bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a high Edinburgh Postnatal Depression Scale score on obstetric and perinatal outcomes
Authors: Navaratne Pathmila , Foo Xin Y , Kumar Sailesh
Published: September 2016

The aim of this retrospective study was to characterise intrapartum and neonatal outcomes in women with an antenatally recorded Edinburgh Postnatal Depression Score (EPDS) ≤ 9 compared with women with a score of ≥12 at a major Australian tertiary maternity hospital. Women with scores ≥12 are at particularly high risk of major depressive symptomatology. There were 20512 (78.6%) women with a score ≤ 9 and 2708 (10.4%) had a score ≥ 12. Category 1 caesarean sections where there was immediate threat to life (maternal or fetal) were more common in women with EPDS scores ≥12 (5.2% vs. 4.3%, OR 1.24 95% CI 1.03–1.49, p = 0.024). Pre-term birth (<37 weeks) was also more common (11.7% vs. 8.6%, OR 1.38 95% CI 1.21–1.57, p < 0.001). Women with high scores had higher rates of babies with birth weights <5th centile (6.2% vs. 4.4%, p < 0.001). Apgar score < 7 at 5 minutes were more frequent in the high EPDS group (3.1% vs. 2%, OR 1.52 95% CI 1.18–1.93, p < 0.001). Resuscitation at birth (34.4% vs. 30.6%, p < 0.001) and neonatal death (0.48% vs. 0.13%, OR 2.52 95% CI 1.2–5.0, p < 0.001) were higher in babies of these women. These results suggest poorer intrapartum and neonatal outcomes for women with high EPDS scores.
Toll-Like Receptor 9 Activation Rescues Impaired Antibody Response in Needle-free Intradermal DNA Vaccination
Authors: Arunachalam Prabhu S. , Mishra Ria , Badarinath Krithika , Selvam Deepak , Payeli Sravan K. , Stout Richard R. , Ranga Udaykumar
Published: September 2016

The delivery of plasmid DNA to the skin can target distinct subsets of dermal dendritic cells to confer a superior immune response. The needle-free immunization technology offers a reliable, safe and efficient means to administer intradermal (ID) injections. We report here that the ID injection of DNA vectors using an NF device (NF-ID) elicits a superior cell-mediated immune response, at much lesser DNA dosage, comparable in magnitude to the traditional intramuscular immunization. However, the humoral response is significantly impaired, possibly at the stage of B cell isotype switching. We found that the NF-ID administration deposits the DNA primarily on the epidermis resulting in a rapid loss of the DNA as well as the synthesized antigen due to the faster regeneration rate of the skin layers. Therefore, despite the immune-rich nature of the skin, the NF-ID immunization of DNA vectors may be limited by the impaired humoral response. Additional booster injections are required to augment the antibody response. As an alternative and a viable solution, we rescued the IgG response by coadministration of a Toll-like receptor 9 agonist, among other adjuvants examined. Our work has important implication for the optimization of the emerging needle-free technology for ID immunization.
Schizophyllum commune has an extensive and functional alternative splicing repertoire
Authors: Gehrmann Thies , Pelkmans Jordi F. , Lugones Luis G. , Wösten Han A. B. , Abeel Thomas , Reinders Marcel J. T.
Published: September 2016

Recent genome-wide studies have demonstrated that fungi possess the machinery to alternatively splice pre-mRNA. However, there has not been a systematic categorization of the functional impact of alternative splicing in a fungus. We investigate alternative splicing and its functional consequences in the model mushroom forming fungus Schizophyllum commune. Alternative splicing was demonstrated for 2,285 out of 12,988 expressed genes, resulting in 20% additional transcripts. Intron retentions were the most common alternative splicing events, accounting for 33% of all splicing events, and 43% of the events in coding regions. On the other hand, exon skipping events were rare in coding regions (1%) but enriched in UTRs where they accounted for 57% of the events. Specific functional groups, including transcription factors, contained alternatively spliced genes. Alternatively spliced transcripts were regulated differently throughout development in 19% of the 2,285 alternatively spliced genes. Notably, 69% of alternatively spliced genes have predicted alternative functionality by loss or gain of functional domains, or by acquiring alternative subcellular locations. S. commune exhibits more alternative splicing than any other studied fungus. Taken together, alternative splicing increases the complexity of the S. commune proteome considerably and provides it with a rich repertoire of alternative functionality that is exploited dynamically.
Transmission of survival signals through Delta-like 1 on activated CD4+ T cells
Authors: Furukawa Takahiro , Ishifune Chieko , Tsukumo Shin-ichi , Hozumi Katsuto , Maekawa Yoichi , Matsui Naoko , Kaji Ryuji , Yasutomo Koji
Published: September 2016

Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remains unclear. In this report we demonstrate that the CD4+ T cell Notch ligand Dll1 transduces signals required for their survival. Co-transfer of CD4+ T cells from Dll1−/− and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1−/− mice compared with control cells. Dll1−/− mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1−/− mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data demonstrate that Dll1 is an independent regulator of Notch-signaling important for the survival of activated CD4+ T cells and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses.
Entanglement and nonclassicality in four-mode Gaussian states generated via parametric down-conversion and frequency up-conversion
Authors: Arkhipov Ievgen I. , Peřina Jan , Haderka Ondřej , Allevi Alessia , Bondani Maria
Published: September 2016

