bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Immunodeficiency Virus Type 1 Capsid Mutation N74D Alters Cyclophilin A Dependence and Impairs Macrophage Infection
Authors: Ambrose Zandrea , Lee KyeongEun , Ndjomou Jean , Xu Hongzhan , Oztop Ilker , Matous James , Takemura Taichiro , Unutmaz Derya , Engelman Alan , Hughes Stephen H. , KewalRamani Vineet N. 
Published: February 2012

ABSTRACT
The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages.
Passively Transmitted gp41 Antibodies in Babies Born from HIV-1 Subtype C-Seropositive Women: Correlation between Fine Specificity and Protection
Authors: Diomede L. , Nyoka S. , Pastori C. , Scotti L. , Zambon A. , Sherman G. , Gray C. M. , Sarzotti-Kelsoe M. , Lopalco L. 
Published: February 2012

ABSTRACT

HIV-exposed, uninfected (EUN) babies born to HIV-infected mothers are examples of natural resistance to HIV infection. In this study, we evaluated the titer and neutralizing potential of gp41-specific maternal antibodies and their correlation with HIV transmission in HIV-infected mother-child pairs. Specific gp41-binding and -neutralizing antibodies were determined in a cohort of 74 first-time mother-child pairs, of whom 40 mothers were infected with HIV subtype C. Within the infected mother cohort, 16 babies were born infected and 24 were PCR negative and uninfected at birth (i.e., exposed but uninfected). Thirty-four HIV-uninfected and HIV-unexposed mother-child pairs were included as controls. All HIV-positive mothers and their newborns showed high IgG titers to linear epitopes within the HR1 region and to the membrane-proximal (MPER) domain of gp41; most sera also recognized the disulfide loop immunodominant epitope (IDE). Antibody titers to the gp41 epitopes were significantly lower in nontransmitting mothers (
P
< 0.01) and in the EUN babies (
P
< 0.005) than in HIV-positive mother-child pairs. Three domains of gp41, HR1, IDE, and MPER, elicited antibodies that were effectively transmitted to EUN babies. Moreover, in EUN babies, epitopes overlapping the 2F5 epitope (ELDKWAS), but not the 4E10 epitope, were neutralization targets in two out of four viruses tested. Our findings highlight important epitopes in gp41 that appear to be associated with exposure without infection and would be important to consider for vaccine design.
HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes
Authors: Tong Tommy , Crooks Ema T. , Osawa Keiko , Binley James M. 
Published: February 2012

ABSTRACT

Hypothetically, since native HIV-1 Env trimers are exclusively recognized by neutralizing antibodies, they might induce the neutralizing antibodies in a vaccine setting. This idea has not been evaluated due to the difficulty of separating trimers from nonfunctional Env (uncleaved gp160 and gp41 stumps). The latter are immunodominant and induce nonneutralizing antibodies. We previously showed that nonfunctional Env can be selectively cleared from virus-like particle (VLP) surfaces by enzyme digests (E. T. Crooks, T. Tong
,
K. Osawa, and J. M. Binley, J.Virol. 85:5825, 2011). Here, we investigated the effects of these digests on the antigenicity of VLPs and their sensitivity to neutralization. Before digestion, WT VLPs (bearing wild-type Env) and UNC VLPs (bearing uncleaved gp160) were recognized by various Env-specific monoclonal antibodies (MAbs), irrespective of their neutralizing activity, a result which is consistent with the presence of nonfunctional Env. After digestion, only neutralizing MAbs recognized WT VLPs, consistent with selective removal of nonfunctional Env (i.e., “trimer VLPs”). Digests eliminated the binding of all MAbs to UNC VLPs, again consistent with removal of nonfunctional Env. An exception was MAb 2F5, which weakly bound to digested UNC VLPs and bald VLPs (bearing no Env), perhaps due to lipid cross-reactivity. Trimer VLPs were infectious, and their neutralization sensitivity was largely comparable to that of undigested WT VLPs. However, they were ∼100-fold more sensitive to the MAbs 4E10 and Z13e1, suggesting increased exposure of the gp41 base. Importantly, a scatterplot analysis revealed a strong correlation between MAb binding and neutralization of trimer VLPs. This suggests that trimer VLPs bear essentially pure native trimer that should allow its unfettered evaluation in a vaccine setting.
Virus-Activated Interferon Regulatory Factor 7 Upregulates Expression of the Interferon-Regulated
BST2
Gene Independently of Interferon Signaling
Authors: Bego Mariana G. , Mercier Johanne , Cohen Éric A. 
Published: February 2012

