bluuebunny/crossref_metadata_2025 huggingface dataset:
Antarctic geoconservation: a review of current systems and practices
Authors: HUGHES KEVIN A. , LÓPEZ-MARTÍNEZ JERÓNIMO , FRANCIS JANE E. , CRAME J. ALISTAIR , CARCAVILLA LUIS , SHIRAISHI KAZUYUKI , HOKADA TOMOKAZU , YAMAGUCHI AKIRA
Published: February 2016

The prohibition of commercial mineral resource extraction through the Antarctic Treaty System has removed one significant source of potential damage to Antarctica's geological and geomorphological values. However, given the on-going increase in Antarctic tourism and scientific footprint, some high-quality geological features may be vulnerable to human impact, such as damage due to the construction of logistical facilities, unregulated collection of geological specimens or oversampling for scientific purposes. The Protocol on Environmental Protection to the Antarctic Treaty puts in place a framework for the protection of Antarctica's environmental, scientific, historic, wilderness and aesthetic values. However, the Antarctic Protected Area system is still immature and further implementation of existing management tools may be required to protect the diverse range of vulnerabilities, qualities and spatial scales represented in the geology and geomorphology of the continent. At sites where high-quality mineralogical or palaeontological specimens exist in limited quantities, considerations of how best to prevent oversampling and manage access to remaining material may be supported by assessment of cumulative impacts. Examination of the level of Antarctic specimen loans from a selection of national geological collections suggested that existing publically accessible geological collections could be better utilized, which could reduce environmental impact and oversampling at vulnerable Antarctic sites.
Advising, Consenting, Delaying, and Expediting: Senator Influences on Presidential Appointments
Authors: Box-Steffensmeier Janet M. , Campisano Charles P. , Hitt Matthew P. , Scott Kevin M.
Published: February 2016

When, how, and under what conditions can individual legislators affect presidential appointments? Since the early 1900s, the senatorial norm of the blue slip has played a key role in the confirmation process of federal district and appeals court judges, and it is an important aspect of the individual prerogative that characterizes senatorial behavior more broadly. We analyze newly available blue slips, covering the historical period 1933–1960. We show that the blue slip functioned in this era most often to support and expedite nominations, indicating that senators used this device to shape the nominations agenda in this period. Additionally, we analyze the factors that contributed to an individual senator's decision to support or oppose a nominee, or return a blue slip at all, finding that senators were more likely to return positive blue slips when the Judiciary Committee chair was not a coalition ally. We argue that while blue slips did at times provide an early warning for poor nominees, they more often offered a means by which senators ensured that their desired nominees were confirmed swiftly. The positive role of the blue slip demonstrates that this device protected the individual prerogatives of senators, allowing them a degree of agenda-setting authority with regard to nominees in the weak parties era.
Practical coinduction
Authors: KOZEN DEXTER , SILVA ALEXANDRA
Published: February 2016

Induction is a well-established proof principle that is taught in most undergraduate programs in mathematics and computer science. In computer science, it is used primarily to reason about inductively defined datatypes such as finite lists, finite trees and the natural numbers. Coinduction is the dual principle that can be used to reason about coinductive datatypes such as infinite streams or trees, but it is not as widespread or as well understood. In this paper, we illustrate through several examples the use of coinduction in informal mathematical arguments. Our aim is to promote the principle as a useful tool for the working mathematician and to bring it to a level of familiarity on par with induction. We show that coinduction is not only about bisimilarity and equality of behaviors, but also applicable to a variety of functions and relations defined on coinductive datatypes.
A quantum algorithm to approximate the linear structures of Boolean functions
Authors: LI HONGWEI , YANG LI
Published: February 2016

A quantum algorithm to determine approximations of linear structures of Boolean functions is presented and analysed. Similar results have already been published (see Simon's algorithm) but only for some promise versions of the problem, and it has been shown that no exponential quantum speedup can be obtained for the general (no promise) version of the problem. In this paper, no additional promise assumptions are made. The approach presented is based on the method used in the Bernstein–Vazirani algorithm to identify linear Boolean functions and on ideas from Simon's period finding algorithm. A proper combination of these two approaches results here to a polynomial-time approximation to the linear structures set. Specifically, we show how the accuracy of the approximation with high probability changes according to the running time of the algorithm. Moreover, we show that the time required for the linear structure determine problem with high success probability is related to so called relative differential uniformityδfof a Boolean functionf. Smaller differential uniformity is, shorter time is needed.
Are Tertiary Care Paediatricians Prepared for Disaster Situations?
Authors: Mortelmans Luc J.M. , Maebe Sofie , Dieltiens Greet , Anseeuw Kurt , Sabbe Marc B. , Van de Voorde Patrick
Published: February 2016

Introduction

Children, with their specific vulnerabilities and needs, make up to more than 20% of society, so they are at risk of getting involved in disasters. Are the specialists treating them for medical problems in daily life also capable to deal with them in disaster situations?

Hypothesis/Problem

The goals of this study were to evaluate perceived knowledge and capability of tertiary pediatricians to deal with disasters, to identify promoting factors, and to evaluate education need and willingness to work.

