bluuebunny/crossref_metadata_2025_split huggingface dataset:
The economic implications of sylvatic rabies eradication in Italy
Authors: Sartore S. , Mulatti P. , Trestini S. , Lorenzetto M. , Gagliazzo L. , Marangon S. , Bonfanti L. 
Published: August 2017

SummaryAfter more than 10 years of absence, sylvatic rabies re‐appeared in Italy in 2008. To prevent disease spread, three oral rabies vaccination (ORV) campaigns targeting red foxes were performed through manual distribution of vaccine baits between January and September 2009. As these campaigns proved unsuccessful, at the end of December 2009, baits started being distributed using helicopters, allowing uniform coverage of larger areas in a shorter time period. From winter 2009 to autumn 2016, a total of 15 ORV campaigns (four emergency, four regular and seven preventive ORV) were implemented through aerial distribution of baits. In this study, we assessed the costs of the aerial ORV campaigns, which were aimed at eradicating the disease and reobtaining the rabies‐free status. Cumulative costs per km2 were estimated at €59.45 during emergency campaigns and ranged between €51.94 and €65.67 in the regular vaccinations. The main portion of costs for ORV programmes were related to baits supply and distribution: €49.24 (82.83%) in emergency campaigns and from €40.33 to € 43.35 in regular ORVs (71.97% and 66.02%, respectively). At the end of each ORV campaign, the efficacy of vaccination activities was estimated by assessing the proportion of foxes testing positive for tetracycline biomarker in jawbone, indicating bait intake. Results revealed that the proportion of foxes that ingested baits varied between 70.97% and 95.51%. Statistical analysis indicated that reducing the density of dropped baits could potentially lead to a cost‐saving of 22.81%, still maintaining a satisfactory level of bait intake by the fox population.
5‐Aminoimidazole‐4‐carboxamide ribonucleotide prevents fat gain following the cessation of voluntary physical activity
Authors: Ruegsegger Gregory N. , Sevage Joseph A. , Childs Thomas E. , Grigsby Kolter B. , Booth Frank W. 
Published: August 2017

New Findings
What is the central question of this study?
We investigated whether 5‐aminoimidazole‐4‐carboxamide‐1‐beta‐D‐ribofuranoside (AICAR) could prevent acute increases in body fat and changes in omental and subcutaneous adipose tissue following the sudden transition from physical activity to physical inactivity.

What is the main finding and its importance?
AICAR prevented fat gains following the transition from physical activity to inactivity to levels comparable to rats that remained physically active. AICAR and continuous physical activity produced depot‐specific changes in cyclin A1 mRNA and protein that were associated with the prevention of fat gain. These findings suggest that targeting AMP‐activated protein kinase signalling could oppose rapid adipose mass growth.

The transition from physical activity to inactivity is associated with drastic increases in ‘catch‐up’ fat that in turn foster the development of many obesity‐associated maladies. We tested whether 5‐aminoimidazole‐4‐carboxamide‐1‐beta‐D‐ribofuranoside (AICAR) treatment would prevent gains in body fat following the sudden transition from a physically active state to an inactive state by locking a voluntary running wheel. Male Wistar rats were either sedentary (SED) or given wheel access for 4 weeks, at which time rats with wheels continued running (RUN), had their wheel locked (WL) or had WL with daily AICAR injection (WL + AICAR) for 1 week. RUN and WL + AICAR prevented gains in body fat compared with SED and WL (P < 0.001). Cyclin A1 mRNA, a marker of cell proliferation, was decreased in omental, but not subcutaneous adipose tissue, in RUN and WL + AICAR compared with SED and WL groups (P < 0.05). Both cyclin A1 mRNA and protein were positively associated with gains in fat mass (P < 0.05). Cyclin A1 mRNA in omental, but not subcutaneous, adipose tissue was negatively correlated with p‐AMPK levels (P < 0.05). Differences in fat gain and omental mRNA and protein levels were independent of changes in food intake and in differences in select hypothalamic mRNAs. These findings suggest that AICAR treatment prevents acute gains in adipose tissue following physical inactivity to levels of rats that continuously run, and that together, continuous physical activity and AICAR could, at least initially in these conditions, exert similar inhibitory effects on adipogenesis in a depot‐specific manner.
Effect of Body Composition on Physiological Responses to Cold-Water Immersion and the Recovery of Exercise Performance
Authors: Stephens Jessica M. , Halson Shona L. , Miller Joanna , Slater Gary J. , Chapman Dale W. , Askew Christopher D. 
Published: August 2017

