bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual‐specificity phosphatase 26 (DUSP26) stimulates Aβ42 generation by promoting amyloid precursor protein axonal transport during hypoxia
Authors: Jung Sunmin , Nah Jihoon , Han Jonghee , Choi Seon‐Guk , Kim Hyunjoo , Park Jaesang , Pyo Ha‐Kyung , Jung Yong‐Keun 
Published: February 2016

AbstractAmyloid beta peptide (Aβ) is a pathological hallmark of Alzheimer's disease (AD) and is generated through the sequential cleavage of amyloid precursor protein (APP) by β‐ and γ‐secretases. Hypoxia is a known risk factor for AD and stimulates Aβ generation by γ‐secretase; however, the underlying mechanisms remain unclear. In this study, we showed that dual‐specificity phosphatase 26 (DUSP26) regulates Aβ generation through changes in subcellular localization of the γ‐secretase complex and its substrate C99 under hypoxic conditions. DUSP26 was identified as a novel γ‐secretase regulator from a genome‐wide functional screen using a cDNA expression library. The phosphatase activity of DUSP26 was required for the increase in Aβ42 generation through γ‐secretase, but this regulation did not affect the amount of the γ‐secretase complex. Interestingly, DUSP26 induced the accumulation of C99 in the axons by stimulating anterograde transport of C99‐positive vesicles. Additionally, DUSP26 induced c‐Jun N‐terminal kinase (JNK) activation for APP processing and axonal transport of C99. Under hypoxic conditions, DUSP26 expression levels were elevated together with JNK activation, and treatment with JNK inhibitor SP600125, or the DUSP26 inhibitor NSC‐87877, reduced hypoxia‐induced Aβ generation by diminishing vesicle trafficking of C99 to the axons. Finally, we observed enhanced DUSP26 expression and JNK activation in the hippocampus of AD patients. Our results suggest that DUSP26 mediates hypoxia‐induced Aβ generation through JNK activation, revealing a new regulator of γ‐secretase‐mediated APP processing under hypoxic conditions.
imageWe propose the role of phosphatase dual‐specificity phosphatase 26 (DUSP26) in the selective regulation of Aβ42 production in neuronal cells under hypoxic stress. Induction of DUSP26 causes JNK‐dependent shift in the subcellular localization of γ‐secretase and C99 from the cell body to axons for Aβ42 generation. These findings provide a new strategy for developing new therapeutic targets to arrest AD progression.
Anorexia is Associated with Stress‐Dependent Orexigenic Responses to Exogenous Neuropeptide Y
Authors: Yi J. , Delp M. S. , Gilbert E. R. , Siegel P. B. , Cline M. A. 
Published: February 2016

Chicken lines that have been divergently selected for either low (LWS) or high (HWS) body weight at 56 days of age for more than 57 generations have different feeding behaviours in response to a range of i.c.v. injected neurotransmitters. The LWS have different severities of anorexia, whereas the HWS become obese. Previously, we demonstrated that LWS chicks did not respond, whereas HWS chicks increased food intake, after central injection of neuropeptide Y (NPY). The present study aimed to determine the molecular mechanisms underlying the loss of orexigenic function of NPY in LWS. Chicks were divided into four groups: stressed LWS and HWS on day of hatch, and control LWS and HWS. The stressor was a combination of food deprivation and cold exposure. On day 5 post‐hatch, each chick received an i.c.v. injection of vehicle or 0.2 nmol of NPY. Only the LWS stressed group did not increase food intake in response to i.c.v. NPY. Hypothalamic mRNA abundance of appetite‐associated factors was measured at 1 h post‐injection. Interactions of genetic line, stress and NPY treatment were observed for the mRNA abundance of agouti‐related peptide (AgRP) and synaptotagmin 1 (SYT1). Intracerebroventricular injection of NPY decreased and increased AgRP and SYT1 mRNA, respectively, in the stressed LWS and increased AgRP mRNA in stressed HWS chicks. Stress was associated with increased NPY, orexin receptor 2, corticotrophin‐releasing factor receptor 1, melanocortin receptor 3 (MC3R) and growth hormone secretagogue receptor expression. In conclusion, the loss of responsiveness to exogenous NPY in stressed LWS chicks may be a result of the decreased and increased hypothalamic expression of AgRP and MC3R, respectively. This may induce an intensification of anorexigenic melanocortin signalling pathways in LWS chicks that block the orexigenic effect of exogenous NPY. These results provide insights onto the anorexic condition across species, and especially for forms of inducible anorexia such as human anorexia nervosa.
In ovo testosterone treatment reduces long‐term survival of female pigeons: a preliminary analysis after nine years of monitoring
Authors: Matson K. D. , Riedstra B. , Tieleman B. I. 
Published: February 2016

