bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a 12-week lifestyle education intervention with or without partial meal replacement in Thai adults with obesity and metabolic syndrome: a randomised trial
Authors: Chaiyasoot Kusuma , Sarasak Rungnapha , Pheungruang Banchamaphon , Dawilai Suwitcha , Pramyothin Pornpoj , Boonyasiri Adhiratha , Supapueng Orawan , Jassil Friedrich C. , Yamwong Preyanuj , Batterham Rachel L.
Published: April 2018

Background/Objectives

There have been no studies examining the efficacy of meal replacement (MR) on weight loss and metabolic syndrome (MS) improvement in Southeast Asians. Thus, we undertook a 12-week randomised trial to evaluate the effect of a lifestyle education intervention alone (LEI) or with partial MR (LEI + MR) in obese Thai adults with MS.

Subjects/Methods

A total of 110 patients were randomised to receive either LEI or LEI + MR. Both groups received LEI to achieve weight loss. LEI + MR group additionally received two MR daily to replace either breakfast, lunch or dinner. Mean ± SE body mass index of all participants was 34.6 ± 0.6 kg/m2, mean ± SE age was 42.5 ± 1.1 years and 83% of patients were female. Both groups were compared for anthropometric and cardiometabolic indices at 12-week. Body weight was also compared at weeks 38 and 64.

Results

At 12 weeks, both groups exhibited statistically significant percentage weight loss (%WL) compared to initial weight but greater %WL was observed in LEI + MR compared to LEI, 2.9% vs. 1.5%, respectively (p < 0.05). MS criteria such as waist circumference and blood pressure improved significantly in both groups compared to baseline. However, improvement in fasting plasma glucose (FPG) was only significant in LEI + MR, and more participants with impaired FPG at baseline in LEI + MR (42.9%) than LEI (19%) returned to normal FPG at 12 weeks (p < 0.05). HbA1c, fasting insulin and HOMA-IR in LEI + MR were significantly lower than with LEI. At the end of the 12-week intervention period, 16% of participants no longer fulfilled MS criteria. A statistically significant weight loss from baseline persisted until 38 weeks but no longer reached statistically significant difference between groups

Conclusions

LEI and LEI + MR were acceptable and led to improvement in weight and MS. LEI + MR group exhibited additional weight reduction and glycemic benefits at 12 weeks.
Regulation of DNA damage repair and lipid uptake by CX3CR1 in epithelial ovarian carcinoma
Authors: Xie Jia , Gurler Main Hilal , Sacks Joelle D. , Muralidhar Goda G. , Barbolina Maria V.
Published: April 2018

Failure of currently used cytotoxic chemotherapy is one of the main reasons behind high mortality from metastatic high grade serous ovarian carcinoma. We found that high expression of a receptor for fractalkine (CX3CR1) significantly correlated with shorter survival of patients with serous ovarian carcinoma treated with cytotoxic DNA damage chemotherapies, and reduction of CX3CR1 expression resulted in sensitization to several DNA damaging modalities, including x-ray radiation and cisplatin. Here, we show that CX3CR1 plays a role in double-strand DNA break response and repair by regulating expression of RAD50 by a MYC-dependent mechanism. We demonstrate that downregulation of CX3CR1 alone and in a combination with irradiation affects peritoneal metastasis in an organ-specific manner; we show that CX3CR1 regulates lipid uptake which could control omental metastasis. This study identifies CX3CR1 as a novel potential target for sensitization of ovarian carcinoma to DNA damage therapies and reduction of peritoneal carcinomatosis.
Molecularly specific detection of bacterial lipoteichoic acid for diagnosis of prosthetic joint infection of the bone
Authors: Pickett Julie E. , Thompson John M. , Sadowska Agnieszka , Tkaczyk Christine , Sellman Bret R. , Minola Andrea , Corti Davide , Lanzavecchia Antonio , Miller Lloyd S. , Thorek Daniel LJ
Published: April 2018

