bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xin‐deficient mice display myopathy, impaired contractility, attenuated muscle repair and altered satellite cell functionality
Authors: Al‐Sajee D. , Nissar A. A. , Coleman S. K. , Rebalka I. A. , Chiang A. , Wathra R. , van der Ven P. F. M. , Orfanos Z. , Hawke T. J. 
Published: January 2015

AbstractAimXin is an F‐actin‐binding protein expressed during development of cardiac and skeletal muscle. We used Xin‐/‐ mice to determine the impact of Xin deficiency on different aspects of skeletal muscle health, including functionality and regeneration.MethodsXin‐/‐ skeletal muscles and their satellite cell (SC) population were investigated for the presence of myopathic changes by a series of histological and immunofluorescent stains on resting uninjured muscles. To further understand the effect of Xin loss on muscle health and its SCs, we studied SCs responses following cardiotoxin‐induced muscle injury. Functional data were determined using in situ muscle stimulation protocol.ResultsCompared to age‐matched wild‐type (WT), Xin‐/‐ muscles exhibited generalized myopathy and increased fatigability with a significantly decreased force recovery post‐fatiguing contractions. Muscle regeneration was attenuated in Xin‐/‐ mice. This impaired regeneration prompted an investigation into SC content and functionality. Although SC content was not different, significantly more activated SCs were present in Xin‐/‐ vs. WT muscles. Primary Xin‐/‐ myoblasts displayed significant reductions (approx. 50%) in proliferative capacity vs. WT; a finding corroborated by significantly decreased MyoD‐positive nuclei in 3 days post‐injury Xin‐/‐ muscle vs. WT. As more activated SCs did not translate to more proliferating myoblasts, we investigated whether Xin‐/‐ SCs displayed an exaggerated loss by apoptosis. More apoptotic SCs (TUNEL+/Pax7+) were present in Xin‐/‐ muscle vs. WT. Furthermore, more Xin‐/‐ myoblasts were expressing nuclear caspase‐3 compared to WT at 3 days post‐injury.ConclusionXin deficiency leads to a myopathic condition characterized by increased muscle fatigability, impaired regeneration and SC dysfunction.
Identifying designatable units for intraspecific conservation prioritization: a hierarchical approach applied to the lake whitefish species complex (Coregonusspp.)
Authors: Mee Jonathan A. , Bernatchez Louis , Reist Jim D. , Rogers Sean M. , Taylor Eric B. 
Published: January 2015

AbstractThe concept of the designatable unit (DU) affords a practical approach to identifying diversity below the species level for conservation prioritization. However, its suitability for defining conservation units in ecologically diverse, geographically widespread and taxonomically challenging species complexes has not been broadly evaluated. The lake whitefish species complex (Coregonusspp.) is geographically widespread in the Northern Hemisphere, and it contains a great deal of variability in ecology and evolutionary legacy within and among populations, as well as a great deal of taxonomic ambiguity. Here, we employ a set of hierarchical criteria to identifyDUs within the Canadian distribution of the lake whitefish species complex. We identified 36DUs based on (i) reproductive isolation, (ii) phylogeographic groupings, (iii) local adaptation and (iv) biogeographic regions. The identification ofDUs is required for clear discussion regarding the conservation prioritization of lake whitefish populations. We suggest conservation priorities among lake whitefishDUs based on biological consequences of extinction, risk of extinction and distinctiveness. Our results exemplify the need for extensive genetic and biogeographic analyses for any species with broad geographic distributions and the need for detailed evaluation of evolutionary history and adaptive ecological divergence when defining intraspecific conservation units.
Donor‐derived equine mesenchymal stem cells suppress proliferation of mismatched lymphocytes
Authors: Ranera B. , Antczak D. , Miller D. , Doroshenkova T. , Ryan A. , McIlwraith C. W. , Barry F. 
Published: January 2015

