bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary ractopamine promotes growth, feed efficiency and carcass responses over a wide range of available lysine levels in finisher boars and gilts
Authors: Rikard-Bell C. V. , Pluske J. R. , van Barneveld R. J. , Mullan B. P. , Edwards A. C. , Gannon N. J. , Henman D. J. , Dunshea F. R.
Published: November 2012

The aim of this study was to investigate the performance and carcass responses of finisher boars and gilts offered a range of dietary lysine levels and three levels of dietary ractopamine hydrochloride (RAC). The study involved three experiments of 90 pigs each, totalling 270 individually penned pigs in a 2 by 5 by 3 factorial design comprising two sexes (gilts, boars), five levels of dietary lysine [0.40, 0.48, 0.56, 0.64, and 0.72 g available lysine per MJ of digestible energy (DE), respectively] and three RAC dose regimes (0, 5 and 10 mg/kg) for 28 days. An outbreak of pneumonia (Actinobaccilus pleuropneumonia) at Day 26 in Experiment 1 compromised Day 28 data; however, Day 21 data was considered suitable across all three experiments. The results indicate that 0.56 g available lysine/MJ DE is sufficient to maximise average daily gain (ADG), feed conversion ratio (FCR) and carcass weight in gilts. Control boars indicated that ADG and FCR were not limited by the lysine : energy ratios fed in this study. Increasing levels of dietary lysine linearly increased ADG (P < 0.001), improved FCR (P < 0.001) and increased carcass weight (P = 0.001). Likewise, increasing dietary RAC further improved ADG (P = 0.001), FCR (P = 0.002) and carcass weight (P = 0.075) linearly. The critical lysine levels calculated for ADG and FCR in gilts fed diets supplemented with RAC were less than required for controls. Boars had higher critical lysine levels than gilts when supplemented with dietary RAC, and increasing dietary RAC increased critical lysine levels for ADG and FCR in gilts and boars. An interaction (P = 0.016) between dietary lysine and RAC occurred for FCR, such that the response to 5 mg/kg dietary RAC diminished in diets containing 0.64 g and 0.72 g available lysine/MJ DE; however, these diets elicited a response when supplemented with 10 mg/kg RAC. Responses in ADG, FCR and carcass weight to dietary RAC were noted when dietary lysine was at or below the current recommendations for RAC diets, and it was suggested that this may have been due to reduced efficiency of lysine utilisation due to chronic disease challenge. A Sex × RAC interaction (P = 0.027) occurred for carcass P2, indicating the higher RAC dose reduced carcass P2 in boars but not in gilts. When formulating finisher pig diets between 60 and 90 kg liveweight, consideration of the lysine : energy requirements for boars and gilts is needed in order to maximise ADG, FCR and carcass characteristics. When supplementing pigs with dietary RAC, a wide range of lysine : energy levels maybe employed; however, this is dependent on RAC inclusion level and probably herd health.
A Green Method for Preparing CuCl Nanocrystal in Deep Eutectic Solvent
Authors: Zhang Fenghua , Lai Junling , Huang Ying , Li Fei , Luo Genxiang , Chu Gang
Published: November 2012

Cuprous chloride (CuCl) is extensively used as a catalyst in organic synthesis, and as a desulfurising, decolourising and deodorising agent in the petroleum industry. The traditional synthesis of CuCl nanocrystal powders, which has already caused a big problem in the environment, was via reducing copper(II) by using different additives and a quantity of concentrated acid. In this paper, we report an ecologically and environmental friendly route to prepare nanocrystalline CuCl powders, simply by using the CuCl2 and copper powders in a deep eutectic solvent (DES) at room temperature. The obtained CuCl nanocrystals were characterised by XRD, SEM and XPS techniques, and a possible formation mechanism was also proposed.
Detection of Advanced Glycation End-Products (AGEs) During Dry-State Storage of ?-Lactoglobulin/Lactose
Authors: Jongberg Sisse , Rasmussen Michael , Skibsted Leif H. , Olsen Karsten
Published: November 2012

Glycation of whey proteins is primarily affected by temperature, water activity, and pH, and leads to changes of the functional and nutritional properties of the proteins. In the case of prolonged storage of mixtures of lactose and β-lactoglobulin as a model for dried dairy products under mild heat treatment (60–70°C) in a restricted water environment (aw 0.64) at pH 7, Nϵ-(carboxymethyl)lysine (CML) and furosine were formed concomitant with glycation of β-lactoglobulin. Indirect ELISA using polyclonal antibodies against advanced glycation end products (AGEs) was shown to correlate with analyses of CML using HPLC and may be used for quality control of dried dairy products. The glycation changed the solubility properties of the protein by forming polymeric carbohydrate products of β-lactoglobulin and AGEs as characterised by SDS–PAGE.
Cholesterol increases kinetic, energetic, and mechanical stability of the human β2-adrenergic receptor
Authors: Zocher Michael , Zhang Cheng , Rasmussen Søren G. F. , Kobilka Brian K. , Müller Daniel J.
Published: November 2012

