bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of sex-specific virulence in infectious diseases
Authors: Úbeda Francisco , Jansen Vincent A. A.
Published: December 2016

Fatality rates of infectious diseases are often higher in men than women. Although this difference is often attributed to a stronger immune response in women, we show that differences in the transmission routes that the sexes provide can result in evolution favouring pathogens with sex-specific virulence. Because women can transmit pathogens during pregnancy, birth or breast-feeding, pathogens adapt, evolving lower virulence in women. This can resolve the long-standing puzzle on progression from Human T-cell Lymphotropic Virus Type 1 (HTLV-1) infection to lethal Adult T-cell Leukaemia (ATL); a progression that is more likely in Japanese men than women, while it is equally likely in Caribbean women and men. We argue that breastfeeding, being more prolonged in Japan than in the Caribbean, may have driven the difference in virulence between the two populations. Our finding signifies the importance of investigating the differences in genetic expression profile of pathogens in males and females.
Trapping gases in metal-organic frameworks with a selective surface molecular barrier layer
Authors: Tan Kui , Zuluaga Sebastian , Fuentes Erika , Mattson Eric C. , Veyan Jean-François , Wang Hao , Li Jing , Thonhauser Timo , Chabal Yves J.
Published: December 2016

The main challenge for gas storage and separation in nanoporous materials is that many molecules of interest adsorb too weakly to be effectively retained. Instead of synthetically modifying the internal surface structure of the entire bulk—as is typically done to enhance adsorption—here we show that post exposure of a prototypical porous metal-organic framework to ethylenediamine can effectively retain a variety of weakly adsorbing molecules (for example, CO, CO2, SO2, C2H4, NO) inside the materials by forming a monolayer-thick cap at the external surface of microcrystals. Furthermore, this capping mechanism, based on hydrogen bonding as explained byab initiomodelling, opens the door for potential selectivity. For example, water molecules are shown to disrupt the hydrogen-bonded amine network and diffuse through the cap without hindrance and fully displace/release the retained small molecules out of the metal-organic framework at room temperature. These findings may provide alternative strategies for gas storage, delivery and separation.
Constructivist developmental theory is needed in developmental neuroscience
Authors: Arsalidou Marie , Pascual-Leone Juan
Published: December 2016

Neuroscience techniques provide an open window previously unavailable to the origin of thoughts and actions in children. Developmental cognitive neuroscience is booming, and knowledge from human brain mapping is finding its way into education and pediatric practice. Promises of application in developmental cognitive neuroscience rests however on better theory-guided data interpretation. Massive amounts of neuroimaging data from children are being processed, yet published studies often do not frame their work within developmental models—in detriment, we believe, to progress in this field. Here we describe some core challenges in interpreting the data from developmental cognitive neuroscience, and advocate the use of constructivist developmental theories of human cognition with a neuroscience interpretation.
Selective perturbation of cognitive conflict in the human brain–A combined fMRI and rTMS study
Authors: Peschke Claudia , Köster Raphael , Korsch Margarethe , Frühholz Sascha , Thiel Christiane M. , Herrmann Manfred , Hilgetag Claus C.
Published: December 2016

We investigated if single and double conflicts are processed separately in different brain regions and if they are differentially vulnerable to TMS perturbation. Fifteen human volunteers performed a single (Flanker or Simon) conflict task or a double (Flanker and Simon) conflict task in a combined functional Magnetic Resonance Imaging (fMRI) and Transcranial Magnetic Stimulation (TMS) study. The fMRI approach aimed at localizing brain regions involved in interference resolution induced by single Flanker (stimulus-stimulus, S-S) and Simon (stimulus-response, S-R) conflicts as well as regions involved in the double conflict condition. The data revealed a distinct activation in the right intraparietal sulcus (IPS) for Flanker interference and in the right middle frontal gyrus (MFG) for the double interference condition. The causal functional role of these brain regions was then examined in the same volunteers by using offline TMS over right IPS and right MFG. TMS perturbation of the right IPS increased the Flanker effect, but had no effect in the Simon or double conflict condition. In contrast, perturbation of the right MFG had no effect on any of the conflict types. These findings suggest a causal role of the right IPS in the processing of the single conflict of Flanker (stimulus-stimulus) interference.
Sexual dimorphic function of IL-17 in salivary gland dysfunction of the C57BL/6.NOD-Aec1Aec2 model of Sjögren’s syndrome
Authors: Voigt Alexandria , Esfandiary Lida , Wanchoo Arun , Glenton Patricia , Donate Amy , Craft William F. , Craft Serena L. M. , Nguyen Cuong Q.
Published: December 2016