SummaryEarly exposure to steroid hormones, as in the case of an avian embryo exposed yolk testosterone, can impact the biology of an individual in different ways over the course of its life. While many early‐life effects of yolk testosterone have been documented, later‐life effects remain poorly studied. We followed a cohort of twenty captive pigeons hatched in 2005. Half of these birds came from eggs with experimentally increased concentrations of testosterone; half came from control eggs. Preliminary results suggest non‐random mortality during the birds’ first nine years of life. Hitherto, all males have survived, and control females have survived better than testosterone‐treated ones. Despite inherent challenges, studies of later‐life consequences of early‐life exposure in longer‐lived species can offer new perspectives that are precluded by studies of immediate outcomes or shorter‐lived species.
Potential market size and impact of hepatitis C treatment in low‐ and middle‐income countries
Authors: Woode M. E. , Abu‐Zaineh M. , Perriëns J. , Renaud F. , Wiktor S. , Moatti J.‐P. 
Published: February 2016

SummaryThe introduction of direct‐acting antiviral agents (DAAs) has made hepatitis C infection curable in the vast majority of cases and the elimination of the infection possible. Although initially too costly for large‐scale use, recent reductions in DAA prices in some low‐ and middle‐income countries (LaMICs) has improved the prospect of many people having access to these drugs/medications in the future. This article assesses the pricing and financing conditions under which the uptake of DAAs can increase to the point where the elimination of the disease in LaMICs is feasible. A Markov simulation model is used to study the dynamics of the infection with the introduction of treatment over a 10‐year period. The impact on HCV‐related mortality and HCV incidence is assessed under different financing scenarios assuming that the cost of the drugs is completely paid for out‐of‐pocket or reduced through either subsidy or drug price decreases. It is also assessed under different diagnostic and service delivery capacity scenarios separately for low‐income (LIC), lower‐middle‐income (LMIC) and upper‐middle‐income countries (UMIC). Monte Carlo simulations are used for sensitivity analyses. At a price of US$ 1680 per 12‐week treatment duration (based on negotiated Egyptian prices for an all oral two‐DAA regimen), most of the people infected in LICs and LMICs would have limited access to treatment without subsidy or significant drug price decreases. However, people in UMICs would be able to access it even in the absence of a subsidy. For HCV treatment to have a significant impact on mortality and incidence, a significant scaling‐up of diagnostic and service delivery capacity for HCV infection is needed.
Safety and efficacy of sofosbuvir‐containing regimens in hepatitis C‐infected patients with impaired renal function
Authors: Saxena Varun , Koraishy Farrukh M. , Sise Meghan E. , Lim Joseph K. , Schmidt Monica , Chung Raymond T. , Liapakis Annmarie , Nelson David R. , Fried Michael W. , Terrault Norah A. ,   HCV‐TARGET
Published: February 2016

AbstractBackground & AimsRenal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF‐containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR).MethodsHCV‐TARGET database is a multicentre, longitudinal ‘real‐world’ treatment cohort.ResultsA total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4–6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m2. Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post‐transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400–1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82–83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV‐free regimens. Patients with baseline eGFR≤30 and eGFR 31–45 had similar frequencies of efficacy and safety outcomes.ConclusionsSustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m2) treated with SOF‐containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF‐containing regimens.
The unexpected mating system of the androdioecious barnacle Chelonibia testudinaria (Linnaeus 1758)
Authors: Ewers‐Saucedo Christine , Hope Neva B. , Wares John P. 
Published: February 2016

