bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-Identified Priorities Leading to Attempted Suicide
Authors: Stulz Niklaus , Hepp Urs , Gosoniu Dominic G. , Grize Leticia , Muheim Flavio , Weiss Mitchell G. , Riecher-Rössler Anita
Published: August 2017

Abstract. Background: Attempted suicide is a major public health problem. Aim: The aim of this study was to identify patient-identified problems and triggers typically leading to attempted suicide. Method: A representative sample of 66 adult patients was recruited from all clinical sites and psychiatrists who treat patients after attempted suicide in the Canton of Basel-City (Switzerland). Patients were diagnosed using the Structured Clinical Interview for DSM-IV (SCID) and interviewed with a local adaptation of the Explanatory Model Interview Catalogue (EMIC) to study underlying problems and triggers of attempted suicide. Results: Of the patients, 92.4% had at least one DSM-IV disorder, with depressive disorders being the most prevalent disorder. Although half (50.0%) of the patients identified a health problem, 71.2% identified an interpersonal conflict as underlying problem leading to the suicide attempt. Furthermore, an interpersonal conflict was identified as the trigger of the suicide attempt by more than half of the patients (54.5%). Limitations: The study included German-speaking patients only. Conclusion: According to patients, interpersonal problems often amplify underlying psychiatric problems, leading to suicide attempts. Social and interpersonal stressors should be acknowledged with integrated clinical and social interventions to prevent suicidal behavior in patients and populations.
Observing Mercury’s Brilliant Flares from Earth
Authors: Underwood Emily
Published: August 2017

Researchers make the first short-term observation of sodium flares in Mercury’s exosphere.
Long noncoding RNA CRNDE promotes colorectal cancer cell proliferation via epigenetically silencing DUSP5/CDKN1A expression
Authors: Ding Jie , Li Juan , Wang HaiYan , Tian Yun , Xie Min , He XueZhi , Ji Hao , Ma Zhonghua , Hui Bingqing , Wang Keming , Ji Guozhong
Published: August 2017

Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.
MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5
Authors: Du Bin , Dai Xiao-meng , Li Shuang , Qi Guo-long , Cao Guang-xu , Zhong Ying , Yin Pei-di , Yang Xue-song
Published: August 2017

As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.
Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin
Authors: Bayona-Feliu Aleix , Casas-Lamesa Anna , Reina Oscar , Bernués Jordi , Azorín Fernando
Published: August 2017

Linker histone H1 is an important structural component of chromatin that stabilizes the nucleosome and compacts the nucleofilament into higher-order structures. The biology of histone H1 remains, however, poorly understood. Here we show thatDrosophilahistone H1 (dH1) prevents genome instability as indicated by the increased γH2Av (H2AvS137P) content and the high incidence of DNA breaks and sister-chromatid exchanges observed in dH1-depleted cells. Increased γH2Av occurs preferentially at heterochromatic elements, which are upregulated upon dH1 depletion, and is due to the abnormal accumulation of DNA:RNA hybrids (R-loops). R-loops accumulation is readily detectable in G1-phase, whereas γH2Av increases mainly during DNA replication. These defects induce JNK-mediated apoptosis and are specific of dH1 depletion since they are not observed when heterochromatin silencing is relieved by HP1a depletion. Altogether, our results suggest that histone H1 prevents R-loops-induced DNA damage in heterochromatin and unveil its essential contribution to maintenance of genome stability.
The Microbial Ecosystem Distinguishes Chronically Diseased Tissue from Adjacent Tissue in the Sigmoid Colon of Chronic, Recurrent Diverticulitis Patients
Authors: Schieffer Kathleen M. , Sabey Kate , Wright Justin R. , Toole David R. , Drucker Rebecca , Tokarev Vasily , Harris Leonard R. , Deiling Sue , Eshelman Melanie A. , Hegarty John P. , Yochum Gregory S. , Koltun Walter A. , Lamendella Regina , Stewart David B.
Published: August 2017

Diverticular disease is commonly associated with the older population in the United States. As individual’s age, diverticulae, or herniation of the mucosa through the colonic wall, develop. In 10–25% of individuals, the diverticulae become inflamed, resulting in diverticulitis. The gut ecosystem relies on the interaction of bacteria and fungi to maintain homeostasis. Although bacterial dysbiosis has been implicated in the pathogenesis of diverticulitis, associations between the microbial ecosystem and diverticulitis remain largely unstudied. This study investigated how the cooperative network of bacteria and fungi differ between a diseased area of the sigmoid colon chronically affected by diverticulitis and adjacent non-affected tissue. To identify mucosa-associated microbes, bacterial 16S rRNA and fungal ITS sequencing were performed on chronically diseased sigmoid colon tissue (DT) and adjacent tissue (AT) from the same colonic segment. We found that Pseudomonas and Basidiomycota OTUs were associated with AT while Microbacteriaceae and Ascomycota were enriched in DT. Bipartite co-occurrence networks were constructed for each tissue type. The DT and AT networks were distinct for each tissue type, with no microbial relationships maintained after intersection merge of the groups. Our findings indicate that the microbial ecosystem distinguishes chronically diseased tissue from adjacent tissue.
Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates
Authors: Zhang Lili , Zhang Zesheng , Jasa John , Li Dongli , Cleveland Robin O. , Negahban Mehrdad , Jérusalem Antoine
Published: August 2017

The chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically destroy diseased cells and/or increase cell membrane permeability for drug delivery. However, the biomolecular mechanisms by which shock waves interact with diseased and healthy cellular components remain largely unknown. By integrating atomistic simulations with a novel multiscale numerical framework, this work provides new biomolecular mechanistic perspectives through which many mechanosensitive cellular processes could be quantitatively characterised. Here we examine the biomechanical responses of the chosen representative membrane complexes under rapid mechanical loadings pertinent to therapeutic shock wave conditions. We find that their rupture characteristics do not exhibit significant sensitivity to the applied strain rates. Furthermore, we show that the embedded rigid inclusions markedly facilitate stretch-induced membrane disruptions while mechanically stiffening the associated complexes under the applied membrane stretches. Our results suggest that the presence of rigid molecules in cellular membranes could serve as “mechanical catalysts” to promote the mechanical destructions of the associated complexes, which, in concert with other biochemical/medical considerations, should provide beneficial information for future biomechanical-mediated therapeutics.
MEPicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis
Authors: Edwards Rachel L. , Brothers Robert C. , Wang Xu , Maron Maxim I. , Ziniel Peter D. , Tsang Patricia S. , Kraft Thomas E. , Hruz Paul W. , Williamson Kim C. , Dowd Cynthia S. , John Audrey R. Odom
Published: August 2017

The emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.
Evolutionary shifts in gene expression decoupled from gene duplication across functionally distinct spider silk glands
Authors: Clarke Thomas H. , Garb Jessica E. , Haney Robert A. , Chaw R. Crystal , Hayashi Cheryl Y. , Ayoub Nadia A.
Published: August 2017

Spider silk synthesis is an emerging model for the evolution of tissue-specific gene expression and the role of gene duplication in functional novelty, but its potential has not been fully realized. Accordingly, we quantified transcript (mRNA) abundance in seven silk gland types and three non-silk gland tissues for three cobweb-weaving spider species. Evolutionary analyses based on expression levels of thousands of homologous transcripts and phylogenetic reconstruction of 605 gene families demonstrated conservation of expression for each gland type among species. Despite serial homology of all silk glands, the expression profiles of the glue-forming aggregate glands were divergent from fiber-forming glands. Also surprising was our finding that shifts in gene expression among silk gland types were not necessarily coupled with gene duplication, even though silk-specific genes belong to multi-paralog gene families. Our results challenge widely accepted models of tissue specialization and significantly advance efforts to replicate silk-based high-performance biomaterials.
Lignin Valorization: Two Hybrid Biochemical Routes for the Conversion of Polymeric Lignin into Value-added Chemicals
Authors: Wu Weihua , Dutta Tanmoy , Varman Arul M. , Eudes Aymerick , Manalansan Bianca , Loqué Dominique , Singh Seema
Published: August 2017

Naturally, many aerobic organisms degrade lignin-derived aromatics through conserved intermediates including protocatechuate and catechol. Employing this microbial approach offers a potential solution for valorizing lignin into valuable chemicals for a potential lignocellulosic biorefinery and enabling bioeconomy. In this study, two hybrid biochemical routes combining lignin chemical depolymerization, plant metabolic engineering, and synthetic pathway reconstruction were demonstrated for valorizing lignin into value-added products. In the biochemical route 1, alkali lignin was chemically depolymerized into vanillin and syringate as major products, which were further bio-converted into cis, cis-muconic acid (ccMA) and pyrogallol, respectively, using engineered Escherichia coli strains. In the second biochemical route, the shikimate pathway of Tobacco plant was engineered to accumulate protocatechuate (PCA) as a soluble intermediate compound. The PCA extracted from the engineered Tobacco was further converted into ccMA using the engineered E. coli strain. This study reports a direct process for converting lignin into ccMA and pyrogallol as value-added chemicals, and more importantly demonstrates benign methods for valorization of polymeric lignin that is inherently heterogeneous and recalcitrant. Our approach also validates the promising combination of plant engineering with microbial chassis development for the production of value added and speciality chemicals.
Quantification of lactate from various metabolic pathways and quantification issues of lactate isotopologues and isotopmers
Authors: Zhang Wei , Guo Cheng , Jiang Kezhi , Ying Minfeng , Hu Xun
Published: August 2017

