bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 prevents neurodegeneration by regulating synaptic genes
Authors: Merlo Paola , Frost Bess , Peng Shouyong , Yang Yawei J. , Park Peter J. , Feany Mel 
Published: December 2014

Significance
The transcription factor p53 plays a critical role in the cellular response to DNA damage and has thus been studied intensively in oncogenesis research. However, the role that p53 plays in the response of postmitotic neurons to cellular stress has received less attention. Here we describe an unexpected neuroprotective role for p53 in an in vivo model of tau-mediated neurodegeneration relevant to Alzheimer's disease and related disorders. Further, we identify synaptic function as a novel target pathway for p53 in aging neurons, consistent with the growing evidence for synaptic pathology as an early event in neurodegenerative disease. Our study defines mechanistically a new, conserved role for p53 in protecting postmitotic neurons from degeneration during aging and disease.
Stoichiometry and assembly of mTOR complexes revealed by single-molecule pulldown
Authors: Jain Ankur , Arauz Edwin , Aggarwal Vasudha , Ikon Nikita , Chen Jie , Ha Taekjip 
Published: December 2014

Significance
The mammalian target of rapamycin (mTOR) kinase is a central regulator of cell growth, differentiation, and metabolism. mTOR is assembled into two distinct complexes, mTORC1 and mTORC2. Using single-molecule pulldown (SiMPull), we have determined the stoichiometric composition of mTORCs under growth and stress conditions. We find that both mTORC1 and mTORC2 form obligate dimers, in which major components exist in two copies per complex. Importantly, SiMPull allowed us to distinguish complex disassembly from stoichiometry changes, providing insights into the effects of physiological conditions and the drug rapamycin on mTOR complexes.
Direct interactions promote eviction of the Sir3 heterochromatin protein by the SWI/SNF chromatin remodeling enzyme
Authors: Manning Benjamin J. , Peterson Craig L. 
Published: December 2014

Significance
Heterochromatin is a repressive mode of genetic storage that prevents cellular machineries from accessing DNA sequences. Here, we investigate how a protein machine, called SWI/SNF, can disrupt these heterochromatin structures and facilitate nuclear processes. We identify physical and functional interactions between SWI/SNF and a key heterochromatin protein, silent information regulator 3p (Sir3p).
Bisphosphonates inactivate human EGFRs to exert antitumor actions
Authors: Yuen Tony , Stachnik Agnes , Iqbal Jameel , Sgobba Miriam , Gupta Yogesh , Lu Ping , Colaianni Graziana , Ji Yaoting , Zhu Ling-Ling , Kim Se-Min , Li Jianhua , Liu Peng , Izadmehr Sudeh , Sangodkar Jaya , Bailey Jack , Latif Yathin , Mujtaba Shiraz , Epstein Solomon , Davies Terry F. , Bian Zhuan , Zallone Alberta , Aggarwal Aneel K. , Haider Shozeb , New Maria I. , Sun Li , Narla Goutham , Zaidi Mone 
Published: December 2014

SignificanceFor over three decades, bisphosphonates have been used for the therapy of osteoporosis and skeletal metastasis. Here we show that this class of drugs reduces the viability of tumor cells that are driven by the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases. We also show that bisphosphonates directly bind to and inhibit HER kinases. Because bisphosphonates are inexpensive and readily available worldwide, our findings may have important healthcare implications by offering an affordable and multiuse alternative or adjunct to current therapies for HER-driven malignancy.
Comparison of Tributary Survival Estimates of Steelhead using Cormack–Jolly–Seber and Barker Models: Implications for Sampling Efforts and Designs
Authors: Conner Mary M. , Bennett Stephen N. , Saunders W. Carl , Bouwes Nicolaas 
Published: December 2014