SummaryReasons for performing studyRecently, it has been shown that mesenchymal stem cells (MSCs) do not express the major histocompatibility complex (MHC) II antigen and are able to inhibit proliferation of MHC‐mismatched stimulated lymphocytes, enabling their use as in vivo allogeneic transplants. However, prior to clinical application of allo‐MSCs, in vitro tests are required to confirm the safety of treatment protocols.ObjectivesTo evaluate the immunosuppressive capabilities of equine bone‐marrow‐derived MSCs (BM‐MSCs) on MHC‐mismatched lymphocytes.Study designIn vitro experiment.MethodsPhytohaemagglutinin‐stimulated peripheral blood mononuclear cells (PBMCs) from 3 Thoroughbreds (recipients) were co‐cultured with mismatched BM‐MSCs from 3 Connemara ponies (donors). Proliferation of lymphocytes was monitored by carboxyfluorescein succinimidyl ester labelling and analysed by flow cytometry. In total, 6 horses were haplotyped using microsatellites to confirm mismatching. Optimisation of the conditions to stimulate Thoroughbred lymphocytes and titration of equine anti‐CD4 and anti‐CD8 antibodies were performed. Connemara pony and Thoroughbred BM‐MSCs were isolated, expanded and characterised by tri‐lineage differentiation. Finally, BM‐MSCs from both breeds were set up in co‐culture at different ratios with stimulated Thoroughbred lymphocytes. Proliferation of CD4+ and CD8+ cells was determined by flow cytometry.ResultsA high proportion of CD4/CD8 double‐positive lymphocytes were found in freshly isolated PBMCs, although this percentage decreased after 4 days of culture. Mismatched BM‐MSCs inhibited proliferation of stimulated lymphocytes in a dose‐dependent manner, with the greatest suppression occurring at a 1:10 ratio of BM‐MSCs to PBMCs. Proliferation of CD4+ and CD8+ subpopulations decreased in 1:10 co‐culture, with statistical significance in the case of CD8+ cells, while that of the CD4/CD8 double‐positive population was similar to the phytohaemagglutinin control.ConclusionsThe results demonstrate dose‐dependent immunosuppression of stimulated lymphocytes by mismatched equine BM‐MSCs, supporting their future application in allo‐MSC clinical treatments.
How to achieve full prophylaxis in young boys with severe haemophilia A: different regimens and their effect on early bleeding and venous access
Authors: Nijdam A. , Kurnik K. , Liesner R. , Ljung R. , Nolan B. , Petrini P. , Fischer K. ,   the PedNet study group
Published: January 2015

SummaryTo facilitate early prophylaxis, step‐up regimens starting prophylaxis with infusions 1× week−1were introduced. Choice of initial regimen may affect outcome. This study aims to classify initial prophylactic regimens and compare them on short‐term outcome. From the ‘European Paediatric Network for Haemophilia Management' (PedNet) registry, patients with severe haemophilia A without inhibitors, born 2000–2012, receiving prophylaxis were included. Treatment centres were classified according to the initial frequency of prophylactic infusions and the age at reaching infusions ≥3× week−1. Bleeding, and central venous access device (CVAD) use were compared at age 4 years. In 21 centres with 363 patients, three regimens were identified: (i) start prophylaxis with ≥3× week−1infusions before age three (full: 19% of centres, 18% of patients); (ii) start 1–2× week−1, increasing frequency as soon as possible (asap), reaching ≥3× week−1before age three (43% of centres, 36% of patients); (iii) start 1–2× week−1, increasing frequency according to bleeding (phenotype), reaching ≥3× week−1after age three (38% of centres, 46% of patients). Prophylaxis was started at median 1.2 years on the full and asap regimen vs 1.8 years on the phenotype regimen. Complete prevention of joint bleeds was most effective on the full regimen (32% full vs. 27% asap and 8% phenotype), though at the cost of using mostCVADs (88% full vs. 34% asap and 22% phenotype). The three prophylaxis regimens identified had different effects on early bleeding andCVADuse. This classification provides the first step towards establishing the optimum prophylactic regimen.
Attenuation of microRNA‐16 derepresses the cyclins D1, D2 and E1 to provoke cardiomyocyte hypertrophy
Authors: Huang Shuai , Zou Xiao , Zhu Jie‐Ning , Fu Yong‐Heng , Lin Qiu‐Xiong , Liang Ye‐You , Deng Chun‐Yu , Kuang Su‐Juan , Zhang Meng‐Zhen , Liao Yu‐Lin , Zheng Xi‐Long , Yu Xi‐Yong , Shan Zhi‐Xin 
Published: January 2015

