bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation load estimation model as a predictor of the response to cancer immunotherapy
Authors: Lyu Guan-Yi , Yeh Yu-Hsuan , Yeh Yi-Chen , Wang Yu-Chao 
Published: April 2018

AbstractThe determination of the mutation load, a total number of nonsynonymous point mutations, by whole-exome sequencing was shown to be useful in predicting the treatment responses to cancer immunotherapy. However, this technique is expensive and time-consuming, which hampers its application in clinical practice. Therefore, the objective of this study was to construct a mutation load estimation model for lung adenocarcinoma, using a small set of genes, as a predictor of the immunotherapy treatment response. Using the somatic mutation data downloaded from The Cancer Genome Atlas (TCGA) database, a computational framework was developed. The estimation model consisted of only 24 genes, used to estimate the mutation load in the independent validation cohort precisely (R2 = 0.7626). Additionally, the estimated mutation load can be used to identify the patients with durable clinical benefits, with 85% sensitivity, 93% specificity, and 89% accuracy, indicating that the model can serve as a predictive biomarker for cancer immunotherapy treatment response. Furthermore, our analyses demonstrated the necessity of the cancer-specific models by the constructed melanoma and colorectal models. Since most genes in the lung adenocarcinoma model are not currently included in the sequencing panels, a customized targeted sequencing panel can be designed with the selected model genes to assess the mutation load, instead of whole-exome sequencing or the currently used panel-based methods. Consequently, the cost and time required for the assessment of mutation load may be considerably decreased, which indicates that the presented model is a more cost-effective approach to cancer immunotherapy response prediction in clinical practice.
Sequence investigation of 34 forensic autosomal STRs with massively parallel sequencing
Authors: Zhang Suhua , Niu Yong , Bian Yingnan , Dong Rixia , Liu Xiling , Bao Yun , Jin Chao , Zheng Hancheng , Li Chengtao 
Published: April 2018

AbstractSTRs vary not only in the length of the repeat units and the number of repeats but also in the region with which they conform to an incremental repeat pattern. Massively parallel sequencing (MPS) offers new possibilities in the analysis of STRs since they can simultaneously sequence multiple targets in a single reaction and capture potential internal sequence variations. Here, we sequenced 34 STRs applied in the forensic community of China with a custom-designed panel. MPS performance were evaluated from sequencing reads analysis, concordance study and sensitivity testing. High coverage sequencing data were obtained to determine the constitute ratios and heterozygous balance. No actual inconsistent genotypes were observed between capillary electrophoresis (CE) and MPS, demonstrating the reliability of the panel and the MPS technology. With the sequencing data from the 200 investigated individuals, 346 and 418 alleles were obtained via CE and MPS technologies at the 34 STRs, indicating MPS technology provides higher discrimination than CE detection. The whole study demonstrated that STR genotyping with the custom panel and MPS technology has the potential not only to reveal length and sequence variations but also to satisfy the demands of high throughput and high multiplexing with acceptable sensitivity.
Clinical and Molecular Epidemiology of Human Parainfluenza Viruses 1–4 in Children from Viet Nam
Authors: Linster Martin , Do Lien Anh Ha , Minh Ngo Ngoc Quang , Chen Yihui , Zhe Zhu , Tuan Tran Anh , Tuan Ha Manh , Su Yvonne C. F. , van Doorn H. Rogier , Moorthy Mahesh , Smith Gavin J. D. 
Published: April 2018

