bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of High-mobility Group Protein A Isoforms and Their Clinicopathologic Significance in Primary Retinoblastoma
Authors: Singh Mithalesh K. , Singh Lata , Sen Seema , Pushker Neelam , Sharma Anjana , Ahamad Feeroj C. , Chawla Bhavna , Kashyap Seema 
Published: December 2015

Background:
High-mobility group proteins A (HMGA) are more abundant in rapidly dividing and transformed cells. These are a group of proteins regulating tumorigenesis and tumor invasion. Increased expression of HMGA1 and HMGA2 has been reported in various benign and malignant tumors. The aim of the present study was to analyze expression of HMGA1 and HMGA2 proteins in retinoblastoma.

Methods:
Protein expression of HMGA1 and HMGA2 in 80 formalin-fixed retinoblastoma tissues was performed by immunohistochemistry, and their mRNA expressions were analyzed on 40 fresh primary enucleated retinoblastoma samples by semiquantitative reverse transcription polymerase chain reaction. Results were then correlated with clinicopathologic parameters.

Results:
Immunohistochemical analysis of HMGA1 and HMGA2 was seen in 56.25% and 58.75% of retinoblastoma cases, respectively. mRNA expressions of HMGA1 and HMGA2 was found to be 57.55% and 62.5%, respectively. The mRNA results correlated well with immunostaining results. Expression of both HMGA1 and HMGA2 was significantly associated with choroidal invasion and poor tumor differentiation.

Conclusions:
HMGA1 and HMGA2 proteins may contribute to tumorigenesis of Rb. Expression of HMGA1 and HMGA2 predicts poor prognosis and could serve as a therapeutic target in the management of RB. Further experiments are needed to determine the role of these proteins as therapeutic targets in tumorigenesis.
Fast near-whole brain imaging in adult Drosophila during responses to stimuli and behavior
Authors: Aimon Sophie , Katsuki Takeo , Jia Tongqiu , Grosenick Logan , Broxton Michael , Deisseroth Karl , Sejnowski Terrence J. , Greenspan Ralph J. 
Published: December 2015

AbstractWhole brain recordings give us a global perspective of the brain in action. In this study, we describe a method using light field microscopy to record near-whole brain calcium and voltage activity, at high speed, in behaving adult flies. We first obtained global activity maps for various stimuli and behaviors. Notably, we found that brain activity increased on a global scale when the fly walked but not when it groomed. This global increase with walking was particularly strong in dopamine neurons. Second, we extracted maps of spatially distinct sources of activity as well as their time series using principal component analysis and independent component analysis. The characteristic shapes in the maps matched the anatomy of sub-neuropil regions and in some cases a specific neuron type. Brain structures that responded to light and odor were consistent with previous reports, confirming the new technique’s validity. We also observed previously uncharacterized behavior-related activity, as well as patterns of spontaneous voltage activity.
Anatomy of public-private partnerships: their creation, financing and renegotiations
Authors: Sarmento Joaquim Miranda , Renneboog Luc 
Published: December 2015

Purpose– As public-private partnerships (PPPs) have become more widespread, doubts and criticisms about this type of infrastructural projects have emerged. The authors describe the PPP framework, discuss the financial structure and risk-sharing processes, and dissect the structure and organisation. The authors address the following questions: what are the main organisational characteristics of PPPs? How does the private sector structure and finance PPPs? And why and how are PPP contracts renegotiated? The paper aims to discuss these issues.Design/methodology/approach– This paper draws on extensive theoretical and empirical research, which is presented in a literature overview on PPPs and their renegotiations. A comprehensive review is carried out and two case studies are developed to investigate the reasons behind success and failure of PPPs and the renegotiation of contracts.Findings– Incomplete contracts and the long duration of concessions can bring uncertainty and change to PPPs. Joint decision making can be difficult due to different parties involved. Renegotiation outcomes tend to rely on the position of the government. In Fertagus, the private sector asked for financial help led to a very balanced agreement. Conversely, Lusoponte renegotiations were initiated by the government, which significantly changed the project. Instead of relying solely on commercial revenues, Lusoponte was substantial financed by public funds.Research limitations/implications– Incomplete contracts and the long duration of concessions bring about much uncertainty to PPPs.Ex postdecision making in PPPs in the wake of changing risks is difficult as it necessarily involves negotiations between the public sector and the private firm. The paper shows that marked differences in renegotiation outcomes emerge. In one case study, the private sector asked for financial help and the negotiation outcome was a very balanced agreement. Conversely, renegotiations in a second case were initiated by the government mainly for political reasons, resulted in a significant change in the PPP’s structure, risk, financing, and returns, and yielded a large public losses.Practical implications– Contrasting successful and unsuccessful PPPs enables the reader to examine the opportunities and pitfalls in case of PPP renegotiations, which frequently occur. He can gain insight in the determinants of negotiation outcomes and the importance of a governmental PPP entity as well as of an independent monitor such as a court of audits.Originality/value– This paper should be useful for both academics and practitioners and should help increase the understanding of the several stages, structures, and renegotiation processes associated with PPPs.
Understanding the motivation and context for alliancing in the Australian construction industry
Authors: Walker Derek H.T. , Lloyd-Walker Beverley M. 
Published: December 2015