Methods

A survey looking for demographics, hospital disaster planning, estimated risk and capability for disasters, training, and willingness to work, and a set of six content assessment questions to evaluate knowledge, were presented to emergency pediatricians and pediatric emergency physicians in specialized tertiary centers.

Results

The response rate was 51%. Thirty-five percent had disaster training and 53% felt that disaster education should be obligatory in their curriculum. Risk for disasters was estimated from 2.4/10 for nuclear incidents to 7.6/10 for major trauma. Self-estimated capability for these situations ranged from 1.8/10 in nuclear incidents to 7.6/10 in major trauma. Unconditional willingness to work ranged from 37% in nuclear situations to 68% in pandemics. Mean score on the questions was 2.06/6. Training, knowledge of antidote and personal protective equipment (PPE) use, self-estimated capability, and exposure were significant predictors for higher scores. Willingness to work correlated significantly with age, self-estimated capability, and risk estimation. In case of chemical and nuclear incidents, there was correlation with knowledge on the use of decontamination, PPE, and radio-detection devices.

Conclusion

Despite a clear perception of the risks and a high willingness to work, preparedness is limited. The major conclusion is that basics of disaster management should be included in pediatric training.

MortelmansLJM,MaebeS,DieltiensG,AnseeuwK,SabbeMB,Van de VoordeP.Are tertiary care paediatricians prepared for disaster situations?Prehosp Disaster Med.2016;31(2):126–131.
Cultural Event and Urban Regeneration: Lessons from Liverpool as the 2008 European Capital of Culture
Authors: Liu Yi-De
Published: February 2016

For many European cities, a key motivation in developing event strategies is to use an event as a catalyst for urban regeneration. One type of event that is particularly used as a means of urban development is the European Capital of Culture (ECOC) initiative. Based on a case study of the 2008 ECOC Liverpool, this article aims at conceptualising the significance of this major event for a city’s economic, cultural and social regenerations. In terms of economic regeneration, the role of the ECOC has been central in creating Liverpool’s visitor economy and reshaping the city’s image. Liverpool planned different themes for eight consecutive years as a way to ensure economic sustainability. As far as cultural regeneration is concerned, the ECOC contributed to the cultural regeneration of Liverpool by stimulating cultural participation and interest from the demand side, as well as improving cultural provision and collaboration in the cultural sector from the supply side. As for social regeneration, Liverpool treated access development as a policy guideline and considered the ECOC as an opportunity to enhance the sense of place. The most significant lesson learned from Liverpool is its long-term planning and the efforts made to integrate the ECOC into the overall urban development strategy. As a result, a more balanced and long-term effect on urban regeneration could be achieved.
Algorithms and Programs
Authors: Mehlhorn Kurt
Published: February 2016

This article is based on the Erasmus Lecture that I delivered at the 2014 Annual Meeting of the Academia Europaea in Barcelona. I will discuss my early fascination for the field, as well as algorithms, programs, laws of computation, the double role of informatics as a mathematical and engineering discipline, and my effort to teach informatics to non-majors and the general public.
Disagreement on Sustainability Policy within the Social Sciences?
Authors: Van Den Bergh Jeroen C.J.M.
Published: February 2016

One can find many proposals for policy responses to global environmental problems. Different disciplines – notably economics, geography, innovation studies, policy and political sciences, psychology and sociology – offer partly inconsistent advice. This undermines the social-political acceptance of policies as voters and politicians are likely to be left confused. To decide about an adequate sustainability policy mix we need to concur on the core problems such a mix has to tackle. I address four of these hereafter. Each one involves important issues of disagreement as well as unresolved questions.
At the Systemic Edge: Expulsions
Authors: Sassen Saskia
Published: February 2016

I use the term ‘expelled’ to describe a diversity of conditions. They include the growing numbers of the abjectly poor, of the displaced in poor countries who are warehoused in formal and informal refugee camps, of the minoritized and persecuted in rich countries who are warehoused in prisons, of workers whose bodies are destroyed on the job and rendered useless at far too young an age, of able-bodied surplus populations warehoused in ghettoes and slums. But I also include the fact that pieces of the biosphere are being expelled from their life space – and I insist that the tame language of climate change does not quite capture the fact, at ground level, of vast expanses of dead land and dead water. My argument is that this massive and very diverse set of expulsions is actually signaling a deeper systemic transformation, one documented in bits and pieces in multiple specialized studies but not quite narrated as an overarching dynamic that is taking us into a new phase of global capitalism – and global destruction. As an analytic category, expulsion is to be distinguished from the more common ‘social exclusion’: the latter happens inside a system and in that sense can be reduced, ameliorated, and even eliminated. As I conceive of them,1expulsions happen at the systemic edge. At this time, I see the proliferation of such systemic edges deep inside national territories as more significant than the borders of the interstate system – which are open for some and closed for others. In brief, the types of complex systems that are the focus of the larger research project of which the present article forms a part contain multiple systemic edges: they partly reflect the multiplying of negative conditions in the diverse domains contained in such systems, from prisons and refugee camps to financial exploitations and environmental destructions. None of this is new, but the sharp escalation towards negative outcomes since the 1980s in much of the world does invite a question as to the sustainability of it all.
Using a mixed-methods approach to measure impact of a school-based nutrition and media education intervention study on fruit and vegetable intake of Italian children
Authors: Grassi Elena , Evans Alexandra , Ranjit Nalini , Pria Simona Dalla , Messina Laura
Published: February 2016

Objective

The purpose of the present study was to investigate the impact of a school-based nutrition and media education intervention on the promotion of fruit and vegetable consumption to help prevent childhood obesity.