AbstractHPIVs are serologically and genetically grouped into four species that account for up to 10% of all hospitalizations due to acute respiratory infection in children under the age of five. Genetic and epidemiological data for the four HPIVs derived from two pediatric cohorts in Viet Nam are presented. Respiratory samples were screened for HPIV1–4 by real-time PCR. Demographic and clinical data of patients infected with different HPIV were compared. We used a hemi-nested PCR approach to generate viral genome sequences from HPIV-positive samples and conducted a comprehensive phylogenetic analysis. In total, 170 samples tested positive for HPIV. HPIV3 was most commonly detected in our cohort and 80 co-detections of HPIV with other respiratory viruses were found. Phylogenetic analyses suggest local endemic circulation as well as punctuated introductions of new HPIV lineages. Viral gene flow analysis revealed that Viet Nam is a net importer of viral genetic diversity. Epidemiological analyses imply similar disease severity for all HPIV species. HPIV sequences from Viet Nam formed local clusters and were interspersed with sequences from diverse geographic regions. Combined, this new knowledge will help to investigate global HPIV circulation patterns in more detail and ultimately define more suitable vaccine strains.
Molecular Epidemiology of the HIV Epidemic in Three German Metropolitan Regions – Cologne/Bonn, Munich and Hannover, 1999–2016
Authors: Stecher Melanie , Chaillon Antoine , Eberle Josef , Behrens Georg M. N. , Eis-Hübinger Anna-Maria , Lehmann Clara , Jablonka Alexandra , Bogner Johannes , Fätkenheuer Gerd , Spinner Christoph D. , Wasmuth Jan-Christian , Kaiser Rolf , Mehta Sanjay R. , Vehreschild Joerg Janne , Hoenigl Martin 
Published: April 2018

AbstractUsing HIV sequence data to characterize clusters of HIV transmission may provide insight into the epidemic. Phylogenetic and network analyses were performed to infer putative relationships between HIV-1 partial pol sequences from 2,774 individuals receiving care in three German regions between 1999–2016. The regions have in common that they host some of the largest annual festivals in Europe (Carnival and Oktoberfest). Putative links with sequences (n = 150,396) from the Los Alamos HIV Sequence database were evaluated. A total of 595/2,774 (21.4%) sequences linked with at least one other sequence, forming 184 transmission clusters. Clustering individuals were significantly more likely to be younger, male, and report sex with men as their main risk factor (p < 0.001 each). Most clusters (77.2%) consisted exclusively of men; 41 (28.9%) of these included men reporting sex with women. Thirty-two clusters (17.4%) contained sequences from more than one region; clustering men were significantly more likely to be in a position bridging regional HIV epidemics than clustering women (p = 0.027). We found 236 clusters linking 547 sequences from our sample with sequences from the Los Alamos database (n = 1407; 31% from other German centres). These results highlight the pitfalls of focusing HIV prevention efforts on specific risk groups or specific locales.
Metabolic systems analysis of LPS induced endothelial dysfunction applied to sepsis patient stratification
Authors: McGarrity Sarah , Anuforo Ósk , Halldórsson Haraldur , Bergmann Andreas , Halldórsson Skarphéðinn , Palsson Sirus , Henriksen Hanne H. , Johansson Pär Ingemar , Rolfsson Óttar 
Published: April 2018

AbstractEndothelial dysfunction contributes to sepsis outcome. Metabolic phenotypes associated with endothelial dysfunction are not well characterised in part due to difficulties in assessing endothelial metabolismin situ. Here, we describe the construction of iEC2812, a genome scale metabolic reconstruction of endothelial cells and its application to describe metabolic changes that occur following endothelial dysfunction. Metabolic gene expression analysis of three endothelial subtypes using iEC2812 suggested their similar metabolism in culture. To mimic endothelial dysfunction, anin vitrosepsis endothelial cell culture model was established and the metabotypes associated with increased endothelial permeability and glycocalyx loss after inflammatory stimuli were quantitatively defined through metabolomics. These data and transcriptomic data were then used to parametrize iEC2812 and investigate the metabotypes of endothelial dysfunction. Glycan production and increased fatty acid metabolism accompany increased glycocalyx shedding and endothelial permeability after inflammatory stimulation. iEC2812 was then used to analyse sepsis patient plasma metabolome profiles and predict changes to endothelial derived biomarkers. These analyses revealed increased changes in glycan metabolism in sepsis non-survivors corresponding to metabolism of endothelial dysfunction in culture. The results show concordance between endothelial health and sepsis survival in particular between endothelial cell metabolism and the plasma metabolome in patients with sepsis.
Conserved and novel responses to cytokinin treatments during flower and fruit development in Brassica napus and Arabidopsis thaliana
Authors: Zuñiga-Mayo Victor M. , Baños-Bayardo Cesar R. , Díaz-Ramírez David , Marsch-Martínez Nayelli , de Folter Stefan 
Published: April 2018

