bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of an Oral Somatostatin DNA Vaccine without Antibiotic Resistance Gene in Promoting Growth of Piglets
Authors: Han Y.‐G. , Liang A.‐X. , Han L. , Guo A.‐Z. , Jiang X.‐P. , Yang L.‐G. 
Published: January 2014

AbstractThis study aimed to evaluate the efficacy and safety of an oral DNA vaccine against somatostatin (SS) (pGS/2SS‐asd, encoding two copies of somatostatin genes) mediated by attenuated Salmonella choleraesuis C500 without antibiotic resistance gene on piglets growth. A total of 50 piglets were uniformly divided into five groups. The animals in the first three groups were orally given vaccine in dose of either 5 × 1010, 5 × 109 or 5 × 108 colony‐forming units (CFU). The remaining two groups were orally administered with either bacteria C500 (containing pVAX‐asd plasmid without somatostatin gene) or phosphate‐buffered saline (PBS) as controls. The results indicated that the vaccine induced SS‐specific antibodies in a dose‐dependent pattern. Compared with the PBS control, animals in the high‐dose group showed lower SS levels and higher growth hormone (GH) levels in sera. Average daily gain of animals in the high‐dose group was increased by 32.88% and 26.46% during 4 and 8 weeks, respectively. Anti‐SS antibodies were positively correlated with either GH levels or average daily gain at week 8 after primary immunization (P < 0.05). Faecal, soil and water samples originating from immunized piglets and surrounding environment were collected. The target gene (the fusion gene GS/2SS) of C500 (pGS/2SS‐asd) was not detected by PCR amplification in these samples, indicating that the surrounding environment was not contaminated by residual recombinant bacteria. In conclusion, the vaccine without antibiotic resistance gene is attributable to improve growth performance of piglets through an influence on GH secretion. Moreover, the immunization did not contaminate the surrounding environment of animals.
Administration of Sulfatide to Ameliorate Type I Diabetes in Non‐Obese Diabetic Mice
Authors: Rhost S. , Löfbom L. , Månsson J.‐E. , Lehuen A. , Blomqvist M. , Cardell S. L. 
Published: January 2014

AbstractThe endogenous glycosphingolipid sulfatide is a ligand for CD1d‐restricted type II natural killer T (NKT) lymphocytes. Through the action of these cells, sulfatide treatment has been shown to modulate the immune response in mouse models for autoimmune diseases, infections and tumour immunity. Sulfatide exists naturally in different organs including the pancreas, where sulfatide co‐localizes with insulin within the Langerhans islet β‐cells, targets for the immune destruction in type 1 diabetes (T1D). Human T1D patients, but not patients with type 2 diabetes nor healthy individuals, have autoantibodies against sulfatide in serum, suggesting that sulfatide induces an immune response in the natural course of T1D in humans. Here, we investigate sulfatide as an autoantigen and a modulator of autoimmune disease in the murine model for T1D, the non‐obese diabetic (NOD) mice. We demonstrate that aged NOD mice displayed serum autoantibody reactivity to sulfatide; however, this reactivity did not correlate with onset of T1D. Repeated administration of sulfatide did not result in an increase in serum reactivity to sulfatide. Moreover, a multidose sulfatide treatment of female NOD mice initiated at an early (5 weeks of age), intermediate (8 weeks of age) or late (12 weeks of age) phase of T1D progression did not influence the incidence of disease. Thus, we demonstrate that a fraction of NOD mice develop autoantibody reactivity to sulfatide; however, we fail to demonstrate that sulfatide treatment reduces the incidence of T1D in this mouse strain.
Improved pan‐specific MHC class I peptide‐binding predictions using a novel representation of the MHC‐binding cleft environment
Authors: Carrasco Pro S. , Zimic M. , Nielsen M. 
Published: January 2014

