrochemical properties of the free base 5,10,15,20-tetrakis(1,3-benzodioxole)porphyrin ( H 2 P ), and its manganese and iron complexes ( MnP and FeP , respectively) were studied in dichloromethane with tetra-butyl ammonium hexafluorophosphate (TBAPF6) as supporting electrolyte. The free base undergoes two monoelectronic oxidations at +0.71 and +0.96 V vs. Ag / Ag +, corresponding to the formations of the π-cation radical and dication. Two reductions were observed at -1.53 and -1.87 V corresponding to the formation of π-anion and dianion species. The cyclic voltammograms of the Mn III and Fe III complexes also showed a reversible process centered in the metal ion with E1/2 values at -0.61 and -0.59 V, respectively. In a typical experiment, in situ spectroelectrochemical response showed a decrease of the Soret band at 422 nm, a red shift of the Q-bands, and the new low intensity bands between 800–950 nm range. Structural features and spectroscopic assignments were proposed and discussed based on semi-empirical (molecular mechanics MMFF and ZINDO/S (Zerner method of intermediate neglect of differential overlap for spectroscopy) calculations.
Safety of Targeting ROR1 in Primates with Chimeric Antigen Receptor–Modified T Cells
Authors: Berger Carolina , Sommermeyer Daniel , Hudecek Michael , Berger Michael , Balakrishnan Ashwini , Paszkiewicz Paulina J. , Kosasih Paula L. , Rader Christoph , Riddell Stanley R. 
Published: October 2014

Abstract
Genetic engineering of T cells for adoptive transfer by introducing a tumor-targeting chimeric antigen receptor (CAR) is a new approach to cancer immunotherapy. A challenge for the field is to define cell surface molecules that are both preferentially expressed on tumor cells and can be safely targeted with T cells. The orphan tyrosine kinase receptor ROR1 is a candidate target for T-cell therapy with CAR-modified T cells (CAR-T cells) because it is expressed on the surface of many lymphatic and epithelial malignancies and has a putative role in tumor cell survival. The cell surface isoform of ROR1 is expressed in embryogenesis but absent in adult tissues except for B-cell precursors and low levels of transcripts in adipocytes, pancreas, and lung. ROR1 is highly conserved between humans and macaques and has a similar pattern of tissue expression. To determine if low-level ROR1 expression on normal cells would result in toxicity or adversely affect CAR-T cell survival and/or function, we adoptively transferred autologous ROR1 CAR-T cells into nonhuman primates. ROR1 CAR-T cells did not cause overt toxicity to normal organs and accumulated in bone marrow and lymph node sites, where ROR1-positive B cells were present. The findings support the clinical evaluation of ROR1 CAR-T cells for ROR1+ malignancies and demonstrate the utility of nonhuman primates for evaluating the safety of immunotherapy with engineered T cells specific for tumor-associated molecules that are homologous between humans and nonhuman primates. Cancer Immunol Res; 3(2); 206–16. ©2014 AACR.
Carbon monoxide inhibits sprouting angiogenesis and vascular endothelial growth factor receptor-2 phosphorylation
Authors: Hewett Peter W. , Fujisawa Takeshi , Sissaoui Samir , Cai Meng , Gueron Geraldine , Al-Ani Bahjat , Cudmore Melissa , Ahmed Faraz S. , Wong Michael K. K. , Wegiel Barbara , Otterbein Leo E. , Vítek Libor , Ramma Wenda , Wang Keqing , Ahmed Asif , Ahmad Shakil 
Published: October 2014

SummaryCarbon monoxide (CO) is a gaseous autacoid known to positively regulate vascular tone; however, its role in angiogenesis is unknown. The aim of this study was to investigate the effect of CO on angiogenesis and vascular endothelial growth factor (VEGF) receptor-2 phosphorylation. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor-reduced Matrigel and treated with a CO-releasing molecule (CORM-2) or exposed to CO gas (250 ppm). Here, we report the surprising finding that exposure to CO inhibits vascular endothelial growth factor (VEGF)-induced endothelial cell actin reorganisation, cell proliferation, migration and capillary-like tube formation. Similarly, CO suppressed VEGF-mediated phosphorylation of VEGFR-2 at tyrosine residue 1175 and 1214 and basic fibroblast growth factor- (FGF-2) and VEGF-mediated Akt phosphorylation. Consistent with these data, mice exposed to 250 ppm CO (1h/day for 14 days) exhibited a marked decrease in FGF-2-induced Matrigel plug angiogenesis (p<0.05). These data establish a new biological function for CO in angiogenesis and point to a potential therapeutic use for CO as an anti-angiogenic agent in tumour suppression.
Imaging the elastic modulus of human platelets during thrombininduced activation using scanning ion conductance microscopy
Authors: Rheinlaender Johannes , Vogel Sebastian , Seifert Jan , Schächtele Marc , Borst Oliver , Lang Florian , Gawaz Meinrad , Schäffer Tilman E. 
Published: October 2014