Purpose
– The purpose of this paper is to explore and explain the circumstances in which a highly collaborative integrated project delivery form such an alliance is the most appropriate choice of delivering infrastructure projects.

Design/methodology/approach
– The paper draws upon two previously published studies on alliancing to enable gathering insights from a quantitative study with some qualitative data that indicates project alliance delivery performance is high and suggests why it may be adopted as a project delivery form. A second qualitative study recently completed and published on integrated collaborative forms of project delivery such as alliances is re-analysed to better understand how and why this form may be successful. Together these two studies allowed a focus on the motivation to form an alliance and specific conditions relating to the alliance party’s level of ability and willingness to deeply collaborate.

Findings
– The motivation to deeply collaborate may be triggered by specific internal and external trigger mechanisms. These are identified in the paper together with discussion about the requirement of parties to have sufficient knowledge, skills, attributes and experience to collaborate at a deeply engaged level.

Research limitations/implications
– The data used in the studies were from large scale infrastructure construction projects. The examples are mainly drawn from countries where collaboration is common and culturally acceptable; results may not apply to cultures, country or workplace, where high levels of competition are seen to be the optimal strategy for project delivery success. Also, the data were drawn from construction project management (PM). Other project-based areas such as professional services for example may present a different context and hence a different rationale.

Practical implications
– The study provides deep insights about the nature of collaboration. It may have wider applicability.

Social implications
– Project organising is a social activity with social implications for how they are delivered that affect internal as well as external stakeholders. Being mindful about the motivation to choose a particular delivery form is important.

Originality/value
– This is a new area of research in PM and the world faces a massive demand for large scale complex projects. This paper may provide a rational to drive policy in project delivery choices.
Implications of the use of different payment models
Authors: Villalba-Romero Felix , Liyanage Champika 
Published: December 2015

Purpose– The purpose of this paper is to illustrate the payment models and financing structures used for road Infrastructure projects under public private partnerships (PPPs) in the UK. Comparison of funding and financial structures in the selected case studies exposes the risks and values of the models of payment utilised. This research also aims to identify relationships with payment certainty and financing debt restructuring.Design/methodology/approach– The paper compares several case studies representing the evolution of private finance initiative road infrastructure in the UK context. Templates were completed using semi- structured interviews during data collection; and a qualitative content analysis approach was employed for case study analysis.Findings– Lessons learned from using different payment methods show the benefit and limitations of adopting different forms of PPP in road development. Refinancing of projects presents substantial risks to the viability of a project, and benefits gained by the private sector. Further, refinancing brings no significant benefits to the public sector as well.Practical implications– Performance of selected case studies highlights emerging issues that need to be considered when adopting a PPP procurement route in roads projects. Financial markets have supported these projects under different risk profiles and payment models. They also have the potential to play a greater part in capitalising long-term investment in road projects and increase private sector participation in infrastructure development, generating more competition and innovation.Originality/value– This paper provides case study comparison and practical implications of recent PPP developments in road provision in the UK and the evolution of public policy in the subject.
Two separate key enzymes and two pathway‐specific transcription factors are involved in fusaric acid biosynthesis in Fusarium fujikuroi
Authors: Studt Lena , Janevska Slavica , Niehaus Eva‐Maria , Burkhardt Immo , Arndt Birgit , Sieber Christian M. K. , Humpf Hans‐Ulrich , Dickschat Jeroen S. , Tudzynski Bettina 
Published: December 2015