AbstractMajor histocompatibility complex (MHC) molecules play a key role in cell‐mediated immune responses presenting bounded peptides for recognition by the immune system cells. Several in silico methods have been developed to predict the binding affinity of a given peptide to a specific MHC molecule. One of the current state‐of‐the‐art methods for MHC class I is NetMHCpan, which has a core ingredient for the representation of the MHC class I molecule using a pseudo‐sequence representation of the binding cleft amino acid environment. New and large MHC–peptide‐binding data sets are constantly being made available, and also new structures of MHC class I molecules with a bound peptide have been published. In order to test if the NetMHCpan method can be improved by integrating this novel information, we created new pseudo‐sequence definitions for the MHC‐binding cleft environment from sequence and structural analyses of different MHC data sets including human leukocyte antigen (HLA), non‐human primates (chimpanzee, macaque and gorilla) and other animal alleles (cattle, mouse and swine). From these constructs, we showed that by focusing on MHC sequence positions found to be polymorphic across the MHC molecules used to train the method, the NetMHCpan method achieved a significant increase in the predictive performance, in particular, of non‐human MHCs. This study hence showed that an improved performance of MHC‐binding methods can be achieved not only by the accumulation of more MHC–peptide‐binding data but also by a refined definition of the MHC‐binding environment including information from non‐human species.
A selection strategy in plant transformation based on antisense oligodeoxynucleotide inhibition
Authors: Xie Zhoupeng , Sundström Jens F. , Jin Yunkai , Liu Chunlin , Jansson Christer , Sun Chuanxin 
Published: January 2014

SummaryAntisense oligodeoxynucleotide (asODN) inhibition was developed in the 1970s, and since then has been widely used in animal research. However, in plant biology, the method has had limited application because plant cell walls significantly block efficient uptake of asODN to plant cells. Recently, we have found that asODN uptake is enhanced in a sugar solution. The method has promise for many applications, such as a rapid alternative to time‐consuming transgenic studies, and high potential for studying gene functionality in intact plants and multiple plant species, with particular advantages in evaluating the roles of multiple gene family members. Generation of transgenic plants relies on the ability to select transformed cells. This screening process is based on co‐introduction of marker genes into the plant cell together with a gene of interest. Currently, the most common marker genes are those that confer antibiotic or herbicide resistance. The possibility that traits introduced by selectable marker genes in transgenic field crops may be transferred horizontally is of major public concern. Marker genes that increase use of antibiotics and herbicides may increase development of antibiotic‐resistant bacterial strains or contribute to weed resistance. Here, we describe a method for selection of transformed plant cells based on asODN inhibition. The method enables selective and high‐throughput screening for transformed cells without conferring new traits or functions to the transgenic plants. Due to their high binding specificity, asODNs may also find applications as plant‐specific DNA herbicides.
Extensive amplification of the E2F transcription factor binding sites by transposons during evolution of Brassica species
Authors: Hénaff Elizabeth , Vives Cristina , Desvoyes Bénédicte , Chaurasia Ankita , Payet Jordi , Gutierrez Crisanto , Casacuberta Josep M. 
Published: January 2014

SummaryTransposable elements (TEs) are major players in genome evolution. The effects of their movement vary from gene knockouts to more subtle effects such as changes in gene expression. It has recently been shown that TEs may contain transcription factor binding sites (TFBSs), and it has been proposed that they may rewire new genes into existing transcriptional networks. However, little is known about the dynamics of this process and its effect on transcription factor binding. Here we show that TEs have extensively amplified the number of sequences that match the E2F TFBS during Brassica speciation, and, as a result, as many as 85% of the sequences that fit the E2F TFBS consensus are within TEs in some Brassica species. We show that these sequences found within TEs bind E2Fa in vivo, which indicates a direct effect of these TEs on E2F‐mediated gene regulation. Our results suggest that the TEs located close to genes may directly participate in gene promoters, whereas those located far from genes may have an indirect effect by diluting the effective amount of E2F protein able to bind to its cognate promoters. These results illustrate an extreme case of the effect of TEs in TFBS evolution, and suggest a singular way by which they affect host genes by modulating essential transcriptional networks.
A model for transport of a viral membrane protein through the early secretory pathway: minimal sequence and endoplasmic reticulum lateral mobility requirements
Authors: Serra‐Soriano Marta , Pallás Vicente , Navarro José A. 
Published: January 2014