Interleukin (IL)-17 is one of the critical inflammatory cytokines that plays a direct role in development of Sjögren’s syndrome (SjS), a systemic autoimmune disease characterized by a progressive chronic attack against the exocrine glands. The expression levels of IL-17 are correlated with a number of essential clinical parameters such as focus score and disease duration in human patients. Significantly immunological differences of Th17 cells were detected at the onset of clinical disease in female SjS mice compared to males. To further define the role of IL-17 in SjS and elucidate its involvement in the sexual dimorphism, we examined the systemic effect of IL-17 by genetically ablating Il-17 in the C57BL/6.NOD-Aec1Aec2, spontaneous SjS murine model. The results indicate that IL-17 is a potent inflammatory molecule in the induction of chemoattractants, cytokines, and glandular apoptosis in males and females. Elimination of IL-17 reduced sialadenitis more drastically in females than males. IL-17 is highly involved in modulating Th2 cytokines and altering autoantibody profiles which has a greater impact on changing plasma cells and germinal center B cell populations in females than males. The result supports a much more important role for IL-17 and demonstrates the sexual dimorphic function of IL-17 in SjS.
In vivo Assessment of Antioxidant and Wound Healing Improvement of a New Schiff Base Derived Co (II) Complex in Rats
Authors: El-Ferjani Rashd. M. , Ahmad Musa , Dhiyaaldeen Summaya M. , Harun Farah Wahida , Ibrahim Mohamed Yousif , Adam Hoyam , Mohd. Yamin Bohari , Al-Obaidi Mazen M. Jamil , Batran Rami Al
Published: December 2016

Co (II) complex (CMLA) was investigated to evaluate the rate of wound healing in rats. Animals were placed into four groups: gum acacia, Intrasite gel, 10 and 20 mg/ml of CMLA. Wounds were made on the dorsal neck area, then treated with Intrasite gel or CMLA; both of these treatments led to faster healing than with gum acacia. Histology of the wounds dressed with CMLA or Intrasite gel displayed a smaller scar width, required less time to heal and showed more collagen staining and fewer inflammatory cells in comparison to wounds dressed with the vehicle. Immunohistochemistry for Hsp70 and TGF-β showed greater staining intensity in the treated groups compared to the vehicle group. Bax staining was less intense in treated groups compared to the vehicle group, suggesting that CMLA and Intrasite gel provoked apoptosis, responsible for the development of granulation tissue into a scar. CD31 protein analysis showed that the treated groups enhanced angiogenesis and increased vascularization compared to the control group. Furthermore, a significant increase in the levels of GPx and SOD and a decrease in MDA were also observed in the treated groups. This results suggest that CMLA is a potentially promising agent for the wounds treatment.
A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans
Authors: Khanna Amit , Kumar Jitendra , Vargas Misha A. , Barrett LaKisha , Katewa Subhash , Li Patrick , McCloskey Tom , Sharma Amit , Naudé Nicole , Nelson Christopher , Brem Rachel , Killilea David W. , Mooney Sean D. , Gill Matthew , Kapahi Pankaj
Published: December 2016

Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature. In recent years, the chemical identities of pheromone signals that modulate dauer entry have been characterized. However, signals derived from bacteria, the major source of nutrients for C. elegans, remain poorly characterized. To systematically identify bacterial components that influence dauer formation and aging in C. elegans, we utilized the individual gene deletion mutants in E. coli (K12). We identified 56 diverse E. coli deletion mutants that enhance dauer formation in an insulin-like receptor mutant (daf-2) background. We describe the mechanism of action of a bacterial mutant cyaA, that is defective in the production of cyclic AMP, which extends lifespan and enhances dauer formation through the modulation of TGF-β (daf-7) signaling in C. elegans. Our results demonstrate the importance of bacterial components in influencing developmental decisions and lifespan in C. elegans. Furthermore, we demonstrate that C. elegans is a useful model to study bacterial-host interactions.
Crystal Structure of Escherichia coli originated MCR-1, a phosphoethanolamine transferase for Colistin Resistance
Authors: Hu Menglong , Guo Jiubiao , Cheng Qipeng , Yang Zhiqiang , Chan Edward Wai Chi , Chen Sheng , Hao Quan
Published: December 2016

MCR-1 is a phosphoethanolamine (pEtN) transferase that modifies the pEtN moiety of lipid A, conferring resistance to colistin, which is an antibiotic belonging to the class of polypeptide antibiotics known as polymyxins and is the last-line antibiotic used to treat multidrug resistant bacterial infections. Here we determined the crystal structure of the catalytic domain of MCR-1 (MCR-1-ED), which is originated in Escherichia coli (E. coli). MCR-1-ED was found to comprise several classical β-α-β-α motifs that constitute a “sandwich” conformation. Two interlaced molecules with different phosphorylation status of the residue T285 could give rise to two functional statuses of MCR-1 depending on the physiological conditions. MCR-1, like other known pEtN transferases, possesses an enzymatic site equipped with zinc binding residues. Interestingly, two zinc ions were found to mediate intermolecular interactions between MCR-1-ED molecules in one asymmetric unit and hence concatenation of MCR-1, allowing the protein to be oligomer. Findings of this work shall provide important insight into development of effective and clinically useful inhibitors of MCR-1 or structurally similar enzymes.
Cerebral infarction pattern in tuberculous meningitis
Authors: Tai Mei-Ling Sharon , Viswanathan Shanthi , Rahmat Kartini , Nor Hazman Mohd , Kadir Khairul Azmi Abdul , Goh Khean Jin , Ramli Norlisah , Bakar Fatimah Kamila Abu , Zain Norzaini Rose Mohd , Yap Jun Fai , Ong Beng Hooi , Rafia Mohd Hanip , Tan Chong Tin
Published: December 2016

