bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overreliance on the Hexon Gene, Leading to Misclassification of Human Adenoviruses
Authors: Singh Gurdeep , Robinson Christopher M. , Dehghan Shoaleh , Schmidt Timothy , Seto Donald , Jones Morris S. , Dyer David W. , Chodosh James 
Published: February 2012

ABSTRACT
The genome of human adenovirus (HAdV) D30 was sequenced in depth. Sequence assembly and analysis revealed two distinct viral sequences with identical hexon genes, which were the same as the one previously reported for HAdV-D30. However, one of the two viruses was found to be a recombinant of HAdV-D29. Exclusive reliance on serum neutralization can lead to mischaracterization of adenoviruses and miss coinfections. Whole-genome sequencing remains the gold standard for proper classification of HAdVs.
Quantification and Analysis of Thymidine Kinase Expression from Acyclovir-Resistant G-String Insertion and Deletion Mutants in Herpes Simplex Virus-Infected Cells
Authors: Pan Dongli , Coen Donald M. 
Published: February 2012

ABSTRACT
To be clinically relevant, drug-resistant mutants must both evade drug action and retain pathogenicity. Many acyclovir-resistant herpes simplex virus mutants from clinical isolates have one or two base insertions (G8 and G9) or one base deletion (G6) in a homopolymeric run of seven guanines (G string) in the gene encoding thymidine kinase (TK). Nevertheless, G8 and G9 mutants express detectable TK activity and can reactivate from latency in mice, a pathogenicity marker. On the basis of studies using cell-free systems, ribosomal frameshifting can explain this ability to express TK. To investigate frameshifting in infected cells, we constructed viruses that express epitope-tagged versions of wild-type and mutant TKs. We measured TK activity by plaque autoradiography and expression of frameshifted and unframeshifted TK polypeptides using a very sensitive immunoprecipitation-Western blotting method. The G6 mutant expressed ∼0.01% of wild-type levels of TK polypeptide. For the G9 mutant, consistent with previous results, much TK expression could be ascribed to reversion. For the G8 mutant, from these assays and pulse-labeling studies, we determined the ratio of synthesis of frameshifted to unframeshifted polypeptides to be 1:100. The effects of stop codons before or after the G string argue that frameshifting can initiate within the first six guanines. However, frameshifting efficiency was altered by stop codons downstream of the string in the 0 frame. The G8 mutant expressed only 0.1% of the wild-type level of full-length TK, considerably lower than estimated previously. Thus, remarkably low levels of TK are sufficient for reactivation from latency in mice.
The Genome Sequence of the Emerging Common Midwife Toad Virus Identifies an Evolutionary Intermediate within Ranaviruses
Authors: Mavian Carla , López-Bueno Alberto , Balseiro Ana , Casais Rosa , Alcamí Antonio , Alejo Alí 
Published: February 2012

ABSTRACT
Worldwide amphibian population declines have been ascribed to global warming, increasing pollution levels, and other factors directly related to human activities. These factors may additionally be favoring the emergence of novel pathogens. In this report, we have determined the complete genome sequence of the emerging common midwife toad ranavirus (CMTV), which has caused fatal disease in several amphibian species across Europe. Phylogenetic and gene content analyses of the first complete genomic sequence from a ranavirus isolated in Europe show that CMTV is an amphibian-like ranavirus (ALRV). However, the CMTV genome structure is novel and represents an intermediate evolutionary stage between the two previously described ALRV groups. We find that CMTV clusters with several other ranaviruses isolated from different hosts and locations which might also be included in this novel ranavirus group. This work sheds light on the phylogenetic relationships within this complex group of emerging, disease-causing viruses.
Residue Y161 of Influenza Virus Hemagglutinin Is Involved in Viral Recognition of Sialylated Complexes from Different Hosts
Authors: Wang Minxiu , Tscherne Donna M. , McCullough Christopher , Caffrey Michael , García-Sastre Adolfo , Rong Lijun 
Published: February 2012