13C-labeled glucose combined with chromatography and mass spectrometry enables us to decipher the percentage of lactate generated from various metabolic pathways. We showed that lactate derived from glycolysis, pentose phosphate pathway, Krebs cycle, and other sources accounted for 82–90%, 6.0–11%, 0.67–1.8% and 1.5–7.9%, respectively, depending on different types of cells. When using glucose isotopomers ([1-13C]-, [3-13C]-, [4-13C]-, and [6-13C]glucose) or isotopologues ([1,2-13C2]- and [1,2,3-13C3]glucose) for tracing, the ratio of lactate derived from glucose carbon 1, 2, 3 over 4, 5, 6 via glycolysis varied significantly, ranging from 1.6 (traced with [1,2-13C2]glucose) to 0.85 (traced with [6-13C]glucose), but the theoretical ratio should be 1. The odd results might be caused by intramolecular 13C, which may significantly affect lactate fragmentation under tandem mass spectrometry condition, leading to erroneous quantification. Indeed, the fragmentation efficiency of [U-13C]lactate, [2,3-13C]lactate, and [3-13C]lactate were 1.4, 1.5 and 1.2 folds higher than lactate, respectively, but [1-13C]lactate was similar to lactate, suggesting that carbon-13 at different positions could differentially influence lactate fragmentation. This observed phenomenon was inconsistent with the data based on theoretical calculation, according to which activation energies for all lactate isotopomers and isotopologues are nearly identical. The inconsistency suggested a need for further investigation. Our study suggests that calibration is required for quantifying metabolite isotopolugues and isotopomers.
Susceptibility of influenza A(H1N1)/pdm2009, seasonal A(H3N2) and B viruses to Oseltamivir in Guangdong, China between 2009 and 2014
Authors: Liu Shan-shan , Jiao Xiao-yang , Wang Sheng , Su Wen-zhe , Jiang Ling-zhi , Zhang Xin , Ke Chang-wen , Xiong Ping
Published: August 2017

Nasopharyngeal swabs were collected from patients through the influenza surveillance network of the CDC of Guangdong. All specimens between 2009 and 2014 were checked for influenza virus using MDCK cells and further subtyped. Of those collected, 542 H1N1pdm09, 230 A(H3N2)and 448 B viruses selected at random were subjected to fluorescence-based NAI assays. Viral RNA was extracted from resistant isolates, and their NA genes were amplified by RT-PCR. Alignment of nucleotides and amino acids was performed. We performed structural modelling and simulations of mutants using Modeller 9.x and AutoDock and analyzed conformations and binding affinities. All tested seasonal type B and H3N2 viruses from 2009 to 2014 remained sensitive to oseltamivir. However, there were five strains (out of 198 tested isolates acquired between June and September 2013) that were resistant to oseltamivir. Another three resistant strains were identified among isolates from March to April 2014. We found that 2013/2014 oseltamivir-resistant strains and 2012/2013/2014 oseltamivir-sensitive strains had all or some of the following mutations: N44S, N200S,V241I, I321V,N369K, N386 K and K432E. MutationsV241I, N369K, N386K and K432E, alone or in conjunction with H275Y, had a significant impact on the binding pattern and affinity of oseltamivir for neuraminidase, rendering neuraminidase less susceptible.
CRISPR-Cas9 Mediated Labelling Allows for Single Molecule Imaging and Resolution
Authors: Khan Abdullah O. , Simms Victoria A. , Pike Jeremy A. , Thomas Steven G. , Morgan Neil V.
Published: August 2017

Single molecule imaging approaches like dSTORM and PALM resolve structures at 10–20 nm, and allow for unique insights into protein stoichiometry and spatial relationships. However, key obstacles remain in developing highly accurate quantitative single molecule approaches. The genomic tagging of PALM fluorophores through CRISPR-Cas9 offers an excellent opportunity for generating stable cell lines expressing a defined single molecule probe at endogenous levels, without the biological disruption and variability inherent to transfection. A fundamental question is whether these comparatively low levels of expression can successfully satisfy the stringent labelling demands of super-resolution SMLM. Here we apply CRISPR-Cas9 gene editing to tag a cytoskeletal protein (α-tubulin) and demonstrate a relationship between expression level and the subsequent quality of PALM imaging, and that spatial resolutions comparable to dSTORM can be achieved with CRISPR-PALM. Our approach shows a relationship between choice of tag and the total expression of labelled protein, which has important implications for the development of future PALM tags. CRISPR-PALM allows for nanoscopic spatial resolution and the unique quantitative benefits of single molecule localization microscopy through endogenous expression, as well as the capacity for super-resolved live cell imaging.
The genetic variation rs12143842 in NOS1AP increases idiopathic ventricular tachycardia risk in Chinese Han populations
Authors: Zhang Ronfeng , Chen Feifei , Yu Honjiu , Gao Lianjun , Yin Xiaomeng , Dong Yingxue , Yang Yanzong , Xia Yunlong
Published: August 2017

Genome-wide association studies identified that the common T of rs12143842 in NOS1AP is associated with a QT/QTc interval in European populations. In this study, we test the association between the variation rs12143842 in NOS1AP and idiopathic ventricular tachycardia (IVT). A case-control association study examining rs12143842 was performed in two independent cohorts. The Northern cohort enrolled 277 IVT patients and 728 controls from a Chinese Gene ID population. The Central cohort enrolled 301 IVT patients and 803 matched controls. Genotyping was performed using high-resolution melt analysis. The minor T allele of the rs12143842 SNP was significantly associated with decreased IVT risk in the Northern cohort (adjusted P = 0.024, OR 0.71(0.52~0.96)), and this association was replicated in an independent Central Gene ID cohort (adjusted P = 0.029, OR 0.78 (0.62~0.97)). The association was more significant in the combined population (adjusted P = 0.001, OR 0.76 (0.64~0.90)). The P values for the genotypic association were significant for the dominant (P < 0.001) and additive (P = 0.001) models. The minor T allele for the SNP rs12143842 in NOS1AP is significantly associated with IVT. NOS1AP might be a novel gene affecting IVT, and further functional studies should be performed.
Non-thermal plasma-treated solution demonstrates antitumor activity against pancreatic cancer cells in vitro and in vivo
Authors: Liedtke Kim Rouven , Bekeschus Sander , Kaeding André , Hackbarth Christine , Kuehn Jens-Peter , Heidecke Claus-Dieter , von Bernstorff Wolfram , von Woedtke Thomas , Partecke Lars Ivo
Published: August 2017