Discriminating sterile inflammation from infection, especially in cases of aseptic loosening versus an actual prosthetic joint infection, is challenging and has significant treatment implications. Our goal was to evaluate a novel human monoclonal antibody (mAb) probe directed against the Gram-positive bacterial surface molecule lipoteichoic acid (LTA). Specificity and affinity were assessed in vitro. We then radiolabeled the anti-LTA mAb and evaluated its effectiveness as a diagnostic imaging tool for detecting infection via immunoPET imaging in an in vivo mouse model of prosthetic joint infection (PJI). In vitro and ex vivo binding of the anti-LTA mAb to pathogenic bacteria was measured with Octet, ELISA, and flow cytometry. The in vivo PJI mouse model was assessed using traditional imaging modalities, including positron emission tomography (PET) with [18F]FDG and [18F]NaF as well as X-ray computed tomography (CT), before being evaluated with the zirconium-89-labeled antibody specific for LTA ([89Zr]SAC55). The anti-LTA mAb exhibited specific binding in vitro to LTA-expressing bacteria. Results from imaging showed that our model could reliably simulate infection at the surgical site by bioluminescent imaging, conventional PET tracer imaging, and bone morphological changes by CT. One day following injection of both the radiolabeled anti-LTA and isotype control antibodies, the anti-LTA antibody demonstrated significantly greater (P < 0.05) uptake at S. aureus-infected prosthesis sites over either the same antibody at sterile prosthesis sites or of control non-specific antibody at infected prosthesis sites. Taken together, the radiolabeled anti-LTA mAb, [89Zr]SAC55, may serve as a valuable diagnostic molecular imaging probe to help distinguish between sterile inflammation and infection in the setting of PJI. Future studies are needed to determine whether these findings will translate to human PJI.
Mitochondrial NADP+-dependent isocitrate dehydrogenase deficiency increases cisplatin-induced oxidative damage in the kidney tubule cells
Authors: Kong Min Jung , Han Sang Jun , Kim Jee In , Park Jeen-Woo , Park Kwon Moo
Published: April 2018

Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) plays an important role in the formation of NADPH, which is critical for the maintenance of mitochondrial redox balance. Cis-diamminedichloroplatinum II (cisplatin), an effective anticancer drug, induces oxidative stress-related nephrotoxicity, limiting its use. Therefore, we investigated whether IDH2, which is a critical enzyme in the NADPH-associated mitochondrial antioxidant system, is involved in cisplatin nephrotoxicity. Idh2 gene-deleted (Idh2−/−) mice and wild-type (Idh2
+/+
) littermates were treated with cisplatin, with or without 2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito-T), a mitochondria-specific antioxidant. Cisplatin-induced renal functional and morphological impairments were greater in Idh2−/− mice than in Idh2
+/+
mice. Mito-T mitigated those impairments in both Idh2−/− and Idh2
+/+
mice and this mitigation was greater in Idh2−/− than in Idh2
+/+
mice. Cisplatin impaired IDH2 function in the mitochondria, decreasing mitochondrial NADPH and GSH levels and increasing H2O2 generation; protein, lipid, and DNA oxidation; mitochondrial damage; and apoptosis. These cisplatin-induced changes were much more severe in Idh2−/− mice than in Idh2
+/+
mice. Mito-T treatment attenuated cisplatin-induced alterations in both Idh2−/− and Idh2
+/+
mice and this mitigation was greater in Idh2−/− than in Idh2
+/+
mice. Altogether, these data demonstrate that cisplatin induces the impairment of the mitochondrial IDH2-NADPH-GSH antioxidant system and IDH2 deficiency aggravates cisplatin-induced mitochondrial oxidative damage, inducing more severe nephrotoxicity. This suggests that the mitochondrial IDH2-NADPH-GSH antioxidant system is a target for the prevention of cisplatin-induced kidney cell death.
Modulation of alternative splicing induced by paclitaxel in human lung cancer
Authors: Zhu Ziran , Chen Dan , Zhang Wenjing , Zhao Jinyao , Zhi Lili , Huang Fang , Ji Haoyu , Zhang Jinrui , Liu Han , Zou Lijuan , Wang Yang
Published: April 2018