ABSTRACT

Influenza A virus glycoprotein hemagglutinin (HA) binds to host cell surface sialic acid (SA)-terminated sugars in glycoproteins to initiate viral entry. It is thought that avian influenza viruses preferentially bind to
N
-acetylneuraminic acid α3 (NeuAcα3) sugars, while human influenza viruses exhibit a preference for NeuAcα6-containing sugars. Thus, species-specific SA(s) is one of the determinants in viral host tropism. The SA binding pocket of the HA1 subunit has been extensively studied, and a number of residues important for receptor binding have been identified. In this study, we examined the potential roles of seven highly conserved HA surface-located amino acid residues in receptor binding and viral entry using an H5 subtype. Among them, mutant Y161A showed cell-type-dependent viral entry without obvious defects in HA protein expression or viral incorporation. This mutant also displayed dramatically different ability in agglutinating different animal erythrocytes. Oligosaccharide binding analysis showed that substituting alanine at Y161 of HA changed the SA binding preference from NeuAc to
N
-glycolylneuraminic acid (NeuGc). Rescued mutant Y161A viruses demonstrated a 5- to 10-fold growth defect, but they were robust in viral replication and plaque forming ability. Our results demonstrate that Y161 is a critical residue involved in recognition of different SA species. This residue may play a role in determining influenza virus host tropism.
Diabetes and raised blood glucose as risk factors for future suicide: cohort study of 1 234 927 Korean men and women: Table 1
Authors: David Batty G , Kivimaki Mika , Park Il Su , Jee Sun Ha 
Published: February 2012

BackgroundA diagnosis of diabetes has been shown to be a risk factor for suicide in selected studies. The link between blood glucose and future suicide has yet to be examined.AimTo examine if diabetes and blood glucose level are associated with a raised risk of suicide.MethodsThe Korean Cancer Prevention Study is a cohort of 1 329 525 individuals (482 618 women) aged 30–95 years at baseline. A fasting serum specimen was assayed for blood glucose, and diabetes status was categorised into five groups based on existing definitions. Study members were followed for mortality experience over 14 years.ResultsThere were 472 suicide deaths (389 in men and 83 in women) during the follow-up. In men, there was a ‘J’-shaped diabetes–suicide death relation. Thus, while the highest suicide rates were apparent in those with type 2 diabetes and there was an incremental fall in suicide risk with decreasing blood glucose level, an inflection was seen in the low-normal group. Similar results were apparent in women, although there was no raised risk in the lowest blood glucose group.ConclusionIn the present cohort, diabetes (both existing and study detected) but not raised blood glucose was a risk factor for completed suicide.
Hoffmann reflex is increased after 14 days of daily repeated Achilles tendon vibration for the soleus but not for the gastrocnemii muscles
Authors: Lapole Thomas , Pérot Chantal 
Published: February 2012

In a previous study, Achilles tendon vibrations were enough to improve the triceps surae (TS) activation capacities and also to slightly increase TS Hoffmann reflex (H-reflex) obtained by summing up soleus (Sol) and gastrocnemii (GM and GL) EMGs. The purpose of the present study was to analyze separately Sol and GM or GL reflexes to account for different effects of the vibrations on the reflex excitability of the slow soleus and of the gastrocnemii muscles. A control group (n = 13) and a vibration group (n = 16) were tested in pre-test and post-test conditions. The Achilles tendon vibration program consisted of 1 h of daily vibration (frequency: 50 Hz) applied during 14 days. Maximal Sol, GM and GL H-reflexes, and M-waves were recorded, and their Hmax/Mmax ratios gave the index of reflex excitability. After the vibration protocol, only Sol Hmax/Mmax was enhanced (p < 0.001). The enhanced Sol reflex excitability after vibration is in favor of a decrease in the pre-synaptic inhibition due to the repeated vibrations and the high solicitation of the reflex pathway. Those results of a short period of vibration applied at rest may be limited to the soleus because of its high density in muscle spindles and slow motor units, both structures being very sensitive to vibrations.
Detraining-induced alterations in metabolic and fitness markers after a multicomponent exercise-training program in older men
Authors: Ratel Sébastien , Gryson Céline , Rance Mélanie , Penando Stéphane , Bonhomme Cécile , Le Ruyet Pascale , Duclos Martine , Boirie Yves , Walrand Stéphane 
Published: February 2012

The aim of the present study was to investigate the effects of a 8-week detraining period after a 16-week multicomponent training program including strength and aerobic exercises on the main determinants of aerobic fitness, muscle strength and some metabolic markers in 24 older subjects (60.2 ± 3.0 years). The oxygen uptake at the second ventilatory threshold (VO2VT2) and at the end of exercise (VO2max), maximum voluntary contraction force (MVC) of knee extensors and some metabolic indexes, i.e., insulin sensitivity, blood lipid profile, inflammatory cytokines, and endothelial function, were evaluated at baseline and after the training and detraining periods. The training program induced significant improvements in VO2VT2 (16%, p < 0.05), VO2max (14%, p < 0.05), MVC (6.5%, p < 0.05), insulin sensitivity (16%, p < 0.05), and endothelial function (p < 0.05) but induced no significant change in lipid profile and inflammatory cytokines. Interestingly, VO2VT2 and VO2max (mL·min–1·kg–1) scores remained significantly above pretraining values after the 8-week detraining period. However, the detraining period reversed MVC values, the insulin sensitivity and endothelial function to baseline levels. To conclude, the 8-week detraining partially reversed the major components of aerobic fitness but totally abolished the gains in muscle strength and some metabolic indexes after a 16-week multicomponent training program in older men. Taken as a whole, the results of this study emphasize the importance of exercise prescriptions for older subjects and the need not to interrupt exercise-training over a prolonged period.
Activation of mTOR signalling in young and old human skeletal muscle in response to combined resistance exercise and whey protein ingestion
Authors: Farnfield Michelle M. , Breen Leigh , Carey Kate A. , Garnham Andrew , Cameron-Smith David 
Published: February 2012