Pancreatic cancer is associated with a high mortality rate. In advanced stage, patients often experience peritoneal carcinomatosis. Using a syngeneic murine pancreatic cancer cell tumor model, the effect of non-thermal plasma (NTP) on peritoneal metastatic lesions was studied. NTP generates reactive species of several kinds which have been proven to be of relevance in cancer. In vitro, exposure to both plasma and plasma-treated solution significantly decreased cell viability and proliferation of 6606PDA cancer cells, whereas mouse fibroblasts were less affected. Repeated intraperitoneal treatment of NTP-conditioned medium decreased tumor growth in vivo as determined by magnetic resonance imaging, leading to reduced tumor mass and improved median survival (61 vs 52 days; p < 0.024). Tumor nodes treated by NTP-conditioned medium demonstrated large areas of apoptosis with strongly inhibited cell proliferation. Contemporaneously, no systemic effects were found. Apoptosis was neither present in the liver nor in the gut. Also, the concentration of different cytokines in splenocytes or blood plasma as well as the distribution of various hematological parameters remained unchanged following treatment with NTP-conditioned medium. These results suggest an anticancer role of NTP-treated solutions with little to no systemic side effects being present, making NTP-treated solutions a potential complementary therapeutic option for advanced tumors.
Micron-scale mapping of megagauss magnetic fields using optical polarimetry to probe hot electron transport in petawatt-class laser-solid interactions
Authors: Chatterjee Gourab , Singh Prashant Kumar , Robinson A. P. L. , Blackman D. , Booth N. , Culfa O. , Dance R. J. , Gizzi L. A. , Gray R. J. , Green J. S. , Koester P. , Kumar G. Ravindra , Labate L. , Lad Amit D. , Lancaster K. L. , Pasley J. , Woolsey N. C. , Rajeev P. P.
Published: August 2017

The transport of hot, relativistic electrons produced by the interaction of an intense petawatt laser pulse with a solid has garnered interest due to its potential application in the development of innovative x-ray sources and ion-acceleration schemes. We report on spatially and temporally resolved measurements of megagauss magnetic fields at the rear of a 50-μm thick plastic target, irradiated by a multi-picosecond petawatt laser pulse at an incident intensity of ~1020 W/cm2. The pump-probe polarimetric measurements with micron-scale spatial resolution reveal the dynamics of the magnetic fields generated by the hot electron distribution at the target rear. An annular magnetic field profile was observed ~5 ps after the interaction, indicating a relatively smooth hot electron distribution at the rear-side of the plastic target. This is contrary to previous time-integrated measurements, which infer that such targets will produce highly structured hot electron transport. We measured large-scale filamentation of the hot electron distribution at the target rear only at later time-scales of ~10 ps, resulting in a commensurate large-scale filamentation of the magnetic field profile. Three-dimensional hybrid simulations corroborate our experimental observations and demonstrate a beam-like hot electron transport at initial time-scales that may be attributed to the local resistivity profile at the target rear.
Random lasing in human tissues embedded with organic dyes for cancer diagnosis
Authors: Wang Yu , Duan Zhuojun , Qiu Zhu , Zhang Peng , Wu Jianwei , Zhang Dingke , Xiang Tingxiu
Published: August 2017

Various nanostructures found in biological organisms are often complex and they exhibit unique optical functions. This study surprisingly found that typical random lasing occurs in cancerous human tissues embedded with the nanotextured organic dye 4-(dicyanomethylene)-2-tert-butyl-6-(1,1,7,7- tetramethyljulolidyl-9-enyl)-4H-pyran (DCJTB). Hematoxylin and eosin stain images show that there are more laser resonators in cancerous tissues, caused by a large number of disordered scatters. It is also noteworthy that the random lasing thresholds were found to relate to the tumor malignancy grade. Consequently, the resulting typical random lasing resonators differ between cancerous tissues in different malignancy grades. Further studies are warranted to investigate tissue optical spectroscopy in the field of cancer diagnostics.
Evaluation of Candidate Reference Genes for Quantitative Gene Expression Analysis in Spodoptera exigu
a after Long-time Exposure to Cadmium
Authors: Płachetka-Bożek Anna , Augustyniak Maria
Published: August 2017