ABSTRACT

BST-2/tetherin is an interferon (IFN)-inducible host restriction factor that inhibits the release of many enveloped viruses and functions as a negative-feedback regulator of IFN production by plasmacytoid dendritic cells. Currently, mechanisms underlying
BST2
transcriptional regulation by type I IFN remain largely unknown. Here, we demonstrate that the
BST2
promoter is a secondary target of the IFN cascade and show that a single IRF binding site is sufficient to render this promoter responsive to IFN-α. Interestingly, expression of IRF-1 or virus-activated forms of IRF-3 and IRF-7 stimulated the
BST2
promoter even under conditions where type I IFN signaling was inhibited. Indeed, vesicular stomatitis virus could directly upregulate BST-2 during infection of mouse embryonic fibroblasts through a process that required IRF-7 but was independent from the type I IFN cascade; however, in order to achieve optimal BST-2 induction, the type I IFN cascade needed to be engaged through activation of IRF-3. Furthermore, using human peripheral blood mononuclear cells, we show that BST-2 upregulation is part of an early intrinsic immune response since TLR8 and TLR3 agonists, known to trigger pathways that mediate activation of IRF proteins, could upregulate BST-2 prior to engagement of the type I IFN pathway. Collectively, our findings reveal that
BST2
is activated by the same signals that trigger type I IFN production, outlining a regulatory mechanism ensuring that production of type I IFN and expression of a host restriction factor involved in the IFN negative-feedback loop are closely coordinated.
Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design
Authors: Bonsignori Mattia , Montefiori David C. , Wu Xueling , Chen Xi , Hwang Kwan-Ki , Tsao Chun-Yen , Kozink Daniel M. , Parks Robert J. , Tomaras Georgia D. , Crump John A. , Kapiga Saidi H. , Sam Noel E. , Kwong Peter D. , Kepler Thomas B. , Liao Hua-Xin , Mascola John R. , Haynes Barton F. 
Published: February 2012

ABSTRACT
Plasma from a small subset of subjects chronically infected with HIV-1 shows remarkable magnitude and breadth of neutralizing activity. From one of these individuals (CH0219), we isolated two broadly neutralizing antibodies (bnAbs), CH01 and VRC-CH31, from two clonal lineages of memory B cells with distinct specificities (variable loop 1 and 2 [V1V2] conformational specificity and CD4-binding site specificity, respectively) that recapitulate 95% of CH0219 serum neutralization breadth. These data provide proof of concept for an HIV-1 vaccine that aims to elicit bnAbs of multiple specificities.
Cheese can reduce indexes that estimate fatty acid desaturation. Results from the Oslo Health Study and from experiments with human hepatoma cells
Authors: Høstmark Arne T. , Lunde Marianne S.H. 
Published: February 2012

Previously, cheese intake was shown to be inversely related to serum triglycerides, raising the possibility that cheese might inhibit triglyceride synthesis, which is governed by fatty acid desaturases. Therefore, analyses were done to study whether cheese intake was associated with indexes that reflect fatty acid desaturation in 121 healthy ethnic Norwegians aged 40–45 years, a subsample from the Oslo Health Study (N = 18 777). Experiments with human hepatoma cells (HepG2) were done to clarify whether cheese might have a causal effect on desaturases. Fatty acid distribution in lipids of human sera and HepG2 cells was determined by gas chromatography. Δ9-Desaturase was estimated by the (16:1,n-7)/(16:0) and (18:1,n-9)/(18:0) ratios, abbreviated ds9_1 and ds9_2, and Δ5-desaturase (ds5) by the (20:4,n-6)/(18:2,n-6) ratio. Correlation, ANOVA, and multiple linear regression models were used to study associations. Oslo Health Study: Subjects with cheese intake >4–6 times per week had 33% lower ds9_1 and 16% lower ds5 than subjects with intake ≤ 4–6 times per week. The cheese intake vs. ds5 association prevailed when adjusting for sex, time since last meal, fatty fish, vegetables, fruit–berries, fruit juice, cod liver oil, coffee, alcohol, body mass index, physical activity, length of education, and smoking. HepG2 cells: An ethanol extract of Jarlsberg cheese lowered the desaturase indexes. Inhibition of ds9_1 increased with increasing amount cheese extract added. Thus, cheese may contain inhibitors of desaturases, thereby providing an explanation for the previously reported negative association between cheese intake and triglycerides.
High-power resistance exercise induces MAPK phosphorylation in weightlifting trained men
Authors: Galpin Andrew J. , Fry Andrew C. , Chiu Loren Z.F. , Thomason Donald B. , Schilling Brian K. 
Published: February 2012