Purpose: To explore the influence of body composition on thermal responses to cold-water immersion (CWI) and the recovery of exercise performance. Methods: Male subjects were stratified into 2 groups: low fat (LF; n = 10) or high fat (HF; n = 10). Subjects completed a high-intensity interval test (HIIT) on a cycle ergometer followed by a 15-min recovery intervention (control [CON] or CWI). Core temperature (Tc), skin temperature, and heart rate were recorded continuously. Performance was assessed at baseline, immediately post-HIIT, and 40 min postrecovery using a 4-min cycling time trial (TT), countermovement jump (CMJ), and isometric midthigh pull (IMTP). Perceptual measures (thermal sensation [TS], total quality of recovery [TQR], soreness, and fatigue) were also assessed. Results: Tc and TS were significantly lower in LF than in HF from 10 min (Tc, LF 36.5°C ± 0.5°C, HF 37.2°C ± 0.6°C; TS, LF 2.3 ± 0.5 arbitrary units [a.u.], HF 3.0 ± 0.7 a.u.) to 40 min (Tc, LF 36.1°C ± 0.6°C, HF 36.8°C ±0.7°C; TS, LF 2.3 ± 0.6 a.u., HF 3.2 ± 0.7 a.u.) after CWI (P < .05). Recovery of TT performance was significantly enhanced after CWI in HF (10.3 ± 6.1%) compared with LF (3.1 ± 5.6%, P = .01); however, no differences were observed between HF (6.9% ±5.7%) and LF (5.4% ± 5.2%) with CON. No significant differences were observed between groups for CMJ, IMTP, TQR, soreness, or fatigue in either condition. Conclusion: Body composition influences the magnitude of Tc change during and after CWI. In addition, CWI enhanced performance recovery in the HF group only. Therefore, body composition should be considered when planning CWI protocols to avoid overcooling and maximize performance recovery.
Energy Cost Expression for a Youth Compendium of Physical Activities: Rationale for Using Age Groups
Authors: Pfeiffer Karin A. , Watson Kathleen B. , McMurray Robert G. , Bassett David R. , Butte Nancy F. , Crouter Scott E. , Herrmann Stephen D. , Trost Stewart G. , Ainsworth Barbara E. , Fulton Janet E. , Berrigan David , _ _ 
Published: August 2017

Purpose: This study compared the accuracy of physical activity energy expenditure (PAEE) prediction using 2 methods of accounting for age dependency versus 1 standard (single) value across all ages. Methods: PAEE estimates were derived by pooling data from 5 studies. Participants, 6–18 years (n = 929), engaged in 14 activities while in a room calorimeter or wearing a portable metabolic analyzer. Linear regression was used to estimate the measurement error in PAEE (expressed as youth metabolic equivalent) associated with using age groups (6–9, 10–12, 13–15, and 16–18 y) and age-in-years [each year of chronological age (eg, 12 = 12.0–12.99 y)] versus the standard (a single value across all ages). Results: Age groups and age-in-years showed similar error, and both showed less error than the standard method for cycling, skilled, and moderate- to vigorous-intensity activities. For sedentary and light activities, the standard had similar error to the other 2 methods. Mean values for root mean square error ranged from 0.2 to 1.7 youth metabolic equivalent across all activities. Error reduction ranged from −0.2% to 21.7% for age groups and −0.23% to 18.2% for age-in-years compared with the standard. Conclusions: Accounting for age showed lower errors than a standard (single) value; using an age-dependent model in the Youth Compendium is recommended.
Impact of Exposure of Methicillin-Resistant Staphylococcus aureus to Polyhexanide
In Vitro
and
In Vivo
Authors: Renzoni A. , Von Dach E. , Landelle C. , Diene S. M. , Manzano C. , Gonzales R. , Abdelhady W. , Randall C. P. , Bonetti E. J. , Baud D. , O'Neill A. J. , Bayer A. , Cherkaoui A. , Schrenzel J. , Harbarth S. , François P. 
Published: August 2017

