bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between Retinoschisin and Norrin: Physical or Functional Relationship?
Authors: Sudha Dhandayuthapani , Chidambaram Subbulakshmi , Arunachalam Jayamuruga Pandian 
Published: May 2018

ABSTRACTBackgroundRetinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations inRS1andNDPgenes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping clinical features of Norrie disease and retinoschisis in aNDPknock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular mechanism and relationship between the two disorders have still not been understood.ObjectiveIn this study, we aim to investigate the association between retinoschisin (RS1) and norrin (NDP) usingin vitroandin silicoapproaches.MethodSpecific protein-protein interaction between RS1 and NDP was determined in human retina by co-immunoprecipitation assay and immunoblotting. The immunoprecipitated complexes of RS1 and NDP were analyzed using MALDI-TOF mass spectrometry to validate the findings. STRING database was used to explore the functional relationship.ResultsCo-immunoprecipitation and immunoblotting demonstrated lack of a direct interaction between RS1 and NDP. This was further substantiated by analyzing the immunoprecipitation complexes using MALDI-TOF mass spectrometry. STRING did not reveal any direct functional association between the two proteins.ConclusionWhile literature suggest the existence of digenic involvement ofRS1andNDPin the pathophysiology of retinoschisis and Norrie disease, our data provides evidence for lack of a physical interaction between the two proteins. However, we cannot exclude the possibility of an indirect functional association as our analyses point to MAP kinase signaling pathway, which is presumed to be the link between them.
Large-scale experimental removal of non-native slider turtles has unexpected consequences on basking behavior for both conspecifics and a native, threatened turtle
Authors: Lambert Max R. , McKenzie Jennifer M. , Screen Robyn M. , Clause Adam G. , Johnson Benjamin J. , Mount Genevieve G. , Shaffer H. Bradley , Pauly Gregory B. 
Published: May 2018

AbstractThe red-eared slider turtle (Trachemys scripta elegans; RES) is one of the world’s most invasive species. Native to the central United States, RES are now widely established in freshwater habitats across the globe, largely due to release of unwanted pets. Laboratory and mesocosm experiments suggest that introduced RES are competitively dominant to native turtles, but such competition remains untested in the wild. Here, we experimentally removed introduced RES to test whether they compete for critical basking habitat with native, threatened western pond turtles (Emys marmorata; WPT), a species being considered for listing under the U.S. Endangered Species Act. Following removal, we found that both the remaining RES as well as WPT altered their basking distribution but in a manner inconsistent with strong interspecific competition. However, these findings suggest strong intraspecific competition for basking sites amongst RES and that interspecific competition between WPT and introduced RES likely occurs at higher RES densities. Our works suggests RES influence the behavior of native species in the wild and indicates that RES removal may be most beneficial at high RES densities. This experiment highlights the importance of considering experimental venue when evaluating competition between native and non-native species and should encourage conservation biologists to treat removal efforts as experiments.
Intestinal microbiota of whitefish (Coregonussp.) species pairs and their hybrids in natural and controlled environment
Authors: Sevellec Maelle , Laporte Martin , Bernatchez Alex , Derome Nicolas , Bernatchez Louis 
Published: May 2018