Design

The 10-week-long intervention included sessions on nutrition education and media literacy. It also included a health communication media-based campaign workshop during which the children created posters, newsletters and video commercials related to fruits and vegetables targeted to their parents. For evaluation purposes, the study utilized a mixed-methods approach, including a quasi-experimental study (with one intervention group and one control group) and a focus group study.

Setting

Four different elementary schools in Treviso (Veneto Region of Italy) agreed to participate in the research.

Subjects

The target population for the study included 10-year-old Italian children and their parents.

Results

Data indicate that this intervention was effective for children but not for parents. Evaluation results show that the intervention was effective in significantly increasing children’s fruit and vegetable intake (P<0·05) and all psychosocial determinants (P<0·05).

Conclusions

The study results confirm the efficacy of a school-based health and media education intervention to address the children’s obesity issue and, in particular, to increase children’s fruit and vegetable intake. The study also opens a new perspective on the theoretical constructs investigated, because the development of ‘ability of expression’ could be considered one of the most important factors to determine the efficacy of the intervention.
Differences in body dissatisfaction, weight-management practices and food choices of high-school students in the Bangkok metropolitan region by gender and school type
Authors: Chongwatpol Pitipa , Gates Gail E
Published: February 2016

Objective

The present study aimed to compare body dissatisfaction, food choices, physical activity and weight-management practices by gender and school type.

Design

A questionnaire was used to obtain height, weight, body image perception using Stunkard’s figure rating scale, food choices, physical activity and weight-management practices.

Setting

Nine single- and mixed-gender schools located in Bangkok Metropolitan Region, Thailand.

Subjects

Students in 10th–12th grade, aged 15–18 years (n2082).

Results

Only 18 % of females and 21 % of males did not indicate body dissatisfaction. About 66 % of females selected a thinner ideal figure than their current figure. Among males, 44 % wanted a thinner figure, but 35 % wanted a bigger figure. However, univariate analysis found differences by school type but not gender in the degree of body dissatisfaction; students in single-gender schools had more body dissatisfaction. Females reported using more weight-management practices but less physical activity, while males reported healthier food choices. Participants in single-gender schools had healthier food choices compared with those in mixed-gender schools. Adolescents who were at increased risk of a greater degree of body dissatisfaction were females, attended single-gender schools, had lower household income, higher BMI and less physical activity.

Conclusions

Most participants reported being dissatisfied with their current body shape, but the type and level of dissatisfaction and use of weight-management practices differed by gender and type of school. These findings suggest that programmes to combat body dissatisfaction should address different risk factors in males and females attending single- and mixed-gender schools.
Fluorescence-Detected Linear Dichroism of Wood Cell Walls in Juvenile Serbian Spruce: Estimation of Compression Wood Severity
Authors: Savić Aleksandar , Mitrović Aleksandra , Donaldson Lloyd , Simonović Radosavljević Jasna , Bogdanović Pristov Jelena , Steinbach Gabor , Garab Győző , Radotić Ksenija
Published: February 2016

Fluorescence-detected linear dichroism (FDLD) microscopy provides observation of structural order in a microscopic sample and its expression in numerical terms, enabling both quantitative and qualitative comparison among different samples. We applied FDLD microscopy to compare the distribution and alignment of cellulose fibrils in cell walls of compression wood (CW) and normal wood (NW) on stem cross-sections of juvenile Picea omorika trees. Our data indicate a decrease in cellulose fibril order in CW compared with NW. Radial and tangential walls differ considerably in both NW and CW. In radial walls, cellulose fibril order shows a gradual decrease from NW to severe CW, in line with the increase in CW severity. This indicates that FDLD analysis of cellulose fibril order in radial cell walls is a valuable method for estimation of CW severity.
PPI in the PLEASANT trial: involving children with asthma and their parents in designing an intervention for a randomised controlled trial based within primary care
Authors: Boote Jonathan , Julious Steven , Horspool Michelle , Elphick Heather , Smithson W. Henry , Norman Paul
Published: February 2016

Aims

We describe how patient and public involvement (PPI) was integrated into the design of an intervention for a randomised controlled trial (RCT) based within primary care. The RCT, known as the PLEASANT trial, aimed to reduce unscheduled medical contacts in children with asthma associated with start of the new school year in September with a simple postal intervention, highlighting the importance of maintaining asthma medication for helping to prevent increased asthma exacerbations.

Background

PPI is a key feature of UK health research policy, and is often a requirement of funding from the National Institute for Health Research. There are few detailed accounts of PPI in the design and conduct of clinical trials in the PPI literature for researchers to learn from.

Methods

We held PPI consultation events to determine whether the proposed intervention for the trial was acceptable to children with asthma and their parents, and to ascertain whether enhancements should be made. Two PPI consultation events were held with children with asthma and their parents, prior to the research commencing. Detailed field notes were taken by the research team at each consultation event.