SummaryFusaric acid (FSA) is a mycotoxin produced by several fusaria, including the rice pathogen Fusarium fujikuroi. Genes involved in FSA biosynthesis were previously identified as a cluster containing a polyketide synthase (PKS)‐encoding (FUB1) and four additional genes (FUB2‐FUB5). However, the biosynthetic steps leading to FSA as well as the origin of the nitrogen atom, which is incorporated into the polyketide backbone, remained unknown. In this study, seven additional cluster genes (FUB6‐FUB12) were identified via manipulation of the global regulator FfSge1. The extended FUB gene cluster encodes two Zn(II)2Cys6 transcription factors: Fub10 positively regulates expression of all FUB genes, whereas Fub12 is involved in the formation of the two FSA derivatives, i.e. dehydrofusaric acid and fusarinolic acid, serving as a detoxification mechanism. The major facilitator superfamily transporter Fub11 functions in the export of FSA out of the cell and is essential when FSA levels become critical. Next to Fub1, a second key enzyme was identified, the non‐canonical non‐ribosomal peptide synthetase Fub8. Chemical analyses of generated mutant strains allowed for the identification of a triketide as PKS product and the proposition of an FSA biosynthetic pathway, thereby unravelling the unique formation of a hybrid metabolite consisting of this triketide and an amino acid moiety.
The versatile TolC‐like Slr1270 in the cyanobacterium Synechocystis sp. PCC 6803
Authors: Oliveira Paulo , Martins Nuno M. , Santos Marina , Pinto Filipe , Büttel Zsófia , Couto Narciso A. S. , Wright Phillip C. , Tamagnini Paula 
Published: December 2015

SummaryHere we report on the functional characterization of the hypothetical protein Slr1270, a TolC homologue in Synechocystis sp. PCC 6803. Analysis of a slr1270 insertion deletion mutant and respective wild‐type revealed that the mutant presents increased susceptibility to antibiotics. In addition, a detailed study of the exoproteome showed that Slr1270 mediates protein secretion. Among the protein substrates dependent on Slr1270 function, we found the S‐layer structural component. Electron microscopy studies of the slr1270 mutant showed that the S‐layer is indeed absent. The requirement of functional Slr1270 for protein secretion and drug resistance mechanisms suggests that Slr1270 plays a role similar to that described for TolC in other bacteria. Additional phenotypic traits could also be observed, including slower growth rates at low temperature, impairment in biofilm formation and increased activity of enzymes detoxifying reactive oxygen species. Furthermore, an increased capacity of outer membrane vesicles (OMVs) formation and release was also found in the slr1270 mutant, a feature that has not yet been observed in bacteria lacking TolC. This work highlights the marked physiological fitness that the TolC‐like Slr1270 bestows to the photosynthetic model Synechocystis sp. PCC 6803 and presents a valuable model for studying OMVs formation and release.
The genome analysis of Candidatus Burkholderia crenata reveals that secondary metabolism may be a key function of the Ardisia crenata leaf nodule symbiosis
Authors: Carlier Aurelien , Fehr Linda , Pinto‐Carbó Marta , Schäberle Till , Reher Raphael , Dessein Steven , König Gabriele , Eberl Leo 
Published: December 2015

SummaryA majority of Ardisia species harbour Burkholderia sp. bacteria within specialized leaf nodules. The bacteria are transmitted hereditarily and have not yet been cultured outside of their host. Because the plants cannot develop beyond the seedling stage without their symbionts, the symbiosis is considered obligatory. We sequenced for the first time the genome of Candidatus Burkholderia crenata (Ca. B. crenata), the leaf nodule symbiont of Ardisia crenata. The genome of Ca. B. crenata is the smallest Burkholderia genome to date. It contains a large amount of insertion sequences and pseudogenes and displays features consistent with reductive genome evolution. The genome does not encode functions commonly associated with plant symbioses such as nitrogen fixation and plant hormone metabolism. However, we identified unique genes with a predicted role in secondary metabolism in the genome of Ca. B. crenata. Specifically, we provide evidence that the bacterial symbionts are responsible for the synthesis of compound FR900359, a cyclic depsipeptide with biomedical properties previously isolated from leaves of A. crenata.
Microbial eukaryotic distributions and diversity patterns in a deep‐sea methane seep ecosystem
Authors: Pasulka Alexis L. , Levin Lisa A. , Steele Josh A. , Case David H. , Landry Michael R. , Orphan Victoria J. 
Published: December 2015