AbstractIt is becoming increasingly clear that wild animals have never existed without symbiotic interactions with microbiota. Therefore, investigating relationships between microbiota and their host is essential towards a full understanding of how animal evolve and adapt to their environment. The Lake Whitefish (Coregonus clupeaformis) is a well-documented model for the study of ecological speciation, where the dwarf species (limnetic niche specialist) evolved independently and repeatedly from the normal species (benthic niche specialist). In this study, we compared the transient intestinal microbiota among five wild sympatric species pairs of whitefish as well as captive representatives of dwarf and normal species and their reciprocal hybrids reared in identical controlled conditions. We sequenced the 16s rRNA gene V3-V4 regions of the transient intestinal microbiota present in a total of 185 whitefish to (i) test for parallelism in the transient intestinal microbiota among sympatric pairs of whitefish, (ii) test for transient intestinal microbiota differences among dwarf, normal and both hybrids reared under identical conditions and (iii) compare intestinal microbiota between wild and captive whitefish. A significant effect of host species on microbiota taxonomic composition was observed in the wild when all lakes where analyzed together, and species effect was observed in three of the five species pairs. In captive whitefish, an influence of host (normal, dwarf and hybrids) was also detected on microbiota taxonomic composition and tens of genera specific to dwarf, normal or hybrids were highlighted. Hybrid microbiota was not intermediate; instead its composition fell outside of that observed in the parental forms and this was observed in both reciprocal hybrid crosses. Interestingly, six genera formed a bacterial core which was present in captive and wild whitefish, suggesting a horizontal microbiota transmission. Although diet appeared to be a major driving force for microbiota evolution, our results suggested a more complex interaction among the host, the microbiota and the environment leading to three distinct evolutionary paths of the intestinal microbiota.
Polyomavirus T-Antigen InducesAPOBEC3BExpression using a LXCXE-Dependent and TP53-Independent Mechanism
Authors: Starrett Gabriel J. , Serebrenik Artur A. , Roelofs Pieter A. , Verhalen Brandy , McCann Jennifer L. , Jarvis Matthew C. , Stewart Teneale A. , Law Emily K , Krupp Annabel , Jiang Mengxi , Martens John W. M. , Span Paul N. , Cahir-McFarland Ellen , Harris Reuben S. 
Published: May 2018

ABSTRACTAPOBEC3B is a single-stranded DNA cytosine deaminase with beneficial innate antiviral functions. However, misregulated APOBEC3B can also be detrimental by inflicting APOBEC signature C-to-T and C-to-G mutations in genomic DNA of multiple cancer types. Polyomaviruses and papillomaviruses use dominant oncoproteins to induce APOBEC3B overexpression, perhaps to their own benefit, but little is known about the cellular mechanisms hijacked by these viruses to do so. Here we investigate the molecular mechanism of APOBEC3B upregulation by the polyomavirus large T-antigen. First, truncated T-antigen (truncT) is sufficient for APOBEC3B upregulation and the RB interacting motif (LXCXE), but not the TP53 inhibition domain, is required. Second, upregulated APOBEC3B is strongly nuclear and partially localized to virus replication centers. Third, genetic knockdown of RB1 alone or in combination with RBL1 and/or RBL2 is insufficient to suppress truncT-mediated induction ofAPOBEC3B. Fourth, CDK4/6 inhibition by palbociclib is also insufficient to suppress truncT-mediated induction ofAPOBEC3B. Fifth, global gene expression analyses in a wide range of human cancers show significant associations between expression ofAPOBEC3Band other genes known to be regulated by the RB/E2F axis. These experiments combine to implicate the RB/E2F axis in promotingAPOBEC3Btranscription, yet they also suggest that the polyomavirus RB binding motif has in addition to RB inactivation at least one additional function for triggeringAPOBEC3Bupregulation in virus-infected cells.IMPORTANCEThe APOBEC3B DNA cytosine deaminase is overexpresssed in many different cancers and correlated with elevated frequencies of C-to-T and C-to-G mutations in 5’-TC motifs, oncogene activation, acquired drug resistance, and poor clinical outcomes. The mechanisms responsible for APOBEC3B overexpression are not fully understood. Here, we show that the polyomavirus truncated T-antigen (truncT) triggers APOBEC3B overexpression through its RB-interacting motif, LXCXE, which in turn likely enables one or more E2F family transcription factors to promoteAPOBEC3Bexpression. This work strengthens the mechanistic linkage between active cell cycling, APOBEC3B overexpression, and cancer mutagenesis. Although this mechanism damages cellular genomes, viruses may leverage it to promote evolution, immune escape, and pathogenesis. The cellular portion of the mechanism may also be relevant to non-viral cancers, where genetic mechanisms often activate the RB/E2F axis and APOBEC3B mutagenesis contributes to tumor evolution.
Synthetic-evolution reveals that phosphoregulation of the mitotic kinesin-5 Cin8 is constrained
Authors: Goldstein Alina , Goldman Darya , Valk Ervin , Loog Mart , Holt Liam J. , Gheber Larisa 
Published: May 2018