AbstractAndrodioecy was first described by Darwin in his seminal work on barnacle diversity; he identified males and hermaphrodites in the same reproductive population. Today, we realize that many androdioecious plants and animals share astonishing similarities, particularly with regard to their evolutionary history and mating system. Notably, these species were ancestrally dioecious, and their mating system has the following characteristics: hermaphrodites self‐fertilize frequently, males are more successful in large mating groups, and males have a mating advantage. A male mating advantage makes androdioecy more likely to persist over evolutionary times. Androdioecious barnacles, however, appear to persist as an outlier with a different evolutionary trajectory: they originate from hermaphroditic species. Although sexual systems of androdioecious barnacles are known, no information on the mating system of androdioecious barnacles is available. This study assessed the mating system of the androdioecious barnacle Chelonibia testudinaria. In contrast to other androdioecious species, C. testudinaria does not self‐fertilize, males do not have a mating advantage over hermaphrodites, and the average mating group is quite small, averaging only three individuals. Mating success is increased by proximity to the mate and penis length. Taken together, the mating system of C. testudinaria is unusual in comparison with other androdioecious plants and animals, and the lack of a male mating advantage suggests that the mating system alone does not provide an explanation for the maintenance of androdioecy in this species. Instead, we propose that sex‐specific life history equalizes male and hermaphroditic overall fitness.
The invasive bighead goby Ponticola kessleri displays large‐scale genetic similarities and small‐scale genetic differentiation in relation to shipping patterns
Authors: Adrian‐Kalchhauser I. , Hirsch P. E. , Behrmann‐Godel J. , N'Guyen A. , Watzlawczyk S. , Gertzen S. , Borcherding J. , Burkhardt‐Holm P. 
Published: February 2016

AbstractColonization events, range expansions and species invasions leave genetic signatures in the genomes of invasive organisms and produce intricate special patterns. Predictions have been made as to how those patterns arise, but only very rarely, genetic processes can be monitored in real time during range expansions. In an attempt to change that, we track a very recently established invasive population of a fish species, the bighead goby Ponticola kessleri, with high temporal and spatial resolution through 2 years to identify patterns over time. We then compare Swiss and German samples of bighead goby along the river Rhine using microsatellites, mitochondrial D‐loop sequences and geometric morphometrics to investigate geographic patterns. We detect weak temporal and strong geographic patterns in the data, which are inconsistent with isolation by distance and indicate long range transport. In search of an explanation for our observations, we analyse the vector properties and travel patterns of commercial vessels on the river Rhine. We present evidence that freshwater cargo ships and tankers are plausible vectors for larvae of invasive goby species. We also present indications that cargo ships and tankers act as differential vectors for this species. In summary, we present genetic data at unique temporal resolution from a vertebrate invasion front and substantiate the paramount role of commercial shipping in freshwater fish translocations.
Thermogenic respiratory processes drive the exponential increase of volatile organic compound emissions in Macrozamia cycad cones
Authors: Terry L. Irene , Roemer Robert B. , Booth David T. , Moore Chris J. , Walter Gimme H. 
Published: February 2016

AbstractAn important outcome of plant thermogenesis is increased emissions of volatiles that mediate pollinator behaviour. We investigated whether the large increase in emissions, mainly the monoterpene ß‐myrcene (>90%), during daily thermogenic events of Macrozamia macleayi and lucida cycad cones are due solely to the influence of high cone temperatures or are, instead, a result of increased respiratory rates during thermogenesis. We concurrently measured temperature, oxygen consumption and ß‐myrcene emission profiles during thermogenesis of pollen cones under typical environmental temperatures and during experimental manipulations of cone temperatures and aerobic conditions, all in the dark. The exponential rise in ß‐myrcene emissions never occurred without a prior, large increase in respiration, whereas an increase in cone temperature alone did not increase emissions. When respiration during thermogenesis was interrupted by anoxic conditions, ß‐myrcene emissions decreased. The increased emission rates are not a result of increased cone temperature per se (through increased enzyme activity or volatilization of stored volatiles) but are dependent on biosynthetic pathways associated with increased respiration during thermogenesis that provide the carbon, energy (ATP) and reducing compounds (NADPH) required for ß‐myrcene production through the methylerythritol phosphate (MEP) pathway. These findings establish the significant contribution of respiration to volatile production during thermogenesis.
Pharmacokinetics and target attainment of mycophenolate in pediatric renal transplant patients
Authors: Martial Lisa C. , Jacobs Bart A. W. , Cornelissen Elisabeth A. M. , de Haan Anton F. J. , Koch Birgit C. P. , Burger David M. , Aarnoutse Rob E. , Schreuder Michiel F. , Brüggemann Roger J.M. 
Published: February 2016