Power is critical to muscle performance, specifically in athletic populations. Mitogen-activated protein kinase (MAPK) pathways (extracellular signal-regulated protein kinase (ERK 1/2), p38, and c-Jun NH2-terminal kinase (JNK)) are intracellular signal transduction mechanisms that partially regulate exercise-induced skeletal muscle alterations. These pathways are highly responsive to exercise, but their reaction to high power, multi-joint resistance exercise is yet to be examined. Nine weightlifting-trained men performed 15 sets of three repetitions of a dynamic clean pull exercise at 85% of their one repetition maximum. Vastus lateralis biopsies were obtained prior to (pre) and after the 8th (mid) and 15th set (post) of exercise. Three subjects returned to serve as non-exercising controls for a similar sequence of biopsies (CON). The ratio of phosphorylated MAPK to total MAPK increased significantly for p38 (3.0 fold, p < 0.05) and JNK (2.4 fold, p < 0.05) by the mid biopsy. ERK 1/2 phosphorylation followed a similar trend (2.3 fold) (p = 0.052). The ratio of phosphorylation to total MAPK did not differ from mid to post biopsy. None of the pathways were phosphorylated above resting in the CON condition (p > 0.05), and thus the biopsy procedure itself did not account for the entire increase in MAPK phosphorylation during EX. These data indicate MAPK pathways are activated early and remain elevated throughout the duration of high power resistance exercise. These findings help describe the mechanisms partially responsible for chronic adaptations in response to high intensity, high power resistance training in humans.
A short bout of stair climbing–descending exercise attenuates postprandial hyperglycemia in middle-aged males with impaired glucose tolerance
Authors: Takaishi Tetsuo , Imaeda Kenro , Tanaka Tsutomu , Moritani Toshio , Hayashi Tatsuya 
Published: February 2012

Exercise is a useful modality to ameliorate postprandial hyperglycemia. Here we show that a short bout (∼6 min) of stair climbing–descending exercise (STAIR) starting at 90 min after meal accelerates the decrease in blood glucose concentrations in middle-aged sedentary men with impaired glucose tolerance, although STAIR is easy to perform and keeps the exercise intensity at a moderate level.
Use of vitamin and mineral supplements in long-term care home residents
Authors: Viveky Navita , Toffelmire Lynda , Thorpe Lilian , Billinsky Jennifer , Alcorn Jane , Hadjistavropoulos Thomas , Whiting Susan J. 
Published: February 2012

Vitamin–mineral supplementation may offer older adults health and cognition-related benefits but overuse may contribute to polypharmacy. We examined the prevalence of supplement usage in long-term care facility (LTC) residents (≥65 years of age). As cognition may be affected by nutrition, we also examined use in those with diagnosis of dementia and those with no dementia diagnosis. The prevalence of supplement usage and overall “pill count” from pharmaceutical use was assessed in 189 LTC residents and a subsample of 56 older adults with dementia diagnosis, respectively. Participants were residing in an LTC facility of a mid-size metropolitan area during 2009. The average use of supplements was 1.0 per day for all residents, with 35% taking vitamin D supplements, 20% multivitamins, and 26% calcium. Supplement use was similar (p ≥ 0.05) for those with dementia diagnosis (53%, average 2.0 per day) and for those without such diagnosis (45%, average 2.2 per day). Usage ranged between 1–6 supplements per day. In both of these groups, ∼73% of users were taking vitamin D. The number of prescribed medications ranged from 4 to 24 (average 10.2) in a subsample of residents whose supplement intake was 0 to 6 (average 2). These findings suggest an overall low rate of supplement use, with no significant differences (p ≥ 0.05) in use between residents with and without dementia diagnosis. However, some residents were at risk for supplement overuse.
Type 1 diabetes impairs vitamin B6 metabolism at an early stage of women’s adulthood
Authors: Massé Priscilla G. , Boudreau Jaclyn , Tranchant Carole C. , Ouellette Rodney , Ericson Karen L. 
Published: February 2012