Multipartite entanglement and nonclassicality of four-mode Gaussian states generated in two simultaneous nonlinear processes involving parametric down-conversion and frequency up-conversion are analyzed assuming the vacuum as the initial state. Suitable conditions for the generation of highly entangled states are found. Transfer of the entanglement from the down-converted modes into the up-converted ones is also suggested. The analysis of the whole set of states reveals that sub-shot-noise intensity correlations between the equally-populated down-converted modes, as well as the equally-populated up-converted modes, uniquely identify entangled states. They represent a powerful entanglement identifier also in other cases with arbitrarily populated modes.
Behavioural and neural modulation of win-stay but not lose-shift strategies as a function of outcome value in Rock, Paper, Scissors
Authors: Forder Lewis , Dyson Benjamin James
Published: September 2016

Competitive environments in which individuals compete for mutually-exclusive outcomes require rational decision making in order to maximize gains but often result in poor quality heuristics. Reasons for the greater reliance on lose-shift relative to win-stay behaviour shown in previous studies were explored using the game of Rock, Paper, Scissors and by manipulating the value of winning and losing. Decision-making following a loss was characterized as relatively fast and relatively inflexible both in terms of the failure to modulate the magnitude of lose-shift strategy and the lack of significant neural modulation. In contrast, decision-making following a win was characterized as relatively slow and relatively flexible both in terms of a behavioural increase in the magnitude of win-stay strategy and a neural modulation of feedback-related negativity (FRN) and stimulus-preceding negativity (SPN) following outcome value modulation. The win-stay/lose-shift heuristic appears not to be a unified mechanism, with the former relying on System 2 processes and the latter relying on System 1 processes. Our ability to play rationally appears more likely when the outcome is positive and when the value of wins are low, highlighting how vulnerable we can be when trying to succeed during competition.
Identification of a novel human deoxynivalenol metabolite enhancing proliferation of intestinal and urinary bladder cells
Authors: Warth Benedikt , Del Favero Giorgia , Wiesenberger Gerlinde , Puntscher Hannes , Woelflingseder Lydia , Fruhmann Philipp , Sarkanj Bojan , Krska Rudolf , Schuhmacher Rainer , Adam Gerhard , Marko Doris
Published: September 2016

The mycotoxin deoxynivalenol (DON) is an abundant contaminant of cereal based food and a severe issue for global food safety. We report the discovery of DON-3-sulfate as a novel human metabolite and potential new biomarker of DON exposure. The conjugate was detectable in 70% of urine samples obtained from pregnant women in Croatia. For the measurement of urinary metabolites, a highly sensitive and selective LC-MS/MS method was developed and validated. The method was also used to investigate samples from a duplicate diet survey for studying the toxicokinetics of DON-3-sulfate. To get a preliminary insight into the biological relevance of the newly discovered DON-sulfates, in vitroexperiments were performed. In contrast to DON, sulfate conjugates lacked potency to suppress protein translation. However, surprisingly we found that DON-sulfates enhanced proliferation of human HT-29 colon carcinoma cells, primary human colon epithelial cells (HCEC-1CT) and, to some extent, also T24 bladder cancer cells. A proliferative stimulus, especially in tumorigenic cells raises concern on the potential impact of DON-sulfates on consumer health. Thus, a further characterization of their toxicological relevance should be of high priority.
Antibacterial activity of a modified unfilled resin containing a novel polymerizable quaternary ammonium salt MAE-HB
Authors: Huang Li , Yu Fan , Sun Xiang , Dong Yan , Lin Ping-ting , Yu Hao-han , Xiao Yu-hong , Chai Zhi-guo , Xing Xiao-dong , Chen Ji-hua
Published: September 2016

Resins with strong and long-lasting antibacterial properties are critical for the prevention of secondary dental caries. In this study, we evaluated the antibacterial effect and the underlying mechanism of action of an unfilled resin incorporating 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB) against Streptococcus mutans UA159 (S. mutans UA159). MAE-HB was added into unfilled resin at 10 mass%, and unfilled resin without MAE-HB served as the control. Bacterial growth was inhibited on 10%-MAE-HB unfilled resin compared with the control at 1 d, 7 d, 30 d, or 180 d (P < 0.05). The growth inhibitory effect was independent of the incubation time (P > 0.05). No significant differences in the antibacterial activities of eluents from control versus 10%-MAE-HB unfilled resins were observed at any time point (P > 0.05). The number of bacteria attached to 10%-MAE-HB unfilled resin was considerably lower than that to control. Fe-SEM and CLSM showed that 10%-MAE-HB unfilled resin disturbed the integrity of bacterial cells. Expression of the bacterial glucosyltransferases, gtfB and gtfC, was lower on 10%-MAE-HB unfilled resin compared to that on control (P < 0.05). These data indicate that incorporation of MAE-HB confers unfilled resin with strong and long-lasting antibacterial effects against S. mutans.
A novel testate amoebae trait-based approach to infer environmental disturbance in Sphagnum peatlands
Authors: Marcisz Katarzyna , Colombaroli Daniele , Jassey Vincent E. J. , Tinner Willy , Kołaczek Piotr , Gałka Mariusz , Karpińska-Kołaczek Monika , Słowiński Michał , Lamentowicz Mariusz
Published: September 2016