AbstractMPA is an immunosuppressive agent used to prevent graft rejection after renal transplantation. MPA shows considerable inter‐ and intraindividual variability in exposure in children and has a defined therapeutic window, and TDM is applied to individualize therapy. We aimed to study the exposure to MPA measured as the AUC in pediatric renal transplant patients, to identify factors influencing exposure and to assess target attainment. Children transplanted between 1998 and 2014 in a single center were included. Two groups were identified: Group 1 (AUC <3 wk post‐transplantation) and Group 2 (AUC >18 months post‐transplantation). Therapeutic targets were set at: AUC0–12h of 30–60 mg h/L. A total of 39 children were included in Group 1 (median age 13.3 yr) vs. 14 in Group 2 (median age 13.4 yr). AUC0–12h was 29.7 mg h/L in Group 1 and 56.6 mg h/L in Group 2, despite a lower dosage in Group 2 (584 and 426 mg/m2, respectively). About 46% of patients reached the target AUC0–12h in Group 1. Time since transplantation and serum creatinine were significantly associated with MPA exposure (p < 0.001), explaining 36% of the variability. Individualization of the mycophenolate dose by more intense and more early TDM could improve target attainment.
A Panel Regression Study on Multiple Predictors of Environmental Concern for 82 Countries Across Seven Years*
Authors: Hao Feng 
Published: February 2016

ObjectiveThis article evaluates the extent to which economic affluence, ecological degradation, integration into the world polity, and economic globalization each contributes to the change in environmental concern in 82 countries across seven years.MethodUsing multivariate panel regression, I have analyzed a combined data set of four waves of World Values Surveys and three waves of surveys from the International Social Survey Program.ResultsFindings reveal that exposure to ecological degradation is positively related to growing environmental concern, whereas economic affluence has a negative association. In addition, integration into the world polity does not affect environmental concern and the two indicators of economic globalization have mixed impact.ConclusionThis study demonstrates that potentially influential factors have different influence over public environmental concern. Thus, a parsimonious explanation is inadequate since there is no universalistic factor that can account for all variations in environmental concern.
Electoral Consequences of Lawmaking Activities for State Legislative Incumbents*
Authors: Hogan Robert E. , Kromer Mileah K. , Wrzenski Rhonda L. 
Published: February 2016

ObjectiveDo incumbent state legislators who introduce many bills or have high passage rates for their proposals receive an electoral benefit for these efforts? If so, where is such an electoral advantage manifested? Is it a direct effect whereby voters are more likely to recognize and reward a legislator's productivity? Or is the effect more indirect whereby potential candidates are less likely to challenge an active incumbent?MethodsThese questions are addressed in an analysis of legislative elections in 18 states over two election cycles.ResultsWithin the low‐information environment of state legislative elections, there is evidence of both direct and indirect effects of lawmaking activities. Higher rates of bill passage decrease the likelihood that incumbents are challenged in primaries. Bill passage also reduces the likelihood they face well‐financed opponents in the general election. Incumbents who introduce more legislation ultimately receive larger vote shares in general elections.ConclusionsIntroducing and passing legislation can enhance an incumbent's prospects for reelection.
Parfit on Personal Identity: Its Analysis and (Un)importance
Authors: Persson Ingmar 
Published: February 2016