Findings

At the first consultation event, parents and children endorsed the trial’s rationale, made suggestions to the wording of the trial intervention letter, and made recommendations about to whom the letter should be sent out. At the second consultation event, parents discussed the timing of the intervention, commented on the lay summary of the Research Ethics Application, and were invited to join the trial’s steering committee, while the children selected a logo for the study. PPI has resulted in enhancements to the PLEASANT study’s intervention. A further PPI consultation event is scheduled for the end of the trial, in order for children with asthma and their parents to contribute to the trial’s dissemination strategy.
Understanding Agricultural Price Range Systems as Trade Restraints: Peru–Agricultural Products
Authors: SAGGI KAMAL , WU MARK
Published: February 2016

An agricultural price range system (PRS) aims to stabilize local prices in an open economy via the use of import duties that vary with international prices. The policy is inherently distortionary and welfare-reducing for a small open economy, at least according to the canonical economic model. We offer an explanation for why a government concerned with national welfare may nevertheless implement such a policy when faced with risk aversion and imperfect insurance markets. We also highlight open questions arising out of the Peru–Agricultural Products dispute for the WTO's Appellate Body to address in order to clarify how a PRS consistent with WTO rules could be designed. Finally, we discuss the possibility that a WTO member might resort to a free trade agreement (FTA) to preserve its flexibility to implement a PRS and how an FTA provision of this sort ought to be treated in WTO litigation.
Satellites Reveal a Temporary Carbon Sink over Australia
Authors: Wheeling Kate
Published: February 2016

Satellite measurements of atmospheric carbon dioxide provide insights into how droughts and floods influence the carbon cycle on the semiarid continent of Australia.
Can Meteorite Impacts Disturb a Planet's Magnetic Field?
Authors: Wheeling Kate
Published: February 2016

Such disturbances probably do not occur on our own planet, but evidence for them might still exist elsewhere in the solar system.
Tracking Carbon in the Alaskan Arctic
Authors: Wheeling Kate
Published: February 2016

Researchers trace carbon through Arctic soils and find an unlikely source of methane and surprisingly low methane oxidation in watersheds throughout northern Alaska.
The energetics of anabolism in natural settings
Authors: LaRowe Douglas E , Amend Jan P
Published: February 2016

The environmental conditions that describe an ecosystem define the amount of energy available to the resident organisms and the amount of energy required to build biomass. Here, we quantify the amount of energy required to make biomass as a function of temperature, pressure, redox state, the sources of C, N and S, cell mass and the time that an organism requires to double or replace its biomass. Specifically, these energetics are calculated from 0 to 125 °C, 0.1 to 500 MPa and −0.38 to +0.86 V using CO2, acetate or CH4 for C, NO3− or NH4+ for N and SO42− or HS− for S. The amounts of energy associated with synthesizing the biomolecules that make up a cell, which varies over 39 kJ (g cell)−1, are then used to compute energy-based yield coefficients for a vast range of environmental conditions. Taken together, environmental variables and the range of cell sizes leads to a ~4 orders of magnitude difference between the number of microbial cells that can be made from a Joule of Gibbs energy under the most (5.06 × 1011 cells J−1) and least (5.21 × 107 cells J−1) ideal conditions. When doubling/replacement time is taken into account, the range of anabolism energies can expand even further.
Protistan community analysis: key findings of a large-scale molecular sampling
Authors: Grossmann Lars , Jensen Manfred , Heider Dominik , Jost Steffen , Glücksman Edvard , Hartikainen Hanna , Mahamdallie Shazia S , Gardner Michelle , Hoffmann Daniel , Bass David , Boenigk Jens
Published: February 2016

Protists are perhaps the most lineage-rich of microbial lifeforms, but remain largely unknown. High-throughput sequencing technologies provide opportunities to screen whole habitats in depth and enable detailed comparisons of different habitats to measure, compare and map protistan diversity. Such comparisons are often limited by low sample numbers within single studies and a lack of standardisation between studies. Here, we analysed 232 samples from 10 sampling campaigns using a standardised PCR protocol and bioinformatics pipeline. We show that protistan community patterns are highly consistent within habitat types and geographic regions, provided that sample processing is standardised. Community profiles are only weakly affected by fluctuations of the abundances of the most abundant taxa and, therefore, provide a sound basis for habitat comparison beyond random short-term fluctuations in the community composition. Further, we provide evidence that distribution patterns are not solely resulting from random processes. Distinct habitat types and distinct taxonomic groups are dominated by taxa with distinct distribution patterns that reflect their ecology with respect to dispersal and habitat colonisation. However, there is no systematic shift of the distribution pattern with taxon abundance.
Topographical pathways guide chemical microswimmers
Authors: Simmchen Juliane , Katuri Jaideep , Uspal William E. , Popescu Mihail N. , Tasinkevych Mykola , Sánchez Samuel
Published: February 2016