Species’ functional traits are closely related to ecosystem processes through evolutionary adaptation, and are thus directly connected to environmental changes. Species’ traits are not commonly used in palaeoecology, even though they offer powerful advantages in understanding the impact of environmental disturbances in a mechanistic way over time. Here we show that functional traits of testate amoebae (TA), a common group of palaeoecological indicators, can serve as an early warning signal of ecosystem disturbance and help determine thresholds of ecosystem resilience to disturbances in peatlands. We analysed TA traits from two Sphagnum-dominated mires, which had experienced different kinds of disturbances in the past 2000 years – fire and peat extraction, respectively. We tested the effect of disturbances on the linkages between TA community structure, functional trait composition and functional diversity using structural equation modelling. We found that traits such as mixotrophy and small hidden apertures (plagiostomic apertures) are strongly connected with disturbance, suggesting that these two traits can be used as palaeoecological proxies of peatland disturbance. We show that TA functional traits may serve as a good proxy of past environmental changes, and further analysis of trait-ecosystem relationships could make them valuable indicators of the contemporary ecosystem state.
Flipper strokes can predict energy expenditure and locomotion costs in free-ranging northern and Antarctic fur seals
Authors: Jeanniard-du-Dot Tiphaine , Trites Andrew W. , Arnould John P. Y. , Speakman John R. , Guinet Christophe
Published: September 2016

Flipper strokes have been proposed as proxies to estimate the energy expended by marine vertebrates while foraging at sea, but this has never been validated on free-ranging otariids (fur seals and sea lions). Our goal was to investigate how well flipper strokes correlate with energy expenditure in 33 foraging northern and Antarctic fur seals equipped with accelerometers, GPS, and time-depth recorders. We concomitantly measured field metabolic rates with the doubly-labelled water method and derived activity-specific energy expenditures using fine-scale time-activity budgets for each seal. Flipper strokes were detected while diving or surface transiting using dynamic acceleration. Despite some inter-species differences in flipper stroke dynamics or frequencies, both species of fur seals spent 3.79 ± 0.39 J/kg per stroke and had a cost of transport of ~1.6–1.9 J/kg/m while diving. Also, flipper stroke counts were good predictors of energy spent while diving (R2 = 0.76) and to a lesser extent while transiting (R2 = 0.63). However, flipper stroke count was a poor predictor overall of total energy spent during a full foraging trip (R2 = 0.50). Amplitude of flipper strokes (i.e., acceleration amplitude × number of strokes) predicted total energy expenditure (R2 = 0.63) better than flipper stroke counts, but was not as accurate as other acceleration-based proxies, i.e. Overall Dynamic Body Acceleration.
Diversity distribution patterns of Chinese endemic seed plant species and their implications for conservation planning
Authors: Huang Jihong , Huang Jianhua , Lu Xinghui , Ma Keping
Published: September 2016

Endemism is an important concept in biogeography and biodiversity conservation. China is one of the richest countries in biodiversity, with very high levels of plant endemism. In this study, we analysed the distribution patterns of diversity, the degree of differentiation and the endemicity of Chinese endemic seed plants using the floristic unit as a basic spatial analysis unit and 11 indices. The analysis was based on distribution data of 24,951 native seed plant species (excluding subspecies and varieties) and 12,980 Chinese endemic seed plant species, which were sourced from both specimen records and published references. The distribution patterns of Chinese endemic flora were generally consistent but disproportionate across China for diversity, degree of differentiation and endemicity. The South Hengduan Mountains Subregion had the highest values for all indices. At the regional level, both the Hengduan Mountains and the Central China regions were highest in diversity and degrees of differentiation. However, both the rate of local endemic to native species and the rate of local to Chinese endemic species were highest in the Taiwan Region and the South Taiwan Region. The Hengduan Mountains Region and the Central China Region are two key conservation priority areas for Chinese endemic seed plants.
Genetic characterization of two fully sequenced multi-drug resistant plasmids pP10164-2 and pP10164-3 from Leclercia adecarboxylata
Authors: Sun Fengjun , Zhou Dongsheng , Sun Qiang , Luo Wenbo , Tong Yigang , Zhang Defu , Wang Qian , Feng Wei , Chen Weijun , Fan Yahan , Xia Peiyuan
Published: September 2016

We previously reported the complete sequence of the resistance plasmid pP10164-NDM, harboring blaNDM (conferring carbapenem resistance) and bleMBL (conferring bleomycin resistance), which is recovered from a clinical Leclercia adecarboxylata isolate P10164 from China. This follow-up work disclosed that there were still two multidrug-resistant (MDR) plasmids pP10164-2 and pP10164-3 coexisting in this strain. pP10164-2 and pP10164-3 were completely sequenced and shown to carry a wealth of resistance genes, which encoded the resistance to at least 10 classes of antibiotics (β-lactams. macrolides, quinolones, aminoglycosides, tetracyclines, amphenicols, quaternary ammonium compounds, sulphonamides, trimethoprim and rifampicin) and 7 kinds of heavy mental (mercury, silver, copper, nickel, chromate, arsenic and tellurium). All of these antibiotic resistance genes are associated with mobile elements such as transposons, integrons and insertion sequence-based transposable units, constituting a total of three novel MDR regions, two in pP10164-2 and the other one in pP10164-3. Coexistence of three resistance plasmids pP10164-NDM, pP10164-2 and pP10164-3 makes L. adecarboxylata P10164 tend to become extensively drug-resistant.
The Healthy Infant Nasal Transcriptome: A Benchmark Study
Authors: Chu Chin-Yi , Qiu Xing , Wang Lu , Bhattacharya Soumyaroop , Lofthus Gerry , Corbett Anthony , Holden-Wiltse Jeanne , Grier Alex , Tesini Brenda , Gill Steven R. , Falsey Ann R. , Caserta Mary T. , Walsh Edward E. , Mariani Thomas J.
Published: September 2016