Purpose: To investigate the impact of whey protein ingestion and resistance exercise training on the phosphorylation of mRNA translational signalling proteins in the skeletal muscle of young and old men. Methods: Sixteen healthy young (aged 18–25 years) and 15 healthy older men (aged 60–75 years) completed 12 weeks of resistance exercise and were randomly assigned to consume a whey protein (WPI) or placebo drink after each session. Muscle biopsies were collected before and 2 h after an acute exercise bout at the beginning and the end of training. Results: All subjects significantly increased strength after following strength training. Phosphorylation of mTOR was significantly greater in the WPI groups compared with placebo for both younger and older subjects. Phosphorylation of p70S6K, eIF4G, and 4EBP1 was greater for older subjects consuming WPI. Phosphorylation of rpS6, eIF4G, and 4EBP1 tended to increase in the younger subjects that had consumed WPI. Post-training, younger subjects demonstrated a similar pattern of mTOR phosphorylation as seen pre-training. In contrast, the initial heightened phosphorylation of mTOR, p70S6K, rpS6, and eIF4G in older muscle to combined resistance exercise and WPI ingestion became less pronounced after repeated training sessions. Conclusions: In the untrained state, resistance exercise coupled with WPI increases the phosphorylation of proteins involved in mRNA translation compared with exercise alone. Post-training, WPI- and exercise-induced protein phosphorylation was reduced in older men, but not in younger men. Thus, strategies to induce hypertrophy should utilize protein and resistance training concurrently. Further investigations should delineate interventions that will maintain sensitivity to anabolic stimuli in older populations.
The effects of acute alcohol consumption and eccentric muscle damage on neuromuscular function
Authors: Barnes Matthew. J. , Mündel Toby , Stannard Stephen R. 
Published: February 2012

Voluntary and electrically stimulated muscular performance was examined to identify the effects of acute alcohol consumption on neuromuscular function in the presence and absence of exercise-induced muscle damage (EIMD). After initial neuromuscular performance measures were made, 12 subjects completed a bout of eccentric exercise (EX) using the quadriceps muscles of 1 leg while the remaining 11 subjects did not exercise (NX). Subjects then consumed either an alcoholic beverage containing 1 g·kg–1body weight (ALC) or a nonalcoholic beverage (OJ). On another occasion the contralateral leg of both groups was tested and those in the EX group performed an equivalent bout of eccentric exercise after which the other beverage was consumed. Measurements of neuromuscular function were made pre-exercise and 36 and 60 h post-beverage consumption. Creatine kinase (CK) was measured pre-exercise and at 12, 36, and 60 h. Significantly greater (p < 0.01) decrements in maximal voluntary isometric contraction were observed with EX ALC at 36 and 60 h compared with EX OJ, and no change was seen in the NX group. Significant decreases in voluntary activation were observed at 36 h (p = 0.003) and 60 h (p = 0.01) with EX ALC only. Elevations in CK were observed at all posteccentric exercise time points (all p < 0.05) under both EX OJ and ALC. No change in electromyography or low-frequency fatigue was observed under either treatment in either group. These results suggest that decreased neural drive appears to contribute to alcohol’s effect on the magnitude of EIMD-related decrements in voluntary force generation.
Effects of prior heavy-intensity exercise on oxygen uptake and muscle deoxygenation kinetics of a subsequent heavy-intensity cycling and knee-extension exercise
Authors: Cleland Sarah Margaret , Murias Juan Manuel , Kowalchuk John Michael , Paterson Donald Hugh 
Published: February 2012