AbstractCyclins/retinoblastoma protein (pRb) pathway participates in cardiomyocyte hypertrophy. MicroRNAs (miRNAs), the endogenous small non‐coding RNAs, were recognized to play significant roles in cardiac hypertrophy. But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy. This study investigates the potential role of microRNA‐16 (miR‐16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy. An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC), and in a mouse with transverse aortic constriction (TAC) and in a mouse with subcutaneous injection of phenylephrine (PE) respectively. In addition, a cell model of hypertrophy was also achieved based on PE‐promoted neonatal rat ventricular cardiomyocyte and based on Ang‐II‐induced neonatal mouse ventricular cardiomyocyte respectively. We demonstrated that miR‐16 expression was markedly decreased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats and mice. Overexpression of miR‐16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes, and inhibition of miR‐16 induced a hypertrophic phenotype in cardiomyocytes. Expressions of cyclins D1, D2 and E1, and the phosphorylated pRb were increased in hypertrophic myocardium and hypertrophic cardiomyocytes, but could be reversed by enforced expression of miR‐16. Cyclins D1, D2 and E1, not pRb, were further validated to be modulated post‐transcriptionally by miR‐16. In addition, the signal transducer and activator of transcription‐3 and c‐Myc were activated during myocardial hypertrophy, and inhibitions of them prevented miR‐16 attenuation. Therefore, attenuation of miR‐16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2 and E1, and activating cyclin/Rb pathway, revealing that miR‐16 might be a target to manage cardiac hypertrophy.
Staff attitudes towards people with intellectual disabilities in Japan and the United States
Authors: Horner‐Johnson W. , Keys C. B. , Henry D. , Yamaki K. , Watanabe K. , Oi F. , Fujimura I. , Graham B. C. , Shimada H. 
Published: January 2015

AbstractBackgroundStaff attitudes may affect choices available to persons with intellectual disabilities (ID). This study examined attitudes towards people with ID among staff working with people with ID in Japan and the United States.MethodAttitudes of staff working with people with ID in Japan and the United States were compared using the Community Living Attitudes Scale, Intellectual Disabilities Form. Responses were examined via multivariate analysis of variance.ResultsIn unadjusted analyses, Japanese staff exhibited a greater tendency towards Sheltering and Exclusion of people with ID and lower endorsement of Empowerment and Similarity of people with ID. After controlling for covariates, the country effect was no longer significant for Sheltering and Exclusion. Age and education were significantly associated with attitudes in the adjusted model.ConclusionsWhile attitudes in Japan appeared less supportive of community inclusion of people with ID, some of the differences between countries were attributable to other staff characteristics such as age and education. Findings provide new information about how attitudes of staff in each country compare with each other.
Chromosome inversions, adaptive cassettes and the evolution of species' ranges
Authors: Kirkpatrick Mark , Barrett Brian 
Published: January 2015

AbstractA chromosome inversion can spread when it captures locally adapted alleles or when it is introduced into a species by hybridization with adapted alleles that were previously absent. We present a model that shows how both processes can cause a species range to expand. Introgression of an inversion that carries novel, locally adapted alleles is a particularly powerful mechanism for range expansion. The model supports the earlier proposal that introgression of an inversion triggered a large range expansion of a malaria mosquito. These results suggest a role for inversions as cassettes of genes that can accelerate adaptation by crossing species boundaries, rather than protecting genomes from introgression.
LACK, a RACK1 ortholog, facilitates cytochrome c oxidase subunit expression to promote Leishmania major fitness
Authors: Cardenas Daviel , Carter Pamela M. , Nation Catherine S. , Pizarro Juan C. , Guidry Jessie , Aiyar Ashok , Kelly Ben L. 
Published: January 2015

SummaryLeishmania are kinetoplastid parasites that cause the sandfly‐transmitted disease leishmaniasis. To maintain fitness throughout their infectious life cycle, Leishmania must undergo rapid metabolic adaptations to the dramatically distinct environments encountered during transition between sandfly and vertebrate hosts. We performed proteomic and immunoblot analyses of attenuated L. major strains deficient for LACK, the Leishmania ortholog of the mammalian receptor for activated c kinase (RACK1), that is important for parasite thermotolerance and virulence. This approach identified cytochrome c oxidase (LmCOX) subunit IV as a LACK‐dependent fitness protein. Consistent with decreased levels of LmCOX subunit IV at mammalian temperature, and in amastigotes, LmCOX activity and mitochondrial function were also impaired in LACK‐deficient L. major under these conditions. Importantly, overexpression of LmCOX subunit IV in LACK‐deficient L. major restored thermotolerance and macrophage infectivity. Interestingly, overexpression of LmCOX subunit IV enhanced LmCOX subunit VI expression at mammalian temperature. Collectively, our data suggest LACK promotes Leishmania adaptation to the mammalian host environment by sustaining LmCOX subunit IV expression and hence energy metabolism in response to stress stimuli such as heat. These findings extend the repertoire of RACK1 protein utility to include a role in mitochondrial function.
Novel export control of a Legionella Dot/Icm substrate is mediated by dual, independent signal sequences
Authors: Jeong Kwang Cheol , Sutherland Molly C. , Vogel Joseph P. 
Published: January 2015