Tuberculous meningitis (TBM) causes significant morbidity and mortality. The primary objective was to re-examine the concept of “TB zone” and “ischaemic zone” in cerebral infarction in patients with tuberculous meningitis. The secondary objective was to evaluate cerebral infarction, vasculitis and vasospasm in tuberculous meningitis infections. Between 2009 and 2014, TBM patients were recruited. Neuroimaging was performed and findings of cerebral infarction, vasculitis and vasospasm were recorded. Infarcts were classified based on arterial supply and Hsieh’s classification. Fifty-one TBM patients were recruited of whom 34 patients (67%) had cerebral infarction. Based on Hsieh’s classification, 20 patients (59%) had infarcts in both “TB zone” and “ischaemic zones”. 12 patients (35%) had infarcts in “ischaemic zone” and two (6%) patients had infarcts in “TB zone”. In terms of vascular supply, almost all patients (35/36) had infarcts involving perforators and cortical branches. 25 patients (73%) and 14 patients (41%) had infarcts supplied by lateral lenticulostriate and medial lenticulostriate arteries respectively. 15 patients (37%) had vasculitis. Vasospasm was present in six patients (15%). 29 patients (85%) with cerebral infarction also had leptomeningeal enhancement (p = 0.002). In summary, infarcts involved mainly perforators and cortical branches, rather than “TB zone” versus “ischaemic zone”.
Observation of an exceptional point in a two-dimensional ultrasonic cavity of concentric circular shells
Authors: Shin Younghoon , Kwak Hojeong , Moon Songky , Lee Sang-Bum , Yang Juhee , An Kyungwon
Published: December 2016

We report observation of an exceptional point in circular shell ultrasonic cavities in both theory and experiment. In our theoretical analysis we first observe two interacting mode groups, fluid- and solid-based modes, in the acoustic cavities and then show the existence of an EP of these mode groups exhibiting a branch-point topological structure of eigenfrequencies around the EP. We then confirm the mode patterns as well as eigenfrequency structure around the EP in experiments employing the schlieren method, thereby demonstrating utility of ultrasound cavities as experimental platform for investigating non-Hermitian physics.
Functional proteomics-aided selection of protease inhibitors for herbivore insect control
Authors: Rasoolizadeh Asieh , Munger Aurélie , Goulet Marie-Claire , Sainsbury Frank , Cloutier Conrad , Michaud Dominique
Published: December 2016

Studies have reported the potential of protease inhibitors to engineer insect resistance in transgenic plants but the general usefulness of this approach in crop protection still remains to be established. Insects have evolved strategies to cope with dietary protease inhibitors, such as the use of proteases recalcitrant to inhibition, that often make the selection of effective inhibitors very challenging. Here, we used a functional proteomics approach for the ‘capture’ of Cys protease targets in crude protein extracts as a tool to identify promising cystatins for plant improvement. Two cystatins found to differ in their efficiency to capture Cys proteases of the coleopteran pest Leptinotarsa decemlineata also differed in their usefulness to produce transgenic potato lines resistant to this insect. Plants expressing the most potent cystatin at high level had a strong repressing effect on larval growth and leaf intake, while plants expressing the weakest cystatin showed no effect on both two parameters compared to untransformed parental line used for genetic transformation. Our data underline the relevance of considering the whole range of possible protease targets when selecting an inhibitor for plant pest control. They also confirm the feasibility of developing cystatin-expressing transgenics resistant to a major pest of potato.
Exchanges of genomic domains between poliovirus and other cocirculating species C enteroviruses reveal a high degree of plasticity
Authors: Bessaud Maël , Joffret Marie-Line , Blondel Bruno , Delpeyroux Francis
Published: December 2016

The attenuated Sabin strains contained in the oral poliomyelitis vaccine are genetically unstable, and their circulation in poorly immunized populations can lead to the emergence of pathogenic circulating vaccine-derived polioviruses (cVDPVs). The recombinant nature of most cVDPV genomes and the preferential presence of genomic sequences from certain cocirculating non-polio enteroviruses of species C (EV-Cs) raise questions about the permissiveness of genetic exchanges between EV-Cs and the phenotypic impact of such exchanges. We investigated whether functional constraints limited genetic exchanges between Sabin strains and other EV-Cs. We bypassed the natural recombination events by constructing 29 genomes containing a Sabin 2 capsid-encoding sequence and other sequences from Sabin 2 or from non-polio EV-Cs. Most genomes were functional. All recombinant viruses replicated similarly in vitro, but recombination modulated plaque size and temperature sensitivity. All viruses with a 5′UTR from Sabin 2 were attenuated in mice, whereas almost all viruses with a non-polio 5′UTR caused disease. These data highlight the striking conservation of functional compatibility between different genetic domains of cocirculating EV-Cs. This aspect is only one of the requirements for the generation of recombinant cVDPVs in natural conditions, but it may facilitate the generation of viable intertypic recombinants with diverse phenotypic features, including pathogenicity.
Effective energy harvesting from a single electrode based triboelectric nanogenerator
Authors: Kaur Navjot , Bahadur Jitendra , Panwar Vinay , Singh Pushpendra , Rathi Keerti , Pal Kaushik
Published: December 2016