This study examined the effects of prior heavy-intensity exercise on the adjustment of pulmonary oxygen uptake (VO2p) and muscle deoxygenation Δ[HHb] during the transition to subsequent heavy-intensity cycling (CE) or knee-extension (KE) exercise. Nine young adults (aged 24 ± 5 years) performed 4 repetitions of repeated bouts of heavy-intensity exercise separated by light-intensity CE and KE, which included 6 min of baseline exercise, a 6-min step of heavy-intensity exercise (H1), 6-min recovery, and a 6-min step of heavy-intensity exercise (H2). Exercise was performed at 50 r·min–1 or contractions per minute per leg. Oxygen uptake (VO2) mean response time was ∼20% faster (p < 0.05) during H2 compared with H1 in both modalities. Phase 2 time constants (τ) were not different between heavy bouts of CE (H1, 29.6 ± 6.5 s; H2, 28.0 ± 4.6 s) or KE exercise (H1, 31.6 ± 6.7 s; H2, 29.8 ± 5.6 s). The VO2 slow component amplitude was lower (p < 0.05) in H2 in both modalities (CE, 0.19 ± 0.06 L·min–1; KE, 0.12 ± 0.07 L·min–1) compared with H1 (CE, 0.29 ± 0.09 L·min–1; KE, 0.18 ± 0.07 L·min–1), with the contribution of the slow component to the total VO2 response reduced (p < 0.05) in H2 during both exercise modes. The effective τHHb was similar between bouts for CE (H1, 18.2 ± 3.0 s; H2, 18.0 ± 3.6 s) and KE exercise (H1, 26.0 ± 7.0 s; H2, 24.0 ± 5.8 s). The ΔHHb slow component was reduced during H2 in both CE and KE (p < 0.05). In conclusion, phase 2 VO2p was unchanged with priming exercise; however, a faster mean response time of VO2p during the heavy-intensity exercise preceded by a priming heavy-intensity exercise was attributed to a smaller slow component and reduced muscle deoxygenation indicative of improved muscle O2 delivery during the second bout of exercise.
Combined effects of aerobic exercise and high-carbohydrate meal on plasma acylated ghrelin and levels of hunger
Authors: Becker Geórgia Franco , Macedo Rodrigo Cauduro Oliveira , Cunha Giovani dos Santos , Martins Jocelito Bijoldo , Laitano Orlando , Reischak-Oliveira Alvaro 
Published: February 2012

The present study investigated the effect of an aerobic exercise bout associated with a high-carbohydrate (CHO) meal on plasma levels of acylated ghrelin and hunger sensation. Eight healthy males performed an exercise (ET) and a control (CT) trial. In ET, participants performed a 60-min cycling exercise (∼70% of maximal oxygen uptake) after consuming a high-CHO meal. In the CT, participants remained at rest throughout the whole period after consuming the high-CHO meal. Hunger sensation was assessed and blood samples were taken to determine the levels of acylated ghrelin, glucose, insulin, total cholesterol (TC), and triglycerides (TG). There was suppression of hunger after consuming the meal in ET and CT (p = 0.028 and p = 0.011, respectively). Hunger increased in CT in the period correspondent to the exercise session (p = 0.017) and remained suppressed in the ET. The area under the curve for acylated ghrelin showed that its levels were lower in the ET compared with CT in the period of the exercise plus the immediate period (1 h) postexercise (60.7 vs. 96.75 pg·mL–1·2 h–1, respectively; p = 0.04). Inverse correlations between acylated ghrelin levels and insulin, TC, and TG levels at different time points were observed. In conclusion, these findings suggest that 1 bout of aerobic exercise maintains the meal-induced suppression of hunger. The mechanism underlying this effect may involve the exercise-induced suppression of acylated ghrelin. These results implicate that the combination of a high-CHO meal and aerobic exercise may effectively improve appetite control and body weight management.
The Aurora Kinase A Inhibitor MLN8237 Enhances Cisplatin-Induced Cell Death in Esophageal Adenocarcinoma Cells
Authors: Sehdev Vikas , Peng DunFa , Soutto Mohammed , Washington M. Kay , Revetta Frank , Ecsedy Jeffrey , Zaika Alexander , Rau Tilman T. , Schneider-Stock Regine , Belkhiri Abbes , El-Rifai Wael 
Published: February 2012