SummaryThe Legionella pneumophila Dot/Icm T4SS injects ∼ 300 protein effector proteins into host cells. Dot/Icm substrates have been proposed to contain a carboxy‐terminal signal sequence that is necessary and sufficient for export, although both traits have been demonstrated for only a small fraction of these proteins. In this study, we discovered that export of the substrate SidJ is mediated by dual signal sequences that include a conventional C‐terminal domain and a novel internal motif. The C‐terminal signal sequence facilitates secretion of SidJ into host cells at early points of infection, whereas the internal signal sequence mediates secretion at later time points. Interestingly, only the internal signal sequence is necessary for complementation of the intracellular growth defect of a ΔsidJ mutant. Although this is the first report of a Dot/Icm substrate being secreted by an internal signal sequence, many other substrates may be exported in a similar manner. In addition, efficient translocation of SidJ is dependent on the chaperone‐like type IV adaptors IcmS/IcmW. Five IcmS/IcmW binding domains that are distinct from both signal sequences were elucidated and, interestingly, only secretion mediated by the internal signal sequence requires IcmS/IcmW. Thus, Legionella employs multiple sophisticated molecular mechanisms to regulate the export of SidJ.
Integration of chemotaxis, transport and catabolism in Pseudomonas putida and identification of the aromatic acid chemoreceptor PcaY
Authors: Luu Rita A. , Kootstra Joshua D. , Nesteryuk Vasyl , Brunton Ceanne N. , Parales Juanito V. , Ditty Jayna L. , Parales Rebecca E. 
Published: January 2015

SummaryAromatic and hydroaromatic compounds that are metabolized through the β‐ketoadipate catabolic pathway serve as chemoattractants for Pseudomonas putida F1. A screen of P. putida F1 mutants, each lacking one of the genes encoding the 18 putative methyl‐accepting chemotaxis proteins (MCPs), revealed that pcaY encodes the MCP required for metabolism–independent chemotaxis to vanillate, vanillin, 4‐hydroxybenzoate, benzoate, protocatechuate, quinate, shikimate, as well as 10 substituted benzoates that do not serve as growth substrates for P. putida F1. Chemotaxis was induced during growth on aromatic compounds, and an analysis of a pcaY‐lacZ fusion revealed that pcaY is expressed in the presence of β‐ketoadipate, a common intermediate in the pathway. pcaY expression also required the transcriptional activator PcaR, indicating that pcaY is a member of the pca regulon, which includes three unlinked gene clusters that encode five enzymes required for the conversion of 4‐hydroxybenzoate to tricarboxylic acid cycle intermediates as well as the major facilitator superfamily transport protein PcaK. The 4‐hydroxybenzoate permease PcaK was shown to modulate the chemotactic response by facilitating the uptake of 4‐hydroxybenzoate, which leads to the accumulation of β‐ketoadipate, thereby increasing pcaY expression. The results show that chemotaxis, transport and metabolism of aromatic compounds are intimately linked in P. putida.
AEF1/MPR25 is implicated in RNA editing of plastid atpF and mitochondrial nad5, and also promotes atpF splicing in Arabidopsis and rice
Authors: Yap Aaron , Kindgren Peter , Colas des Francs‐Small Catherine , Kazama Tomohiko , Tanz Sandra K. , Toriyama Kinya , Small Ian 
Published: January 2015