Paclitaxel is utilized as the first-line chemotherapeutic regimen for the majority of advanced non-small-cell lung carcinoma. However, whether paclitaxel could suppress cancer progression through modulating RNA alternative splicing remains largely unknown. Here, we demonstrated the effects of paclitaxel on cell proliferation inhibition, cell cycle arrest, and apoptosis. Mechanistically, paclitaxel leads to transcriptional alteration of networks involved in DNA replication and repair, chromosome segregation, chromatin silencing at rDNA, and mitosis at the transcriptional level. Moreover, paclitaxel regulates a number of cancer-associated RNA alternative splicing events, including genes involved in cellular response to DNA damage stimulus, preassembly of GPI anchor in ER membrane, transcription, and DNA repair. In particular, paclitaxel modulates the splicing of ECT2, a key factor involved in the regulation of cytokinesis. Briefly, paclitaxel favors the production of ECT2-S, the short splicing isoforms of ECT2, thereby inhibiting cancer cell proliferation. Our study provides mechanistic insights of paclitaxel on RNA alternative splicing regulation, thus to offer a potential novel route for paclitaxel to inhibit cancer progression.
Publisher Correction: Optimal compressed representation of high throughput sequence data via light assembly
Authors: Ginart Antonio A. , Hui Joseph , Zhu Kaiyuan , Numanagić Ibrahim , Courtade Thomas A. , Sahinalp S. Cenk , Tse David N.
Published: April 2018

The original version of this Article contained errors in the affiliations of the authors Ibrahim Numanagić and Thomas A. Courtade, which were incorrectly given as ‘Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA 94720, USA’ and ‘Computer Science & Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA’, respectively. Also, the hyperlink for the source code in the Data Availability section was incorrectly given as https://github.iu.edu/kzhu/assembltrie, which links to a page that is not publicly accessible. The source code is publicly accessible at https://github.com/kyzhu/assembltrie. Furthermore, in the PDF version of the Article, the right-hand side of Figure 3 was inadvertently cropped. These errors have now been corrected in both the PDF and HTML versions of the Article.
Distinct mutational signatures characterize concurrent loss of polymerase proofreading and mismatch repair
Authors: Haradhvala N. J. , Kim J. , Maruvka Y. E. , Polak P. , Rosebrock D. , Livitz D. , Hess J. M. , Leshchiner I. , Kamburov A. , Mouw K. W. , Lawrence M. S. , Getz G.
Published: April 2018

Fidelity of DNA replication is maintained using polymerase proofreading and the mismatch repair pathway. Tumors with loss of function of either mechanism have elevated mutation rates with characteristic mutational signatures. Here we report that tumors with concurrent loss of both polymerase proofreading and mismatch repair function have mutational patterns that are not a simple sum of the signatures of the individual alterations, but correspond to distinct, previously unexplained signatures: COSMIC database signatures 14 and 20. We then demonstrate that in all five cases in which the chronological order of events could be determined, polymerase epsilon proofreading alterations precede the defect in mismatch repair. Overall, we illustrate that multiple distinct mutational signatures can result from different combinations of a smaller number of mutational processes (of either damage or repair), which can influence the interpretation and discovery of mutational signatures.
The topological requirements for robust perfect adaptation in networks of any size
Authors: Araujo Robyn P. , Liotta Lance A.
Published: April 2018