Achieving control over the directionality of active colloids is essential for their use in practical applications such as cargo carriers in microfluidic devices. So far, guidance of spherical Janus colloids was mainly realized using specially engineered magnetic multilayer coatings combined with external magnetic fields. Here we demonstrate that step-like submicrometre topographical features can be used as reliable docking and guiding platforms for chemically active spherical Janus colloids. For various topographic features (stripes, squares or circular posts), docking of the colloid at the feature edge is robust and reliable. Furthermore, the colloids move along the edges for significantly long times, which systematically increase with fuel concentration. The observed phenomenology is qualitatively captured by a simple continuum model of self-diffusiophoresis near confining boundaries, indicating that the chemical activity and associated hydrodynamic interactions with the nearby topography are the main physical ingredients behind the observed behaviour.
De novo transcriptome sequencing and gene expression profiling of spinach (Spinacia oleracea L.) leaves under heat stress
Authors: Yan Jun , Yu Li , Xuan Jiping , Lu Ying , Lu Shijun , Zhu Weimin
Published: February 2016

Spinach (Spinacia oleracea) has cold tolerant but heat sensitive characteristics. The spinach variety ‘Island,’ is suitable for summer periods. There is lack molecular information available for spinach in response to heat stress. In this study, high throughput de novo transcriptome sequencing and gene expression analyses were carried out at different spinach variety ‘Island’ leaves (grown at 24 °C (control), exposed to 35 °C for 30 min (S1) and 5 h (S2)). A total of 133,200,898 clean reads were assembled into 59,413 unigenes (average size 1259.55 bp). 33,573 unigenes could match to public databases. The DEG of controls vs S1 was 986, the DEG of control vs S2 was 1741 and the DEG of S1 vs S2 was 1587. Gene Ontology (GO) and pathway enrichment analysis indicated that a great deal of heat-responsive genes and other stress-responsive genes were identified in these DEGs, suggesting that the heat stress may have induced an extensive abiotic stress effect. Comparative transcriptome analysis found 896 unique genes in spinach heat response transcript. The expression patterns of 13 selected genes were verified by RT-qPCR (quantitative real-time PCR). Our study found a series of candidate genes and pathways that may be related to heat resistance in spinach.
Robotic lower limb prosthesis design through simultaneous computer optimizations of human and prosthesis costs
Authors: Handford Matthew L. , Srinivasan Manoj
Published: February 2016

Robotic lower limb prostheses can improve the quality of life for amputees. Development of such devices, currently dominated by long prototyping periods, could be sped up by predictive simulations. In contrast to some amputee simulations which track experimentally determined non-amputee walking kinematics, here, we explicitly model the human-prosthesis interaction to produce a prediction of the user’s walking kinematics. We obtain simulations of an amputee using an ankle-foot prosthesis by simultaneously optimizing human movements and prosthesis actuation, minimizing a weighted sum of human metabolic and prosthesis costs. The resulting Pareto optimal solutions predict that increasing prosthesis energy cost, decreasing prosthesis mass and allowing asymmetric gaits all decrease human metabolic rate for a given speed and alter human kinematics. The metabolic rates increase monotonically with speed. Remarkably, by performing an analogous optimization for a non-amputee human, we predict that an amputee walking with an appropriately optimized robotic prosthesis can have a lower metabolic cost – even lower than assuming that the non-amputee’s ankle torques are cost-free.
Crystal structure of SEL1L: Insight into the roles of SLR motifs in ERAD pathway
Authors: Jeong Hanbin , Sim Hyo Jung , Song Eun Kyung , Lee Hakbong , Ha Sung Chul , Jun Youngsoo , Park Tae Joo , Lee Changwook
Published: February 2016

Terminally misfolded proteins are selectively recognized and cleared by the endoplasmic reticulum-associated degradation (ERAD) pathway. SEL1L, a component of the ERAD machinery, plays an important role in selecting and transporting ERAD substrates for degradation. We have determined the crystal structure of the mouse SEL1L central domain comprising five Sel1-Like Repeats (SLR motifs 5 to 9; hereafter called SEL1Lcent). Strikingly, SEL1Lcent forms a homodimer with two-fold symmetry in a head-to-tail manner. Particularly, the SLR motif 9 plays an important role in dimer formation by adopting a domain-swapped structure and providing an extensive dimeric interface. We identified that the full-length SEL1L forms a self-oligomer through the SEL1Lcent domain in mammalian cells. Furthermore, we discovered that the SLR-C, comprising SLR motifs 10 and 11, of SEL1L directly interacts with the N-terminus luminal loops of HRD1. Therefore, we propose that certain SLR motifs of SEL1L play a unique role in membrane bound ERAD machinery.
Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance
Authors: Liu Ying , Takahashi Yoshinori , Desai Neelam , Zhang Jun , Serfass Jacob M. , Shi Yu-Guang , Lynch Christopher J. , Wang Hong-Gang
Published: February 2016