SummaryRNA editing is an essential mechanism that modifies target cytidines to uridine in both mitochondrial and plastid mRNA. Target sites are recognized by pentatricopeptide repeat (PPR) proteins. Using bioinformatics predictions based on the code describing sequence recognition by PPR proteins, we have identified an Arabidopsis editing factor required for editing of atpF in plastids. A loss‐of‐function mutation in ATPF EDITING FACTOR 1 (AEF1, AT3G22150) results in severe variegation, presumably due to decreased plastid ATP synthase levels. Loss of editing at the atpF site is coupled with a large decrease in splicing of the atpF transcript, even though the editing site is within an exon and 53 nucleotides distant from the splice site. The rice orthologue of AEF1, MPR25, has been reported to be required for editing of a site in mitochondrial nad5 transcripts, and we confirm that editing of the same site is affected in the Arabidopsis aef1 mutant. We also show that splicing of chloroplast atpF transcripts is affected in the rice mpr25 mutant. AEF1 is thus highly unusual for an RNA editing specificity factor in that it has functions in both organelles.
Development of a Search Tool to Identify Structural Design Principles for Bioinspired Materials Design
Authors: Tsenn Joanna , Linsey Julie S. , McAdams Daniel A. 
Published: January 2015

Natural materials are often more efficient and tend to have a wider range and combination of properties than do present-day engineered materials. Biological materials are composed from a limited set of components, but are able to achieve great diversity in their properties. The variation in properties is largely due to the different arrangements of the materials components, which form unique structures. We believe that there are underlying structural design principles, relating material structure to material properties, that commonly appear in biological materials. Because nature itself achieves highly effective design solutions, the utilization of these natural design principles could similarly improve the effectiveness of engineered materials. Materials scientists need a way to abstract relevant structural design principles from the myriad of biological materials articles for the development of bioinspired materials.
This research involves the development of a data mining tool that will quickly identify potential structural design principles of biological materials with respect to a chosen material property or combination of properties. This paper presents the first stage of this process: information retrieval. An algorithm is developed to extract structural design principles’ key terms and relevant passages for specified material properties from a corpus of materials journal articles. The development of this search tool is explained beginning with the determination of search term categories and appropriate search terms and continuing to the refinement of the program algorithm. An evaluation of the tool is also described comparing the program’s results to those of a manual search for the structure-property relationships. The program identified 98% of the manually found structural design principle key terms, although many unanticipated passages were returned as well. Finally, the future work needed to improve the program is presented.
InTenso+ System: Measured Centre of Gravity Locations and Inertia Tensors of Road Vehicles
Authors: Gobbi Massimiliano , Mastinu Giampiero , Pennati Mario , Previati Giorgio 
Published: January 2015

The InTenso+ system has been developed at Politecnico di Milano (Technical University of Milan) for the measurement of the centre of gravity location and of the inertia tensor of vehicles and their components (such as gearboxes and engines). The test rig is basically a multi-bar pendulum carrying the body under investigation and oscillating from well-known initial conditions. By means of a proper mathematical procedure, the mass properties of the body are accurately measured within a very short time.
The InTenso+ System has been employed for a number of measurements of the mass properties of road vehicles. In this paper, the measured data are collected and analyzed.
Formulas for the estimation of the mass properties (mass, centre of gravity location and inertia tensor) from easily accessible vehicle data are proposed and tested against the measured values. It is confirmed that the mass properties coming from the considered estimations are useless if accurate simulations of the dynamic behavior of a vehicle have to be performed.
MBS Motion Equation Without Explicit Definition of Body-Fixed Reference Frames
Authors: Müller Andreas 
Published: January 2015

Any description of rigid body motions requires body-fixed RFRs since the latter kinematically represent the bodies and are necessary to define their inertia properties. Consequently there is no formulation without RFR. Nevertheless this does not necessarily mean that the definition of body-fixed RFRs is an indispensable step in MBS modeling.
A formulation without body-fixed reference frames is one that does not involve explicit definition of body-fixed frames to express the kinematics and the inertia data of an MBS. In this paper a formulation is presented that only requires a single spatial inertial frame to model all kinematic and dynamic properties of the MBS. It only requires the joint kinematics (axis and position vector) as well as the inertia tensors w.r.t. the spatial inertial frame in a reference configuration the MBS. That is, the inertia tensors of all rigid bodies are expressed w.r.t. a virtual body-fixed references frame that coincides with the spatial inertia frame in the reference configuration.
Avoiding the explicit introduction of body-fixed reference frames significantly simplifies the MBS modeling. This is not only beneficial for manual modeling but also gives rise to much simpler MBS codes. The approach is discussed for tree-topology MBS as well as for closed loop systems. It is demonstrated for a planar slider-crank examples.