Responses by resident cells are likely to play a key role in determining the severity of respiratory disease. However, sampling of the airways poses a significant challenge, particularly in infants and children. Here, we report a reliable method for obtaining nasal epithelial cell RNA from infants for genome-wide transcriptomic analysis and describe baseline expression characteristics in an asymptomatic cohort. Nasal epithelial cells were collected by brushing of the inferior turbinates and gene expression was interrogated by RNA-seq analysis. Reliable recovery of RNA occurred in the absence of adverse events. We observed high expression of epithelial cell markers and similarity to the transcriptome for intrapulmonary airway epithelial cells. We identified genes displaying low and high expression variability, both inherently and in response to environmental exposures. The greatest gene expression differences in this asymptomatic cohort were associated with the presence of known pathogenic viruses and/or bacteria. Robust bacteria-associated gene expression patterns were significantly associated with the presence of Moraxella. In summary, we have developed a reliable method for interrogating the infant airway transcriptome by sampling the nasal epithelium. Our data demonstrates both the fidelity and feasibility of our methodology and describes normal gene expression and variation within a healthy infant cohort.
Region-specific growth restriction of brain following preterm birth
Authors: Iwata Sachiko , Katayama Reiji , Kinoshita Masahiro , Saikusa Mamoru , Araki Yuko , Takashima Sachio , Abe Toshi , Iwata Osuke
Published: September 2016

Regional brain sizes of very-preterm infants at term-equivalent age differ from those of term-born peers, which have been linked with later cognitive impairments. However, dependence of regional brain volume loss on gestational age has not been studied in detail. To investigate the spatial pattern of brain growth in neonates without destructive brain lesions, head MRI of 189 neonates with a wide range of gestational age (24–42 weeks gestation) was assessed using simple metrics measurements. Dependence of MRI findings on gestational age at birth (Agebirth) and the corrected age at MRI scan (AgeMRI) were assessed. The head circumference was positively correlated with AgeMRI, but not Agebirth. The bi-parietal width, deep grey matter area and the trans-cerebellar diameter were positively correlated with both Agebirth and AgeMRI. The callosal thickness (positive), atrial width of lateral ventricle (negative) and the inter-hemispheric distance (negative) were exclusively correlated with Agebirth. The callosal thickness and cerebral/cerebellar transverse diameters showed predominant dependence on Agebirth over AgeMRI, suggesting that brain growth after preterm-birth was considerably restricted or even became negligible compared with that in utero. Such growth restriction after preterm birth may extensively affect relatively more matured infants, considering the linear relationships observed between brain sizes and Agebirth.
Expression of immunoproteasome genes is regulated by cell-intrinsic and –extrinsic factors in human cancers
Authors: Rouette Alexandre , Trofimov Assya , Haberl David , Boucher Geneviève , Lavallée Vincent-Philippe , D’Angelo Giovanni , Hébert Josée , Sauvageau Guy , Lemieux Sébastien , Perreault Claude
Published: September 2016

Based on transcriptomic analyses of thousands of samples from The Cancer Genome Atlas, we report that expression of constitutive proteasome (CP) genes (PSMB5, PSMB6, PSMB7) and immunoproteasome (IP) genes (PSMB8, PSMB9, PSMB10) is increased in most cancer types. In breast cancer, expression of IP genes was determined by the abundance of tumor infiltrating lymphocytes and high expression of IP genes was associated with longer survival. In contrast, IP upregulation in acute myeloid leukemia (AML) was a cell-intrinsic feature that was not associated with longer survival. Expression of IP genes in AML was IFN-independent, correlated with the methylation status of IP genes, and was particularly high in AML with an M5 phenotype and/or MLL rearrangement. Notably, PSMB8 inhibition led to accumulation of polyubiquitinated proteins and cell death in IPhigh but not IPlow AML cells. Co-clustering analysis revealed that genes correlated with IP subunits in non-M5 AMLs were primarily implicated in immune processes. However, in M5 AML, IP genes were primarily co-regulated with genes involved in cell metabolism and proliferation, mitochondrial activity and stress responses. We conclude that M5 AML cells can upregulate IP genes in a cell-intrinsic manner in order to resist cell stress.
The Capacity of Cognitive Control Estimated from a Perceptual Decision Making Task
Authors: Wu Tingting , Dufford Alexander J. , Mackie Melissa-Ann , Egan Laura J. , Fan Jin
Published: September 2016