The steroid cholesterol is an essential component of eukaryotic membranes, and it functionally modulates membrane proteins, including G protein-coupled receptors. To reveal insight into how cholesterol modulates G protein-coupled receptors, we have used dynamic single-molecule force spectroscopy to quantify the mechanical strength and flexibility, conformational variability, and kinetic and energetic stability of structural segments stabilizing the human β2-adrenergic receptor (β2AR) in the absence and presence of the cholesterol analog cholesteryl hemisuccinate (CHS). CHS considerably increased the kinetic, energetic, and mechanical stability of almost every structural segment at sufficient magnitude to alter the structure and functional relationship of β2AR. One exception was the structural core segment of β2AR, which establishes multiple ligand binding sites, and its properties were not significantly influenced by CHS.
G9a functions as a molecular scaffold for assembly of transcriptional coactivators on a subset of Glucocorticoid Receptor target genes
Authors: Bittencourt Danielle , Wu Dai-Ying , Jeong Kwang Won , Gerke Daniel S. , Herviou Laurie , Ianculescu Irina , Chodankar Rajas , Siegmund Kimberly D. , Stallcup Michael R.
Published: November 2012

Histone H3 lysine-9 methyltransferase G9a/EHMT2/KMT1C is a key corepressor of gene expression. However, activation of a limited number of genes by G9a (independent of its catalytic activity) has also been observed, although the precise molecular mechanisms are unknown. By using RNAi in combination with gene expression microarray analysis, we found that G9a functions as a positive and a negative transcriptional coregulator for discrete subsets of genes that are regulated by the hormone-activated Glucocorticoid Receptor (GR). G9a was recruited to GR-binding sites (but not to the gene body) of its target genes and interacted with GR, suggesting recruitment of G9a by GR. In contrast to its corepressor function, positive regulation of gene expression by G9a involved G9a-mediated enhanced recruitment of coactivators CARM1 and p300 to GR target genes. Further supporting a role for G9a as a molecular scaffold for its coactivator function, the G9a-specific methyltransferase inhibitor UNC0646 did not affect G9a coactivator function but selectively decreased G9a corepressor function for endogenous target genes. Overall, G9a functioned as a coactivator for hormone-activated genes and as a corepressor in support of hormone-induced gene repression, suggesting that the positive or negative actions of G9a are determined by the gene-specific regulatory environment and chromatin architecture. These findings indicate distinct mechanisms of G9a coactivator vs. corepressor functions in transcriptional regulation and provide insight into the molecular mechanisms of G9a coactivator function. Our results also suggest a physiological role of G9a in fine tuning the set of genes that respond to glucocorticoids.
Competitive binding of CUGBP1 and HuR to occludin mRNA controls its translation and modulates epithelial barrier function
Authors: Yu Ting-Xi , Rao Jaladanki N. , Zou Tongtong , Liu Lan , Xiao Lan , Ouyang Miao , Cao Shan , Gorospe Myriam , Wang Jian-Ying
Published: November 2012

RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HuR are highly expressed in epithelial tissues and modulate the stability and translation of target mRNAs. Here we present evidence that CUGBP1 and HuR jointly regulate the translation of occludin and play a crucial role in the maintenance of tight junction (TJ) integrity in the intestinal epithelial cell monolayer. CUGBP1 and HuR competed for association with the same occludin 3′-untranslated region element and regulated occludin translation competitively and in opposite directions. CUGBP1 overexpression decreased HuR binding to occludin mRNA, repressed occludin translation, and compromised the TJ barrier function, whereas HuR overexpression inhibited CUGBP1 association with occludin mRNA and promoted occludin translation, thereby enhancing the barrier integrity. Repression of occludin translation by CUGBP1 was due to the colocalization of CUGBP1 and tagged occludin RNA in processing bodies (P-bodies), and this colocalization was prevented by HuR overexpression. These findings indicate that CUGBP1 represses occludin translation by increasing occludin mRNA recruitment to P-bodies, whereas HuR promotes occludin translation by blocking occludin mRNA translocation to P-bodies via the displacement of CUGBP1.
Effect of aluminium on hydrogen-induced fracture behaviour in austenitic Fe–Mn–C steel
Authors: Ryu Joo Hyun , Kim Sung Kyu , Lee Chong Soo , Suh Dong-Woo , Bhadeshia H. K. D. H.
Published: November 2012

It is known empirically that the addition of aluminium as a solute in high-Mn austenitic steels dramatically improves their resistance to hydrogen-induced embrittlement. A variety of experimental techniques, including the characterization of trapping sites and high-resolution observation of fracture facets, have been used to reveal the mechanism by which aluminium induces this effect. It is found that transgranular fracture is promoted by the segregation of hydrogen to mechanical twin interfaces and to any ϵ-martensite that is induced during deformation. Because aluminium increases the stacking fault energy of austenite, the tendency for mechanical twinning is reduced, and the formation of deformation-induced martensite eliminated. These two effects contribute to the resistance of the aluminium-alloyed steel to hydrogen embrittlement.
Fig mosaic emaravirus p4 protein is involved in cell-to-cell movement
Authors: Ishikawa Kazuya , Maejima Kensaku , Komatsu Ken , Netsu Osamu , Keima Takuya , Shiraishi Takuya , Okano Yukari , Hashimoto Masayoshi , Yamaji Yasuyuki , Namba Shigetou
Published: November 2012