The arch-shaped single electrode based triboelectric nanogenerator (TENG) is fabricated using thin film of reduced graphene oxide nanoribbons (rGONRs) with polyvinylidene fluoride (PVDF) polymer used as binder to effectively convert mechanical energy into electrical energy. The incorporation of rGONRs in PVDF polymer enhances average surface roughness of rGONRs/PVDF thin film. With the combination of the enhancement of average roughness and production of functional groups, which indicate improve charge storage capacity of prepared film. Furthermore, the redox peaks obtained through cyclic voltammetry were identified more in rGONRs/PVDF composite in comparison to pristine rGONRs to confirm charge transfer capability of film. Herein, the output performance was discussed experimentally as well as theoretically, maximum voltage was obtained to be 0.35 V. The newly designed TENG to harvest mechanical energy and opens up many new avenues of research in the energy harvesting applications.
Distinct Interactions between Fronto-Parietal and Default Mode Networks in Impaired Consciousness
Authors: Long Jinyi , Xie Qiuyou , Ma Qing , Urbin M. A. , Liu Liqing , Weng Ling , Huang Xiaoqi , Yu Ronghao , Li Yuanqing , Huang Ruiwang
Published: December 2016

Existing evidence suggests that the default-mode network (DMN) and fronto-pariatal network (FPN) play an important role in altered states of consciousness. However, the brain mechanisms underlying impaired consciousness and the specific network interactions involved are not well understood. We studied the topological properties of brain functional networks using resting-state functional MRI data acquired from 18 patients (11 vegetative state/unresponsive wakefulness syndrome, VS/UWS, and 7 minimally conscious state, MCS) and compared these properties with those of healthy controls. We identified that the topological properties in DMN and FPN are anti-correlated which comes, in part, from the contribution of interactions between dorsolateral prefrontal cortex of the FPN and precuneus of the DMN. Notably, altered nodal connectivity strength was distance-dependent, with most disruptions appearing in long-distance connections within the FPN but in short-distance connections within the DMN. A multivariate pattern-classification analysis revealed that combination of topological patterns between the FPN and DMN could predict conscious state more effectively than connectivity within either network. Taken together, our results imply distinct interactions between the FPN and DMN, which may mediate conscious state.
Endotoxins are associated with visceral fat mass in type 1 diabetes
Authors: Lassenius Mariann I. , Ahola Aila J. , Harjutsalo Valma , Forsblom Carol , Groop Per-Henrik , Lehto Markku
Published: December 2016

Bacterial lipopolysaccharides (LPS), potent inducers of inflammation, have been associated with chronic metabolic disturbances. Obesity is linked to dyslipidemia, increased body adiposity, and endotoxemia. We investigated the cross-sectional relationships between serum LPS activity and body adiposity as well as inflammation in 242 subjects with type 1 diabetes. Body fat distribution was measured by DXA and serum LPS activity by the limulus amebocyte lysate end-point assay. Since no interaction between visceral fat mass and sex was observed, data were pooled for the subsequent analyses. LPS was independently associated with visceral fat mass, when adjusted for traditional risk factors (age, sex, kidney status, hsCRP, insulin sensitivity). In the multivariate analysis, serum LPS activity and triglyceride concentrations had a joint effect on visceral fat mass, independent of these factors alone. A combination of high LPS and high hsCRP concentrations was also observed in those with the largest visceral fat mass. In conclusion, high serum LPS activity levels were associated with visceral fat mass in subjects with type 1 diabetes strengthening its role in the development of central obesity, inflammation and insulin resistance.
Differential transcription profiles of long non-coding RNAs in primary human brain microvascular endothelial cells in response to meningitic Escherichia coli
Authors: Yang Ruicheng , Huang Fei , Fu Jiyang , Dou Beibei , Xu Bojie , Miao Ling , Liu Wentong , Yang Xiaopei , Tan Chen , Chen Huanchun , Wang Xiangru
Published: December 2016

Accumulating studies have indicated the influence of long non-coding RNAs (lncRNAs) on various biological processes as well as disease development and progression. However, the lncRNAs involved in bacterial meningitis and their regulatory effects are largely unknown. By RNA-sequencing, the transcriptional profiles of host lncRNAs in primary human brain microvascular endothelial cells (hBMECs) in response to meningiticEscherichia coliwere demonstrated. Here, 25,257 lncRNAs were identified, including 24,645 annotated lncRNAs and 612 newly found ones. A total of 895 lncRNAs exhibited significant differences upon infection, among which 382 were upregulated and 513 were downregulated (≥2-fold,p < 0.05). Via bioinformatic analysis, the features of these lncRNAs, their possible functions, and the potential regulatory relationships between lncRNAs and mRNAs were predicted. Moreover, we compared the transcriptional specificity of these differential lncRNAs among hBMECs, human astrocyte cell U251, and human umbilical vein endothelial cells, and demonstrated the novel regulatory effects of proinflammatory cytokines on these differential lncRNAs. To our knowledge, this is the first time the transcriptional profiles of host lncRNAs involved inE. coli-induced meningitis have been reported, which shall provide novel insight into the regulatory mechanisms behind bacterial meningitis involving lncRNAs, and contribute to better prevention and therapy of CNS infection.
OnabotulinumtoxinA Urethral Sphincter Injection as Treatment for Non-neurogenic Voiding Dysfunction – A Randomized, Double-Blind, Placebo-Controlled Study
Authors: Jiang Yuan-Hong , Wang Chung-Cheng , Kuo Hann-Chorng
Published: December 2016