Robustness, and the ability to function and thrive amid changing and unfavorable environments, is a fundamental requirement for living systems. Until now it has been an open question how large and complex biological networks can exhibit robust behaviors, such as perfect adaptation to a variable stimulus, since complexity is generally associated with fragility. Here we report that all networks that exhibit robust perfect adaptation (RPA) to a persistent change in stimulus are decomposable into well-defined modules, of which there exist two distinct classes. These two modular classes represent a topological basis for all RPA-capable networks, and generate the full set of topological realizations of the internal model principle for RPA in complex, self-organizing, evolvable bionetworks. This unexpected result supports the notion that evolutionary processes are empowered by simple and scalable modular design principles that promote robust performance no matter how large or complex the underlying networks become.
Author Correction: Nitrogen-rich organic soils under warm well-drained conditions are global nitrous oxide emission hotspots
Authors: Pärn Jaan , Verhoeven Jos T. A. , Butterbach-Bahl Klaus , Dise Nancy B. , Ullah Sami , Aasa Anto , Egorov Sergey , Espenberg Mikk , Järveoja Järvi , Jauhiainen Jyrki , Kasak Kuno , Klemedtsson Leif , Kull Ain , Laggoun-Défarge Fatima , Lapshina Elena D. , Lohila Annalea , Lõhmus Krista , Maddison Martin , Mitsch William J. , Müller Christoph , Niinemets Ülo , Osborne Bruce , Pae Taavi , Salm Jüri-Ott , Sgouridis Fotis , Sohar Kristina , Soosaar Kaido , Storey Kathryn , Teemusk Alar , Tenywa Moses M. , Tournebize Julien , Truu Jaak , Veber Gert , Villa Jorge A. , Zaw Seint Sann , Mander Ülo
Published: April 2018

The original version of this Article contained an error in the first sentence of the Acknowledgements section, which incorrectly referred to the Estonian Research Council grant identifier as “PUTJD618”. The correct version replaces the grant identifier with “PUTJD619”. This has been corrected in both the PDF and HTML versions of the Article.
A functional genomic screen in vivo identifies CEACAM5 as a clinically relevant driver of breast cancer metastasis
Authors: Powell Emily , Shao Jiansu , Picon Hector M. , Bristow Christopher , Ge Zhongqi , Peoples Michael , Robinson Frederick , Jeter-Jones Sabrina L. , Schlosberg Christopher , Grzeskowiak Caitlin L. , Yang Fei , Wu Yun , Wistuba Ignacio , Moulder Stacy L. , Symmans William F. , Scott Kenneth L. , Edwards John R. , Liang Han , Heffernan Timothy P. , Piwnica-Worms Helen
Published: April 2018

Tumor cells disseminate early in tumor development making metastasis-prevention strategies difficult. Identifying proteins that promote the outgrowth of disseminated tumor cells may provide opportunities for novel therapeutic strategies. Despite multiple studies demonstrating that the mesenchymal-to-epithelial transition (MET) is critical for metastatic colonization, key regulators that initiate this transition remain unknown. We serially passaged lung metastases from a primary triple negative breast cancer xenograft to the mammary fat pads of recipient mice to enrich for gene expression changes that drive metastasis. An unbiased transcriptomic signature of potential metastatic drivers was generated, and a high throughput gain-of-function screen was performed in vivo to validate candidates. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) was identified as a metastatic driver. CEACAM5 overproduction enriched for an epithelial gene expression pattern and facilitated tumor outgrowth at metastatic sites. Tissues from patients with metastatic breast cancer confirmed elevated levels of CEACAM5 in lung metastases relative to breast tumors, and an inverse correlation between CEACAM5 and the mesenchymal marker vimentin was demonstrated. Thus, CEACAM5 facilitates tumor outgrowth at metastatic sites by promoting MET, warranting its investigation as a therapeutic target and biomarker of aggressiveness in breast cancer.
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

The 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

STRs 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

HPIVs 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

Using 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

Endothelial 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

Hormones 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

Our 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

The 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

Global 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

In 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

A 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

The 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

Ce 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.
Publisher Correction: Polarized electron beams elastically scattered by atoms as a tool for testing fundamental predictions of quantum mechanics
Authors: Dapor Maurizio
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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

The 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

Optimal 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.
Nano-sized Molecularly Imprinted Polymers as Artificial Antibodies
Authors: Canfarotta F. , Cecchini A. , Piletsky S.
Published: April 2018