AbstractEsophageal adenocarcinomas are poorly responsive to chemotherapeutics. This study aimed to determine the levels of Aurora kinase A (AURKA) and the therapeutic potential of MLN8237, an investigational AURKA inhibitor, alone and in combination with cisplatin. Using quantitative real-time PCR, we detected frequent AURKA gene amplification (15 of 34, 44%) and mRNA overexpression (37 of 44, 84%) in esophageal adenocarcinomas (P &lt; 0.01). Immunohistochemical analysis showed overexpression of AURKA in more than two-thirds of esophageal adenocarcinoma tissue samples (92 of 132, 70%; P &lt; 0.001). Using FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, with constitutive AURKA overexpression and mutant p53, we observed inhibition of colony formation with a single treatment of 0.5 μmol/L MLN8237 (P &lt; 0.05). This effect was further enhanced in combination with 2.5 μmol/L cisplatin (P &lt; 0.001). Twenty-four hours after treatment with the MLN8237 or MLN8237 and cisplatin, cell-cycle analyses showed a sharp increase in the percentage of polyploid cells (P &lt; 0.001). This was followed by an increase in the percentage of cells in the sub-G1 phase at 72 hours, concordant with the occurrence of cell death (P &lt; 0.001). Western blot analysis showed higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP with the combined treatment, as compared with a single-agent treatment. Using xenograft models, we showed an enhanced antitumor role for the MLN8237 and cisplatin combination, as compared with single-agent treatments (P &lt; 0.001). In conclusion, this study shows frequent overexpression of AURKA and suggests that MLN8237 could be an effective antitumor agent, which can be combined with cisplatin for a better therapeutic outcome in esophageal adenocarcinomas. Mol Cancer Ther; 11(3); 763–74. ©2012 AACR.
Navitoclax (ABT-263) Reduces Bcl-xL–Mediated Chemoresistance in Ovarian Cancer Models
Authors: Wong Maureen , Tan Nguyen , Zha Jiping , Peale Franklin V. , Yue Peng , Fairbrother Wayne J. , Belmont Lisa D. 
Published: February 2012

Abstract
To examine the potential of combining Bcl-2 family inhibitors with chemotherapy in ovarian cancer, we evaluated a panel of 27 ovarian cancer cell lines for response to the combination of navitoclax (formerly ABT-263) and paclitaxel or gemcitabine. The majority of cell lines exhibited a greater than additive response to either combination, as determined by the Bliss independence model, and more than 50% of the ovarian cell lines exhibited strong synergy for the navitoclax/paclitaxel combination. To identify biomarkers for tumors likely to respond to this combination, we evaluated the protein levels of intrinsic apoptosis pathway components. Bcl-xL seems necessary, but not sufficient, for navitoclax/paclitaxel synergy in vitro, suggesting that exclusion of patients whose tumors have low or undetectable Bcl-xL would enrich for patients responsive to the combination. We evaluated Bcl-xL levels in ovarian cancer tumor tissue from 40 patients (20 taxane responsive and 20 with poor response to taxane) and found that patients with high Bcl-xL were less sensitive to taxane treatment (10 of 12) Bcl-xL positive patients, P = 0.014). These data support the use of navitoclax in combination with taxane-based therapy in ovarian cancer patients with high levels of Bcl-xL. Mol Cancer Ther; 11(4); 1026–35. ©2012 AACR.
MYC-Driven Tumorigenesis Is Inhibited by WRN Syndrome Gene Deficiency
Authors: Moser Russell , Toyoshima Masafumi , Robinson Kristin , Gurley Kay E. , Howie Heather L. , Davison Jerry , Morgan Martin , Kemp Christopher J. , Grandori Carla 
Published: February 2012

AbstractMYC-induced DNA damage is exacerbated in WRN-deficient cells, leading to replication stress and accelerated cellular senescence. To determine whether WRN deficiency impairs MYC-driven tumor development, we used both xenograft and autochthonous tumor models. Conditional silencing of WRN expression in c-MYC overexpressing non–small cell lung cancer xenografts impaired both tumor establishment and tumor growth. This inhibitory effect of WRN knockdown was accompanied by increased DNA damage, decreased proliferation, and tumor necrosis. In the Eμ-Myc mouse model of B-cell lymphoma, a germline mutation in the helicase domain of Wrn (WrnΔhel/Δhel) resulted in a significant delay in emergence of lethal lymphomas, extending tumor-free survival by more than 30%. Analysis of preneoplastic B cells from Eμ-Myc Wrn mutant mice revealed increased DNA damage, elevation of senescence markers, and decreased proliferation in comparison with cells from age-matched Eμ-Myc mice. Immunohistochemical and global gene expression analysis of overt Eμ-Myc WrnΔhel/Δhel lymphomas showed a marked increase in expression of the CDK inhibitor, p16Ink4a, as well as elevation of TAp63, a known mediator of senescence. Collectively, these studies show that in the context of Myc-associated tumorigenesis, loss of Wrn amplifies the DNA damage response, both in preneoplastic and neoplastic tissue, engaging activation of tumor suppressor pathways. This leads to inhibition of tumor growth and prolonged tumor-free survival. Targeting WRN or its enzymatic function could prove to be an effective strategy in the treatment of MYC-associated cancers. Mol Cancer Res; 10(4); 535–45. ©2012 AACR.