AbstractCdk1 has been found to phosphorylate the majority of its substrates in disordered regions. These phosphorylation sites do not appear to require precise positioning for their function. The mitotic kinesin-5 Cin8 was shown to be phosphoregulated at three Cdk1 sites in disordered loops within its catalytic motor domain. Here, we examined the flexibility of Cin8 phosphoregulation by analyzing the phenotypes of synthetic Cdk1-sites that were systematically generated by single amino-acid substitutions, starting from a phosphodeficient variant of Cin8. Out of 29 synthetic Cdk1 sites that we created, eight were non-functional; 19 were neutral, similar to the phosphodeficient variant; and two gave rise to phosphorylation-dependent spindle phenotypes. Of these two, one site resulted in novel phosphoregulation, and only one site, immediately adjacent to a native Cdk1 site, produced phosphoregulation similar to wild-type. This study shows that, while the gain of a single phosphorylation site can confer regulation and modulate the dynamics of the spindle, to achieve optimal regulation of a mitotic kinesin-5 motor protein, phosphoregulation has to be site-specific and precise.
Effect ofLactobacillus reuterion intestinal microflora and immune parameters: involvement of sex differences
Authors: He Jiayi , Wu Lingyi , Wu Zhen , Pan Daodong , Guo Yuxing , Zeng Xiaoqun , Lian Liwei 
Published: May 2018

AbstractProbiotic candidateL. reuteriwas screened out forin vivoexperiments based on a relatively higher gastrointestinal tolerance and moderate adhesiveness. As results shown inin-vivoexperiments, a significantly higher level of IL-12 at low-dose group was found both in females and males. Higher levels of T-lymphocytes were also observed in females compared to control group, however, males displayed a reduction expcept for CD8-positive cells in ileum. In comparison to the control group, the relative abundance of phylotypes in the phylumBacteroidetes(genus ofBacteroides,Prevotella) andFirmicutes(genus ofClostridiumIV) exihibited a reserve shift between sexes afterL. reuteriintervened. Meanwhile, the relative abundance of several taxa (Acetobacteroides,Lactobcaillus,bacillus) also differed markedly in sexes at low-dose group, together with microbiota diversity, as indicated by Shannon index.ImportanceSexual dimorphism has triggered researchers’ attention. However, the relationship between immune parameters and gut microbiota caused byLactobacillusat different dosage are not fully elucidated. In present research, the possible probiotic role ofL. reuteriDMSZ 8533 on immunomodulation and effect on fecal microbiota composition were investigated. Our findings demonstrate the importance of L. reuteri DMSZ 8533 as a potential probiotic strain with an immunomodulatory effect, which also alters the microflora composition depending on the sex of the host.
Protein Docking using Constrained Self-adaptive Differential Evolution Algorithm
Authors: Sudha S. , Baskar S. , Krishnaswamy S. 
Published: May 2018

AbstractThe objective of protein docking is to achieve a relative orientation and an optimized conformation between two proteins that results in a stable structure with the minimized potential energy. Constrained Self-adaptive Differential Evolution (Cons_SaDE) algorithm is used to find the minimum energy conformation using proposed constraints such as boundary surface complementary interactions, non-bonded inter-atomic allowed distances, and finding of interaction and non-interaction sites. With these constraints, Cons_SaDE is efficient enough to explore the promising solutions by gradually self-adapting the strategies and parameters learnt from their previous experiences. Modified sampling scheme called Rotate Only Representation is used to represent a docking conformation. GROMOS53A6 force field is used to find the potential energy. To test the performance of this algorithm, few bound and unbound complexes from Protein Data Bank (PDB) and few easy, medium and difficult complexes from Zlab benchmark4.0 are used. Buried Surface Area, Root Mean Square Deviation (RMSD) and Correlation Coefficient are some of the metrics applied to evaluate the best docked conformations. RMSD values of the best docked conformations obtained from five popular docking web servers are compared with Cons_SaDE results and nonparametric statistical tests for multiple comparisons with control method are implemented to show the performance of this algorithm. Cons_SaDE has produced good quality solutions for the most of the data sets considered.
Differential contributions of subthalamic beta rhythms and neural noise to Parkinson motor symptoms
Authors: Martin Stephanie , Iturrate Iñaki , Chavarriaga Ricardo , Leeb Robert , Sobolewski Aleksander , Li Andrew M. , Zaldivar Julien , Peciu-Florianu Iulia , Pralong Etienne , Castro-Jiménez Mayte , Benninger David , Vingerhoets François , Knight Robert T. , Bloch Jocelyne , Millán José del R. 
Published: May 2018