The use of antibodies (Abs) and enzymes in diagnostic assays is widely accepted and, to date, represents the gold standard in terms of sensitivity and affinity. Abs are routinely used in many diagnostic assays but they suffer from short shelf-life, high costs of manufacturing and relatively poor stability, especially at extremes of temperature and pH. The use of molecularly imprinted polymer (MIP) nanoparticles can overcome these problems. Compared with Abs, the synthesis of MIPs is simpler and more cost-effective and, moreover, does not require involvement of animals. In addition, MIPs show high stability and excellent mechanical properties, and can be prepared virtually for any target. NanoMIPs, sometimes called ″plastic antibodies″, are nanostructured polymer particles capable of selectively recognising the said target. Thanks to their size, they represent a viable alternative to Abs, as demonstrated by their recent application in several diagnostic fields. Herein, we review the most common synthetic approaches in the manufacture of nanoMIPs, together with some recent examples of the use of nanoMIPs in diagnostics, in particular within sensors, assays and for imaging purposes.
Theoretical and Computational Strategies in Molecularly Imprinted Polymer Development
Authors: Nicholls Ian A. , Olsson Gustaf D. , Karlsson Björn C. G. , Suriyanarayanan Subramanian , Wiklander Jesper G.
Published: April 2018

Theoretical and computational studies of molecular imprinting have helped provide valuable insights concerning the nature of the molecular-level events underlying the recognition characteristics of molecularly imprinted materials. Here, we first present an overview of a thermodynamic treatment of factors governing the behaviour of these functional materials, and then a summary of the development and current status of the use of computational strategies for studying aspects of molecular imprinting and the resulting material properties.
Designing of Biomimetic Molecularly Imprinted Catalysts
Authors: Dong Z. Y. , Liu J. Q.
Published: April 2018

In this chapter, we summarized the recent advances of the research topic on biomimetic molecularly imprinted catalysts. The introduction of biomimetic catalysts was briefly reviewed to represent a basic comprehension on the state-of-the-art of artificial enzymes. Then, biomimetic molecularly imprinted catalysts were highlighted with respect to molecular catalysis and even supramolecular catalysis. The highlights suggested that a number of chemical reactions, such as oxidation, reduction, elimination, and carbon–carbon bond formation and more, can efficiently be catalyzed by molecularly imprinted catalysts. Owing to the selectivity features of molecular recognition originating from molecularly imprinted catalysts, these synthetic materials will be promising for a wide use in sensing applications for environmental monitoring, clinical diagnostics, the detection of organisms and toxins, and security.
Electrosynthesized Molecularly Imprinted Polymers for Chemosensing: Fundamentals and Applications
Authors: Mazzotta E. , Rella S. , Turco A. , Malitesta C.
Published: April 2018

This chapter describes molecularly imprinted polymers prepared by electropolymerization (eMIPs) and their use in chemical sensing applications, with a special focus on electrochemical ones. A survey of the works published on the topic in the last five years is presented, after a general introduction on the fundamentals of chemical sensors, electropolymerization process and imprinting technology, describing also different types of electrochemical sensors based on eMIPs and relevant commonly used detection schemes. An overview of typical electroactive functional monomers used in the electrosynthesis of MIPs for chemosensor applications is reported, including a section dedicated to the latest achievements in the application of nanomaterials to the development of eMIP sensors. Strategies used for the determination of different analytes as well as efforts for enhancing the imprinting effect and sensing performances are presented and critically discussed.
Recent advances in LIBS and XRF for the analysis of plants
Authors: Arantes de Carvalho Gabriel Gustinelli , Bueno Guerra Marcelo Braga , Adame Andressa , Nomura Cassiana Seimi , Oliveira Pedro Vitoriano , Pereira de Carvalho Hudson Wallace , Santos Dário , Nunes Lidiane Cristina , Krug Francisco José
Published: April 2018

Review of recent developments in quantitative analysis and microchemical imaging of plants by LIBS and XRF.
Recent advances in alkyne-based click polymerizations
Authors: Huang Die , Liu Yong , Qin Anjun , Tang Ben Zhong
Published: April 2018

The recent progress in alkyne-based click polymerizations and their application in the preparation of new functional polymers are summarized. The challenges and opportunities in this area are also briefly discussed.
Long-lived charge separation in dye–semiconductor assemblies: a pathway to multi-electron transfer reactions
Authors: Sundin Elin , Abrahamsson Maria
Published: April 2018