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increases the need for development of alternative decolonization molecules. The absence of reported severe adverse reactions and bacterial resistance to polyhexanide makes it an excellent choice as a topical antiseptic. In the present study, we evaluated the
in vitro
and
in vivo
capacity to generate strains with reduced polyhexanide susceptibility and cross-resistance with chlorhexidine and/or antibiotics currently used in clinic. Here we report the
in vitro
emergence of reduced susceptibility to polyhexanide by prolonged stepwise exposure to low concentrations in broth culture. Reduced susceptibility to polyhexanide was associated with genomic changes in the
mprF
and
purR
genes and with concomitant decreased susceptibility to daptomycin and other cell wall-active antibiotics. However, the
in vitro
emergence of reduced susceptibility to polyhexanide did not result in cross-resistance to chlorhexidine. During
in vivo
polyhexanide clinical decolonization treatment, neither reduced polyhexanide susceptibility nor chlorhexidine cross-resistance was observed. Together, these observations suggest that polyhexanide could be used safely for decolonization of carriers of chlorhexidine-resistant
S. aureus
strains; they also highlight the need for careful use of polyhexanide at low antiseptic concentrations.
Pharmacokinetics of Intravenous Finafloxacin in Healthy Volunteers
Authors: Taubert Max , Chiesa Joseph , Lückermann Mark , Fischer Carsten , Dalhoff Axel , Fuhr Uwe 
Published: August 2017

ABSTRACT
Finafloxacin is a novel fluoroquinolone exhibiting enhanced activity under acidic conditions and a broad-spectrum antibacterial profile. The present study assessed the pharmacokinetic properties and the safety and tolerability of finafloxacin following intravenous infusions. In this mixed-parallel-group, crossover study, healthy male and female volunteers received single ascending doses (18 volunteers, 200 to 1,000 mg) or multiple ascending doses (40 volunteers, 600 to 1,000 mg) of finafloxacin or placebo. Plasma and urine samples were collected by a dense sampling scheme to determine the pharmacokinetics of finafloxacin using a noncompartmental approach. Standard safety and tolerability data were documented. Finafloxacin had a volume of distribution of 90 to 127 liters (range) at steady state and 446 to 550 liters at pseudoequilibrium, indicating the elimination of a large fraction before pseudoequilibrium was reached. Areas under the concentration-time curves and maximum plasma concentrations (geometric means) increased slightly more than proportionally (6.73 to 45.9 μg · h/ml and 2.56 to 20.2 μg/ml, respectively), the terminal elimination half-life increased (10.6 to 17.1 h), and the urinary recovery decreased (44.2% to 31.7%) with increasing finafloxacin doses (single doses of 200 to 1,000 mg). The pharmacokinetic profiles suggested multiphasic elimination by both glomerular filtration and saturable tubular secretion. The values of the parameters were similar for single and multiple administrations. The coefficient of variation for the between-subject variability of exposure ranged from 10% (≤600 mg) to 38% (>600 mg). Adverse events were mild and nonspecific, with no dependence of adverse events on dose or treatment (including placebo) being detected. Despite a relatively high interindividual variability at higher doses, the level of exposure following intravenous administration of finafloxacin appears to be predictable. Individual elimination processes should be evaluated in more detail. Finafloxacin exhibited a favorable safety and tolerability profile. (This study has been registered at ClinicalTrials.gov under registration no. NCT01910883.)
Impairment of Hematopoietic Precursor Cell Activation during the Granulopoietic Response to Bacteremia in Mice with Chronic-Plus-Binge Alcohol Administration
Authors: Shi Xin , Lin Yuan-Ping , Gao Bin , Zhang Ping 
Published: August 2017