Bif-1 is a membrane-curvature inducing protein that is implicated in the regulation of autophagy and tumorigenesis. Here, we report that Bif-1 plays a critical role in regulating lipid catabolism to control the size of lipid droplets and prevent the development of obesity and insulin resistance upon aging or dietary challenge. Our data show that Bif-1 deficiency promotes the expansion of adipose tissue mass without altering food intake or physical activities. While Bif-1 is dispensable for adipose tissue development, its deficiency reduces the basal rate of adipose tissue lipolysis and results in adipocyte hypertrophy upon aging. The importance of Bif-1 in lipid turnover is not limited to adipose tissue since fasting and refeeding-induced lipid droplet clearance is also attenuated by Bif-1 loss in the liver. Interestingly, obesity induced by a high fat-diet or Bif-1 deficiency downregulates the expression of proteins involved in the autophagy-lysosomal pathway, including Atg9a and Lamp1 in the adipose tissue. These findings thus identify Bif-1 as a novel regulator of lipid homeostasis to prevent the pathogenesis of obesity and its associated metabolic complications.
The distinct clinical features and prognosis of the CD10+MUM1+ and CD10−Bcl6−MUM1− diffuse large B-cell lymphoma
Authors: Lu Ting-Xun , Miao Yi , Wu Jia-Zhu , Gong Qi-Xing , Liang Jin-Hua , Wang Zhen , Wang Li , Fan Lei , Hua Dong , Chen Yao-Yu , Xu Wei , Zhang Zhi-Hong , Li Jian-Yong
Published: February 2016

Using an immunohistochemistry (IHC) based method, diffuse large B-cell lymphoma (DLBCL) can be classified into germinal center B-cell (GCB) and non-GCB subtypes. However, the prognostic value of Hans algorithm was contradictory in the literature. Using IHC and fluorescence in situ hybridization, we analyzed the antibodies applied in Hans algorithm and other genetic factors in 601 DLBCL patients and prognostic value of Hans algorithm in 306 cases who were treated with chemoimmunotherapy. The results showed that patients with GCB subtype have better overall survival (OS) and progression-free survival (PFS) than non-GCB cases. However, to some extent, double positive (CD10+MUM1+, DP) and triple negative (CD10−Bcl6−MUM−, TN) showed different clinical characteristics and prognosis to others that were assigned to the same cell-of-origin group. The DP group showed similar OS (median OS: both not reached, P = 0.3650) and PFS (median PFS: 47.0 vs. 32.7 months, P = 0.0878) with the non-GCB group while the TN group showed similar OS (median OS: both not reached, P = 0.9278) and PFS (median PFS: both not reached, P = 0.9420) with the GCB group. In conclusion, Recognition of specific entities in Hans algorithm could help us to accurately predict outcome of the patients and choose the best clinical management for them.
Clostridium butyricum in combination with specific immunotherapy converts antigen-specific B cells to regulatory B cells in asthmatic patients
Authors: Liao Hong-Ying , Tao Li , Zhao Jian , Qin Jie , Zeng Gu-Cheng , Cai Song-Wang , Li Yun , Zhang Jian , Chen Hui-Guo
Published: February 2016

The effect of antigen specific immunotherapy (SIT) on asthma is supposed to be improved. Published data indicate that administration of probiotics alleviates allergic diseases. B cells play important roles in the pathogenesis of allergic diseases. This study aims to modulate antigen specific B cell property by the administration of Clostridium butyrate (CB) in combination with SIT. The results showed that after a 3-month treatment, the total asthma clinical score and serum specific IgE were improved in the patients treated with SIT, which was further improved in those treated with both SIT and CB, but not in those treated with CB alone. Treatment with SIT and CB increased p300 and STAT3 activation, up regulated the IL-10 gene transcription and increased the frequency of peripheral antigen specific B cells. In conclusion, administration with SIT in combination with CB converts Der p 1 specific B cells to regulatory B cells in asthma patients allergic to Der p 1. The data suggest a potential therapeutic remedy in the treatment of allergic diseases.
Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice
Authors: Hu Junjie , Che Li , Li Lei , Pilo Maria G. , Cigliano Antonio , Ribback Silvia , Li Xiaolei , Latte Gavinella , Mela Marta , Evert Matthias , Dombrowski Frank , Zheng Guohua , Chen Xin , Calvisi Diego F.
Published: February 2016

Activation of the AKT/mTOR cascade and overexpression of c-Met have been implicated in the development of human hepatocellular carcinoma (HCC). To elucidate the functional crosstalk between the two pathways, we generated a model characterized by the combined expression of activated AKT and c-Met in the mouse liver. Co-expression of AKT and c-Met triggered rapid liver tumor development and mice required to be euthanized within 8 weeks after hydrodynamic injection. At the molecular level, liver tumors induced by AKT/c-Met display activation of AKT/mTOR and Ras/MAPK cascades as well as increased lipogenesis and glycolysis. Since a remarkable lipogenic phenotype characterizes liver lesions from AKT/c-Met mice, we determined the requirement of lipogenesis in AKT/c-Met driven hepatocarcinogenesis using conditional Fatty Acid Synthase (FASN) knockout mice. Of note, hepatocarcinogenesis induced by AKT/c-Met was fully inhibited by FASN ablation. In human HCC samples, coordinated expression of FASN, activated AKT and c-Met proteins was detected in a subgroup of biologically aggressive tumors. Altogether, our study demonstrates that co-activation of AKT and c-Met induces HCC development that depends on the mTORC1/FASN pathway. Suppression of mTORC1 and/or FASN might be highly detrimental for the growth of human HCC subsets characterized by concomitant induction of the AKT and c-Met cascades.
Enhanced electrostatic force microscopy reveals higher-order DNA looping mediated by the telomeric protein TRF2
Authors: Kaur Parminder , Wu Dong , Lin Jiangguo , Countryman Preston , Bradford Kira C. , Erie Dorothy A. , Riehn Robert , Opresko Patricia L. , Wang Hong
Published: February 2016