Cognitive control refers to the processes that permit selection and prioritization of information processing in different cognitive domains to reach the capacity-limited conscious mind. Although previous studies have suggested that the capacity of cognitive control itself is limited, a direct quantification of this capacity has not been attempted. In this behavioral study, we manipulated the information rate of cognitive control by parametrically varying both the uncertainty of stimul measured as information entropy and the exposure time of the stimuli. We used the relationship between the participants’ response accuracy and the information rate of cognitive control (in bits per second, bps) in the model fitting to estimate the capacity of cognitive control. We found that the capacity of cognitive control was approximately 3 to 4 bps, demonstrating that cognitive control as a higher-level function has a remarkably low capacity. This quantification of the capacity of cognitive control may have significant theoretical and clinical implications.
Flavonoids are determinants of freezing tolerance and cold acclimation in Arabidopsis thaliana
Authors: Schulz Elisa , Tohge Takayuki , Zuther Ellen , Fernie Alisdair R. , Hincha Dirk K.
Published: September 2016

In plants from temperate climates such asArabidopsis thalianalow, non-freezing temperatures lead to increased freezing tolerance in a process termed cold acclimation. This process is accompanied by massive changes in gene expression and in the content of primary metabolites and lipids. In addition, most flavonols and anthocyanins accumulate upon cold exposure, along with most transcripts encoding transcription factors and enzymes of the flavonoid biosynthetic pathway. However, no evidence for a functional role of flavonoids in plant freezing tolerance has been shown. Here, we present a comprehensive analysis using qRT-PCR for transcript, LC-MS for flavonoid and GC-MS for primary metabolite measurements and an electrolyte leakage assay to determine freezing tolerance of 20 mutant lines in twoArabidopsisaccessions that are affected in different steps of the flavonoid biosynthetic pathway. This analysis provides evidence for a functional role of flavonoids in plant cold acclimation. The accumulation of flavonoids in the activation tagging mutant linepap1-Dimproved, while reduced flavonoid content in different knock-out mutants impaired leaf freezing tolerance. Analysis of the different knock-out mutants suggests redundancy of flavonoid structures, as the lack of flavonols or anthocyanins could be compensated by other compound classes.
Tooth wear as a means to quantify intra-specific variations in diet and chewing movements
Authors: Calandra Ivan , Labonne Gaëlle , Schulz-Kornas Ellen , Kaiser Thomas M. , Montuire Sophie
Published: September 2016

In mammals, tooth function, and its efficiency, depends both on the mechanical properties of the food and on chewing dynamics. These aspects have rarely been studied in combination and/or at the intra-specific level. Here we applied 3D dental surface texture analysis to a sample of field voles (Microtus agrestis) trapped from Finnish Lapland at different seasons and localities to test for inter-population variations. We also explored intra-individual variation in chewing dynamics by analysing two facets on the second upper molars. Our results confirm that the two localities have similar environments and that the voles feed on the same items there. On the other hand, the texture data suggest that diets are seasonally variable, probably due to varying concentrations of abrasives. Lastly, the textures on the buccal facets are more isotropic and their direction deviates more from the mesial chewing direction than the lingual facets. We interpret these results as reflecting food, rather than chewing, movements, where food particles are more guided on the lingual side of the molars. This has implications for the application of dental microwear analysis to fossils: only homologous facets can be compared, even when the molar row seems to constitute a functional unit.
Stereological analyses of the whole human pancreas
Authors: Poudel Ananta , Fowler Jonas L. , Zielinski Mark C. , Kilimnik German , Hara Manami
Published: September 2016

The large size of human tissues requires a practical stereological approach to perform a comprehensive analysis of the whole organ. We have developed a method to quantitatively analyze the whole human pancreas, as one of the challenging organs to study, in which endocrine cells form various sizes of islets that are scattered unevenly throughout the exocrine pancreas. Furthermore, the human pancreas possesses intrinsic characteristics of intra-individual variability, i.e. regional differences in endocrine cell/islet distribution, and marked inter-individual heterogeneity regardless of age, sex and disease conditions including obesity and diabetes. The method is built based on large-scale image capture, computer-assisted unbiased image analysis and quantification, and further mathematical analyses, using widely-used software such as Fiji/ImageJ and MATLAB. The present study includes detailed protocols of every procedure as well as all the custom-written computer scripts, which can be modified according to specific experimental plans and specimens of interest.
Modulation of yeast telomerase activity by Cdc13 and Est1 in vitro
Authors: Chen Yu-Fan , Lu Chia-Ying , Lin Yi-Chien , Yu Tai-Yuan , Chang Chun-Ping , Li Jing-Ru , Li Hung-Wen , Lin Jing-Jer
Published: September 2016

Telomerase is the enzyme involved in extending telomeric DNA. Control of telomerase activity by modulating its access to chromosome ends is one of the most important fundamental mechanisms. This study established an in vitro yeast telomerase reconstitution system that resembles telomere replication in vivo. In this system, a tailed-duplex DNA formed by telomeric DNA was employed to mimic the structure of telomeres. The core catalytic components of telomerase Est2/Tlc1 RNA were used as the telomeric DNA extension machinery. Using the reconstituted systems, this study found that binding of Cdc13 to telomeric DNA inhibited the access of telomerase to its substrate. The result was further confirmed by a single-molecule approach using the tethered-particle motion (TPM)-based telomerase assay. The findings also showed that the inhibitory effect can be relieved by telomerase-associated protein Est1, consistent with the role of Cdc13 and Est1 in regulating telomere extension in vivo. Significantly, this study found that the DNA binding property of Cdc13 was altered by Est1, providing the first mechanistic evidence of Est1 regulating the access of telomerase to its substrate. Thus, the roles of Cdc13 and Est1 in modulating telomerase activity were clearly defined using the in vitro reconstituted system.
Transmembrane Helices Tilt, Bend, Slide, Torque, and Unwind between Functional States of Rhodopsin
Authors: Ren Zhong , Ren Peter X. , Balusu Rohith , Yang Xiaojing
Published: September 2016