Studies on the transcriptional control of gene expression play an important role in many areas of biology. Reference genes, which are often referred to as housekeeping genes, such as GAPDH, G3PDH, EF2, RpL7A, RpL10, TUBα and Actin, have traditionally been assumed to be stably expressed in all conditions, and they are frequently used to normalize mRNA levels between different samples in qPCR analysis. However, it is known that the expression of these genes is influenced by numerous factors, such as experimental conditions. The difference in gene expression underlies a range of biological processes, including development, reproduction and behavior. The aim of this study was to show the problems associated with using reference genes in the qPCR technique, in a study on inbred strains of Spodoptera exigua selected toward cadmium resistance. We present and discuss our results and observations, and give some recommendations concerning the use and limitations of housekeeping genes as internal standards, especially in research on insects. Our results suggest that holometabolism and poikilothermia, as well as time since metamorphosis and the level of exposure to the selective factor (cadmium in this case), have a significant effect on the expression of reference genes.
Effect of Genetic Information and Information About Caffeine Content on Caffeine Withdrawal Symptoms
Authors: Mills Llewellyn , Dar-Nimrod Ilan , Colagiuri Ben
Published: August 2017

This study sought to test the effect of genetic information and information about the caffeine content of a beverage on caffeine withdrawal, specifically if: (1) being informed that one has tested positive for a gene related to caffeine withdrawal can produce an exaggerated caffeine withdrawal response during abstinence; (2) belief that one has consumed caffeine leads to a reduction in withdrawal symptoms when no caffeine is consumed. Regular coffee drinkers were given a bogus genetic test and were told either that they had tested positive or negative for a gene related to withdrawal. After 24-hour caffeine abstinence withdrawal symptoms were measured using a self-report caffeine withdrawal scale, and then again after a cup of decaffeinated coffee. Half the participants were told their coffee was caffeinated and half were told truthfully that it was decaffeinated. Participants told the coffee was caffeinated reported a greater reduction in withdrawal symptoms than those told it was decaffeinated. Differing genetic test result information produced no difference in reported withdrawal symptoms. These results indicate that information about the dose of caffeine administered can influence withdrawal symptoms, but that genetic information does not have a universal ability to produce nocebo effects across all sensory and cognitive domains.
Glaucoma is associated with plasmin proteolytic activation mediated through oxidative inactivation of neuroserpin
Authors: Gupta Vivek , Mirzaei Mehdi , Gupta Veer Bala , Chitranshi Nitin , Dheer Yogita , Vander Wall Roshana , Abbasi Mojdeh , You Yuyi , Chung Roger , Graham Stuart
Published: August 2017

Neuroserpin is a serine protease inhibitor that regulates the activity of plasmin and its activators in the neuronal tissues. This study provides novel evidence of regulatory effect of the neuroserpin on plasmin proteolytic activity in the retina in glaucoma. Human retinal and vitreous tissues from control and glaucoma subjects as well as retinas from experimental glaucoma rats were analysed to establish changes in plasmin and neuroserpin activity. Neuroserpin undergoes oxidative inactivation in glaucoma which leads to augmentation of plasmin activity. Neuroserpin contains several methionine residues in addition to a conserved reactive site methionine and our study revealed enhanced oxidation of Met residues in the serpin under glaucoma conditions. Met oxidation was associated with loss of neuroserpin inhibitory activity and similar findings were observed in the retinas of superoxide dismutase (SOD) mutant mice that have increased oxidative stress. Treatment of purified neuroserpin with H2O2 further established that Met oxidation inversely correlated with its plasmin inhibitory activity. Dysregulation of the plasmin proteolytic system associated with increased degradation of the extracellular matrix (ECM) proteins in the retina. Collectively, these findings delineate a novel molecular basis of plasmin activation in glaucoma and potentially for other neuronal disorders with implications in disease associated ECM remodelling.
Emotions alter muscle proprioceptive coding of movements in humans
Authors: Ackerley Rochelle , Aimonetti Jean-Marc , Ribot-Ciscar Edith
Published: August 2017

Emotions can evoke strong reactions that have profound influences, from gross changes in our internal environment to small fluctuations in facial muscles, and reveal our feelings overtly. Muscles contain proprioceptive afferents, informing us about our movements and regulating motor activities. Their firing reflects changes in muscle length, yet their sensitivity can be modified by the fusimotor system, as found in animals. In humans, the sensitivity of muscle afferents is modulated by cognitive processes, such as attention; however, it is unknown if emotional processes can modulate muscle feedback. Presently, we explored whether muscle afferent sensitivity adapts to the emotional situation. We recorded from single muscle afferents in the leg, using microneurography, and moved the ankle joint of participants, while they listened to evocative classical music to induce sad, neutral, or happy emotions, or sat passively (no music). We further monitored their physiological responses using skin conductance, heart rate, and electromyography measures. We found that muscle afferent firing was modified by the emotional context, especially for sad emotions, where the muscle spindle dynamic response increased. We suggest that this allows us to prime movements, where the emotional state prepares the body for consequent behaviour-appropriate reactions.
Antibacterial activity and effect on gingival cells of microwave-pulsed non-thermal atmospheric pressure plasma in artificial saliva
Authors: Seo Sang-Hee , Han Ihn , Lee Han Seol , Choi Jin Joo , Choi Eun Ha , Kim Kyoung-Nam , Park Gyungsoon , Kim Kwang-Mahn
Published: August 2017