Shelterin protein TRF2 modulates telomere structures by promoting dsDNA compaction and T-loop formation. Advancement of our understanding of the mechanism underlying TRF2-mediated DNA compaction requires additional information regarding DNA paths in TRF2-DNA complexes. To uncover the location of DNA inside protein-DNA complexes, we recently developed the Dual-Resonance-frequency-Enhanced Electrostatic force Microscopy (DREEM) imaging technique. DREEM imaging shows that in contrast to chromatin with DNA wrapping around histones, large TRF2-DNA complexes (with volumes larger than TRF2 tetramers) compact DNA inside TRF2 with portions of folded DNA appearing at the edge of these complexes. Supporting coarse-grained molecular dynamics simulations uncover the structural requirement and sequential steps during TRF2-mediated DNA compaction and result in folded DNA structures with protruding DNA loops as seen in DREEM imaging. Revealing DNA paths in TRF2 complexes provides new mechanistic insights into structure-function relationships underlying telomere maintenance pathways.
Precise AuxPt1−x Alloy Nanoparticle Array of Tunable Composition for Catalytic Applications
Authors: Jahn Sarah , Lechner Sebastian J. , Freichels Helene , Möller Martin , Spatz Joachim P.
Published: February 2016

A 3-dimensional Block Copolymer Micellar nanoLithography (BCML) process was used to prepare AuxPt1−x alloy nanoparticles (NPs) monodisperse in size and composition, strongly anchored onto SiO2-particles (0.2 wt.% AuxPt1−x/SiO2). The particles possess a face-centered cubic (fcc) crystal structure and their size could be varied from 3–12 nm. We demonstrate the uniformity of the Au/Pt composition by analyzing individual NPs by energy-dispersive X-ray spectroscopy. The strongly bound AuxPt1−x NPs catalyzed the oxidation of CO with high activity. Thermal ageing experiments in pure CO2 as well as in ambient atmosphere demonstrated stability of the size distribution for times as long as 22 h.
Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P3 with the pleckstrin homology domain of an oomycete cellulose synthase
Authors: Kuang Guanglin , Bulone Vincent , Tu Yaoquan
Published: February 2016

Saprolegnia monoicais a model organism to investigateSaprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year.S. monoicacontains cellulose synthases vital for oomycete growth. However, the molecular mechanism of the cellulose biosynthesis process in the oomycete growth is still poorly understood. Some cellulose synthases ofS. monoica, such as SmCesA2, are found to contain a plecsktrin homology (PH) domain, which is a protein module widely found in nature and known to bind to phosphoinositides, a class of signaling compounds involved in many biological processes. Understanding the molecular interactions between the PH domain and phosphoinositides would help to unravel the cellulose biosynthesis process of oomycetes. In this work, the binding profile of PtdIns (3,4,5) P3, a typical phosphoinositide, with SmCesA2-PH was studied by molecular docking, molecular dynamics and metadynamics simulations. PtdIns (3,4,5) P3is found to bind at a specific site located at β1, β2 and β1-β2 loop of SmCesA2-PH. The high affinity of PtdIns (3,4,5) P3to SmCesA2-PH is contributed by the free phosphate groups, which have electrostatic and hydrogen-bond interactions with Lys88, Lys100 and Arg102 in the binding site.
Specific cell surface labeling of GPCRs using split GFP
Authors: Jiang Wen-Xue , Dong Xu , Jiang Jing , Yang Yu-Hong , Yang Ju , Lu Yun-Bi , Fang San-Hua , Wei Er-Qing , Tang Chun , Zhang Wei-Ping
Published: February 2016

Specific cell surface labeling is essential for visualizing the internalization processes of G-protein coupled receptors (GPCRs) and for gaining mechanistic insight of GPCR functions. Here we present a rapid, specific and versatile labeling scheme for GPCRs at living-cell membrane with the use of a split green fluorescent protein (GFP). Demonstrated with two GPCRs, GPR17 and CysLT2R, we show that two β-stands (β-stands 10 and 11) derived from a superfolder GFP (sfGFP) can be engineered to one of the three extracellular loop of a GPCR. The complementary fragment of sfGFP has nine β-strands (β-stands 1-9) that carries the mature fluorophore and can be proteolytically derived from the full-length sfGFP. Separately the GFP fragments are non-fluorescent, but become fluorescent upon assembly, thus allowing specific labeling of the target proteins. The two GFP fragments rapidly assemble and the resulting complex is extremely tight under non-denaturing conditions, which allows real-time and quantitative assessment of the internalized GPCRs. We envision that this labeling scheme will be of great use for labeling other membrane proteins in various biological and pharmacological applications.
CRISPR/Cas9-mediated gene knockout in the mouse brain using in utero electroporation
Authors: Shinmyo Yohei , Tanaka Satoshi , Tsunoda Shinichi , Hosomichi Kazuyoshi , Tajima Atsushi , Kawasaki Hiroshi
Published: February 2016