AbstractThis article examines Derek Parfit's claim inReasons and Personsthat personal identity consists in non‐branching psychological continuity with the right kind of cause. It argues that such psychological accounts of our identity fail, but that their main rivals, biological or animalist accounts do not fare better. Instead it proposes an error‐theory to the effect that common sense takes us to be identical to our bodies on the erroneous assumption that our minds belong non‐derivatively to them, whereas they in fact belong to them derivatively in virtue of belonging to some proper parts of them, namely certain features of their brains. However, these features do not meet another necessary condition of being the subject or owner of our minds: the condition of being “accessible” so that we can attribute our mental states to them in everyday life. There is also the problem of specifying these features more precisely. Nothing meets these two conditions, so we are not identical to anything. This conclusion fits well with Parfit's claim that personal identity is not what matters. But although this negative claim is true, it is suggested that Parfit's positive account of what matters is mistaken: it is rather psychological similarity than psychological continuity/connectedness that matters.
Transfusion of irradiated red blood cell units with a potassium adsorption filter: A randomized controlled trial
Authors: Cid Joan , Villegas Vanessa , Carbassé Gloria , Alba Cristina , Perea Dolores , Lozano Miguel 
Published: February 2016

BACKGROUNDThe irradiation of red blood cells (RBCs) causes damage of the RBC membrane with increased potassium (K) leak during storage compared with nonirradiated RBC units of similar age. A previous in vitro study showed a mean reduction of K of 94 ± 5% with a potassium adsorption filter (PAF).STUDY DESIGN AND METHODSA prospective, single‐center, nonblinded, randomized controlled trial (RCT) was designed to evaluate the safety and efficacy of transfusing irradiated RBC units with the PAF. Patients 18 years of age or older who received irradiated RBC units due to chemotherapy‐induced anemia were randomly assigned to receive irradiated RBC units with the PAF (PAF group) or with the standard blood infusion set (control group). Primary outcome measures were safety and efficacy of the PAF (absolute change in hemoglobin [Hb] and K, respectively, in patient's blood values after transfusing the irradiated RBC units with or without the PAF).RESULTSA total of 63 irradiated RBC units were transfused to 17 patients in the control group, and a total of 56 irradiated RBC units were transfused to 13 patients in the PAF group. The absolute change of Hb (9.3 ± 6.3 g/L vs. 8.1 ± 5.8 g/L; p = 0.3) and the absolute change of K (−0.01 ± 0.4 mmol/L vs. −0.01 ± 0.3 mmol/L; p = 0.2) were comparable between the two groups of the trial.CONCLUSIONThe transfusion of 1 irradiated RBC unit with the PAF was as safe and efficacious as the transfusion of 1 irradiated RBC unit with the standard blood infusion set in patients with chemotherapy‐induced anemia.
Effect of nitrogen fertilization on camelina seed yield, yield components, and downy mildew infection
Authors: Jiang Yunfei* , Caldwell Claude D. 
Published: February 2016

Camelina [Camelina sativa (L.) Crantz] has potential in aquaculture, livestock feed production, and the biofuel industry. It is necessary to determine the appropriate production technology for the newly introduced crop under different environmental conditions. The objective of this 2-year study was to measure the response of five camelina genotypes in terms of seed yield, yield components, and disease incidence to applied nitrogen (N) at multiple sites in the Maritime provinces of eastern Canada. The factorial experiment was set up as a randomized complete block design. The two factors were six N rates (0, 25, 50, 100, 150, and 200 kg ha−1 N) and five genotypes of camelina (Calena, CDI002, CDI005, CDI007, and CDI008). The interactive effect of N rates and genotypes was considered. Results showed that camelina, which is usually considered a low-input crop, responded positively to increased applied N at rates up to 200 kg ha−1 N. Seed yield responded differently to applied N rates depending on genotype. Branch and pod development were decisive for seed yield. The advanced line CDI007 had the highest yield potential among the five genotypes. Downy mildew infection was positively correlated with applied N rates; however, seed yield was not significantly affected by downy mildew infection.