SummaryViral movement proteins exploit host endomembranes and the cytoskeleton to move within the cell via routes that, in some cases, are dependent on the secretory pathway. For example, melon necrotic spot virus p7B, a type II transmembrane protein, leaves the endoplasmic reticulum (ER) through the COPII‐dependent Golgi pathway to reach the plasmodesmata. Here we investigated the sequence requirements and putative mechanisms governing p7B transport through the early secretory pathway. Deletion of either the cytoplasmic N–terminal region (CR) or the luminal C–terminal region (LR) led to ER retention, suggesting that they are both essential for ER export. Through alanine‐scanning mutagenesis, we identified residues in the CR and LR that are critical for both ER export and for viral cell‐to‐cell movement. Within the CR, alanine substitution of aspartic and proline residues in the DSSP β–turn motif (D7AP10A) led to movement of discrete structures along the cortical ER in an actin‐dependent manner. In contrast, alanine substitution of a lysine residue in the LR (K49A) resulted in a homogenous ER distribution of the movement protein and inhibition of ER–Golgi traffic. Moreover, the ability of p7B to recruit Sar1 to the ER membrane is lost in the D7AP10A mutant, but enhanced in the K49A mutant. In addition, fluorescence recovery after photobleaching revealed that K49A but not D7AP10A dramatically diminished protein lateral mobility. From these data, we propose a model whereby the LR directs actin‐dependent mobility toward the cortical ER, where the cytoplasmic DSSP β–turn favors assembly of COPII vesicles for export of p7B from the ER.
Polymorphism of P53‐Ets/AP1 transactivation region of MDM2 oncogene and its immunohistochemical analysis in canine tumours
Authors: Rezaie A. , Tabandeh M. R. , Noori S. M. A. 
Published: January 2014

AbstractMouse Double Minute‐2 (MDM2) is an ubiquitin ligase which is overexpressed or its promoter polymorphism has been reported in different tumours. The objective of this study was to examine the MDM2 protein expression and its promoter polymorphism in some canine tumours. Twenty specimens were collected from 20 dogs with 15 mammary gland carcinomas, 3 lymphomas, 1 transmissible venereal tumour and 1 trichoblastoma. Samples were analysed immunohistochemically using human antibody against MDM2 protein. PCR and DNA sequencing were carried out to identify MDM2 promoter polymorphism. MDM2 gene was expressed in 13 of 20 samples including 11 mammary carcinomas, 1 lymphoma and 1 trichoblastoma. We found 94% homology between canine and human sequences. Four mutations including G169C, A177G, G291T and A177G were identified in different types of breast carcinomas. An extra p53 response element was found in a mixed mammary carcinoma.
Quantification of beam complexity in intensity‐modulated radiation therapy treatment plans
Authors: Du Weiliang , Cho Sang Hyun , Zhang Xiaodong , Hoffman Karen E. , Kudchadker Rajat J. 
Published: January 2014

Purpose:Excessive complexity in intensity‐modulated radiation therapy (IMRT) plans increases the dose uncertainty, prolongs the treatment time, and increases the susceptibility to changes in patient or target geometry. To date, the tools for quantitative assessment of IMRT beam complexity are still lacking. In this study, The authors have sought to develop metrics to characterize different aspects of beam complexity and investigate the beam complexity for IMRT plans of different disease sites.Methods:The authors evaluated the beam complexity scores for 65 step‐and‐shoot IMRT plans from three sites (prostate, head and neck, and spine) and 26 volumetric‐modulated arc therapy (VMAT) plans for the prostate. On the basis of the beam apertures and monitor unit weights of all segments, the authors calculated the mean aperture area, extent of aperture shape irregularity, and degree of beam modulation for each beam. Then the beam complexity values were averaged to obtain the complexity metrics of the IMRT plans. The authors studied the correlation between the beam complexity metrics and the quality assurance (QA) results. Finally, the effects of treatment planning parameters on beam complexity were studied.Results:The beam complexity scores were not uniform among the prostate IMRT beams from different gantry angles. The lateral beams had larger monitor units and smaller shape irregularity, while the anterior‐posterior beams had larger modulation values. On average, the prostate IMRT plans had the smallest aperture irregularity, beam modulation, and normalized monitor units; the head and neck IMRT plans had large beam irregularity and beam modulation; and the spine stereotactic radiation therapy plans often had small beam apertures, which may have been associated with the relatively large discrepancies between planned and QA measured doses. There were weak correlations between the beam complexity scores and the measured dose errors. The prostate VMAT beams showed greater complexity than the prostate step‐and‐shoot IMRT beams. In the treatment planning process, the beam complexity increased as the minimum segment area decreased and as the number of optimization iterations and the maximum number of segments increased.Conclusions:The proposed metrics were effective in characterizing the beam complexity of different disease sites and for different treatment modalities. Efforts should be made to reduce the unnecessary complexity of IMRT beams to minimize the radiation dose uncertainties.
Ecological Succession and Stochastic Variation in the Assembly of Arabidopsis thaliana Phyllosphere Communities
Authors: Maignien Loïs , DeForce Emelia A. , Chafee Meghan E. , Eren A. Murat , Simmons Sheri L. 
Published: January 2014