Fig mosaic virus (FMV), a member of the newly formed genus Emaravirus, is a segmented negative-strand RNA virus. Each of the six genomic FMV segments contains a single ORF: that of RNA4 encodes the protein p4. FMV-p4 is presumed to be the movement protein (MP) of the virus; however, direct experimental evidence for this is lacking. We assessed the intercellular distribution of FMV-p4 in plant cells by confocal laser scanning microscopy and we found that FMV-p4 was localized to plasmodesmata and to the plasma membrane accompanied by tubule-like structures. A series of experiments designed to examine the movement functions revealed that FMV-p4 has the capacity to complement viral cell-to-cell movement, prompt GFP diffusion between cells, and spread by itself to neighbouring cells. Altogether, our findings demonstrated that FMV-p4 shares several properties with other viral MPs and plays an important role in cell-to-cell movement.
The genetic diversity of Citrus dwarfing viroid populations is mainly dependent on the infected host species
Authors: Tessitori Matilde , Rizza Serena , Reina Antonella , Causarano Giovanni , Di Serio Francesco
Published: November 2012

As with viruses, viroids infect their hosts as polymorphic populations of variants. Identifying possible sources of genetic variability is significant in the case of the species Citrus dwarfing viroid (CDVd) which has been proposed as a dwarfing agent for high-density citrus plantings. Here, a natural CDVd isolate (CMC) was used as an inoculum source for long-term (25 years) and short-term (1 year) bioassays in different citrus host species. Characterization of progenies indicated that the genetic stability of CDVd populations was high in certain hosts (trifoliate orange, Troyer citrange, Etrog citron, Navelina sweet orange), which preserve viroid populations similar to the original CMC isolate even after 25 years. By contrast, CDVd variant populations in Interdonato lemon and Volkamer lemon were completely different to those in the inoculated sources, highlighting how influential the host is on the genetic variability of CDVd populations. Implications for risk assessment of CDVd as a dwarfing agent are discussed.
Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses
Authors: Hillaire Marine L. B. , Vogelzang-van Trierum Stella E. , Kreijtz Joost H. C. M. , de Mutsert Gerrie , Fouchier Ron A. M. , Osterhaus Albert D. M. E , Rimmelzwaan Guus F.
Published: November 2012

Virus-specific CD8+T-cells contribute to protective immunity against influenza A virus (IAV) infections. As the majority of these cells are directed to conserved viral proteins, they may afford protection against IAVs of various subtypes. The present study assessed the cross-reactivity of human CD8+T-lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine-origin triple-reassortant A (H3N2) [A(H3N2)v] viruses that are currently causing an increasing number of human cases in the USA. It was demonstrated that CD8+T-cells induced after seasonal IAV infections exerted lytic activity and produced gamma interferon uponin vitrorestimulation with A(H1N1)pdm09 and A(H3N2)v influenza A viruses. Furthermore, CD8+T-cells directed to A(H1N1)pdm09 virus displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was concluded that cross-reacting T-cells had the potential to afford protective immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree of protection against infection with A(H3N2)v viruses.
Zebrafish genetics gets the Scube on Hedgehog secretion
Authors: Ingham Philip W.
Published: November 2012

Inspired by a zebrafish mutation, two recent studies by Creanga and colleagues (pp. 1312–1325) and Tukachinsky and colleagues have shed new light on the way in which lipidated Hedgehog proteins are secreted and released from expressing cells, suggesting a model for the sequential action of the Disp and Scube2 proteins in this process.
Novel 3′ ends that support translation
Authors: Marzluff William F.
Published: November 2012

The 3′ ends of two large noncoding RNAs, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and MEN β, are formed by cleavage by RNase P and are capped but not polyadenylated. In the November 1, 2012, issue of Genes & Development, Wilusz and colleagues (pp. 2392–2407) show that when these 3′ ends are formed on a GFP reporter, the resulting mRNA is exported to the cytoplasm and translated. The 3′ end forms a novel triple-helical structure that supports export and translation as well as a poly(A) tail does.
Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts
Authors: Larsen Ole H. , Stentoft Jesper , Radia Deepti , Ingerslev Jørgen , Sørensen Benny
Published: November 2012

Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole blood (WB) clot formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes containing 3·2% citrate and corn trypsin inhibitor 18·3 μg/ml. WB [mean platelet count 22 × 109/l (range 0–42)] was spiked in vitro with buffer, donor platelets (+40 × 109/l), rFVIIa (1 or 4 μg/ml), fibrinogen (1 or 3 mg/ml), or combinations of rFVIIa and fibrinogen. Coagulation profiles were recorded by tissue factor (0·03 pmol/l) activated thromboelastometry. Coagulation in ITP was characterized by a prolonged clotting time (CT, 1490 s (mean)) and a low maximum velocity (MaxVel, 3·4 mm × 100/s) and maximum clot firmness (MCF, 38·2 mm). Fibrinogen showed no haemostatic effect, whereas rFVIIa reduced the CT and increased the MaxVel. The combination of fibrinogen and rFVIIa revealed a significant synergistic effect, improving all parameters (CT 794 s, MaxVel 7·9 mm × 100/s, MCF 50·7 mm) even at very low platelet counts. These data suggest that rFVIIa combined with fibrinogen corrects the coagulopathy of ITP even at very low platelet counts, and may represent an alternative to platelet transfusion.
Using longitudinal data from the Health Survey for England to resolve discrepancies in thresholds for haemoglobin in older adults
Authors: Mindell Jennifer , Moody Alison , Ali Ayesha , Hirani Vasant
Published: November 2012