Vitamin B6 (pyridoxine) metabolism in diabetes has never been investigated except for a few reports on plasma pyridoxal 5′-phosphate (PLP). These studies indicated that this most active (coenzyme) vitamer can be reduced. The present clinical investigation aimed to measure all vitamers in blood and urine by high performance liquid chromatography as well as important related factors, in women during active reproductive years. Thirty-two insulin-treated type 1 diabetic (T1D) patients, without renal complication, and 27 well-matched healthy controls, aged 30 to 40 years old, were recruited using rigorous criteria. Both groups had normal hemoglobin and serum albumin levels. Plasma PLP and pyridoxal (PL) did not differ significantly in the T1D group but alkaline phosphatase (ALP) activity was greater (p < 0.01). This produced a shift in plasma PLP-PL profile, as evidenced by a lower plasma PLP/PL ratio (p < 0.05). Enhanced ALP activity meant more PLP being dephosphorylated to PL (the membrane transfer form), with more ending up in erythrocytes to be rephosphorylated in its active form, as suggested by the significant positive correlation (p < 0.001) between plasma PL and erythrocyte PLP. More PL into blood circulation also means more oxidation of this vitamer to 4′-pyridoxic acid in kidneys, as confirmed by the positive correlation between plasma PL and urinary 4′-pyridoxic acid (p < 0.001). The positive correlation (p < 0.001) between ALP activity and glycosylated hemoglobin indicated a direct effect of the disease. The T1D-induced alteration in vitamin B6 metabolism, consecutive to enhanced ALP activity, may put patients at greater risk of vitamin B6 deficiency and diabetic complications.
Epigenetic Differences in Normal Colon Mucosa of Cancer Patients Suggest Altered Dietary Metabolic Pathways
Authors: Silviera Matthew L. , Smith Brian P. , Powell Jasmine , Sapienza Carmen 
Published: February 2012

AbstractWe have compared DNA methylation in normal colon mucosa between patients with colon cancer and patients without cancer. We identified significant differences in methylation between the two groups at 114 to 874 genes. The majority of the differences are in pathways involved in the metabolism of carbohydrates, lipids, and amino acids. We also compared transcript levels of genes in the insulin signaling pathway. We found that the mucosa of patients with cancer had significantly higher transcript levels of several hormones regulating glucose metabolism and significantly lower transcript levels of a glycolytic enzyme and a key regulator of glucose and lipid homeostasis. These differences suggest that the normal colon mucosa of patients with cancer metabolizes dietary components differently than the colon mucosa of controls. Because the differences identified are present in morphologically normal tissue, they may be diagnostic of colon cancer and/or prognostic of colon cancer susceptibility. Cancer Prev Res; 5(3); 374–84. ©2012 AACR.
Very Late Coronary Stent Thrombosis of a Newer-Generation Everolimus-Eluting Stent Compared With Early-Generation Drug-Eluting Stents
Authors: Räber Lorenz , Magro Michael , Stefanini Giulio G. , Kalesan Bindu , van Domburg Ron T. , Onuma Yoshinobu , Wenaweser Peter , Daemen Joost , Meier Bernhard , Jüni Peter , Serruys Patrick W. , Windecker Stephan 
Published: February 2012

Background—
Early-generation drug-eluting stents releasing sirolimus (SES) or paclitaxel (PES) are associated with increased risk of very late stent thrombosis occurring >1 year after stent implantation. It is unknown whether the risk of very late stent thrombosis persists with newer-generation everolimus-eluting stents (EES).