The seven-helical bundle of rhodopsin and other G-protein coupled receptors undergoes structural rearrangements as the transmembrane receptor protein is activated. These structural changes are known to involve tilting and bending of various transmembrane helices. However, the cause and effect relationship among structural events leading to a cytoplasmic crevasse for G-protein binding is less well defined. Here we present a mathematical model of the protein helix and a simple procedure to determine multiple parameters that offer precise depiction of a helical conformation. A comprehensive survey of bovine rhodopsin structures shows that the helical rearrangements during the activation of rhodopsin involve a variety of angular and linear motions such as torsion, unwinding, and sliding in addition to the previously reported tilting and bending. These hitherto undefined motion components unify the results obtained from different experimental approaches, and demonstrate conformational similarity between the active opsin structure and the photoactivated structures in crystallo near the retinal anchor despite their marked differences.
Time to lowest postoperative carcinoembryonic antigen level is predictive on survival outcome in rectal cancer
Authors: Yu Huichuan , Luo Yanxin , Wang Xiaolin , Bai Liangliang , Huang Pinzhu , Wang Lei , Huang Meijin , Deng Yanhong , Wang Jianping
Published: September 2016

This study was to investigate whether the time to the lowest postoperative CEA can predict cancer survival. We enrolled 155 rectal cancer patients in this retrospective and longitudinal cohort study. Deepness of response (DpR) of CEA refers to the relative change of the lowest postoperative CEA level from baseline and time to DpR (TTDpR) refers to the time from surgery to the lowest postoperative CEA level. The median of TTDpR and DpR was 4.5 (range, 3.0–18.0) weeks and −67% (range, −99% to 114%) respectively. Patients with TTDpR </ = 4.5 weeks had better 3-year DFS (81.4% vs. 76.2%; P = 0.059) and OS (95.8% vs. 87.9%; P = 0.047) rate than patients with TTDpR >4.5 weeks. Using TTDpR as a continuous variable, the HR of DFS and OS was 1.13 (95% CI 1.06–1.22, P = 0.001) and 1.17 (95% CI 1.07–1.29, P = 0.001) respectively. On multivariate analysis, the predictive value of prolonged TTDpR remained [adjusted HRs: 1.12 (95% CI 1.03–1.21, P = 0.006) and 1.17 (95% CI 1.06–1.28, P = 0.001)]. These findings remained significant in patients with normal preoperative CEA. Our results showed prolonged TTDpR of CEA independently predicted unfavorable survival outcomes, regardless of whether preoperative CEA was elevated or not.
Interleukin-25 Induces Resistance Against Intestinal Trematodes
Authors: Muñoz-Antoli Carla , Cortés Alba , Santano Rebeca , Sotillo Javier , Esteban J. Guillermo , Toledo Rafael
Published: September 2016

Echinostoma caproni is an intestinal trematode that has been extensively used as an experimental model to investigate the factors determining the resistance to intestinal helminths or the development of chronic infections. ICR mice are permissive hosts for E. caproni in which chronic infections are developed, concomitantly with local Th1 responses, elevated levels of local IFN-γ, inflammation and antibody responses. However, mice develop partial resistance to homologous challenge infections after cure of a primary infection, which converts this subject into an adequate model for the study of the mechanisms generating resistance against intestinal helminths. The purpose of the present study was to compare the immune response induced in primary and secondary infections to elucidate the factors determining the different outcome of the infection in each type of infection. The results obtained indicate that susceptibility is determined by the lack of IL-25 expression in response to primary infection. In contrast, infection in an environment with elevated levels of IL-25, as occurs in challenge infection, results in a Th2 phenotype impairing parasite survival. This was confirmed by treatment of naïve mice with exogenous IL-25 and subsequent infection. Changes induced in goblet cell populations and mucin glycosylation could be implicated in resistance to infection.
Fast and robust fabrication of reusable molds for hydrogel micro-patterning
Authors: De Mets Richard , Hennig Katharina , Bureau Lionel , Balland Martial
Published: September 2016

We present a method to create protein micropatterns onto polyacrylamide hydrogels, in order to control the adhesive confinement of cells in traction force microscopy experiments. The technique is based on patterned polymer brushes that serve as molds that can be re-used without repeating microfabrication steps.
Excited-state dynamics of the medicinal pigment curcumin in a hydrogel
Authors: Harada Takaaki , Lincoln Stephen F. , Kee Tak W.
Published: September 2016

Curcumin is a yellow polyphenol with multiple medicinal effects. We show that excited-state intramolecular hydrogen atom transfer and solvent reorganisation are major photophysical events for curcumin in the PAAC18 hydrogel.
Multifunctional Eu-doped NaGd(MoO4)2 nanoparticles functionalized with poly(l-lysine) for optical and MRI imaging
Authors: Laguna Mariano , Nuñez Nuria O. , Rodríguez Verónica , Cantelar Eugenio , Stepien Grazyna , García María Luisa , de la Fuente Jesús M. , Ocaña Manuel
Published: September 2016