The CRISPR/Cas9 system has recently been adapted for generating knockout mice to investigate physiological functions and pathological mechanisms. Here, we report a highly efficient procedure for brain-specific disruption of genes of interest in vivo. We constructed pX330 plasmids expressing humanized Cas9 and single-guide RNAs (sgRNAs) against the Satb2 gene, which encodes an AT-rich DNA-binding transcription factor and is responsible for callosal axon projections in the developing mouse brain. We first confirmed that these constructs efficiently induced double-strand breaks (DSBs) in target sites of exogenous plasmids both in vitro and in vivo. We then found that the introduction of pX330-Satb2 into the developing mouse brain using in utero electroporation led to a dramatic reduction of Satb2 expression in the transfected cerebral cortex, suggesting DSBs had occurred in the Satb2 gene with high efficiency. Furthermore, we found that Cas9-mediated targeting of the Satb2 gene induced abnormalities in axonal projection patterns, which is consistent with the phenotypes previously observed in Satb2 mutant mice. Introduction of pX330-NeuN using our procedure also resulted in the efficient disruption of the NeuN gene. Thus, our procedure combining the CRISPR/Cas9 system and in utero electroporation is an effective and rapid approach to achieve brain-specific gene knockout in vivo.
One-step generation of triple gene-targeted pigs using CRISPR/Cas9 system
Authors: Wang Xianlong , Cao Chunwei , Huang Jiaojiao , Yao Jing , Hai Tang , Zheng Qiantao , Wang Xiao , Zhang Hongyong , Qin Guosong , Cheng Jinbo , Wang Yanfang , Yuan Zengqiang , Zhou Qi , Wang Hongmei , Zhao Jianguo
Published: February 2016

Pig shows multiple superior characteristics in anatomy, physiology, and genome that have made this species to be more suitable models for human diseases, especially for neurodegenerative diseases, because they have similar cerebral convolutions compared with human neocortex. Recently, CRISPR/Cas9 system shows enormous potential for engineering the pig genome. In this study, we expect to generate human Parkinson’s disease pig model using CRISPR/Cas9 system by simultaneously targeting three distinct genomic loci, parkin/DJ-1/PINK1, in Bama miniature pigs. By co-injection of Cas9 mRNA and multiplexing single guide RNAs (sgRNAs) targeting parkin, DJ-1, and PINK1 genes, respectively, into in vivo derived pronuclear embryos, we simultaneously targeted three distinct genomic loci. The gene modified piglets remain healthy and display normal behavior at the age of 10 months. In addition, despite the high number of sgRNAs were employed in the present study, our trio-based whole-genome sequencing analysis suggested that the incidence of off-target events is low. Our results demonstrate that the simplicity, efficiency, and power of the CRISPR/Cas9 system to allow for the modification of multiple genes in pigs and yield results of high medical value.
Bystanders, parcelling, and an absence of trust in the grooming interactions of wild male chimpanzees
Authors: Kaburu Stefano S. K. , Newton-Fisher Nicholas E.
Published: February 2016

The evolution of cooperation remains a central issue in socio-biology with the fundamental problem of how individuals minimize the risks of being short-changed (‘cheated’) should their behavioural investment in another not be returned. Economic decisions that individuals make during interactions may depend upon the presence of potential partners nearby, which offers co operators a temptation to defect from the current partner. The parcelling model posits that donors subdivide services into parcels to force cooperation, and that this is contingent on opportunities for defection; that is, the presence of bystanders. Here we test this model and the effect of bystander presence using grooming interactions of wild chimpanzees. We found that with more bystanders, initiators gave less grooming at the beginning of the bout and were more likely to abandon a grooming bout, while bouts were less likely to be reciprocated. We also found that the groomer’s initial investment was not higher among frequent groomers or stronger reciprocators, suggesting that contrary to current assumptions, grooming decisions are not based on trust, or bonds, within dyads. Our work highlights the importance of considering immediate social context and the influence of bystanders for understanding the evolution of the behavioural strategies that produce cooperation.
Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina
Authors: O’Koren E. G. , Mathew R. , Saban D. R.
Published: February 2016

The recent paradigm shift that microglia are yolk sac-derived, not hematopoietic-derived, is reshaping our knowledge about the isolated role of microglia in CNS diseases, including degenerative conditions of the retina. However, unraveling microglial-specific functions has been hindered by phenotypic overlap of microglia with monocyte-derived macrophages. The latter are differentiated from recruited monocytes in neuroinflammation, including retina. Here we demonstrate the use of fate mapping wherein microglia and monocyte-derived cells are endogenously labeled with different fluorescent reporters. Combining this method with 12-color flow cytometry, we show that these two populations are definitively distinguishable by phenotype in retina. We prove that retinal microglia have a unique CD45lo CD11clo F4/80lo I-A/I-E− signature, conserved in the steady state and during retinal injury. The latter was observed in the widely used light-induced retinal degeneration model and corroborated in other models, including whole-body irradiation/bone-marrow transplantation. The literature contains conflicting observations about whether microglia, including in the retina, increase expression of these markers in neuroinflammation. We show that monocyte-derived macrophages have elevated expression of these surface markers, not microglia. Our resolution of such phenotypic differences may serve as a robust way to help characterize isolated roles of these cells in retinal neuroinflammation and possibly elsewhere in CNS.