AbstractWe conducted simulations to compare the precision and bias of survival estimates from Cormack–Jolly–Seber (CJS) and Barker models to known parameter values based on empirical data for steelhead/resident Rainbow Trout Oncorhynchus mykiss from the John Day River, Oregon. We simulated seasonal differences in recapture and survival rates, and we varied the number of fish tagged, recapture and resight rates, sample site size, and fish movement (migratory or resident). Survival estimates from the Barker model had higher precision and lower or equal bias in comparison with estimates from the CJS model under almost all simulation scenarios. The precision of Barker survival estimates increased the most as the number of tagged fish increased from 50 to 200 (CV = 0.4–0.09). The Barker model's superior performance was dependent on the availability of resight data; such data are becoming more readily available, especially in places where large numbers of individuals are PIT‐tagged and where an interrogation infrastructure exists (e.g., Columbia River basin). Tagging of 75–100 fish/site during high‐capture periods (e.g., summer and fall) and focusing on the resighting of fish with fixed or mobile interrogators during low‐capture periods (i.e., winter and spring) may be the most cost‐effective strategy for improving estimates of juvenile steelhead survival.Received April 18, 2014; accepted August 26, 2014
Fall Spawning of Atlantic Sturgeon in the Roanoke River, North Carolina
Authors: Smith Joseph A. , Flowers H. Jared , Hightower Joseph E. 
Published: December 2014

AbstractIn 2012, the National Oceanic and Atmospheric Administration (NOAA) declared Atlantic Sturgeon Acipenser oxyrinchus oxyrinchus to be threatened or endangered throughout its range in U.S. waters. Restoration of the subspecies will require much new information, particularly on the location and timing of spawning. We used a combination of acoustic telemetry and sampling with anchored artificial substrates (spawning pads) to detect fall (September–November) spawning in the Roanoke River in North Carolina. This population is included in the Carolina Distinct Population Segment, which was classified by NOAA as endangered. Sampling was done immediately below the first shoals encountered by anadromous fishes, near Weldon. Our collection of 38 eggs during the 21 d that spawning pads were deployed appears to be the first such collection (spring or fall) for wild‐spawned Atlantic Sturgeon eggs. Based on egg development stages, estimated spawning dates were September 17–18 and 18–19 at water temperatures from 25.3°C to 24.3°C and river discharge from 55 to 297 m3/s. These observations about fall spawning and habitat use should aid in protecting critical habitats and planning research on Atlantic Sturgeon spawning in other rivers.Received April 14, 2014; accepted September 9, 2014
ITER-like current ramps in JET with ILW: experiments, modelling and consequences for ITER
Authors: Hogeweij G.M.D. , Calabrò G. , Sips A.C.C. , Maggi C.F. , De Tommasi G.M. , Joffrin E. , Loarte A. , Maviglia F. , Mlynar J. , Rimini F.G. , Pütterich Th. 
Published: December 2014

Abstract
Since the ITER-like wall in JET (JET-ILW) came into operation, dedicated ITER-like plasma current (I
p) ramp-up (RU) and ramp-down (RD) experiments have been performed and matched to similar discharges with the carbon wall (JET-C). The experiments show that access to H-mode early in the I
p RU phase and maintaining H-mode in the I
p RD as long as possible are instrumental to achieve low internal plasma inductance (l
i) and to minimize flux consumption. In JET-ILW, at a given current rise rate similar variations in l
i (0.7–0.9) are obtained as in JET-C. In most discharges no strong W accumulation is observed. However, in some low density cases during the early phase of the I
p

strong core radiation due to W influx led to hollow electron temperature (T
e) profiles. In JET-ILW Z
eff is significantly lower than in JET-C. W significantly disturbs the discharge evolution when the W concentration approaches 10−4; this threshold is confirmed by predictive transport modelling using the CRONOS code. I
p RD experiments in JET-ILW confirm the result of JET-C that sustained H-mode and elongation reduction are both instrumental in controlling l
i.
Mechanical Bowel Preparation for Children Undergoing Elective Colorectal Surgery
Authors: Aldrink Jennifer H. , McManaway Cindy , Wang Wei , Nwomeh Benedict C. 
Published: December 2014