Eu:NaGd(MoO4)2 nanoparticles functionalized with poly(l-lysine) have been fabricated, which exhibit visible red luminescence and good relaxivity values making them suitable for MRI and optical imaging.
A propeller-shaped μ4-carbonate hexanuclear dysprosium complex with a high energetic barrier to magnetisation relaxation
Authors: Holmberg Rebecca J. , Kuo Che-Jung , Gabidullin Bulat , Wang Chia-Wei , Clérac Rodolphe , Murugesu Muralee , Lin Po-Heng
Published: September 2016

A Dy6 complex composed of two Dy3 triangular units was isolated and found to exhibit slow relaxation of the magnetisation under zero applied dc field, resulting in a high energetic barrier to relaxation.
[Ir(C^N)2(N^N)]+ emitters containing a naphthalene unit within a linker between the two cyclometallating ligands
Authors: Bünzli Andreas M. , Pertegás Antonio , Momblona Cristina , Junquera-Hernández José M. , Constable Edwin C. , Bolink Henk J. , Ortí Enrique , Housecroft Catherine E.
Published: September 2016

The effects of introducing a naphthalene unit between the two cyclometallating ligands in [Ir(C^N)2(N^N)]+ emitters in LECS are explored.
Functionalized nonporous silica nanoparticles as carriers for Pt(iv) anticancer prodrugs
Authors: Ravera M. , Gabano E. , Zanellato I. , Perin E. , Arrais A. , Osella D.
Published: September 2016

Conjugate Pt(iv)–silica nanoparticles exhibited better antiproliferative activity than cisplatin and Pt(iv) precursors, due to their more efficient cellular uptake.
Ionic-liquid-assisted synthesis of the phosphorus interhalides [PBr4][IBr2] and [PBr4][I5Br7]
Authors: Hausmann David , Köppe Ralf , Wolf Silke , Roesky Peter W. , Feldmann Claus
Published: September 2016

Ionic-liquid based synthesis results in the phosphorus interhalides [PBr4][IBr2] and [PBr4]2[I5Br7] whereof the latter shows thermal halogen release of 96.8 wt% (≤300 °C).
Design and synthesis of micro–meso–macroporous polymers with versatile active sites and excellent activities in the production of biofuels and fine chemicals
Authors: Liu Fujian , Liu Chen , Kong Weiping , Qi Chenze , Zheng Anmin , Dai Sheng
Published: September 2016

Micro–meso–macroporous polymers with versatile active sites were synthesized by hyper-cross-linking technology, which exhibit excellent activities for catalyzing production of biofuels and fine chemicals.
Electrochemical DNA biosensors based on long-range electron transfer: investigating the efficiency of a fluidic channel microelectrode compared to an ultramicroelectrode in a two-electrode setup
Authors: Horny M.-C. , Lazerges M. , Siaugue J.-M. , Pallandre A. , Rose D. , Bedioui F. , Deslouis C. , Haghiri-Gosnet A.-M. , Gamby J.
Published: September 2016

Forced convection decreases the diffusion layer thickness on microelectrode and promotes a faster DNA collection.
Chitosan bis(halophenylcarbamate)-(isobutyrylamide) based chiral stationary phases for enantiomeric separation
Authors: Tang Sheng , Bin Qin , Feng Zi-Wei , Chen Wei , Huang Shao-Hua , Bai Zheng-Wu
Published: September 2016

Chiral separation materials based on N-isobutyrylated chitosan derivatives with a halogen substituent were prepared and applied for enantiomeric separation.
Efficient palladium-catalyzed C(sp2)–H activation towards the synthesis of fluorenes
Authors: Song Juan , Li Yali , Sun Wei , Yi Chenglong , Wu Hao , Wang Haotian , Ding Keran , Xiao Kang , Liu Chao
Published: September 2016

A newly developed palladium-catalyzed direct arylation via C–H activation adopting diphenylmethane type reactants for the synthesis of fluorene derivatives.
Combination of photoinduced copper(i) catalyzed click chemistry and photosol–gel reaction for the synthesis of hybrid materials
Authors: Maetz E. , Croutxé-Barghorn C. , Delaite C. , Allonas X.
Published: September 2016

We investigate in this work a novel one-step methodology for preparing hybrid materials by combining photoinduced sol–gel polymerization and light-induced CuAAC reaction.
Porous nanostructures of SnSe: role of ionic liquid, tuning of nanomorphology and mechanistic studies
Authors: Das Laboni , Guleria Apurav , Neogy Suman , Adhikari Soumyakanti
Published: September 2016

Porous SnSe nanoparticles have been synthesized in imidazolium based RTILviaelectron beam irradiation. RTIL provides a stabilizing environment as well as anin situsource of reducing radicals for the reduction of precursors.
Selective colorimetric sensing of fluoride in an aqueous solution by amino-naphthoquinone and its Co(ii), Ni(ii), Cu(ii) and Zn(ii) complexes – effect of complex formation on sensing behaviour
Authors: Parthiban C. , Ciattini Samuele , Chelazzi Laura , Elango Kuppanagounder P.
Published: September 2016