AbstractHormones are an important component in the regulatory networks guiding plant development. Cytokinins are involved in different physiological and developmental processes in plants. In the model plant Arabidopsis thaliana, cytokinin application during gynoecium development produces conspicuous phenotypes. On the other hand, Brassica napus, also known as canola, is a crop plant belonging to the Brassicaceae family, as A. thaliana. This makes B. napus a good candidate to study whether the cytokinin responses observed in A. thaliana are conserved in the same plant family. Here, we observed that cytokinin treatment in B. napus affects different traits of flower and fruit development. It increases ovule and seed number, affects stamen filament elongation and anther maturation, and causes a conspicuous overgrowth of tissue in petals and gynoecia. Furthermore, cytokinin recovers replum development in both wild type B. napus and in the A. thaliana rpl ntt double mutant, in which no replum is visible. These results indicate both conserved and novel responses to cytokinin in B. napus. Moreover, in this species, some cytokinin-induced phenotypes are inherited to the next, untreated generation, suggesting that cytokinins may trigger epigenetic modifications.
Cystatin F involvement in adenosine A2A receptor-mediated neuroinflammation in BV2 microglial cells
Authors: Duan Wei , Wang Haoxiang , Fan Qinlin , Chen Lin , Huang Heqing , Ran Hong 
Published: April 2018

AbstractOur previous studies have shown adenosine A2A R activation markedly promotes the expression of cystatin F (CF) and exacerbates the white matter lesions induced by hypoxic brain injuries. Thus, we hypothesized that CF was probably involved in neuroinflammation of activated microglia induced by A2A R activation. We transfected the BV2 cells with a CF shRNA vector and examined the production of pro-inflammatory cytokines in hypoxic-BV2 cells in which A2A R was activated or inactivated to confirm this hypothesis. Additionally, we also investigated the probable signaling pathways involved in modulation of A2A R activation on CF expression in hypoxia-activated BV2 cells. Activation of A2A R promoted CF expression, which was significantly increased after the low glucose and hypoxia treatments in BV2 cells. CF gene knockdown markedly inhibited the increase in the expression of pro-inflammatory cytokines induced by A2A R activation in hypoxic-BV2 cells. Furthermore, the increased expression of the CF induced by A2A R activation was remarkably inhibited in hypoxic-BV2 cells administrated with the PKA inhibitor H-89 and the PKC inhibitor staurosporine. Hence, these results indicate that hypoxia BV2 cells highly express CF, which is involved in A2A R activation-mediated neuroinflammation via the PKA/CREB and PKC/CREB or ERK1/2 signaling pathways.
Transcriptional Profiling of Somatostatin Interneurons in the Spinal Dorsal Horn
Authors: Chamessian Alexander , Young Michael , Qadri Yawar , Berta Temugin , Ji Ru-Rong , Van de Ven Thomas 
Published: April 2018

AbstractThe spinal dorsal horn (SDH) is comprised of distinct neuronal populations that process different somatosensory modalities. Somatostatin (SST)-expressing interneurons in the SDH have been implicated specifically in mediating mechanical pain. Identifying the transcriptomic profile of SST neurons could elucidate the unique genetic features of this population and enable selective analgesic targeting. To that end, we combined the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) method and Fluorescence Activated Nuclei Sorting (FANS) to capture tagged SST nuclei in the SDH of adult male mice. Using RNA-sequencing (RNA-seq), we uncovered more than 13,000 genes. Differential gene expression analysis revealed more than 900 genes with at least 2-fold enrichment. In addition to many known dorsal horn genes, we identified and validated several novel transcripts from pharmacologically tractable functional classes: Carbonic Anhydrase 12 (Car12), Phosphodiesterase 11 A (Pde11a), and Protease-Activated Receptor 3 (F2rl2). In situ hybridization of these novel genes showed differential expression patterns in the SDH, demonstrating the presence of transcriptionally distinct subpopulations within the SST population. Overall, our findings provide new insights into the gene repertoire of SST dorsal horn neurons and reveal several novel targets for pharmacological modulation of this pain-mediating population and treatment of pathological pain.
Cell Cycle Regulation by Alternative Polyadenylation of CCND1
Authors: Wang Qiong , He Guopei , Hou Mengmeng , Chen Liutao , Chen Shangwu , Xu Anlong , Fu Yonggui 
Published: April 2018