AbstractBackgroundExcessive beta oscillatory activity in the subthalamic nucleus (STN) is linked to Parkinson’s disease and associated motor symptoms. However, the relationship between beta activity and motor symptoms has been inconsistent, which may influence the efficacy of closed-loop deep brain stimulation.HypothesisWe hypothesized that this variability is due to the degree of neural noise in STN recordings. Recent evidence has shown that neural noise is influenced by multiple factors, such as development, aging and disease, and could confound measures of beta activity. In this work, we propose a model that disentangles beta oscillatory activity and neural noise in the STN power spectrum.MethodsWe investigated the impact of neural noise on estimations of beta activity and motor symptoms from data recorded bilaterally from the subthalamic nuclei of thirteen Parkinsonian patients.ResultsResults showed that the relationship between beta oscillatory amplitude and motor symptoms (bradykinesia and rigidity) significantly improved when neural noise was removed from the estimation of beta activity.ConclusionThese findings emphasize the importance of modeling neural components independently for understanding physiological processes associated with Parkinson’s disease, and identifying better biomarkers for characterizing symptom severity. Subsequently, we predict that our findings can have a direct application for closed-loop deep brain stimulation on Parkinson’s Disease.
Cryo-EM structures reveal dynamic interplay of nascent chain-processing factors on the ribosome
Authors: Bhakta Sayan , Akbar Shirin , Biswas Chiranjit , Sengupta Jayati 
Published: May 2018

AbstractDuring protein biosynthesis in bacteria, one of the earliest phenomena that a nascent polypeptide chain experiences is the co-translational enzymatic processing. The event includes two enzymatic pathways, deformylation of the N-terminal methionine followed by methionine excision catalyzed by peptide deformylase (PDF) and methionine aminopeptidase (MetAP). The ribosome tunnel exit serves as the podium for recruiting proteins involved in maturation processes of the nascent chain. During the process, the emerging nascent protein likely remains shielded by the chaperone trigger factor (TF).Here, we present the first cryo-EM structures of E. coli ribosome in complex with the nascent chain processing proteins. The structures reveal overlapping binding sites for PDF and MetAP when they bind individually at the tunnel exit site, where proteins L22 and L32 are identified as primary anchoring sites for both proteins. Interestingly however, MetAP has a remarkable ability of repositioning itself to adjacent locations in the presence of PDF and TF at the tunnel exit. Thus, our results disclose an unexpected scanning mechanism that MetAP adopts for context-specific ribosome association.
Circularly shifted filters enable data efficient sequence motif inference with neural networks
Authors: Blum Christopher F. , Kollmann Markus 
Published: May 2018

AbstractMotivationNucleic acids and proteins often have localized sequence motifs that enable highly specific interactions. Due to the biological relevance of sequence motifs, numerous inference methods have been developed. Recently, convolutional neural networks (CNNs) achieved state of the art performance because they can approximate complex motif distributions. These methods were able to learn transcription factor binding sites from ChIP-seq data and to make accurate predictions. However, CNNs learn filters that are difficult to interpret, and networks trained on small data sets often do not generalize optimally to new sequences.ResultsHere we present circular filters, a novel convolutional architecture, that contains all circularly shifted variants of the same filter. We motivate circular filters by the observation that CNNs frequently learn filters that correspond to shifted and truncated variants of the true motif. Circular filters enable learning of non-truncated motifs and allow easy interpretation of the learned filters. We show that circular filters improve motif inference performance over a wide range of hyperparameters. Furthermore, we show that CNNs with circular filters perform better at inferring transcription factor binding motifs from ChIP-seq data than conventional CNNs.Contactmarkus.kollmann@hhu.de
simGWAS: a fast method for simulation of large scale case-control GWAS summarystatistics
Authors: Fortune Mary D. , Wallace Chris 
Published: May 2018