Although various oral pathogens are inactivated by non-thermal atmospheric pressure plasma (NTAPP), the in vivo effects of NTAPP are poorly understood. The first aim of this study was to examine the antibacterial activity of microwave-pulsed NTAPP against Staphylococcus aureus in artificial saliva to mimic oral environmental conditions. The second aim was to determine the influence of microwave-pulsed NTAPP on human gingival fibroblasts (HGFs). The microwave-pulsed NTAPP reduced bacterial viability (as measured by colony forming units [CFU]) to a greater extent in artificial saliva than in saline. Extending the post-treatment incubation time increased bacterial inactivation in artificial saliva compared to saline. HGFs viability was unaffected by microwave-pulsed NTAPP for bacterial inactivation. Rather, HGFs proliferation increased after a 5-min microwave-pulsed NTAPP. Less tumor necrosis factor alpha was released by microwave-pulsed NTAPP-treated HGFs stimulated with lipopolysaccharide (LPS) than by untreated, LPS-stimulated HGFs; thus, plasma appeared to suppress the inflammatory response. Our study suggests that microwave-pulsed NTAPP may have stronger in vivo antibacterial activity than in vitro activity, and that microwave-pulsed NTAPP may have the additional advantage of suppressing gingival inflammatory responses.
Active Components of Leptospira Outer Membrane Protein LipL32 to Toll-Like Receptor 2
Authors: Hsu Shen-Hsing , Hung Cheng-Chieh , Chang Ming-Yang , Ko Yi-Ching , Yang Huang-Yu , Hsu Hsiang-Hao , Tian Ya-Chung , Chou Li-Fang , Pan Rong-Long , Tseng Fan-Gang , Yang Chih-Wei
Published: August 2017

Proteins belonging to the toll-like receptor (TLR) family, particularly TLR2, are the major components of innate immunity against Leptospira infection. The ligands for TLR2 harbor several conserved patterns such as lipidation molecules, leucine-rich repeat (LRR) domains, TLR2 binding motifs, and TLR2 binding structure. In Leptospira, LipL32 interacts with TLR2 on human kidney cells concomitantly stimulating inflammatory responses. However, the binding mechanism of LipL32 to TLR2 is unknown. The computational prediction suggests that β1β2, loop-α3-loop, and α4 domains of LipL32 play vital roles in LipL32-TLR2 complex formation. To test these predictions, protein truncation experiments revealed that LipL32ΔNβ1β2 significantly decreased the affinity to TLR2 while LipL32ΔCα4 slightly reduced it. Interestingly, LipL32ΔCenα3 retained affinity to TLR2 in the absence of Ca2+ ions, indicating that Cenα3 play a role preventing the interaction between LipL32 and TLR2. Furthermore, the critical residues of LipL32 involved in interacting with TLR2 suggested that V35S, L36S and L263S variants significantly decreased the affinity to TLR2. The results further confirm that LipL32 interacts with TLR2 through Nβ1β2 and Cα4 domains of LipL32 as well as LipL32-TLR2 complex formation results from hydrophobic interactions. This study provides a detailed mechanism of the interaction between LipL32 and TLR2 and the residues involved in complex formation.
Percolation Phase Transition of Surface Air Temperature Networks: A new test bed for El Niño/La Niña simulations
Authors: Hua Lijuan , Lu Zhenghui , Yuan Naiming , Chen Lin , Yu Yongqiang , Wang Lu
Published: August 2017

In this work, we studied the air-sea interaction over the tropical central eastern Pacific from a new perspective, climate network. The surface air temperatures over the tropical Pacific were constructed as a network, and the nodes within this network were linked if they have a similar temporal varying pattern. Using three different reanalysis datasets, we verified the percolation phase transition. That is, when the influences of El Niño/La Niña are strong enough to isolate more than 48% of the nodes, the network may abruptly be divided into many small pieces, indicating a change of the network state. This phenomenon was reproduced successfully by a coupled general circulation model, Flexible Global Ocean-Atmosphere-Land System Model Spectral Version 2, but another model, Flexible Global Ocean-Atmosphere-Land System Model Grid-point Version 2, failed. As both models have the same oceanic component, but are with different atmospheric components, the improperly used atmospheric component should be responsible for the missing of the percolation phase transition. Considering that this new phenomenon is only recently noticed, current state-of-the-art models may ignore this process and induce unrealistic simulations. Accordingly, percolation phase transition is proposed as a new test bed, which deserves more attention in the future.
Reference miRNAs for colorectal cancer: analysis and verification of current data
Authors: Danese E. , Minicozzi A. M , Benati M. , Paviati E. , Lima-Oliveira G. , Gusella M. , Pasini F. , Salvagno G. L , Montagnana M. , Lippi G.
Published: August 2017