ABSTRACT

Alcohol abuse impairs immune defense. To study the effect of chronic-plus-binge alcohol exposure on the granulopoietic response, acute alcohol intoxication (intraperitoneal injection of 5 g alcohol/kg body weight) was introduced to mice chronically fed on the Lieber-DeCarli low-fat liquid alcohol diet for 5 weeks. Bacteremia was induced by intravenous injection of
Escherichia coli
. Bacteremia caused a remarkable increase in marrow lin
−
c-kit
+
Sca-1
+
cells. Activation of cell proliferation supported the increase in marrow lin
−
c-kit
+
Sca-1
+
cells. Alcohol administration inhibited this activation of lin
−
c-kit
+
Sca-1
+
cells. The bone marrow of pair-fed control mice receiving intraperitoneal saline stored a large number of mature granulocytes expressing a high level of Gr1 (Gr1
hi
cells). The proportion of Gr1
hi
cells and the total number of Gr1
+
cells were markedly reduced in the bone marrow, along with an increase in the ratio of Gr1
+
granulocytes in peripheral white blood cells following bacteremia.
E. coli
infection stimulated proliferation of granulopoietic precursor cells, resulting in a marked increase in the ratio of immature Gr1
lo
cells in the bone marrow. Alcohol administration itself triggered marrow release of Gr1
+
cells, resulting in reduction of the marrow granulocyte reserve with an elevation of granulocytes in the circulation. Alcohol also impaired activation of granulopoietic precursor proliferation following bacteremia. Alcohol disrupted lipopolysaccharide (LPS)-TLR4-ERK1/2-cyclin D1 signaling and inhibited upregulation of Sca-1 and C/EBPβ expression by lineage-negative marrow cells in response to bacteremia. These results indicate that chronic-plus-binge alcohol exposure inhibits the granulopoietic response by disrupting key cell signaling for hematopoietic precursor cell activation and commitment to granulocyte lineage development.
Opsin-Mediated Inhibition of Bacterioruberin Synthesis in Halophilic Archaea
Authors: Peck Ronald F. , Pleşa Alexandru M. , Graham Serena M. , Angelini David R. , Shaw Emily L. 
Published: August 2017

ABSTRACTHalophilic archaea often inhabit environments with limited oxygen, and many produce ion-pumping rhodopsin complexes that allow them to maintain electrochemical gradients when aerobic respiration is inhibited. Rhodopsins require a protein, an opsin, and an organic cofactor, retinal. We previously demonstrated that inHalobacterium salinarum, bacterioopsin (BO), when not bound by retinal, inhibits the production of bacterioruberin, a biochemical pathway that shares intermediates with retinal biosynthesis. In this work, we used heterologous expression in a related halophilic archaeon,Haloferax volcanii, to demonstrate that BO is sufficient to inhibit bacterioruberin synthesis catalyzed by theH. salinarumlycopene elongase (Lye) enzyme. This inhibition was observed both in liquid culture and in a novel colorimetric assay to quantify bacterioruberin abundance based on the colony color. Addition of retinal to convert BO to the bacteriorhodopsin complex resulted in a partial rescue of bacterioruberin production. To explore if this regulatory mechanism occurs in other organisms, we expressed a Lye homolog and an opsin fromHaloarcula vallismortisinH. volcanii.H. vallismortiscruxopsin-3 expression inhibited bacterioruberin synthesis catalyzed byH. vallismortisLye but had no effect when bacterioruberin synthesis was catalyzed byH. salinarumorH. volcaniiLye. Conversely,H. salinarumBO did not inhibitH. vallismortisLye activity. Together, our data suggest that opsin-mediated inhibition of Lye is potentially widespread and represents an elegant regulatory mechanism that allows organisms to efficiently utilize ion-pumping rhodopsins obtained through lateral gene transfer.IMPORTANCEMany enzymes are complexes of proteins and nonprotein organic molecules called cofactors. To ensure efficient formation of functional complexes, organisms must regulate the production of proteins and cofactors. To study this regulation, we used bacteriorhodopsin from the archaeonHalobacterium salinarum. Bacteriorhodopsin consists of the bacterioopsin protein and a retinal cofactor. In this article, we further characterize a novel regulatory mechanism in which bacterioopsin promotes retinal production by inhibiting a reaction that consumes lycopene, a retinal precursor. By expressingH. salinarumgenes in a different organism,Haloferax volcanii, we demonstrated that bacterioopsin alone is sufficient for this inhibition. We also found that an opsin fromHaloarcula vallismortishas inhibitory activity, suggesting that this regulatory mechanism might be found in other organisms.
Reverse Genetics System Demonstrates that Rotavirus Nonstructural Protein NSP6 Is Not Essential for Viral Replication in Cell Culture
Authors: Komoto Satoshi , Kanai Yuta , Fukuda Saori , Kugita Masanori , Kawagishi Takahiro , Ito Naoto , Sugiyama Makoto , Matsuura Yoshiharu , Kobayashi Takeshi , Taniguchi Koki 
Published: August 2017