ABSTRACT

Bacteria living on the aerial parts of plants (the phyllosphere) are globally abundant and ecologically significant communities and can have significant effects on their plant hosts. Despite their importance, little is known about the ecological processes that drive phyllosphere dynamics. Here, we describe the development of phyllosphere bacterial communities over time on the model plant
Arabidopsis thaliana
in a controlled greenhouse environment. We used a large number of replicate plants to identify repeatable dynamics in phyllosphere community assembly and reconstructed assembly history by measuring the composition of the airborne community immigrating to plant leaves. We used more than 260,000 sequences from the v5v6 hypervariable region of the 16S rRNA gene to characterize bacterial community structure on 32 plant and 21 air samples over 73 days. We observed strong, reproducible successional dynamics: phyllosphere communities initially mirrored airborne communities and subsequently converged to a distinct community composition. While the presence or absence of particular taxa in the phyllosphere was conserved across replicates, suggesting strong selection for community composition, the relative abundance of these taxa was highly variable and related to the spatial association of individual plants. Our results suggest that stochastic events in early colonization, coupled with dispersal limitation, generated alternate trajectories of bacterial community assembly within the context of deterministic selection for community membership.

IMPORTANCE
Commensal bacteria associated with plants help protect their hosts against infection and promote growth. Bacteria associated with plant leaves (the “phyllosphere”) are highly abundant and diverse communities, but we have very limited information about their ecology. Here, we describe the formation of phyllosphere communities on the plant model organism
Arabidopsis thaliana
. We grew a large number of plants in a greenhouse and measured bacterial diversity in the phyllosphere throughout the
Arabidopsis
life cycle. We also measured the diversity of airborne microbes landing on leaves. Our findings show that plants develop distinctive phyllosphere bacterial communities drawn from low-abundance air populations, suggesting the plant environment is favorable for particular organisms and not others. However, we also found that the relative abundances of bacteria in the phyllosphere are determined primarily by the physical proximity of individual plants. This suggests that a mixture of selective and random forces shapes phyllosphere communities.
Seminormal Structure and Fixed Points of Cyclic Relatively Nonexpansive Mappings
Authors: Gabeleh Moosa , Shahzad Naseer 
Published: January 2014

LetAandBbe two nonempty subsets of a Banach spaceX. A mappingT:A∪B→A∪Bis said to be cyclic relatively nonexpansive ifT(A)⊆BandT(B)⊆AandTx-Ty≤x-yfor all (x,y)∈A×B. In this paper, we introduce a geometric notion of seminormal structure on a nonempty, bounded, closed, and convex pair of subsets of a Banach spaceX. It is shown that if (A,B) is a nonempty, weakly compact, and convex pair and (A,B) has seminormal structure, then a cyclic relatively nonexpansive mappingT:A∪B→A∪Bhas a fixed point. We also discuss stability of fixed points by using the geometric notion of seminormal structure. In the last section, we discuss sufficient conditions which ensure the existence of best proximity points for cyclic contractive type mappings.Erratum to “Seminormal Structure and Fixed Points of Cyclic Relatively Nonexpansive Mappings”
Association between Sleep Disturbances and Leisure Activities in the Elderly: A Comparison between Men and Women
Authors: Hellström Amanda , Hellström Patrik , Willman Ania , Fagerström Cecilia 
Published: January 2014

It has been suggested that physical or social activity is associated with fewer sleep disturbances among elderly people. Women report more sleep disturbances than men, which could indicate a variation in activity patterns between the genders. The aim of this study was to investigate associations between sleep disturbances and leisure activities in men and women (n = 945) aged ≥60 years in a Swedish population. Sleep disturbances were measured using eight dichotomous questions and seventeen variables, covering a wide range of leisure activities. Few leisure activities were found to be associated with sleep disturbances and their importance decreased when the models were adjusted for confounders and gender interactions. After clustering the leisure activities and investigating individual activities, sociointellectual activities were shown to be significant for sleep. However, following adjustment for confounders and gender interactions, home maintenance was the only activity significant for sleep. Being a female increased the effect of home maintenance. Besides those leisure activities, poor/fair self-rated health (OR 7.50, CI: 4.27–11.81) and being female (OR 4.86, CI: 2.75–8.61) were found to have the highest association with poor sleep. Leisure activities pursued by elderly people should focus on activities of a sociointellectual nature, especially among women, to promote sleep.
BRCA2 Phosphorylated by PLK1 Moves to the Midbody to Regulate Cytokinesis Mediated by Nonmuscle Myosin IIC
Authors: Takaoka Miho , Saito Hiroko , Takenaka Katsuya , Miki Yoshio , Nakanishi Akira 
Published: January 2014