Anaemia increases with age and is common among older people. Due to its relationship with morbidity and mortality, accurate diagnosis is important. Thresholds defining the diagnosis of anaemia have been the subject of considerable scientific debate, with both higher and lower cut‐offs proposed. High haemoglobin is also a health risk in some but not all studies. Using nationally representative data of 5,329 adults aged 65 + years (Health Survey for England 1998, 2005, 2006), linked to administrative mortality data, this paper describes the relationship between haemoglobin levels and mortality, adjusted for age and other confounders. Among men, a reverse J shaped relationship was observed: relative to the modal group (140–149 g/l), those with ‘mild anaemia’ of 120–129 g/l haemoglobin had a 56% (95% confidence interval 24–96%) greater mortality hazard, and those with ‘severe anaemia’, haemoglobin <120 g/l, had an 87% (39–153%) greater hazard. At the other end of the range, those with haemoglobin ≥160 g/l had 32% (2–70%) greater mortality hazard. Haemoglobin levels in women showed a similar but smaller, non‐significant pattern: hazard ratio 1·32 (0·91–1·92) for severe anaemia (<110 g/l), and 1·30 (0·95–1·79) for high haemoglobin (≥150 g/l). This research supports the use of the World Health Organization thresholds (130 g/l for men, 120 g/l for women).
Improved outcome for children with non‐high risk acute lymphoblastic leukaemia after using an ALL IC‐BFM 2002‐based protocol in Shanghai, China
Authors: Gao Yi‐Jin , Qian Xiao‐Wen , Lu Feng‐Juan , Zhai Xiao‐Wen , Wang Hong‐Sheng , Li Jun
Published: November 2012

We report the outcome of 92 non‐high risk children with acute lymphoblastic leukaemia (ALL) following a Berlin‐Frankfürt‐Münster (BFM) Intercontinental ALL ‐based protocol. Compared with a matched historical control group, we found a lower incidence of treatment‐related early death (1·2% vs. 10·9%, P = 0·015), a higher 6‐year event‐free survival (75·4 ± 4·9% vs. 58·2 ± 6·7%, P = 0·02), reduced total in‐hospital costs per person (US $) (10267·0 vs. 18331·0, P < 0·001) and fewer total in‐hospital days (164 vs. 296, P < 0·001). This ALL‐BFM based protocol was quite tolerable in our institution and will be extended to high‐risk patients.
Food Deprivation and Restriction During late Gestation Affect the Sexual Behavior of Postpartum Female Meadow Voles, Microtus pennsylvanicus
Authors: Sabau Ramona M. , Ferkin Michael H.
Published: November 2012

In many species of small mammals, including meadow voles, Microtus pennsylvanicus, females come into postpartum estrus (PPE) within 12–24 h of giving birth, allowing them to mate and become pregnant while raising the current litter. PPE females show increases in attractivity, proceptivity, and receptivity, the three components of sexual behavior, relative to females not in PPE. Several studies have shown that food deprivation and restriction reduce attractivity, proceptivity, and receptivity of females not in PPE. We tested the hypothesis that food deprivation and restriction during late gestation cause deficits and decrease the attractivity, proceptivity, and receptivity of females when they enter PPE. Our data support the hypothesis. On day 1 of lactation, females that were food deprived and food restricted produced scent marks that were significantly less attractive as those produced by control PPE females. Food deprivation but not food restriction caused females to no longer display significant preferences for the scent marks of males over those of females (proceptivity). Food deprivation and food restriction were sufficient to induce females to become significantly less sexually receptive than control females. Eleven of 12 control PPE females mated, 4 of 12 food‐restricted females mated, and 3 of 12 food‐deprived females mated. Dams facing food deprivation or restriction during late gestation may have to balance the benefits of mating during PPE with the increased costs associated with getting pregnant while they are lactating.
Acetate Metabolism During Hemodialysis
Authors: Weiner Michael W.
Published: November 2012

We infused acetate into normal human subjects and performed kinetic analysis of the plasma and urine values obtained before, during, and after the infusion. The data were best fitted by a first‐order elimination process with a mean metabolic clearance rate of 2.3 L/min. Gotch and Sargent had previously suggested that during dialysis, acetate metabolism was zero order. We performed kinetic modeling of acetate concentrations during dialysis. The data were best fitted to a Michaelis‐Menton model (i.e., first‐order metabolism at low concentrations and saturated at high concentrations). The mean Km for acetate in the dialysis patients was 8.5 mM and the mean Vmax was 18 mmol/min. Patients with a Vmax less than 7 mmol/min usually had a fall in plasma bicarbonate during dialysis while patients with a Vmax greater than 14 mmol/min usually had a rise in bicarbonate during dialysis. It is concluded that during high‐surface‐area dialysis, the capacity for acetate metabolism will affect acid‐base homeostasis. Kinetic modeling will be useful to define acetate‐intolerant patients and may be used to predict patients who will benefit from bicarbonate hemodialysis.
The Effect of Acetate and Bicarbonate Dialysis on Orthostatic Blood Pressure Regulation
Authors: Landwehr D. M. , Okusa M. D.
Published: November 2012

Dialysis‐induced hypotension is probably due to multiple factors which reduce cardiac output and peripheral vascular resistance. That acetate, used in dialysate as a source of bicarbonate, may be one of these factors is suggested from several studies which show improved blood pressure regulation with bicarbonate‐containing dialysate. We have further examined this hypothesis by comparing supine and standing blood pressure changes in nine stable patients during dialysis with acetate or bicarbonate solutions. Although mean weight changes were not different, standing blood pressure was lower after acetate dialysis. Such a hypotensive effect of acetate could result from depression of the force of myocardial contraction and/or from a reduction in peripheral vascular resistance.
Effect of Bicarbonate‐Containing Dialysate on Chronic Hemodialysis Patients: A Comparative Study
Authors: Man N. K. , Fournier G. , Thireau P. , Gaillard J. L. , Funck‐Brentano J.‐L.
Published: November 2012