AbstractMotivationMethods for analysis of GWAS summary statistics have encouraged data sharing and democratised the analysis of different diseases. Ideal validation for such methods is application to simulated data, where some “truth” is known. As GWAS increase in size, so does the computational complexity of such evaluations; standard practice repeatedly simulates and analyses genotype data for all individuals in an example study.ResultsWe have developed a novel method based on an alternative approach, directly simulating GWAS summary data, without individual data as an intermediate step. We mathematically derive the expected statistics for any set of causal variants and their effect sizes, conditional upon control haplotype frequencies (available from public reference datasets). Simulation of GWAS summary output can be conducted independently of sample size by simulating random variates about these expected values. Across a range of scenarios, our method, produces very similar output to that from simulating individual genotypes with a substantial gain in speed even for modest sample sizes. Fast simulation of GWAS summary statistics will enable more complete and rapid evaluation of summary statistic methods as well as opening new potential avenues of research in fine mapping and gene set enrichment analysis.Availability and ImplementationOur method is available under a GPL license as an R package from http://github.com/chr1swallace/simGWASContactcew54@cam.ac.ukSupplementary InformationSupplementary Information is appended.
Identifying micro variables contributing to political risks in international construction projects
Authors: Deng Xiaopeng , Low Sui Pheng , Zhao Xianbo , Chang Tengyuan 
Published: May 2018

PurposeThe purpose of this paper is to explore the micro-level variables contributing to political risks in international construction projects.Design/methodology/approachA total of 25 micro-level variables were identified from the literature review, and a questionnaire survey was performed with 138 professionals from both academia and industry. Then, the Spearman rank correlation was used to test whether there was agreement on ranking between the two respondent groups. Furthermore, the 25 variables were grouped into six underlying factors through the exploratory factor analysis.FindingsThe results indicated that the most critical variables were “project desirability to the host country,” “relationship with governments,” “misconduct of contractors,” “public opposition to the project,” “experiential knowledge of political risks” and “advantageous conditions of contract.” In addition, the opinions within each group were consistent and there was no significant disagreement on the rankings of variables between academics and practitioners. However, the academic and practitioner groups held different opinions on some individual variables. The impact direction of the variables was associated with confusion among the respondents.Originality/valueThe findings presented in this paper can help international construction enterprises effectively manage political risks in international construction projects.
From project partnering towards strategic supplier partnering
Authors: Sundquist Viktoria , Hulthén Kajsa , Gadde Lars Erik 
Published: May 2018

Purpose
Partnering has been at the top of the management agenda in the construction industry for many years as a means of improving performance. Previous research shows that partnering has not reached the desired level of strategic partnering, but stopped at project partnering. The purpose of this paper is to provide an analytical framing for transformation from project partnering towards strategic partnering with suppliers.

Design/methodology/approach
The framework is based on two building blocks: a case study of a contractor involved in implementing strategic partnering with four of its suppliers and a literature review dealing with partnering in construction; and models for close and long-term buyer-supplier collaboration in other contexts.

Findings
Transformation towards strategic partnering should preferably be based on extension of project partnering in two dimensions: extension in time through relationship development with suppliers and extension in space through increasing network orientation across projects.

Practical implications
Succeeding with relationship development and network orientation requires contractors to abandon two significant aspects of established construction logic that serve as significant implementation barriers. Competitive bidding in single projects needs to be replaced by collaboration over series of projects. The decentralisation of authority to the project level needs to be supplemented with increasing centralised decision making.

Originality/value
Previous research showed that despite the considerable interest in partnering there is a lack of systematic theorizing of the phenomenon. This paper contributes to theoretical anchoring through the combining of the case study and the literature review in the abductive approach applied.