SummaryPlatelet activation plays a critical role in haemostasis and thrombosis. It is well-known that platelets generate contractile forces during activation. However, their mechanical material properties have rarely been investigated. Here, we use scanning ion conductance microscopy (SICM) to visualise morphological and mechanical properties of live human platelets at high spatial resolution. We found that their mean elastic modulus decreases during thrombin-induced activation by about a factor of two. We observed a similar softening of platelets during cytochalasin D-induced cytoskeleton depolymerisation. However, thrombin-induced temporal and spatial modulations of the elastic modulus were substantially different from cytochalasin D-mediated changes. We thereby provide new insights into the mechanics of haemostasis and establish SICM as a novel imaging platform for the ex vivo investigation of the mechanical properties of live platelets.
Increased Congenital Heart Defects in Children Born to Women With Systemic Lupus Erythematosus
Authors: Vinet Évelyne , Pineau Christian A. , Scott Susan , Clarke Ann E. , Platt Robert W. , Bernatsky Sasha 
Published: October 2014

Background—
In a large population-based study, we aimed to determine whether children born to women with systemic lupus erythematosus (SLE) have an increased risk of congenital heart defects (CHDs) in comparison with children born to women without SLE.

Methods and Results—
The Offspring of SLE Mothers Registry (OSLER) includes all women who had ≥1 hospitalization for delivery after SLE diagnosis, identified through Quebec’s healthcare databases (1989–2009), and a randomly selected control group of women, matched ≥4:1 for age and year of delivery. We identified children born live to SLE mothers and their matched controls, and ascertained CHD based on ≥1 hospitalization or physician visit with relevant diagnostic codes, within the first 12 months of life. We performed multivariable logistic regression analyses, using the generalized estimating equation method, to adjust for relevant covariates. Five hundred nine women with SLE had 719 children, whereas 5824 matched controls had 8493 children. In comparison with controls, children born to women with SLE experienced more CHD (5.2% [95% confidence interval (CI), 3.7–7.1] versus 1.9% [95% CI, 1.6–2.2], difference 3.3% [95% CI, 1.9–5.2]). In multivariable analyses, children born to women with SLE had a substantially increased risk of CHD (odds ratio, 2.62; 95% CI, 1.77–3.88) in comparison with controls. In addition, in comparison with controls, offspring of SLE mothers had a substantially increased risk of having a CHD repair procedure (odds ratio, 5.82; 95% CI, 1.77–19.09).

Conclusions—
In comparison with children from the general population, children born to women with SLE have an increased risk of CHD, and an increased risk of having a CHD repair procedure, as well.
The Injection of Zonal Momentum by Buoyancy Forcing in a Southern Ocean Model
Authors: Howard Emma , McC. Hogg Andrew , Waterman Stephanie , Marshall David P. 
Published: October 2014

AbstractAn overturning circulation, driven by prescribed buoyancy forcing, is used to set a zonal volume transport in a reentrant channel ocean model with three isopycnal layers. The channel is designed to represent the Southern Ocean such that the forced overturning resembles the lower limb of the meridional overturning circulation (MOC). The relative contributions of wind and buoyancy forcing to the zonal circulation are examined. It is found that the zonal volume transport is strongly dependent on the buoyancy forcing and that the eddy kinetic energy is primarily set by wind stress forcing. The zonal momentum budget integrated over each layer is considered in the buoyancy-forced, wind-forced, and combined forcing case. At equilibrium, sources and sinks of momentum are balanced, but the transient spinup reveals the source of momentum for the current. In the buoyancy-forced case, the forcing creates a baroclinic shear with westward flow in the lower layer, allowing topographic form stress and bottom friction to act as the initial sources of eastward momentum, with bottom friction acting over a longer time frame. In the wind-forced and combined forcing cases, the surface wind stress dominates the initial momentum budget, and the time to reach equilibration is shorter in the combined forcing simulation. These results imply that future changes in the rate of formation of Antarctic Bottom Water may alter the volume transport of the Antarctic Circumpolar Current.
Factors Associated with Domperidone Use as a Galactogogue at an Australian Tertiary Teaching Hospital
Authors: Grzeskowiak Luke E. , Dalton Julia A. , Fielder Andrea L. 
Published: October 2014