SummaryAlthough chemosynthetic ecosystems are known to support diverse assemblages of microorganisms, the ecological and environmental factors that structure microbial eukaryotes (heterotrophic protists and fungi) are poorly characterized. In this study, we examined the geographic, geochemical and ecological factors that influence microbial eukaryotic composition and distribution patterns withinHydrateRidge, a methane seep ecosystem off the coast ofOregon using a combination of high‐throughput 18SrRNAtag sequencing, terminal restriction fragment length polymorphism fingerprinting, and cloning and sequencing of full‐length18S rRNAgenes. Microbial eukaryotic composition and diversity varied as a function of substrate (carbonate versus sediment), activity (low activity versus active seep sites), sulfide concentration, and region (North versusSouthHydrateRidge). Sulfide concentration was correlated with changes in microbial eukaryotic composition and richness. This work also revealed the influence of oxygen content in the overlying water column and water depth on microbial eukaryotic composition and diversity, and identified distinct patterns from those previously observed for bacteria, archaea and macrofauna in methane seep ecosystems. Characterizing the structure of microbial eukaryotic communities in response to environmental variability is a key step towards understanding if and how microbial eukaryotes influence seep ecosystem structure and function.
A comparison of reproductive parameters of female Amur tigers (Panthera tigris altaica) in the wild and captivity
Authors: GU Jiayin , GUO Yurong , STOTT Philip , JIANG Guangshun , MA Jianzhang 
Published: December 2015

AbstractA healthy population of captive Amur tigers might assist recovery of the wild population in Northeast China if individuals were properly prepared and considered suitable for release in the wild. We analyzed the breeding records of 68 female Amur tigers from 1995 to 2010 in the Hengdaohezi Felid Breeding Center of China and compared the reproductive parameters of this population to wild female Amur tigers. We found that the reproductive parameters of the captive population (the age of first parturition, length of gestation and litter survival rate) were not significantly different from those of wild Amur tigers. Differences in birth date and litter size between wild and captive populations may be caused by management protocols for the captive population or insufficient field data from the wild population. Reproductive parameters of females giving birth after losing a litter were similar to parameters of females that did not lose a litter, except for birth date. These results provide no indication of major problems in using captive females for a breeding program for release of cubs into the wild, but additional information is still needed to assess their suitability.
Differences between Western and Asian type 2 diabetes patients in the incidence of vascular complications and mortality: A systematic review of randomized controlled trials on lowering blood glucose
Authors: Li Jing , Dong Yajie , Wu Taixiang , Tong Nanwei 
Published: December 2015

AbstractBackgroundDifferences exist between Western and Asian people with type 2 diabetes (T2D). The aim of the present systematic review was to determine whether there are differences in chronic diabetic vascular complications (CDVCs) and mortality between Western and Asian patients with T2D.MethodsThree databases (EMBASE, MEDLINE, and Cochrane library) were searched for publications from 1966 to March 2013 describing interventional randomized control trials (RCTs) targeting to lower blood glucose levels. The RCTs included had follow‐up durations of at least 4 years as an endpoint or in their initial design, analyzed effects on mortality and/or CDVCs in T2D and compared differences in mortality and/or CDVCs among patients of different ethnicities.ResultsTwo studies, including 19 439 patients with advanced diabetes, were eligible for analysis. Patients were divided into those of Western (including Australia and New Zealand) and Asian ethnicities. The incidence of all‐cause mortality, cardiovascular death, and major coronary events was significantly higher in Western than Asian patients, whereas the incidence of major cerebrovascular events, microvascular events (except for peripheral neuropathy), new or worsening nephropathy, and retinopathy was significantly lower in Western patients. There were no‐between group differences in macrovascular events, including cardiovascular death, non‐fatal myocardial infarction, and non‐fatal stroke.ConclusionsThere are differences in CDVCs and mortality rates between Western and Asian patients with advanced T2D, primarily due to ethnicity‐specific factors (e.g. different genetic background, lifestyle). Knowledge of these disparities may allow more effective monitoring and management of individual patients based on ethnic differences.
Prevalence of diabetes mellitus and its risk factors in urban communities of north Sudan: Population‐based study
Authors: Elmadhoun Wadie M. , Noor Sufian K. , Ibrahim Abd Alaziz A. , Bushara Sarra O. , Ahmed Mohamed H. 
Published: December 2015