Changes in pH and blood gases were studied during hemodialysis with both acetate and bicarbonate dialysates. During acetate dialysis, Pao2 and Paco2 decreased significantly (P < 0.05) from 101 ± 2 to 93 ± 3 mmHg and from 34.4 ± 1.0 to 31.8 ± 0.9 mmHg, respectively, whereas during bicarbonate dialysis neither parameter changed significantly. The final pH was 7.45 ± 0.01 during acetate dialysis and 7.50 ± 0.02 during bicarbonate dialysis. Plasma bicarbonate rose immediately and progressively from 18.9 ± 0.8 to 26.8 ± 0.9 mmol/L with bicarbonate dialysis, whereas the increase was moderate, from 19.6 ± 0.6 to 22.3 ± 0.5 mmol/L, with acetate dialysis. These data indicate that dialysis‐induced hypoxemia was prevented and correction of acidosis was more adequate with bicarbonate dialysis. During a two‐year period on bicarbonate dialysis, total cholesterol, HDL‐cholesterol, and triglycerides did not change significantly when compared to acetate dialysis. The most striking change was the increased tolerance to dialysis with bicarbonate dialysis, which included a 50% reduction in hypotensive episodes and muscle cramps and an almost complete absence of headache, nausea, and vomiting.
A Modified Obesity Proneness Model Predicts Adolescent Weight Concerns and Inability to Self‐Regulate Eating
Authors: Nickelson Jen , Bryant Carol A. , McDermott Robert J. , Buhi Eric R. , DeBate Rita D.
Published: November 2012

BACKGROUND: The prevalence of obesity among high school students has risen in recent decades. Many high school students report trying to lose weight and some engage in disordered eating to do so. The obesity proneness model suggests that parents may influence their offspring's development of disordered eating. This study examined the viability of a modified obesity proneness model in a high school population.

METHODS: Cross‐sectional survey data from a random cluster sample of 1533 students in grades 9–12 from a Florida school district were analyzed using structural equation modeling. Variables included adolescents' weight concerns; inability to self‐regulate eating; and perceptions about maternal comments about adolescents' weight, restrictive feeding practices, and maternal weight‐related concern and values.

RESULTS: All the model's originally proposed relationships were statistically significant, for example perceived maternal weight comments were associated with adolescents' weight concerns (β = 0.64; p < .0001), and perceived maternal restrictive feeding practices were associated with adolescents' inability to self‐regulate eating (β = 0.22; p < .001).

CONCLUSION: Some points of intervention should be subjected to empirical study. These interventions should give mothers guidance about appropriate feeding practices and discourage mothers from making weight‐related comments to their offspring. Together, as 1 component of a multilevel intervention, these behaviors may help prevent disordered eating and obesity.
Simulation Based Optimization for World Line Card Production System
Authors: APAK Sinan , ERCAN Sami
Published: November 2012

Simulation based decision support system is one of the commonly used tool to examine complex production systems. The simulation approach provides process modules which can be adjusted with certain parameters by using data relatively easily obtainable in production process. World Line Card production system simulation is developed to evaluate the optimality of existing production line via using discrete event simulation model with variaty of alternative proposals. The current production system is analysed by a simulation model emphasizing the bottlenecks and the poorly utilized production line. Our analysis identified some improvements and efficient solutions for the existing system.
Application of Response Surface Methodology (RSM) for Optimization of Operating Parameters and Performance Evaluation of Cooling Tower Cold Water Temperature
Authors: RAMAKRISHNAN Ramkumar , ARUMUGAM Ragupathy
Published: November 2012

Performance  of the coolig tower was analysed with various operating parameters and find the minimum cold water temperature. In this study, optimization of operating parameters was investigated. An experimental design was carried out based on central composite design(CCD) with response surface methodology(RSM). This paper presents optimum operating parameters and   the minimum cold water temperature using RSM method.  The RSM was used to evaluate the effects of operating variables and their interaction towards the attainment of their optimum conditions. Based on statistical analysis, water flow, air flow, hot water temperature and packing height were high significant on cold water temperature, with very low probability values(<0.0001). The optimum operating parameters predicted using  RSM method and confirmed through experiment.
A Vitrage of Asteroid Magnetism
Authors: Weiss Benjamin P.
Published: November 2012

A group of stony-iron meteorites record an ancient magnetic field that may reveal an origin far from the asteroidal core.
A Classic Continued Up to the Present
Women Scientists in America
Volume 3, Forging a New World Since 1972

by Margaret W. Rossiter

Johns Hopkins University Press, Baltimore, MD, 2012. 464 pp. $90, £47. ISBN 9781421402338. Paper, $45, £23.50. ISBN 9781421403632.
Authors: Montgomery Georgina M.
Published: November 2012

In this third volume of her historical survey of American women scientists, Rossiter highlights their circumstances, tribulations, and successes since the early 1970s.
Old Challenges, New Faces Await Science Community in 2013
Authors: Mervis Jeffrey
Published: November 2012

When the new Congress convenes in January, the House will be without two of its staunchest advocates for federally funded research, as Judy Biggert (R–IL) and Brian Bilbray (R–CA) lost their seats.
The Evolutionary Allure of Mussels
Authors: Stokstad Erik
Published: November 2012