MicroRNAs (miRNAs) hold great promise in cancer research. The use of appropriate reference miRNAs for normalization of qPCR data is crucial for accurate expression analysis. We present here analysis and verification of current data, proposing a workflow strategy for identification of reference miRNAs in colorectal cancer (CRC). We performed a systematic review of studies aimed to identify stable reference miRNAs in CRC through high-throughput screening. Among the candidate miRNAs selected from the literature we excluded those predicted to target oncogenes or tumor suppressor gene. We then assessed the expression levels of the remaining candidates in exosomes, plasma and tissue samples from CRC patients and healthy controls. The expression stability was evaluated by box-plot, ∆Cq analysis, NormFinder and BestKeeper statistical algorithms. The effects of normalisers on the relative quantification of the oncogenic miR-1290 was also assessed. Our results consistently showed that different combinations of miR-520d, miR-1228 and miR-345 provided the most stably expressed reference miRNAs in the three biological matrices. We identified suitable reference miRNAs for future miRNA expression studies in exosomes plasma and tissues CRC samples. We also provided a novel conceptual framework that overcome the need of performing ex novo identification of suitable reference genes in single experimental systems.
Top canopy nitrogen allocation linked to increased grassland carbon uptake in stands of varying species richness
Authors: Milcu Alexandru , Gessler Arthur , Roscher Christiane , Rose Laura , Kayler Zachary , Bachmann Dörte , Pirhofer-Walzl Karin , Zavadlav Saša , Galiano Lucia , Buchmann Tina , Scherer-Lorenzen Michael , Roy Jacques
Published: August 2017

Models predict that vertical gradients of foliar nitrogen (N) allocation, increasing from bottom to top of plant canopies, emerge as a plastic response to optimise N utilisation for carbon assimilation. While this mechanism has been well documented in monocultures, its relevance for mixed stands of varying species richness remains poorly understood. We used 21 naturally assembled grassland communities to analyse the gradients of N in the canopy using N allocation coefficients (K
N
) estimated from the distribution of N per foliar surface area (KN-F) and ground surface area (KN-G). We tested whether: 1) increasing plant species richness leads to more pronounced N gradients as indicated by higher K
N
-values, 2) K
N
is a good predictor of instantaneous net ecosystem CO2 exchange and 3) functional diversity of leaf N concentration as estimated by Rao’s Q quadratic diversity metric is a good proxy of K
N
. Our results show a negative (for KN-G) or no relationship (for KN-F) between species richness and canopy N distribution, but emphasize a link (positive relationship) between more foliar N per ground surface area in the upper layers of the canopy (i.e. under higher KN-G) and ecosystem CO2 uptake. Rao’s Q was not a good proxy for either K
N
.
Analysis on the Composition/structure and Lacquering Techniques of the Coffin of Emperor Qianlong Excavated from the Eastern Imperial Tombs
Authors: Hao Xinying , Wu Hao , Zhao Yang , Tong Tong , Li Xiaoyuan , Yang Cui , Tang Yun , Shen Xinyu , Tong Hua
Published: August 2017

This article presents the results of an investigation on the coffin of Emperor Qianlong excavated from the Eastern Imperial Tombs of the Qing Dynasty in Zunhua, China. The composition, structure and lacquering techniques used in the manufacturing process were analyzed in this project. Stereoscopic Microscopy, SEM-EDS, XRD, FTIR, Raman, Double-shot Py-GC/MS were used as scientific analytical methods. The results show that the structure of the coffin body consists of a wooden body layer, a lacquer ash layer and a lacquer film pigment layer. The lacquer ash layer consists of nine stucco layers and ten fiber layers on top of each other in an alternating order. The lacquer film pigment layer consists of mineral pigments, lacquer sap, animal gelatin, drying oil, quartz sand and proteinaceous materials. Pigments used in the lacquer film include calcite white, carbon black, cinnabar red and gold. The presence of three distinctive catechols along with the other catechols’ and phenols’ profiles in the lacquer film matrix clearly indicate the species of the lacquer tree was Rhus. Vernicifera. Several distinctive lacquering techniques that improved the coffin body’s stability and mechanical strength were identified in the investigation, including the “wan lacquering”, “painting lacquer above the gold” and “Jin Jiao”.
Risk Factors For Radiation-Induced Skin Ulceration in Percutaneous Coronary Interventions of Chronic Total Occluded Lesions: A 2-Year Observational Study
Authors: Lai Chi-Cheng , Wei Kai-Che , Chen Wen-Yee , Mar Guang-Yuan , Wang Wen-Hwa , Wu Chieh-Shan , Tseng Ching-Jiunn , Yang Kuo-Chung , Chen Lee-Wei , Liu Chun-Peng
Published: August 2017

Relationship between radiation-induced skin ulceration (RSU) and variables in percutaneous coronary interventions (PCI) was rarely reported. RSU is a severe complication in PCIs, especially for chronic total occlusion (CTO) lesions. We investigated the RSUs and their risk factors in patients receiving CTO PCIs over a 2-year period. Data were analyzed using chi-square tests, t-tests and receiver operating characteristic (ROC) curve. Of 238 patients, 11 patients (4.6%) had RSUs all at right upper back. RSUs were significantly associated with use of left anterior oblique (LAO) views (100% vs. 47.1%, p < 0.001), retrograde techniques (36.3% vs. 7.9%, p = 0.012), or a procedure time (PT) defined as a time duration between the first and last angiograms of > 120, 180, or 240 minutes (p < 0.05). ROC analysis showed a long PT was an accurate predictor of RSUs (AUC = 0.88; p < 0.001) at a cut-off of 130 minutes (sensitivity = 0.91, specificity = 0.81). The results showed risk factors for RSUs containing use of large LAO views, retrograde techniques, and prolonged PTs. This study suggests that, to minimize RSU, interventionalists should limit PT to roughly 2 hours in fixed LAO views.
Targeted insertion of an anti-CD2 monoclonal antibody transgene into the GGTA1 locus in pigs using FokI-dCas9
Authors: Nottle Mark B. , Salvaris Evelyn J. , Fisicaro Nella , McIlfatrick Stephen , Vassiliev Ivan , Hawthorne Wayne J. , O’Connell Philip J. , Brady Jamie L. , Lew Andrew M. , Cowan Peter J.
Published: August 2017