AbstractBackgroundDiabetes mellitus (DM) is a major health problem in Africa and worldwide. The prevalence of diabetes is expected to increase at alarming rate in Africa. Its estimated that around 20 million Africans are now living with diabetes, comprising a challenge for health systems at present and in the future. The aim of the present study was to determine the prevalence of undiagnosed and diagnosed DM and impaired glucose tolerance (IGT) in adult urban communities of the River Nile State (RNS), north Sudan.MethodsThe present study was a cross‐sectional community‐based study in which participants were randomly selected from the four main cities of the RNS, on a house‐to‐house basis. Blood glucose was tested and all participants completed a questionnaire to obtain demographic, clinical and social data. Blood pressure and anthropometric measures were also recorded.ResultsIn all, 954 adults (518 females; 54.3%; mean [±SD] age 39.5 ± 16.7 years; range 18–90 years) participated in the survey. The overall prevalence of DM was 19.1% (182/954), whereas that of IGT was 9.5% (91/954). Among the diabetic group, 125 (68.7%) had known diabetes, whereas 57 (31.3%) were newly diagnosed during the study. Increasing age, a family history of diabetes, central obesity, abnormal body mass index, and hypertension were significant risk factors for DM.ConclusionsThere is high prevalence of DM and glucose intolerance in the urban population of the RNS. Screening for diabetes in individuals with any feature of metabolic syndrome is recommended.
Endothelin‐1 suppresses insulin‐stimulated Akt phosphorylation and glucose uptake via GPCR kinase 2 in skeletal muscle cells
Authors: Horinouchi Takahiro , Hoshi Akimasa , Harada Takuya , Higa Tsunaki , Karki Sarita , Terada Koji , Higashi Tsunehito , Mai Yosuke , Nepal Prabha , Mazaki Yuichi , Miwa Soichi 
Published: December 2015

Background and PurposeEndothelin‐1 (ET‐1) reduces insulin‐stimulated glucose uptake in skeletal muscle, inducing insulin resistance. Here, we have determined the molecular mechanisms underlying negative regulation by ET‐1 of insulin signalling.Experimental ApproachWe used the rat L6 skeletal muscle cells fully differentiated into myotubes. Changes in the phosphorylation of Akt was assessed by Western blotting. Effects of ET‐1 on insulin‐stimulated glucose uptake was assessed with [3H]‐2‐deoxy‐d‐glucose ([3H]2‐DG). The C‐terminus region of GPCR kinase 2 (GRK2‐ct), a dominant negative GRK2, was overexpressed in L6 cells using adenovirus‐mediated gene transfer. GRK2 expression was suppressed by transfection of the corresponding short‐interfering RNA (siRNA).Key ResultsIn L6 myotubes, insulin elicited sustained Akt phosphorylation at Thr308 and Ser473, which was suppressed by ET‐1. The inhibitory effects of ET‐1 were prevented by treatment with a selective ETA receptor antagonist and a Gq protein inhibitor, overexpression of GRK2‐ct and knockdown of GRK2. Insulin increased [3H]2‐DG uptake rate in a concentration‐dependent manner. ET‐1 noncompetitively antagonized insulin‐stimulated [3H]2‐DG uptake. Blockade of ETA receptors, overexpression of GRK2‐ct and knockdown of GRK2 prevented the ET‐1‐induced suppression of insulin‐stimulated [3H]2‐DG uptake. In L6 myotubes overexpressing FLAG‐tagged GRK2, ET‐1 facilitated the interaction of endogenous Akt with FLAG‐GRK2.Conclusions and ImplicationsActivation of ETA receptors with ET‐1 suppressed insulin‐induced Akt phosphorylation at Thr308 and Ser473 and [3H]2‐DG uptake in a GRK2‐dependent manner in skeletal muscle cells. These findings suggest that ETA receptors and GRK2 are potential targets for overcoming insulin resistance.