ABSTRACTObjectives:Adult literature supports the elimination of mechanical bowel preparation (MBP) for elective colorectal surgical procedures. Prospective data for the pediatric population regarding the utility of MBP are lacking. The primary aim of this study was to compare infectious complications, specifically anastomotic leak, intraabdominal abscess, and wound infection in patients who received MBP with those who did not.Methods:A randomized pilot study comparing MBP with polyethylene glycol with no MBP was performed. Patients, 0 to 21 years old, undergoing elective colorectal surgery were eligible and randomized within 4 age strata. Statistical analyses were performed using χ2 or Fisher exact test for categorical data and t test or Wilcoxon 2‐sample test for continuous data.Results:Forty‐four patients were enrolled in the study from December 2010 to February 2013, of which 24 (55%) received MBP and 20 (45%) did not. Two patients (5%) had anastomotic leak, 4 (9%) had intraabdominal infection, and 7 (16%) had wound infections. The rate of anastomotic leak, intraabdominal abscess, and wound infection did not differ between the 2 groups.Conclusions:MBP for elective colorectal surgery in children does not affect the incidence of infectious complications. A larger multiinstitutional study is necessary to validate the results of this single‐institution pilot study.
Iron-Binding E3 Ligase Mediates Iron Response in Plants by Targeting Basic Helix-Loop-Helix Transcription Factors
Authors: Selote Devarshi , Samira Rozalynne , Matthiadis Anna , Gillikin Jeffrey W. , Long Terri A. 
Published: December 2014

AbstractIron uptake and metabolism are tightly regulated in both plants and animals. In Arabidopsis (Arabidopsis thaliana), BRUTUS (BTS), which contains three hemerythrin (HHE) domains and a Really Interesting New Gene (RING) domain, interacts with basic helix-loop-helix transcription factors that are capable of forming heterodimers with POPEYE (PYE), a positive regulator of the iron deficiency response. BTS has been shown to have E3 ligase capacity and to play a role in root growth, rhizosphere acidification, and iron reductase activity in response to iron deprivation. To further characterize the function of this protein, we examined the expression pattern of recombinant ProBTS::β-GLUCURONIDASE and found that it is expressed in developing embryos and other reproductive tissues, corresponding with its apparent role in reproductive growth and development. Our findings also indicate that the interactions between BTS and PYE-like (PYEL) basic helix-loop-helix transcription factors occur within the nucleus and are dependent on the presence of the RING domain. We provide evidence that BTS facilitates 26S proteasome-mediated degradation of PYEL proteins in the absence of iron. We also determined that, upon binding iron at the HHE domains, BTS is destabilized and that this destabilization relies on specific residues within the HHE domains. This study reveals an important and unique mechanism for plant iron homeostasis whereby an E3 ubiquitin ligase may posttranslationally control components of the transcriptional regulatory network involved in the iron deficiency response.
Female anoles retain responsiveness to testosterone despite the evolution of androgen‐mediated sexual dimorphism
Authors: Cox Christian L. , Hanninen Amanda F. , Reedy Aaron M. , Cox Robert M. 
Published: December 2014

Summary

The evolution of sexual dimorphism presents a challenge because males and females must express two phenotypes from the same underlying genome. In vertebrates, one solution to this challenge is to link the expression of shared traits to sex steroids. However, even ‘male‐biased’ steroids such as testosterone (T) circulate at biologically significant levels in females, raising the question of whether sexual dimorphism evolves not only through the coupling of trait expression to T in males, but also through the decoupling of trait expression from T in females.

We tested these alternatives by asking whether male and female brown anoles (Anolis sagrei) respond to exogenous T in similar fashion with respect to a suite of sexually dimorphic traits: growth, skeletal morphology, resting metabolism, fat storage, dewlap size and dewlap colour.

First, we established the ontogeny of sexual dimorphism in a colony raised in a laboratory common garden. Next, we treated juveniles of each sex with either T implants or empty implants at 5–8 months of age, when sexual dimorphism first began to develop for most traits.

T stimulated growth in both sexes and largely abolished natural sex differences in growth. This effect was associated with the stimulation of resting metabolism and the diversion of energy from fat and liver stores in both sexes. T also enlarged the dewlap in both sexes, though females never developed dewlaps equal in size to those of males. Finally, T altered the brightness and saturation of the dewlap in both sexes, inducing coloration similar to that of adult males.