Genetic studies have revealed that mussel diversity in North America is even higher than past studies suggested, meaning species that were once thought to be widely distributed could in fact be imperiled.
Slip Sliding Away
Authors: Qiu Jane
Published: November 2012

Fifty percent more meltwater than 15 years ago is gushing from the cavity beneath Pine Island Glacier and a widening gap between the ice and an underwater ridge crest, probably due to sustained melting.
Emergence of OXA-48 and OXA-181 Carbapenemases among Enterobacteriaceae in South Africa and Evidence of
In Vivo
Selection of Colistin Resistance as a Consequence of Selective Decontamination of the Gastrointestinal Tract
Authors: Brink Adrian J. , Coetzee Jennifer , Corcoran Craig , Clay Cornelis G. , Hari-Makkan Danusha , Jacobson Rachael K. , Richards Guy A. , Feldman Charles , Nutt Louise , van Greune Johan , Deetlefs J. D. , Swart Karin , Devenish Lesley , Poirel Laurent , Nordmann Patrice
Published: November 2012

This study reports on the emergence of OXA-48-like carbapenemases among isolates of
Enterobacteriaceae
in South Africa. In addition, the emergence during therapy of a colistin-resistant OXA-181-producing
Klebsiella pneumoniae
isolate was documented following selective digestive tract decontamination with oral colistin, which is therefore strongly discouraged.
Characterization of Hepatitis C Virus Recombinants with Chimeric E1/E2 Envelope Proteins and Identification of Single Amino Acids in the E2 Stem Region Important for Entry
Authors: Carlsen Thomas H. R. , Scheel Troels K. H. , Ramirez Santseharay , Foung Steven K. H. , Bukh Jens
Published: November 2012

The hepatitis C virus (HCV) envelope proteins E1 and E2 play a key role in host cell entry and represent important targets for vaccine and drug development. Here, we characterized HCV recombinants with chimeric E1/E2 complexes
in vitro
. Using genotype 1a/2a JFH1-based recombinants expressing 1a core-NS2, we exchanged E2 with functional isolate sequences of genotypes 1a (alternative isolate), 1b, and 2a. While the 1a-E2 exchange did not impact virus viability, the 2a-E2 recombinant was nonviable. After E2 exchange from three 1b isolates, long delays were observed before spread of infection. For recovered 1b-E2 recombinants, single E2 stem region amino acid changes were identified at residues 706, 707, and 710. In reverse genetic studies, these mutations increased infectivity titers by ∼100-fold, apparently without influencing particle stability or cell binding although introducing slight decrease in particle density. In addition, the 1b-E2 exchange led to a decrease in secreted core protein of 25 to 50%, which was further reduced by the E2 stem region mutations. These findings indicated that compensatory mutations permitted robust infectious virus production, without increasing assembly/release. Studies of E1/E2 heterodimerization showed no differences in intracellular E1/E2 interaction for chimeric constructs with or without E2 stem region mutations. Interestingly, the E2 stem region mutations allowed efficient entry, which was verified in 1a-E1/1b-E2 HCV pseudoparticle assays. A CD81 inhibition assay indicated that the mutations influenced a late step of the HCV entry pathway. Overall, this study identified specific amino acids in the E2 stem region of importance for HCV entry and for production of infectious virus particles.
Human Papillomavirus E7 Induces Rereplication in Response to DNA Damage
Authors: Fan Xueli , Liu Yingwang , Heilman Susan A. , Chen Jason J.
Published: November 2012

Human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis. Genomic instability caused by HPV allows cells to acquire additional mutations required for malignant transformation. Genomic instability in the form of polyploidy has been demonstrated to play an important role in cervical carcinogenesis. We have recently found that HPV-16 E7 oncogene induces polyploidy in response to DNA damage; however, the mechanism is not known. Here we present evidence demonstrating that HPV-16 E7-expressing cells have an intact G
2
checkpoint. Upon DNA damage, HPV-16 E7-expressing cells arrest at the G
2
checkpoint and then undergo rereplication, a process of successive rounds of host DNA replication without entering mitosis. Interestingly, the DNA replication initiation factor Cdt1, whose uncontrolled expression induces rereplication in human cancer cells, is upregulated in E7-expressing cells. Moreover, downregulation of Cdt1 impairs the ability of E7 to induce rereplication. These results demonstrate an important role for Cdt1 in HPV E7-induced rereplication and shed light on mechanisms by which HPV induces genomic instability.
Increasing Expression of MicroRNA 181 Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication and Has Implications for Controlling Virus Infection
Authors: Guo Xue-kun , Zhang Qiong , Gao Li , Li Ning , Chen Xin-xin , Feng Wen-hai
Published: November 2012