Non-neurogenic voiding dysfunction including dysfunctional voiding and detrusor underactivity caused by a spastic or non-relaxing external urethral sphincter can theoretically be treated by injections of botulinum A toxin into the external urethral sphincter. This randomized, double-blind, placebo-controlled trial was designed to determine the clinical efficacy of onabotulinumtoxinA urethral sphincter injections in patients with dysfunctional voiding or detrusor underactivity. Patients with medically refractory dysfunctional voiding (n = 31) or detrusor underactivity (n = 31) were randomly allocated in a 2:1 ratio to receive either onabotulinumtoxinA (100 U) (n = 38) or placebo (normal saline) (n = 24). There were no significant differences in subjective or objective parameters between patients who received onabotulinumtoxinA and those who received saline injection therapy, and the overall success rate was 43.5% (reduction in Patient perception of Bladder Condition by ≥2: onabotulinumtoxinA 36.8% vs placebo 54.2%, p = 0.114). The results were similar between the dysfunctional voiding and detrusor underactivity subgroups; however, a significant reduction in detrusor voiding pressure was only observed in dysfunctional voiding patients who received onabotulinumtoxinA. Repeat urethral sphincter onabotulinumtoxinA injections offered greater therapeutic effects in both dysfunctional voiding and detrusor underactivity patients. For patients with non-neurogenic voiding dysfunction, the success rate of onabotulinumtoxinA urethral sphincter injection was not superior to placebo.
Preparation of Hollow Fe2O3 Nanorods and Nanospheres by Nanoscale Kirkendall Diffusion, and Their Electrochemical Properties for Use in Lithium-Ion Batteries
Authors: Cho Jung Sang , Park Jin-Sung , Kang Yun Chan
Published: December 2016

A novel process for the preparation of aggregate-free metal oxide nanopowders with spherical (0D) and non-spherical (1D) hollow nanostructures was introduced. Carbon nanofibers embedded with iron selenide (FeSe) nanopowders with various nanostructures are prepared via the selenization of electrospun nanofibers. Ostwald ripening occurs during the selenization process, resulting in the formation of a FeSe-C composite nanofiber exhibiting a hierarchical structure. These nanofibers transform into aggregate-free hollow Fe2O3 powders via the complete oxidation of FeSe and combustion of carbon. Indeed, the zero- (0D) and one-dimensional (1D) FeSe nanocrystals transform into the hollow-structured Fe2O3 nanopowders via a nanoscale Kirkendall diffusion process, thus conserving their overall morphology. The discharge capacities for the 1000th cycle of the hollow-structured Fe2O3 nanopowders obtained from the FeSe-C composite nanofibers prepared at selenization temperatures of 500, 800, and 1000 °C at a current density of 1 A g−1 are 932, 767, and 544 mA h g−1, respectively; and their capacity retentions from the second cycle are 88, 92, and 78%, respectively. The high structural stabilities of these hollow Fe2O3 nanopowders during repeated lithium insertion/desertion processes result in superior lithium-ion storage performances.
Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts
Authors: Wu Wei-Bin , Menon Ramkumar , Xu Yue-Ying , Zhao Jiu-Ru , Wang Yan-Lin , Liu Yuan , Zhang Hui-Juan
Published: December 2016

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterised by raised bile acids in foetal-maternal circulation, which threatens perinatal health. During the progression of ICP, the effect of oxidative stress is underscored. Peroxiredoxin-3 (PRDX3) is a mitochondrial antioxidant enzyme that is crucial to balance intracellular oxidative stress. However, the role of PRDX3 in placental trophoblast cells under ICP is not fully understood. We demonstrated that the level of PRDX3 was downregulated in ICP placentas as well as bile acids–treated trophoblast cells and villous explant in vitro. Toxic levels of bile acids and PRDX3 knockdown induced oxidative stress and mitochondrial dysfunction in trophoblast cells. Moreover, silencing of PRDX3 in trophoblast cell line HTR8/SVneo induced growth arrest and cellular senescence via activation of p38-mitogen-activated protein kinase (MAPK) and induction of p21WAF1/CIP and p16INK4A. Additionally, enhanced cellular senescence, determined by senescence-associated beta-galactosidase staining, was obviously attenuated by p38-MAPK inhibitor SB203580. Our data determined that exposure to bile acid decreased PRDX3 level in human trophoblasts. PRDX3 protected trophoblast cells against mitochondrial dysfunction and cellular senescence induced by oxidative stress. Our results suggest that decreased PRDX3 by excessive bile acids in trophoblasts plays a critical role in the pathogenesis and progression of ICP.
Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents
Authors: Wang Fang-Xin , Chen Mu-He , Hu Xiao-Ying , Ye Rui-Rong , Tan Cai-Ping , Ji Liang-Nian , Mao Zong-Wan
Published: December 2016

Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2′-bipyridine-4,4′-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes. The cytotoxicity of these Ir(III) complexes is correlated with the length of their ester groups. Among them, 4a and 4b are found to be highly active against a panel of cancer cells screened, including cisplatin-resistant cancer cells. Mechanism studies in vitro indicate that they undergo hydrolysis of ester bonds, accumulate in mitochondria, and induce a series of cell-death related events mediated by mitochondria. Furthermore, 4a and 4b can induce pro-death autophagy and apoptosis simultaneously. Our study indicates that ester modification is a simple and feasible strategy to enhance the anticancer potency of Ir(III) complexes.
Effect of acute pesticide exposure on bee spatial working memory using an analogue of the radial-arm maze
Authors: Samuelson Elizabeth E. W. , Chen-Wishart Zachary P. , Gill Richard J. , Leadbeater Ellouise
Published: December 2016

Pesticides, including neonicotinoids, typically target pest insects by being neurotoxic. Inadvertent exposure to foraging insect pollinators is usually sub-lethal, but may affect cognition. One cognitive trait, spatial working memory, may be important in avoiding previously-visited flowers and other spatial tasks such as navigation. To test this, we investigated the effect of acute thiamethoxam exposure on spatial working memory in the bumblebee Bombus terrestris, using an adaptation of the radial-arm maze (RAM). We first demonstrated that bumblebees use spatial working memory to solve the RAM by showing that untreated bees performed significantly better than would be expected if choices were random or governed by stereotyped visitation rules. We then exposed bees to either a high sub-lethal positive control thiamethoxam dose (2.5 ng−1 bee), or one of two low doses (0.377 or 0.091 ng−1) based on estimated field-realistic exposure. The high dose caused bees to make more and earlier spatial memory errors and take longer to complete the task than unexposed bees. For the low doses, the negative effects were smaller but statistically significant, and dependent on bee size. The spatial working memory impairment shown here has the potential to harm bees exposed to thiamethoxam, through possible impacts on foraging efficiency or homing.
Longitudinal, observational study on associations between postoperative nutritional vitamin D supplementation and clinical outcomes in esophageal cancer patients undergoing esophagectomy
Authors: Wang Lu , Wang Cong , Wang Jiangfeng , Huang Xiaochen , Cheng Yufeng
Published: December 2016

Vitamin D can exert anticancer effect beyond bone and calcium metabolism. We aimed to investigate whether postoperative vitamin D supplementation affects quality of life (QOL) and survival in esophageal cancer (EC) patients. We utilized the widely used EORTC QLQ-C30 and QLQ-OES18 to assess QOL at EC diagnosis and 24 months after surgery. Generalized estimating equations (GEEs) were used to analysis the association of vitamin D supplement use with QOL. Kaplan-Meier method and Cox regression model were used to evaluate the prognostic value of vitamin D supplementation. The notably improved QOL were found among vitamin D supplementation users compared with non-users (p < 0.05). Kaplan-Meier analysis revealed that vitamin D supplement use was significantly associated with improved disease-free survival (DFS) (p = 0.030), but not related to overall survival (OS) (p = 0.303). The multivariable analysis further demonstrated vitamin D supplement use as an independent prognostic factor for DFS (p = 0.040; HR 0.610; 95% CI 0.381–0.978). In conclusion, these results showed that vitamin D supplement use could serve as a promising intervention to enhancing QOL and prolonging DFS in EC.
Coupling the normal incident light into waveguide modes of DBR mirrors via a diffraction grating
Authors: Yang Wenhong , Sun Shang , Zhang Chen , Li Jiankai , Duan Zonghui , Song Qinghai , Xiao Shumin
Published: December 2016

Here we numerically and experimentally demonstrate the conversion of normally incident light into the guiding modes of distributed Bragg reflector (DBRs) mirror. By fabricating a gold grating onto a 7.5 pairs TiO2/SiO2 DBR mirror, a series of asymmetrical resonances have been formed at the bandgap range of the DBR mirror. The detailed numerical calculations show that these Fano resonances are attributed to the coupling of incident waves into guiding modes of the DBR mirror. Compared with the other resonances, this coupling mechanism can be simply realized and it has also been revealed to be quite robust to the environmental changes, making the conversion between propagating waves and guiding waves to be practically interesting for many applications.
Multi-resolution community detection in massive networks
Authors: Han Jihui , Li Wei , Deng Weibing
Published: December 2016

Aiming at improving the efficiency and accuracy of community detection in complex networks, we proposed a new algorithm, which is based on the idea that communities could be detected from subnetworks by comparing the internal and external cohesion of each subnetwork. In our method, similar nodes are firstly gathered into meta-communities, which are then decided to be retained or merged through a multilevel label propagation process, until all of them meet our community criterion. Our algorithm requires neither any priori information of communities nor optimization of any objective function. Experimental results on both synthetic and real-world networks show that, our algorithm performs quite well and runs extremely fast, compared with several other popular algorithms. By tuning a resolution parameter, we can also observe communities at different scales, so this could reveal the hierarchical structure of the network. To further explore the effectiveness of our method, we applied it to the E-Coli transcriptional regulatory network, and found that all the identified modules have strong structural and functional coherence.
A novel pleuromutilin antibacterial compound, its binding mode and selectivity mechanism
Authors: Eyal Zohar , Matzov Donna , Krupkin Miri , Paukner Susanne , Riedl Rosemarie , Rozenberg Haim , Zimmerman Ella , Bashan Anat , Yonath Ada
Published: December 2016