Female brown anoles retain many of the same tissue‐specific responses to T that occur in males, suggesting that the evolution of androgen‐mediated sexual dimorphism has been achieved largely through the coupling of trait expression to sex differences in circulating T, without an associated decoupling of trait expression from T in females.
Uneven Natural Hedge Effects in the Wheat Sector and Implications for Risk Management Tools
Authors: Feng Siyi , Patton Myles , Binfield Julian , Davis John 
Published: December 2014

SummaryRisk management tools have risen up the EU agricultural policy agenda in recent years due to greater market volatility. Market mechanisms can provide a natural hedge effect that moderates variability in revenue and income but not all regions benefit from this effect to the same extent. Core producing regions tend to benefit more while peripheral producing regions with dissimilar weather conditions benefit relatively little. We quantify the strength of natural hedge effects in the EU soft wheat sector. The two largest producing countries – France and Germany – have highly positively correlated yields and production thus driving EU wheat price changes. Our simulation shows that this hedge effect moderates revenue variability in these two countries by more than a third compared to price variability when crop yield is the only uncertainty source. By contrast, revenue variability in peripheral producing regions is consistently larger than price variability. This implies that there is a greater need for risk management tools in peripheral producing regions than in the core ones. The need for risk management tools is strongly linked to market conditions and so it is imperative that local characteristics are adequately considered if the over‐arching risk management policy framework is to be designed and set up at the EU level.
Why a European Agricultural Insurance Scheme is Not a Good Solution
Authors: Azcárate Tomás García 
Published: December 2014

SummaryWould a European agricultural insurance scheme make sense today? My answer is not really. Even if we believe that weather‐related incidents will be even more likely as a consequence of climate change, representing a significant European challenge, in my view a decentralised approach to insurance is more suited to European agricultural diversities. In addition, an EU scheme would be expensive, financed through the budget discipline, resulting in a significant cut in direct payments. I present a first estimation of potential underlying costs that imply significant budget transfers from some west, north and central European Member States to Member States in south and east Europe. The difficulties, therefore, of finding enough political support for the proposal are obvious. This does not mean that nothing can be done. Already harvest insurance is eligible for EU support in the fruit, vegetable and wine sectors and state aids may also contribute to addressing adverse events. The CAP post‐2014 has introduced a risk management toolkit as a new measure in the Rural Development regulation but we should not be too optimistic about the prominence it will assume in national programming.
Transpulmonary pressure and lung elastance can be estimated by a PEEP‐step manoeuvre
Authors: LUNDIN S. , GRIVANS C. , STENQVIST O. 
Published: December 2014

BackgroundTranspulmonary pressure is a key factor for protective ventilation. This requires measurements of oesophageal pressure that is rarely used clinically. A simple method may be found, if it could be shown that tidal and positive end‐expiratory pressure (PEEP) inflation of the lungs with the same volume increases transpulmonary pressure equally. The aim of the present study was to compare tidal and PEEP inflation of the respiratory system.MethodsA total of 12 patients with acute respiratory failure were subjected to PEEP trials of 0‐4‐8‐12‐16 cmH2O. Changes in end‐expiratory lung volume (ΔEELV) following a PEEP step were determined from cumulative differences in inspiratory‐expiratory tidal volumes. Oesophageal pressure was measured with a balloon catheter.ResultsFollowing a PEEP increase from 0 to 16 cmH2O end‐expiratory oesophageal pressure did not increase (0.5 ± 4.0 cmH2O). Average increase in EELV following a PEEP step of 4 cmH2O was 230 ± 132 ml. The increase in EELV was related to the change in PEEP divided by lung elastance (El) derived from oesophageal pressure as ΔPEEP/El. There was a good correlation between transpulmonary pressure by oesophageal pressure and transpulmonary pressure based on El determined as ΔPEEP/ΔEELV, r2 = 0.80, y = 0.96x, mean bias −0.4 ± 3.0 cmH2O with limits of agreement from 5.4 to −6.2 cmH2O (2 standard deviations).ConclusionPEEP inflation of the respiratory system is extremely slow, and allows the chest wall complex, especially the abdomen, to yield and adapt to intrusion of the diaphragm. As a consequence a change in transpulmonary pressure is equal to the change in PEEP and transpulmonary pressure can be determined without oesophageal pressure measurements.
Alterations in brain leptin signalling in spite of unchanged CSF leptin levels in Alzheimer's disease
Authors: Maioli Silvia , Lodeiro Maria , Merino‐Serrais Paula , Falahati Farshad , Khan Wasim , Puerta Elena , Codita Alina , Rimondini Roberto , Ramirez Maria J. , Simmons Andrew , Gil‐Bea Francisco , Westman Eric , Cedazo‐Minguez Angel ,   the Alzheimer's Disease Neuroimaging Initiative
Published: December 2014