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important viral pathogens in the swine industry. Emerging evidence indicates that the host microRNAs (miRNAs) are involved in host-pathogen interactions. However, whether host miRNAs can target PRRSV and be used to inhibit PRRSV infection has not been reported. Recently, microRNA 181 (miR-181) has been identified as a positive regulator of immune response, and here we report that miR-181 can directly impair PRRSV infection. Our results showed that delivered miR-181 mimics can strongly inhibit PRRSV replication
in vitro
through specifically binding to a highly (over 96%) conserved region in the downstream of open reading frame 4 (ORF4) of the viral genomic RNA. The inhibition of PRRSV replication was specific and dose dependent. In PRRSV-infected Marc-145 cells, the viral mRNAs could compete with miR-181-targeted sequence in luciferase vector to interact with miR-181 and result in less inhibition of luciferase activity, further demonstrating the specific interactions between miR-181 and PRRSV RNAs. As expected, miR-181 and other potential PRRSV-targeting miRNAs (such as miR-206) are expressed much more abundantly in minimally permissive cells or tissues than in highly permissive cells or tissues. Importantly, highly pathogenic PRRSV (HP-PRRSV) strain-infected pigs treated with miR-181 mimics showed substantially decreased viral loads in blood and relief from PRRSV-induced fever compared to negative-control (NC)-treated controls. These results indicate the important role of host miRNAs in modulating PRRSV infection and viral pathogenesis and also support the idea that host miRNAs could be useful for RNA interference (RNAi)-mediated antiviral therapeutic strategies.
Cyclin T1 and CDK9 T-Loop Phosphorylation Are Downregulated during Establishment of HIV-1 Latency in Primary Resting Memory CD4+T Cells
Authors: Budhiraja Sona , Famiglietti Marylinda , Bosque Alberto , Planelles Vicente , Rice Andrew P.
Published: November 2012

P-TEFb, a cellular kinase composed of Cyclin T1 and CDK9, is essential for processive HIV-1 transcription. P-TEFb activity is dependent on phosphorylation of Thr186 in the CDK9 T loop. In resting CD4+T cells which are nonpermissive for HIV-1 replication, the levels of Cyclin T1 and T-loop-phosphorylated CDK9 are very low but increase significantly upon cellular activation. Little is known about how P-TEFb activity and expression are regulated in resting central memory CD4+T cells, one of the main reservoirs of latent HIV-1. We used anin vitroprimary cell model of HIV-1 latency to show that P-TEFb availability in resting memory CD4+T cells is governed by the differential expression and phosphorylation of its subunits. This is in contrast to previous observations in dividing cells, where P-TEFb can be regulated by its sequestration in the 7SK RNP complex. We find that resting CD4+T cells, whether naïve or memory and independent of their infection status, have low levels of Cyclin T1 and T-loop-phosphorylated CDK9, which increase upon activation. We also show that the decrease in Cyclin T1 protein upon the acquisition of a memory phenotype is in part due to proteasome-mediated proteolysis and likely also to posttranscriptional downregulation by miR-150. We also found that HEXIM1 levels are very low inex vivo- andin vitro-generated resting memory CD4+T cells, thus limiting the sequestration of P-TEFb in the 7SK RNP complex, indicating that this mechanism is unlikely to be a driver of viral latency in this cell type.
Critical Roles of Glucocorticoid-Induced Leucine Zipper in Infectious Bursal Disease Virus (IBDV)-Induced Suppression of Type I Interferon Expression and Enhancement of IBDV Growth in Host Cells via Interaction with VP4
Authors: Li Zhonghua , Wang Yongqiang , Li Xiang , Li Xiaoqi , Cao Hong , Zheng Shijun J.
Published: November 2012

Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced immunosuppression has been well established, the underlying exact molecular mechanism for such induction is not very clear. We report here the identification of IBDV VP4 as an interferon suppressor by interaction with the glucocorticoid-induced leucine zipper (GILZ) in host cells. We found that VP4 suppressed the expression of type I interferon in HEK293T cells after tumor necrosis factor alpha (TNF-α) treatment or Sendai virus (SeV) infection and in DF-1 cells after poly(I·C) stimulation. In addition, the VP4-induced suppression of type I interferon could be completely abolished by knockdown of GILZ by small interfering RNA (siRNA). Furthermore, knockdown of GILZ significantly inhibited IBDV growth in host cells, and this inhibition could be markedly mitigated by anti-alpha/beta interferon antibodies in the cell cultures (P< 0.001). Thus, VP4-induced suppression of type I interferon is mediated by interaction with GILZ, a protein that appears to inhibit cell responses to viral infection.
Suppression of HIV-1 Infection by APOBEC3 Proteins in Primary Human CD4
+
T Cells Is Associated with Inhibition of Processive Reverse Transcription as Well as Excessive Cytidine Deamination
Authors: Gillick Kieran , Pollpeter Darja , Phalora Prabhjeet , Kim Eun-Young , Wolinsky Steven M. , Malim Michael H.
Published: November 2012

The Vif protein of human immunodeficiency virus type 1 (HIV-1) promotes viral replication by downregulation of the cell-encoded, antiviral APOBEC3 proteins. These proteins exert their suppressive effects through the inhibition of viral reverse transcription as well as the induction of cytidine deamination within nascent viral cDNA. Importantly, these two effects have not been characterized in detail in human CD4
+
T cells, leading to controversies over their possible contributions to viral inhibition in the natural cell targets of HIV-1 replication. Here we use wild-type and Vif-deficient viruses derived from the CD4
+
T cells of multiple donors to examine the consequences of APOBEC3 protein function at natural levels of expression. We demonstrate that APOBEC3 proteins impart a profound deficiency to reverse transcription from the initial stages of cDNA synthesis, as well as excessive cytidine deamination (hypermutation) of the DNAs that are synthesized. Experiments using viruses from transfected cells and a novel method for mapping the 3′ termini of cDNAs indicate that the inhibition of reverse transcription is not limited to a few specific sites, arguing that APOBEC3 proteins impede enzymatic processivity. Detailed analyses of mutation spectra in viral cDNA strongly imply that one particular APOBEC3 protein, APOBEC3G, provides the bulk of the antiviral phenotype in CD4
+
T cells, with the effects of APOBEC3F and APOBEC3D being less significant. Taken together, we conclude that the dual mechanisms of action of APOBEC3 proteins combine to deliver more effective restriction of HIV-1 than either function would by itself.
Multiple Gag Domains Contribute to Selective Recruitment of Murine Leukemia Virus (MLV) Env to MLV Virions
Authors: Gregory Devon A. , Lyddon Terri D. , Johnson Marc C.
Published: November 2012