The increasing appearance of pathogenic bacteria with antibiotic resistance is a global threat. Consequently, clinically available potent antibiotics that are active against multidrug resistant pathogens are becoming exceedingly scarce. Ribosomes are a main target for antibiotics, and hence are an objective for novel drug development. Lefamulin, a semi-synthetic pleuromutilin compound highly active against multi-resistant pathogens, is a promising antibiotic currently in phase III trials for the treatment of community-acquired bacterial pneumonia in adults. The crystal structure of the Staphylococcus aureus large ribosomal subunit in complex with lefamulin reveals its protein synthesis inhibition mechanism and the rationale for its potency. In addition, analysis of the bacterial and eukaryotes ribosome structures around the pleuromutilin binding pocket has elucidated the key for the drug’s selectivity.
Complementary Log Regression for Sufficient-Cause Modeling of Epidemiologic Data
Authors: Lin Jui-Hsiang , Lee Wen-Chung
Published: December 2016

The logistic regression model is the workhorse of epidemiological data analysis. The model helps to clarify the relationship between multiple exposures and a binary outcome. Logistic regression analysis is readily implemented using existing statistical software, and this has contributed to it becoming a routine procedure for epidemiologists. In this paper, the authors focus on a causal model which has recently received much attention from the epidemiologic community, namely, the sufficient-component cause model (causal-pie model). The authors show that the sufficient-component cause model is associated with a particular ‘link’ function: the complementary log link. In a complementary log regression, the exponentiated coefficient of a main-effect term corresponds to an adjusted ‘peril ratio’, and the coefficient of a cross-product term can be used directly to test for causal mechanistic interaction (sufficient-cause interaction). The authors provide detailed instructions on how to perform a complementary log regression using existing statistical software and use three datasets to illustrate the methodology. Complementary log regression is the model of choice for sufficient-cause analysis of binary outcomes. Its implementation is as easy as conventional logistic regression.
Semen preparation methods and sperm telomere length: density gradient centrifugation versus the swim up procedure
Authors: Zhao Feifei , Yang Qingling , Shi Senlin , Luo Xiaoyan , Sun Yingpu
Published: December 2016

Previous studies have shown that both density gradient centrifugation (DGC) and swim up (SU) procedures can select spermatozoa with longer telomeres for assisted reproduction techniques (ART). However, it is unknown which approach is more effective. The aim of the present study was to compare the effects of these two methods on sperm telomere length (STL). A total of 150 normozoospermic subjects were recruited. STL, DNA fragmentation index (DFI), reactive oxygen species (ROS) content and progressive motility of semen samples were detected before and after the procedures of DGC and SU. When compared to raw semen, the average length of sperm telomeres was significantly longer after the two sperm preparation methods. However, no significant difference was found between the DGC and SU procedures. We also found that semen prepared by the two methods had lower DNA fragmentation, ROS content and sperm progressive motility. However, no significant difference was found in those parameters between the two procedures. This is the first study that compares the effects of the DGC and SU procedures on STL, and the results show that both methods can recover a sperm population with longer STL and better DNA integrity for ART.
Mature dendritic cell derived from cryopreserved immature dendritic cell shows impaired homing ability and reduced anti-viral therapeutic effects
Authors: Zhou Qianqian , Zhang Yulong , Zhao Man , Wang Xiaohui , Ma Cong , Jiang Xinquan , Wu Tao , Wang Donggen , Zhan Linsheng
Published: December 2016

Cryopreservation is critical in reducing redundant operations and also in quality control in dendritic cell (DC) therapy. Full maturation and efficient homing of DCs to T cell-region constitute a crucial aspect of DC immunotherapy; however, the in vivo migration and distribution pattern, as well as the anti-viral effect of DCs that matured from cryopreserved immature DCs (cryoim-mDCs) remain to be revealed. In the present study, we compared cryoim-mDCs with DCs matured from fresh immature DCs (fmDCs) in the aspects of phenotypes, in vivo homing capacities as well as the anti-viral therapeutic effects to further clarify the effect of cryopreservation on DC-based cytotherapy. The results showed that cryopreservation impaired the homing ability of DCs which was associated with the reduced expression of CCR7 and disturbed cytoskeleton arrangement. Moreover, the antigen-specific CD8+ T cell response induced by cryoim-mDCs was much weaker than that induced by fmDCs in both the spleen and liver draining lymph nodes, which provided reduced protection from viral invasions. In conclusion, cryopreservation is a good method to keep the viability of immature DCs, however, the in vivo homing capacity and anti-viral therapeutic effect of DCs matured from frozen immature DCs were hindered to some extent.
High-resolution short-exposure small-animal laboratory x-ray phase-contrast tomography
Authors: Larsson Daniel H. , Vågberg William , Yaroshenko Andre , Yildirim Ali Önder , Hertz Hans M.
Published: December 2016

X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten μm spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-power small-spot liquid-metal-jet electron-impact source. The tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.
Soil aggregation and aggregating agents as affected by long term contrasting management of an Anthrosol
Authors: Zhang Shulan , Wang Renjie , Yang Xueyun , Sun Benhua , Li Qinghui
Published: December 2016