SummarySeveral studies support the relation between leptin and Alzheimer's disease (AD). We show that leptin levels in CSF are unchanged as subjects progress to AD. However, in AD hippocampus, leptin signalling was decreased and leptin localization was shifted, being more abundant in reactive astrocytes and less in neurons. Similar translocation of leptin was found in brains from Tg2576 and apoE4 mice. Moreover, an enhancement of leptin receptors was found in hippocampus of young Tg2576 mice and in primary astrocytes and neurons treated with Aβ1‐42. In contrast, old Tg2576 mice showed decreased leptin receptors levels. Similar findings to those seen in Tg2576 mice were found in apoE4, but not in apoE3 mice. These results suggest that leptin levels are intact, but leptin signalling is impaired in AD. Thus, Aβ accumulation and apoE4 genotype result in a transient enhancement of leptin signalling that might lead to a leptin resistance state over time.
Allergen‐specific basophil reactivity exhibits daily variations in seasonal allergic rhinitis
Authors: Ando N. , Nakamura Y. , Ishimaru K. , Ogawa H. , Okumura K. , Shimada S. , Nakao A. 
Published: December 2014

AbstractIt remains poorly understood how symptoms in allergic rhinitis are most severe during overnight or early in the morning. The circadian clock consisting of a network of several ‘clock genes’ including Clock drives daily rhythms in physiology. This study showed that allergen‐induced surface CD203c expression on basophils in seasonal allergic rhinitis caused by Japanese cedar pollen exhibited a time‐of‐day‐dependent variation associated with temporal variations in canonical circadian clock gene expression. We also found that bone‐marrow‐derived basophils (BM basophils) generated from wild‐type mice exhibited a time‐of‐day‐dependent variation in IgE‐mediated IL‐4 and histamine production, which was not observed in BM basophils generated from Clock‐mutated mice. Therefore, allergen‐specific basophil reactivity shows daily variations depending on the circadian clock activity in basophils, which could partly explain temporal symptomatic variations in allergic rhinitis. Additionally, circadian variations in CD203c expression should be considered for interpretation of this biomarker in clinical research.
Zombies and Originals: How Cultural Theory Informs Stakeholder Management
Authors: Perrault Elise 
Published: December 2014

AbstractThe question of stakeholder salience has recently resurfaced in the suggestion that the ethical foundations of corporate cultures result in stakeholder cultures that largely explain how firms allocate resources among stakeholders. The present article seeks to complement this novel approach to understanding stakeholder management by adding insights from the multilevel influences that create the corporate culture in the first place, and ultimately affect managers in their stakeholder decisions. This article draws on cultural theory to examine how the individuals who compose firms present group and grid solidarity that results in cultural biases in the corporate culture. These cultural biases—individualism, hierarchy, fatalism, and egalitarianism—are then paired with the stakeholder cultures they enable, and inferences are extracted concerning the salience managers are likely to accord to various classes of stakeholders as a result. Future research and managerial implications stemming from this new view on stakeholder management conclude this article.
Ethical Issues that arise in Bankruptcy
Authors: Boettcher Jacques , Cavanagh Gerald , Xu Min 
Published: December 2014

AbstractBankruptcy is designed to give the debtor another chance after a financial failure, and it is often an option that is both more ethical and more efficient than liquidation. We address some basic issues, such as whether Chapter 11 bankruptcy itself is ethical and what elements help one to decide if a particular bankruptcy is ethical. There are many chances for unethical acts during bankruptcy, such as the ethics of a firm that files for Chapter 11 bankruptcy yet has sufficient assets to meet its financial obligations, or the often exorbitant fees that bankruptcy professionals are allowed as well as the apparent partiality demonstrated in some bankruptcy courts.