AbstractGlobal shortening of 3′UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown.CCND1is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells. To investigate the biological function of the APA of CCND1, we edited the weak poly(A) signal (PAS) of the proximal APA site to a canonical PAS using the CRISPR/Cas9 method, which can force the cells to use a proximal APA site. Cell cycle profiling and proliferation assays revealed that the proximal APA sites of CCND1 accelerated the cell cycle and promoted cell proliferation, but UTR-APA and CR-APA act via different molecular mechanisms. These results indicate that PAS editing with CRISPR/Cas9 provides a good method by which to study the biological function of APA.
CNOT6 regulates a novel pattern of mRNA deadenylation during oocyte meiotic maturation
Authors: Vieux Karl-Frédéric , Clarke Hugh J. 
Published: April 2018

AbstractIn many cell types, the length of the poly(A) tail of an mRNA is closely linked to its fate - a long tail is associated with active translation, a short tail with silencing and degradation. During mammalian oocyte development, two contrasting patterns of polyadenylation have been identified. Some mRNAs carry a long poly(A) tail during the growth stage and are actively translated, then become deadenylated and down-regulated during the subsequent stage, termed meiotic maturation. Other mRNAs carry a short tail poly(A) tail and are translationally repressed during growth, and their poly(A) tail lengthens and they become translationally activated during maturation. As well, a program of elimination of this ‘maternal’ mRNA is initiated during oocyte maturation. Here we describe a third pattern of polyadenylation: mRNAs are deadenylated in growing oocytes, become polyadenylated during early maturation and then deadenylated during late maturation. We show that the deadenylase, CNOT6, is present in cortical foci of oocytes and regulates deadenylation of these mRNAs, and that PUF-binding elements (PBEs) regulate deadenylation in mature oocytes. Unexpectedly, maintaining a long poly(A) tail neither enhances translation nor inhibits degradation of these mRNAs. Our findings implicate multiple machineries, more complex than previously thought, in regulating mRNA activity in oocytes.
Facile Tumor Spheroids Formation in Large Quantity with Controllable Size and High Uniformity
Authors: Shi Wentao , Kwon Jean , Huang Yongyang , Tan Jifu , Uhl Christopher G. , He Ran , Zhou Chao , Liu Yaling 
Published: April 2018

AbstractA facile method for generation of tumor spheroids in large quantity with controllable size and high uniformity is presented. HCT-116 cells are used as a model cell line. Individual tumor cells are sparsely seeded onto petri-dishes. After a few days of growth, separated cellular islets are formed and then detached by dispase while maintaining their sheet shape. These detached cell sheets are transferred to dispase-doped media under orbital shaking conditions. Assisted by the shear flow under shaking and inhibition of cell-to-extracellular matrix junctions by dispase, the cell sheets curl up and eventually tumor spheroids are formed. The average size of the spheroids can be controlled by tuning the cell sheet culturing period and spheroid shaking period. The uniformity can be controlled by a set of sieves which were home-made using stainless steel meshes. Since this method is based on simple petri-dish cell culturing and shaking, it is rather facile for forming tumor spheroids with no theoretical quantity limit. This method has been used to form HeLa, A431 and U87 MG tumor spheroids and application of the formed tumor spheroids in drug screening is also demonstrated. The viability, 3D structure, and necrosis of the spheroids are characterized.
An Optical Method for the In-Vivo Characterization of the Biomechanical Response of the Right Ventricle
Authors: Soltani A. , Lahti J. , Järvelä K. , Curtze S. , Laurikka J. , Hokka M. , Kuokkala V.-T. 
Published: April 2018