Retroviruses, like all enveloped viruses, must incorporate viral glycoproteins to form infectious particles. Interactions between the glycoprotein cytoplasmic tail and the matrix domain of Gag are thought to direct recruitment of glycoproteins to native virions for many retroviruses. However, retroviruses can also incorporate glycoproteins from other viruses to form infectious virions known as pseudotyped particles. The glycoprotein murine leukemia virus (MLV) Env can readily form pseudotyped particles with many retroviruses, suggesting a generic mechanism for recruitment. Here, we sought to identify which components of Gag, particularly the matrix domain, contribute to recruitment of MLV Env into retroviral particles. Unexpectedly, we discovered that the matrix domain of HIV-1 Gag is dispensable for generic recruitment, since it could be replaced with a nonviral membrane-binding domain without blocking active incorporation of MLV Env into HIV virions. However, MLV Env preferentially assembles with MLV virions. When MLV and HIV particles are produced from the same cell, MLV Env is packaged almost exclusively by MLV particles, thus preventing incorporation into HIV particles. Surprisingly, the matrix domain of MLV Gag is not required for this selectivity, since MLV Gag containing the matrix domain from HIV is still able to outcompete HIV particles for MLV Env. Although MLV Gag is sufficient for selective incorporation to occur, no single Gag domain dictates the selectivity. Our findings indicate that Env recruitment is more complex than previously believed and that Gag assembly/budding sites have fundamental properties that affect glycoprotein incorporation.
Assessment of simple risk markers for early mortality among HIV-infected patients in Guinea-Bissau: a cohort study
Authors: Oliveira Inés , Andersen Andreas , Furtado Alcino , Medina Candida , da Silva David , da Silva Zacarias J , Aaby Peter , Laursen Alex Lund , Wejse Christian , Eugen-Olsen Jesper ,   for the Bissau HIV cohort study group
Published: November 2012

Background

Decisions about when to start an antiretroviral therapy (ART) are normally based on CD4 cell counts and viral load (VL). However, these measurements require equipment beyond the capacity of most laboratories in low-income and middle-income settings. Thus, there is an urgent need to identify and test simple markers to guide the optimal time for starting and for monitoring the effect of ART in developing countries.

Objectives

(1) To evaluate anthropometric measurements and measurement of plasma-soluble form of the urokinase plasminogen activator receptor (suPAR) levels as potential risk factors for early mortality among HIV-infected patients; (2) to assess whether these markers could help identify patients to whom ART should be prioritised and (3) to determine if these markers may add information to CD4 cell count when VL is not available.

Design

An observational study.

Setting

The largest ART centre in Bissau, Guinea-Bissau.

Participants

1083 ART-naïve HIV-infected patients.

Outcome measures

Associations between baseline anthropometric measurements, CD4 cell counts, plasma suPAR levels and survival were examined using Cox proportional hazards models.

Results

Low body mass index (BMI≤18.5 kg/m2), low mid-upper-arm-circumference (MUAC≤250 mm), low CD4 cell count (≤350 cells/μl) and high suPAR plasma levels (>5.3 ng/ml) were independent predictors of death. Furthermore, mortality among patients with low CD4 cell count, low MUAC or low BMI was concentrated in the highest suPAR quartile.

Conclusions

Irrespective of ART initiation and baseline CD4 count, MUAC and suPAR plasma levels were independent predictors of early mortality in this urban cohort. These markers could be useful in identifying patients at the highest risk of short-term mortality and may aid triage for ART when CD4 cell count is not available or when there is shortness of antiretroviral drugs.
How might the London 2012 Olympics influence health and the determinants of health? Local newspaper analysis of pre-Games pathways and impacts
Authors: Selvanayagam Marinie , Thompson Claire , Taylor Stephanie J C , Cummins Steven , Bourke Liam
Published: November 2012

Objectives

To conduct a content analysis of pre-Games local media coverage of the potential impact on health and the determinants of health in Newham, the site of the Olympic Park.

Design

Local newspaper content analysis.

Setting

Olympic park host site of the London Borough of Newham.

Outcome measures

Media coverage of employment, physical activity and well-being.

Results

Three hundred and 51 articles meeting the inclusion criteria were included in the analysis. The overwhelming majority of the articles took a positive perspective on the Olympic Games being hosted in Newham with less than 10% (32/351) addressing potential adverse effects. The frequency of articles reporting on both employment and well-being increased significantly over time (p=0.002 and p=0.006, respectively). A non-significant increasing trend was observed for physical activity (p=0.146). New employment opportunities and the promotion of physical activity in young people were the pathways most frequently reported in the local media. However, much less attention is devoted to understanding the uncertainties about how much of these new opportunities will directly improve the determinants of health in the Newham population.

Conclusions

Pre-Games reporting on the impact on health and the determinants of health increased over time in the London Borough of Newham, and is overwhelmingly positive. However, specific uncertainties around the true nature of its impact on local employment and physical activity were articulated. Further evaluation of the tangible impacts on population health, and the determinants of health and health inequalities from the London 2012 Olympics, is required.