Methods and Results—

We assessed the risk of stent thrombosis in a cohort of 12 339 patients with unrestricted use of drug-eluting stents (3819 SES, 4308 PES, 4212 EES). Results are incidence rates per 100 person-years after inverse probability of treatment weighting to adjust for group differences. During follow-up of up to 4 years, the overall incidence rate of definite stent thrombosis was lower with EES (1.4 per 100 person-years) compared with SES (2.9; hazard ratio, 0.41; 95% confidence interval, 0.27–0.62;
P
<0.0001) and PES (4.4; hazard ratio, 0.33; 95% confidence interval, 0.23–0.48;
P
<0.0001). The incidence rate per 100 person-years of early (0–30 days), late (31 days–1 year), and very late stent thrombosis amounted to 0.6, 0.1, and 0.6 among EES-treated patients; 1.0, 0.3, and 1.6 among SES-treated patients; and 1.3, 0.7, and 2.4 among PES-treated patients. Differences in favor of EES were most pronounced beyond 1 year, with a hazard ratio of 0.33 (EES versus SES;
P
=0.006) and 0.34 (EES versus PES;
P
<0.0001). There was a lower risk of cardiac death or myocardial with EES compared with PES (hazard ratio, 0.65; 95% confidence interval, 0.56–0.75;
P
<0.0001), which was directly related to the lower risk of stent thrombosis–associated events (EES versus PES: hazard ratio, 0.36; 95% confidence interval, 0.23–0.57).

Conclusion—
Current treatment with EES is associated with a lower risk of very late stent thrombosis compared with early-generation drug-eluting stents.
CT/CT Angiography and MRI Findings Predict Recurrent Stroke After Transient Ischemic Attack and Minor Stroke
Authors: Coutts Shelagh B. , Modi Jayesh , Patel Shiel K. , Demchuk Andrew M. , Goyal Mayank , Hill Michael D. 
Published: February 2012

Background and Purpose—
Transient ischemic attack and minor stroke portend a substantial risk of recurrent stroke. MRI can identify patients at high risk for a recurrent stroke. However, MRI is not commonly available as an emergency. If similarly clinically predictive, a CT/CT angiographic (CTA) imaging strategy would be more widely applicable.

Methods—
Five hundred ten patients with consecutive transient ischemic attack and minor stroke underwent CT/CTA and subsequent MRI. We assessed the risk of recurrent stroke within 90 days using standard clinical variables and predefined abnormalities on the CT/CTA (acute ischemia on CT and/or intracranial or extracranial occlusion or stenosis ≥50%) and MRI (diffusion-weighted imaging-positive).

Results—

There were 36 recurrent strokes (7.1%; 95% CI, 5.0–9.6). Median time to the event was 1 day (interquartile range, 7.5). Median time from onset to CTA was 5.5 hours (interquartile range, 6.4 hours) and to MRI was 17.5 hours (interquartile range, 12 hours). Symptoms ongoing at first assessment (hazard ratio, 2.2; 95% CI, 1.02–4.9), CT/CTA abnormalities (hazard ratio, 4.0; 95% CI, 2.0–8.5), and diffusion-weighted imaging positivity (hazard ratio, 2.2; 95% CI, 1.05–4.7) predicted recurrent stroke. In the multivariable analysis, only CT/CTA abnormalities predicted recurrent stroke. In a secondary analysis, CT/CTA and MRI were not significantly different in their discriminative value in predicting recurrent stroke (0.67; (95% CI, 0.59–0.76 versus 0.59; 95% CI, 0.52–0.67;
P
=0.09).

Conclusions—
Early assessment of the intracranial and extracranial vasculature using CT/CTA predicts recurrent stroke and clinical outcome in patients with transient ischemic attack and minor stroke. In many institutions, CTA is more readily available than MRI and physicians should access whichever technique is more quickly available at their institution.
A Climatology of Disdrometer Measurements of Rainfall in Finland over Five Years with Implications for Global Radar Observations
Authors: Leinonen Jussi , Moisseev Dmitri , Leskinen Matti , Petersen Walter A. 
Published: February 2012

AbstractTo improve the understanding of high-latitude rain microphysics and its implications for the remote sensing of rainfall by ground-based and spaceborne radars, raindrop size measurements have been analyzed that were collected over five years with a Joss–Waldvogel disdrometer located in Järvenpää, Finland. The analysis shows that the regional climate is characterized by light rain and small drop size with narrow size distributions and that the mutual relations of drop size distribution parameters differ from those reported at lower latitudes. Radar parameters computed from the distributions demonstrate that the high latitudes are a challenging target for weather radar observations, particularly those employing polarimetric and dual-frequency techniques. Nevertheless, the findings imply that polarimetric ground radars can produce reliable “ground truth” estimates for space observations and identify dual-frequency radars utilizing a W-band channel as promising tools for observing rainfall in the high-latitude climate.