AbstractThe intraoperative in-vivo mechanical function of the left ventricle has been studied thoroughly using echocardiography in the past. However, due to technical and anatomical issues, the ultrasound technology cannot easily be focused on the right side of the heart during open-heart surgery, and the function of the right ventricle during the intervention remains largely unexplored. We used optical imaging and digital image correlation for the characterization of the right ventricle motion and deformation during open-heart surgery. This work is a pilot study focusing on one patient only with the aim of establishing the framework for long term research. These experiments show that optical imaging and the analysis of the images can be used to obtain similar parameters, and partly at higher accuracy, for describing the mechanical functioning of the heart as the ultrasound technology. This work describes the optical imaging based method to characterize the mechanical response of the heart in-vivo, and offers new insight into the mechanical function of the right ventricle.
Understanding the element segregation and phase separation in the Ce-substituted Nd-(Fe,Co)-B based alloys
Authors: Zhao L. Z. , Zhang J. S. , Ahmed G. , Liao X. F. , Liu Z. W. , Greneche J. M. 
Published: April 2018

AbstractCe substituted Nd2Fe14B (2:14:1)-type permanent magnets have shown increasing potential in the applications due to their high properties/cost ratio. However, the element segregation and phase separation in the Ce substituted magnets have not been fully understood yet. In this work, (Nd1−xCex)25Fe40Co20Al4B11 alloys with high coercivities were prepared by copper mold casting. Based on detailed microstructure and composition analysis, the segregation of rare earth (RE) elements was observed in the as-cast alloys. Nd element prefers to enter into the 2:14:1 phase and the Ce element enter into the 1:2 phase. The existence of the 1:2 phase can promote the element segregation. The alloy shows an abnormal increase of coercivity from 641 kA/m for x = 0.2 to 863 kA/m for x = 0.3. This increase could be attributed to the phase separation of the 2:14:1 phase, which has been confirmed by the microstructural characterization. The present data provides useful information for exploring Ce-containing Nd-Fe-B magnets.
Double domain polyethylenimine-based nanoparticles for integrin receptor mediated delivery of plasmid DNA
Authors: Sadeghpour Hossein , Khalvati Bahman , Entezar-Almahdi Elaheh , Savadi Narjes , Hossaini Alhashemi Samira , Raoufi Mohammad , Dehshahri Ali 
Published: April 2018

AbstractThe objective of the present study is to conjugate L-thyroxine PEI derivative onto another PEI to compensate the amine content of the whole structure which has been utilized for the ligand conjugation. Since αvβ3 integrin receptors are over-expressed on cancer cells and there is binding site for L-thyroxine on these receptors, PEI conjugation by L-thyroxine along with restoring the PEI amine content might be an efficient strategy for targeted delivery using polymeric nanoparticles. The results demonstrated the ability of the PEI conjugate in the formation of nanoparticles with the size of around 210 nm with higher buffering capacity. The conjugated PEI derivative increased the transfection efficiency in the cell lines over-expressing integrin by up to two folds higher than unmodified PEI, whereas in the cell lines lacking the integrin receptors there was no ligand conjugation-associated difference in gene transfer ability. The specificity of transfection demonstrated the delivery of plasmid DNA through integrin receptors. Also, the results of in vivo imaging of the polyplexes revealed that 99mTc-labeled PEI/plasmid DNA complexes accumulated in kidney and bladder 4 h post injection. Therefore, this PEI derivative could be considered as an efficient targeted delivery system for plasmid DNA.
Dietary divergence is associated with increased intra-specific competition in a marine predator
Authors: Ratcliffe Norman , Adlard Stacey , Stowasser Gabrielle , McGill Rona 
Published: April 2018

AbstractOptimal foraging theory predicts that when food is plentiful all individuals should take a small range of preferred prey types, but as competition increases less preferred prey will be included in the diet. This dietary switching may not be uniform among individuals, which produces discrete dietary clusters. We tested this hypothesis for gentoo penguins at Bird Island, South Georgia, using stable isotope analysis and biologging. Competition, in the form of the density of foraging dives, increased markedly from incubation to chick-rearing owing to increased foraging effort. Birds responded behaviourally by exploiting a greater portion of the available foraging radius and increasing dive depths. Dietary niche width doubled and two discrete dietary clusters appeared; one comprising birds that consumed mostly krill and another that ate a greater proportion of demersal fish. There were no differences in morphology between the dietary classes, but birds in the fish class had a tendency to dive deeper, which suggests a behavioural basis for specialization. Our findings are consistent with the hypothesis that intra-specific competition expands the population’s dietary niche width and drives divergence in diets among individuals.