Xenotransplantation from pigs has been advocated as a solution to the perennial shortage of donated human organs and tissues. CRISPR/Cas9 has facilitated the silencing of genes in donor pigs that contribute to xenograft rejection. However, the generation of modified pigs using second-generation nucleases with much lower off-target mutation rates than Cas9, such as FokI-dCas9, has not been reported. Furthermore, there have been no reports on the use of CRISPR to knock protective transgenes into detrimental porcine genes. In this study, we used FokI-dCas9 with two guide RNAs to integrate a 7.1 kilobase pair transgene into exon 9 of the GGTA1 gene in porcine fetal fibroblasts. The modified cells lacked expression of the αGal xenoantigen, and secreted an anti-CD2 monoclonal antibody encoded by the transgene. PCR and sequencing revealed precise integration of the transgene into one allele of GGTA1, and a small deletion in the second allele. The cells were used for somatic cell nuclear transfer to generate healthy male knock-in piglets, which did not express αGal and which contained anti-CD2 in their serum. We have therefore developed a versatile high-fidelity system for knocking transgenes into the pig genome for xenotransplantation purposes.
Molecular characterization of two novel echovirus 18 recombinants associated with hand-foot-mouth disease
Authors: Zhang Haihao , Zhao Yilin , Liu Hongbo , Sun Hao , Huang Xiaoqin , Yang Zhaoqing , Ma Shaohui
Published: August 2017

Human echovirus 18 (E-18) is a member of the enterovirus B species. To date, sixteen full-length genome sequences of E-18 are available in the GenBank database. In this study, we describe the complete genomic characterization of two E-18 strains isolated in Yunnan, China. Pairwise comparisons of the nucleotide sequences and the deduced amino acid sequences revealed that the two Yunnan E-18 strains had 87.5% nucleotide identity and 96.3–96.5% amino acid identity with the Chinese strain. Phylogenetic and bootscanning analyses revealed the two E-18 strains had the highest identity with other several EV-B serotypes than the other E-18 strains in the P3 coding region, especially, 3B region of the Swine Vesicular disease virus (SVDV) strain HK70, indicated that frequent intertypic recombination might have occurred in the two Yunnan strains. This study contributes the complete genome sequences of E-18 to the GenBank database and provides valuable information on the molecular epidemiology of E-18 in China.
Body mass index trajectories in the first two years and subsequent childhood cardio-metabolic outcomes: a prospective multi-ethnic Asian cohort study
Authors: Aris Izzuddin M. , Chen Ling-Wei , Tint Mya Thway , Pang Wei Wei , Soh Shu E. , Saw Seang-Mei , Shek Lynette Pei-Chi , Tan Kok-Hian , Gluckman Peter D. , Chong Yap-Seng , Yap Fabian , Godfrey Keith M. , Kramer Michael S. , Lee Yung Seng
Published: August 2017

We investigated body mass index (BMI) trajectories in the first 2 years of life in 1170 children from an Asian mother-offspring cohort in Singapore, and examined their predictors and associations with childhood cardio-metabolic risk measures at 5 years. Latent class growth mixture modelling analyses were performed to identify distinct BMI z-score (BMIz) trajectories. Four trajectories were identified: 73.2%(n = 857) of the children showed a normal BMIz trajectory, 13.2%(n = 155) a stable low-BMIz trajectory, 8.6%(n = 100) a stable high-BMIz trajectory and 5.0%(n = 58) a rapid BMIz gain after 3 months trajectory. Predictors of the stable high-BMIz and rapid BMIz gain trajectories were pre-pregnancy BMI, gestational weight gain, Malay and Indian ethnicity, while predictors of stable low-BMIz trajectory were preterm delivery and Indian ethnicity. At 5 years, children with stable high-BMIz or rapid BMIz gain trajectories had increased waist-to-height ratios [B(95%CI) 0.02(0.01,0.03) and 0.03(0.02,0.04)], sum of skinfolds [0.42(0.19,0.65) and 0.70(0.36,1.03)SD units], fat-mass index [0.97(0.32,1.63)SD units] and risk of obesity [relative risk 3.22(1.73,6.05) and 2.56 (1.19,5.53)], but not higher blood pressure. BMIz trajectories were more predictive of adiposity at 5 years than was BMIz at 2 years. Our findings on BMIz trajectories in the first 2 years suggest important ethnic-specific differences and impacts on later metabolic outcomes.