Background: Insufficient milk supply is 1 of the most commonly reported reasons for discontinuation of infant breastfeeding. Although domperidone is often used to improve milk supply, knowledge of factors associated with the use of domperidone in clinical practice is scarce. Objective: This study aimed to examine factors associated with the use of domperidone as a galactogogue at the Women’s and Children’s Hospital (WCH), Adelaide. Methods: A retrospective cohort study was conducted, involving women who delivered live-born singletons (N = 21 914) at the WCH between January 2004 and December 2008. Women dispensed domperidone were identified using WCH pharmacy dispensing records. Maternal and infant clinical data were obtained from the WCH Perinatal Statistics Collection. Relationships between maternal/infant demographic and clinical variables and the use of domperidone were examined through univariate and multivariate logistic regression analyses. Results: Key factors associated with an increased likelihood of women receiving domperidone were increasing maternal age (adjusted odds ratio [aOR] = 1.04; 95% confidence interval [CI], 1.03-1.06), maternal obesity (aOR = 1.41; 95% CI, 1.16-1.77), primiparity (aOR = 1.94; 95% CI, 1.63-2.30), delivery by cesarean section (aOR = 1.31; 95% CI, 1.10-1.55), preterm birth (aOR = 3.54; 95% CI, 2.79-4.50), and neonatal hospitalization (aOR = 2.51; 95% CI, 2.01-3.14). In addition, statistically significant trends were observed between increasing socioeconomic status and year of delivery and an increased likelihood of women receiving domperidone (all Ps < .004). Conclusion: These findings are of clinical importance as they not only reinforce previous findings regarding risk factors for women experiencing lactation difficulties but also highlight the need for improved research regarding the rational and efficacious use of domperidone to improve breastfeeding outcomes.
Validation of the Parenting Stress Index–Short Form With Minority Caregivers
Authors: Lee Sang Jung , Gopalan Geetha , Harrington Donna 
Published: October 2014

Objectives: There has been little examination of the structural validity of the Parenting Stress Index–Short Form (PSI-SF) for minority populations in clinical contexts in the Unites States. This study aimed to test prespecified factor structures (one-factor, two-factor, and three-factor models) of the PSI-SF. Methods: This study used confirmatory factor analysis in a sample of 240 predominantly Black and Latino caregivers of children with behavioral difficulties. Results: The three-factor model fit was reasonable, and the criterion validity for the subscale and total scores was good supporting continued cautious use of the PSI-SF for clinical minority populations. Conclusions: The PSI-SF could be integrated as part of screening and intake assessment procedures, which could allow social work practitioners to make more informed decisions about treatment planning, as well as facilitate conversations with caregivers around identifying sources of stress and developing healthy coping strategies.
Transferrin-targeted magnetic/fluorescence micelles as a specific bi-functional nanoprobe for imaging liver tumor
Authors: Qi Hui , Li Zhengzheng , Du Kai , Mu Ketao , Zhou Qing , Liang Shuyan , Zhu Wenzhen , Yang Xiangliang , Zhu Yanhong 
Published: October 2014

Abstract
In order to delineate the location of the tumor both before and during operation, we developed targeted bi-functional polymeric micelles for magnetic resonance (MR) and fluorescence imaging in liver tumors. Hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) were loaded into the polymeric micelles through self-assembly of an amphiphilic block copolymer poly(ethylene glycol)-poly(ϵ-caprolactone). After, transferrin (Tf) and near-infrared fluorescence molecule Cy5.5 were conjugated onto the surface of the polymeric micelles to obtain the nanosized probe SPIO@PEG-b-PCL-Tf/Cy5.5 (SPPTC). Imaging capabilities of this nanoprobe were evaluated both in vitro and in vivo. The accumulation of SPPTC in HepG2 cells increased over SPIO@PEG-b-PCL-Cy5.5 (SPPC) by confocal microscopy. The targeted nanoprobe SPPTC possessed favorable properties on the MR and fluorescence imaging both in vitro and in vivo. The MTT results showed that the nanoprobes were well tolerated. SPPTC had the potential for pre-operation evaluation and intra-operation navigation of tumors in clinic.