Abstract
Cytokinesis is the critical final step in cell division. BRCA2 disruption during cytokinesis is associated with chromosome instability, but mechanistic information is lacking that could be used to prevent cancer cell division. In this study, we report that BRCA2 phosphorylation by the mitotic polo-like kinase (PLK1) governs the localization of BRCA2 to the Flemming body at the central midbody, permitting an interaction with nonmuscle myosin IIC (NM-IIC). Formation of an NM-IIC ring-like structure at the Flemming body shows that the IIC-ring relies on its ATPase activity stimulated by interaction with BRCA2 and associated proteins. Notably, inhibiting this binding inactivated the ATPase activity, causing disassembly of the IIC-ring, defective formation of the midbody, and interruption of cytokinesis. An analysis of cancer-associated mutations in BRCA2 at the PLK1-binding site suggests that they may contribute to cytokinetic defects by altering BRCA2 localization. Our findings suggest that BRCA2-dependent IIC-ring formation is a critical step in proper formation of the midbody, offering an explanation for how chromosome instability may arise in breast cancer. Cancer Res; 74(5); 1518–28. ©2014 AACR.
Axon Guidance Factor SLIT2 Inhibits Neural Invasion and Metastasis in Pancreatic Cancer
Authors: Göhrig Andreas , Detjen Katharina M. , Hilfenhaus Georg , Körner Jan L. , Welzel Martina , Arsenic Ruza , Schmuck Rosa , Bahra Marcus , Wu Jane Y. , Wiedenmann Bertram , Fischer Christian 
Published: January 2014

Abstract
Pancreatic ductal adenocarcinoma (PDAC) metastasizes by neural, vascular, and local invasion routes, which limit patient survival. In nerves and vessels, SLIT2 and its ROBO receptors constitute repellent guidance cues that also direct epithelial branching. Thus, the SLIT2–ROBO system may represent a key pinch point to regulate PDAC spread. In this study, we examined the hypothesis that escaping from repellent SLIT2–ROBO signaling is essential to enable PDAC cells to appropriate their local stromal infrastructure for dissemination. Through immunohistochemical analysis, we detected SLIT2 receptors ROBO1 and ROBO4 on epithelia, nerves, and vessels in healthy pancreas and PDAC specimens, respectively. SLIT2 mRNA expression was reduced in PDAC compared with nontransformed pancreatic tissues and cell lines, suggesting a reduction in SLIT2–ROBO pathway activity in PDAC. In support of this interpretation, restoring the SLIT2 expression in SLIT2-deficient PDAC cells inhibited their bidirectional chemoattraction with neural cells, and more specifically, impaired unidirectional PDAC cell navigation along outgrowing neurites in models of neural invasion. Restoring autocrine/paracrine SLIT2 signaling was also sufficient to inhibit the directed motility of PDAC cells, but not their random movement. Conversely, RNA interference–mediated silencing of ROBO1 stimulated the motility of SLIT2-competent PDAC cells. Furthermore, culture supernatants from SLIT2-competent PDAC cells impaired migration of endothelial cells (human umbilical vein endothelial cells), whereas an N-terminal SLIT2 cleavage fragment stimulated such migration. In vivo investigations of pancreatic tumors with restored SLIT2 expression demonstrated reduced invasion, metastasis, and vascularization, with opposing effects produced by ROBO1 silencing in tumor cells or sequestration of endogenous SLIT2. Analysis of clinical specimens of PDAC showed that those with low SLIT2 mRNA expression exhibited a higher incidence and a higher fraction of tumor-infiltrated lymph nodes. Taken together, our findings argue that disrupting SLIT2–ROBO signaling in PDAC may enhance metastasis and predispose PDAC cells to neural invasion. Cancer Res; 74(5); 1529–40. ©2014 AACR.