Key approaches to achieve long-lived charge separation and promote conduction band mediated electron transfer in dye-sensitized semiconductor assemblies.
Photocatalytic CO2conversion by polymeric carbon nitrides
Authors: Fang Yuanxing , Wang Xinchen
Published: April 2018

CO2is a vital compound for life, and its concentration significantly affects the living environment of the Earth. By mimicking nature photosynthesis, we herein discusses the uses of polymeric carbon nitrides to balance CO2concentration by artificial photocatalysis.
Increased immune cell infiltration in patient-derived tumor explants treated with Traniplatin: an original Pt(iv) pro-drug based on Cisplatin and Tranilast
Authors: Lo Re Daniele , Montagner Diego , Tolan Dina , Di Sanza Claudio , Iglesias Mar , Calon Alexandre , Giralt E.
Published: April 2018

Traniplatin shows increased in vitro cytotoxic activity against colon and lung cancer cells but decreased activity against immune cells in comparison to Cisplatin.
Concomitant desalting and concentration of neuropeptides on a donut-shaped surface pattern for MALDI mass spectrometry
Authors: Yoon Sook , Park Sanghwan , Kim Min Sun , Lee Chang Young
Published: April 2018

We demonstrate a functional surface pattern that desalts and concentrates a highly saline solution of neuropeptides in a single step.
Structures and photophysical performances of (fluoro)salicylate stabilized polyoxo-titanium clusters
Authors: Zhu Bang-Chang , Fang Wei-Hui , Emayavaramban Perumal , Zhang Lei , Zhang Jian
Published: April 2018

The introduction of fluorine in salicylic acid yielded different polyoxo-titanium clusters with distinct photophysical properties.
Ab initioconformational analysis of 1,2,3,4-tetrahydroquinoline and the high-resolution rotational spectrum of its lowest energy conformer
Authors: Luková Kateřina , Nesvadba Radim , Uhlíková Tereza , Obenchain Daniel A. , Wachsmuth Dennis , Grabow Jens-Uwe , Urban Štěpán
Published: April 2018

The tight combination of rotational spectroscopy and quantum-chemical calculations provides an insight into the molecular physics of the lowest energy conformer of 1,2,3,4-tetrahydroquinoline.
Microscopic properties of ionic liquid/organic semiconductor interfaces revealed by molecular dynamics simulations
Authors: Yokota Yasuyuki , Miyamoto Hiroo , Imanishi Akihito , Takeya Jun , Inagaki Kouji , Morikawa Yoshitada , Fukui Ken-ichi
Published: April 2018

Structural and dynamic properties of an ionic liquid are compared on several organic semiconductors.
Ammonolysis of ketene as a potential source of acetamide in the troposphere: a quantum chemical investigation
Authors: Sarkar Saptarshi , Mallick Subhasish , Kumar Pradeep , Bandyopadhyay Biman
Published: April 2018

Quantum chemical calculations at the CCSD(T)/CBS//MP2/aug-cc-pVTZ levels of theory have been carried out to investigate a potential new source of acetamide in Earth's atmosphere through the ammonolysis of the simplest ketene.
Fe–Si networks and charge/discharge-induced phase transitions in Li2FeSiO4 cathode materials
Authors: Lv Xiaobao , Zhao Xin , Wu Shunqing , Nguyen Manh Cuong , Zhu Zizhong , Lin Zijing , Wang Cai-Zhuang , Ho Kai-Ming
Published: April 2018

Structural phase transitions of electrode materials are responsible for poor reversibility during charge/discharge cycling in Li-ion batteries.
A solvent-free in situ synthesis of a hierarchical Co-based zeolite catalyst and its application to tuning Fischer–Tropsch product selectivity
Authors: Mazonde Brighton , Cheng Shilin , Zhang Guihua , Javed Mudassar , Gao Weizhe , Zhang Yu , Tao Meng , Lu Chengxue , Xing Chuang
Published: April 2018

As a distinctive supportable route, the solvent-free synthesis of zeolites not only minimizes the problems of conversional hydrothermal synthesis, but also greatly increases the product yields with advantageous characteristics, such as reduced waste production and a hierarchical pore structure.