Soil aggregation was studied in a 21-year experiment conducted on an Anthrosol. The soil management regimes consisted of cropland abandonment, bare fallow without vegetation and cropping system. The cropping system was combined with the following nutrient management treatments: control (CONTROL, no nutrient input); nitrogen, phosphorus and potassium (NPK); straw plus NPK (SNPK); and manure (M) plus NPK (MNPK). Compared with the CONTROL treatment, the abandonment treatment significantly increased the formation of large soil macroaggregates (>2 mm) and consequently improved the stability of aggregates in the surface soil layer due to enhancement of hyphal length and of soil organic matter content. However, in response to long-term bare fallow treatment aggregate stability was low, as were the levels of aggregating agents. Long term fertilization significantly redistributed macroaggregates; this could be mainly ascribed to soil organic matter contributing to the formation of 0.5–2 mm classes of aggregates and a decrease in the formation of the >2 mm class of aggregates, especially in the MNPK treatment. Overall, hyphae represented a major aggregating agent in both of the systems tested, while soil organic compounds played significantly different roles in stabilizing aggregates in Anthrosol when the cropping system and the soil management regimes were compared.
Aggregation and Gelation of Aromatic Polyamides with Parallel and Anti-parallel Alignment of Molecular Dipole Along the Backbone
Authors: Zhu Dan , Shang Jing , Ye Xiaodong , Shen Jian
Published: December 2016

The understanding of macromolecular structures and interactions is important but difficult, due to the facts that a macromolecules are of versatile conformations and aggregate states, which vary with environmental conditions and histories. In this work two polyamides with parallel or anti-parallel dipoles along the linear backbone, named as ABAB (parallel) and AABB (anti-parallel) have been studied. By using a combination of methods, the phase behaviors of the polymers during the aggregate and gelation, i.e., the forming or dissociation processes of nuclei and fibril, cluster of fibrils, and cluster-cluster aggregation have been revealed. Such abundant phase behaviors are dominated by the inter-chain interactions, including dispersion, polarity and hydrogen bonding, and correlatd with the solubility parameters of solvents, the temperature, and the polymer concentration. The results of X-ray diffraction and fast-mode dielectric relaxation indicate that AABB possesses more rigid conformation than ABAB, and because of that AABB aggregates are of long fibers while ABAB is of hairy fibril clusters, the gelation concentration in toluene is 1 w/v% for AABB, lower than the 3 w/v% for ABAB.
Fabrication of Self-Ordered Alumina Films with Large Interpore Distance by Janus Anodization in Citric Acid
Authors: Ma Yingjun , Wen Yihao , Li Juan , Li Yuxin , Zhang Zhiying , Feng Chenchen , Sun Runguang
Published: December 2016

Self-organized porous anodic alumina (PAA) formed by electrochemical anodization have become a fundamental tool to develop various functional nanomaterials. However, it is still a great challenge to break the interpore distance (Dint) limit (500 nm) by using current anodization technologies of mild anodization (MA) and hard anodization (HA). Here, we reported a new anodization mode named “Janus anodization” (JA) to controllably fabricate self-ordered PAA with large Dint at high voltage of 350–400 V. JA naturally occurs as anodizing Al foils in citric acid solution, which possessing both the characteristics of MA and HA. The process can be divided into two stages: I, slow pore nucleation stage similar to MA; II, unequilibrium self-organization process similar to HA. The as-prepared films had the highest modulus (7.0 GPa) and hardness (127.2 GPa) values compared with the alumina obtained by MA and HA. The optical studies showed that the black films have low reflectance (<10 %) in the wavelength range of 250–1500 nm and photoluminescence property. Dint can be tuned between 645–884 nm by controlling citric acid concentration or anodization voltage. JA is a potential technology to efficiently and controllably fabricate microstructured or hybrid micro- and nanostructured materials with novel properties.
Wnt Ligands Differentially Regulate Toxicity and Translocation of Graphene Oxide through Different Mechanisms in Caenorhabditis elegans
Authors: Zhi Lingtong , Ren Mingxia , Qu Man , Zhang Hanyu , Wang Dayong
Published: December 2016

In this study, we investigated the possible involvement of Wnt signals in the control of graphene oxide (GO) toxicity using the in vivo assay system of Caenorhabditis elegans. In nematodes, the Wnt ligands, CWN-1, CWN-2, and LIN-44, were found to be involved in the control of GO toxicity. Mutation of cwn-1 or lin-44 gene induced a resistant property to GO toxicity and resulted in the decreased accumulation of GO in the body of nematodes, whereas mutation of cwn-2 gene induces a susceptible property to GO toxicity and an enhanced accumulation of GO in the body of nematodes. Genetic interaction assays demonstrated that mutation of cwn-1 or lin-44 was able to suppress the susceptibility to GO toxicity shown in the cwn-2 mutants. Loss-of-function mutations in all three of these Wnt ligand genes resulted in the resistance of nematodes to GO toxicity. Moreover, the Wnt ligands might differentially regulate the toxicity and translocation of GO through different mechanisms. These findings could be important in understanding the function of Wnt signals in the regulation of toxicity from environmental nanomaterials.