The complexation of metal ions with amino-naphthoquinone was found to not only enhance the HBD property of the N–H group but also accomodates ≥50% of water in the sensing medium.
Heptamethylindenyl (Ind*) enables diastereoselective benzamidation of cyclopropenes via Rh(iii)-catalyzed C–H activation
Authors: Semakul Natthawat , Jackson Kelvin E. , Paton Robert S. , Rovis Tomislav
Published: September 2016

The diastereoselective coupling of O-substituted arylhydroxamates and cyclopropenes mediated by Rh(iii) catalysis was successfully developed.
Balanced development of piezoelectricity, Curie temperature, and temperature stability in potassium–sodium niobhrate lead-free ceramics
Authors: Zheng Ting , Wu Wenjuan , Wu Jiagang , Zhu Jianguo , Xiao Dingquan
Published: September 2016

(K,Na)NbO3-based ceramics is highly expected to attain a balance development between piezoelectricity, Curie temperature and temperature stability.
Intracellular cholesterol transport proteins: roles in health and disease
Authors: Soffientini Ugo , Graham Annette
Published: September 2016

Effective cholesterol homoeostasis is essential in maintaining cellular function, and this is achieved by a network of lipid-responsive nuclear transcription factors, and enzymes, receptors and transporters subject to post-transcriptional and post-translational regulation, whereas loss of these elegant, tightly regulated homoeostatic responses is integral to disease pathologies. Recent data suggest that sterol-binding sensors, exchangers and transporters contribute to regulation of cellular cholesterol homoeostasis and that genetic overexpression or deletion, or mutations, in a number of these proteins are linked with diseases, including atherosclerosis, dyslipidaemia, diabetes, congenital lipoid adrenal hyperplasia, cancer, autosomal dominant hearing loss and male infertility. This review focuses on current evidence exploring the function of members of the ‘START’ (steroidogenic acute regulatory protein-related lipid transfer) and ‘ORP’ (oxysterol-binding protein-related proteins) families of sterol-binding proteins in sterol homoeostasis in eukaryotic cells, and the evidence that they represent valid therapeutic targets to alleviate human disease.
Blind test of density-functional-based methods on intermolecular interaction energies
Authors: Taylor DeCarlos E. , Ángyán János G. , Galli Giulia , Zhang Cui , Gygi Francois , Hirao Kimihiko , Song Jong Won , Rahul Kar , Anatole von Lilienfeld O. , Podeszwa Rafał , Bulik Ireneusz W. , Henderson Thomas M. , Scuseria Gustavo E. , Toulouse Julien , Peverati Roberto , Truhlar Donald G. , Szalewicz Krzysztof
Published: September 2016

In the past decade, a number of approaches have been developed to fix the failure of (semi)local density-functional theory (DFT) in describing intermolecular interactions. The performance of several such approaches with respect to highly accurate benchmarks is compared here on a set of separation-dependent interaction energies for ten dimers. Since the benchmarks were unknown before the DFT-based results were collected, this comparison constitutes a blind test of these methods.
Modeling the spectrum of the 2ν2 and ν4 states of ammonia to experimental accuracy
Authors: Pearson John C. , Yu Shanshan , Pirali Olivier
Published: September 2016

The vibrational spectrum of ammonia has received an enormous amount of attention due to its potential prevalence in hot exo-planet atmospheres and persistent challenges in assigning and modeling highly excited and often highly perturbed states. Effective Hamiltonian models face challenges due to strong coupling between the large amplitude inversion and the other small amplitude vibrations. To date, only the ground and ν2 positions could be modeled to experimental accuracy using effective Hamiltonians. Several previous attempts to analyze the 2ν2 and ν4 energy levels failed to model both the microwave and infrared transitions to experimental accuracy. In this work, we performed extensive experimental measurements and data analysis for the 2ν2 and ν4 inversion-rotation and vibrational transitions. We measured 159 new transition frequencies with microwave precision and assigned 1680 new ones from existing Fourier transform spectra recorded in Synchrotron SOLEIL. The newly assigned data significantly expand the range of assigned quantum numbers; combined with all the previously published high-resolution data, the 2ν2 and ν4 states are reproduced to experimental accuracy using a global model described here. Achieving experimental accuracy required inclusion of a number of terms in the effective Hamiltonian that were neglected in previous work. These terms have also been neglected in the analysis of states higher than 2ν2 and ν4 suggesting that the inversion-rotation-vibration spectrum of ammonia may be far more tractable to effective Hamiltonians than previously believed.
Numerical modeling and optimization of the segmented PbTe–BiTe-based thermoelectric leg
Authors: Mei Deqing , Wang Hui , Yao Zhehe , Li Yang
Published: September 2016

The segmentation of thermoelectric materials is an efficient way to improve the overall efficiency of a thermoelectric leg. However, this improvement can be obtained only when the constituent materials are appropriately proportioned. A numerical model is established for optimizing the performance of the segmented leg based on the coupled equations of the thermoelectric with temperature-dependent material properties. The numerical model can be used to determine the optimal length ratio and current density for the segmented leg. On the basis of the numerical model, the performance optimization of the K0.02Pb0.98Te/Bi0.3Sb1.7Te3 segmented leg is performed, and its maximum conversion efficiency and maximum output power are calculated. Results show that the reasonable length ratio design of the thermoelectric leg can take a full advantage of the characteristics of the thermoelectric materials, and it can effectively improve the conversion efficiency and the electrical output power. In addition, the numerical model is validated by finite-element simulated results and experimental results.