ABSTRACTThe use of overlapping open reading frames (ORFs) to synthesize more than one unique protein from a single mRNA has been described for several viruses. Segment 11 of the rotavirus genome encodes two nonstructural proteins, NSP5 and NSP6. The NSP6 ORF is present in the vast majority of rotavirus strains, and therefore the NSP6 protein would be expected to have a function in viral replication. However, there is no direct evidence of its function or requirement in the viral replication cycle yet. Here, taking advantage of a recently established plasmid-only-based reverse genetics system that allows rescue of recombinant rotaviruses entirely from cloned cDNAs, we generated NSP6-deficient viruses to directly address its significance in the viral replication cycle. Viable recombinant NSP6-deficient viruses could be engineered. Single-step growth curves and plaque formation of the NSP6-deficient viruses confirmed that NSP6 expression is of limited significance for RVA replication in cell culture, although the NSP6 protein seemed to promote efficient virus growth.IMPORTANCERotavirus is one of the most important pathogens of severe diarrhea in young children worldwide. The rotavirus genome, consisting of 11 segments of double-stranded RNA, encodes six structural proteins (VP1 to VP4, VP6, and VP7) and six nonstructural proteins (NSP1 to NSP6). Although specific functions have been ascribed to each of the 12 viral proteins, the role of NSP6 in the viral replication cycle remains unknown. In this study, we demonstrated that the NSP6 protein is not essential for viral replication in cell culture by using a recently developed plasmid-only-based reverse genetics system. This reverse genetics approach will be successfully applied to answer questions of great interest regarding the roles of rotaviral proteins in replication and pathogenicity, which can hardly be addressed by conventional approaches.
Coordinate Regulation of TET2 and EBNA2 Controls the DNA Methylation State of Latent Epstein-Barr Virus
Authors: Lu Fang , Wiedmer Andreas , Martin Kayla A. , Wickramasinghe Priyankara J. M. S. , Kossenkov Andrew V. , Lieberman Paul M. 
Published: August 2017

ABSTRACT
Epstein-Barr virus (EBV) latency and its associated carcinogenesis are regulated by dynamic changes in DNA methylation of both virus and host genomes. We show here that the ten-eleven translocation 2 (TET2) gene, implicated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DNA methylation patterning. EBV latency types are defined by DNA methylation patterns that restrict expression of viral latency genes. We show that TET2 mRNA and protein expression correlate with the highly demethylated EBV type III latency program permissive for expression of EBNA2, EBNA3s, and LMP transcripts. We show that short hairpin RNA (shRNA) depletion of TET2 results in a decrease in latency gene expression but can also trigger a switch to lytic gene expression. TET2 depletion results in the loss of hydroxymethylated cytosine and a corresponding increase in cytosine methylation at key regulatory regions on the viral and host genomes. This also corresponded to a loss of RBP-jκ binding and decreased histone H3K4 trimethylation at these sites. Furthermore, we show that the TET2 gene itself is regulated in a fashion similar to that of the EBV genome. Chromatin immunoprecipitation high-throughput sequencing (ChIP-seq) revealed that the TET2 gene contains EBNA2-dependent RBP-jκ and EBF1 binding sites and is subject to DNA methylation-associated transcriptional silencing similar to what is seen in EBV latency type III genomes. Finally, we provide evidence that TET2 colocalizes with EBNA2-EBF1-RBP-jκ binding sites and can interact with EBNA2 by coimmunoprecipitation. Taken together, these findings indicate that TET2 gene transcripts are regulated similarly to EBV type III latency genes and that TET2 protein is a cofactor of EBNA2 and coregulator of the EBV type III latency program and DNA methylation state.

IMPORTANCE
Epstein-Barr virus (EBV) latency and carcinogenesis involve the selective epigenetic modification of viral and cellular genes. Here, we show that TET2, a cellular tumor suppressor involved in active DNA demethylation, plays a central role in regulating the DNA methylation state during EBV latency. TET2 is coordinately regulated and functionally interacts with the viral oncogene EBNA2. TET2 and EBNA2 function cooperatively to demethylate genes important for EBV-driven B-cell growth transformation.