bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association studies of impulsive personality traits (BIS-11 and UPPSP) and drug Experimentation in up to 22,861 adult research participants
Authors: Sanchez-Roige Sandra , Fontanillas Pierre , Elson Sarah L. ,   the 23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Hinds David A. , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McCreight Jennifer C. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A.M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Tung Joyce Y. , Vacic Vladimir , Catherine H. , Gray Joshua C. , Wit Harriet de , MacKillop James , Palmer Abraham A.
Published: September 2018

Background

Impulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse.

Methods

In collaboration with the genetics company 23andMe, Inc., we performed several genome-wide association studies (GWAS) on measures of impulsive personality traits (the short version of the UPPSP Impulsive Behavior Scale, and the Barratt Impulsiveness Scale [BIS-11]) and drug experimentation (the number of drug classes an individual has tried in their lifetime) in up to 22,861 male and female adult research participants of European ancestry.

Results

Impulsive personality traits and drug experimentation showed SNP-heritabilities that ranged from 5 to 11%. Genetic variants in theCADM2locus were significantly associated with the UPPSP Sensation Seeking subscale (P= 8.3 × 10-9, rs139528938) and showed a suggestive association with drug experimentation (P= 3.0 × 10-7, rs2163971; r2= 0.68 with rs139528938);CADM2has been previously associated with measures of risky behaviors and self-reported risk tolerance, cannabis initiation, alcohol consumption, as well as information speed processing, body mass index (BMI) variation and obesity. Furthermore, genetic variants in theCACNA1Ilocus were significantly associated with the UPPSP Negative Urgency subscale (P= 3.8 × 10-8, rs199694726). Multiple subscales from both UPPSP and BIS showed strong genetic correlations (>0.5) with drug experimentation and other substance use traits measured in independent cohorts, including smoking initiation, and lifetime cannabis use. Several UPPSP and BIS subscales were genetically correlated with attention-deficit/hyperactivity disorder (rg= 0.30-0.51, p < 8.69 x 10-3), supporting their validity as endophenotypes.

Conclusions

Our findings demonstrate a role for common genetic contributions to individual differences in impulsivity. Furthermore, our study is the first to provide a genetic dissection of the relationship between different types of impulsive personality traits and various psychiatric disorders.
Pharmacophore-driven Identification of N-Methyl-D-Receptor Antagonists as Potent Neuroprotective Agents Validated UsingIn-VivoStudies
Authors: Sharma Mukta , Mittal Anupama , Singh Aarti , Jainarayanan Ashwin K. , Sharma Swapnil , Paliwal Sarvesh
Published: September 2018

Alzheimer’s disease (AD), the most widespread cause of dementia is delineated by progressive cognitive impairment in the elderly people. During its progression, N-Methyl-D-Aspartate receptor antagonists are known to play a key role in the mechanisms of learning and memory. Extensive side effects alongside other effects on learning and memory have limited the therapeutic significance of various blockers and antagonists of the NMDA receptor. In this study, we identify potential compounds targeted against NMDA. In order to reveal the essential structural features for NMDA receptor, three-dimensional pharmacophore models are constructed based on a set of known NMDA inhibitors. This is followed by virtual screening which results in novel chemical compounds having the potential to inhibit NMDA. The lead compounds are then subjected to molecular docking and assessed by a scoring function, which results in two compounds with high Libdock scores. These compounds also show interactions with important residues at the active site. The compounds are shortlisted on the basis of high estimated activity, fit values, LibDock score, no violation to Lipinski’s and availability for procuring.

Of the shortlisted compounds, one compound satisfying the entire aforementioned criterion is further tested usingin-vivostudies on mice with the help of an eight-arm radial maze. The pharmacophore-based virtual screening protocol presented in this study pave the way forward to address the unmet medical need of Alzheimer disease.
Novel childhood experience suggests eccentricity drives organization of human visual cortex
Authors: Gomez Jesse , Barnett Michael , Grill-Spector Kalanit
Published: September 2018

The functional organization of human high-level visual cortex, such as face and place-selective regions, is strikingly consistent across individuals. A fundamental, unanswered question in neuroscience is what dimensions of visual information constrain the development and topography of this shared brain organization? To answer this question, we scanned with fMRI a unique group of adults who, as children, engaged in extensive experience with a novel stimulus–Pokémon–which are dissimilar from other ecological categories such as faces and places along critical dimensions (foveal bias, rectilinearity, size, animacy) from. We find that experienced adults not only demonstrate distinct and consistent distributed cortical responses to Pokémon, but their activations suggest that it is the experienced retinal eccentricity during childhood that predicts the locus of distributed responses to Pokémon in adulthood. These data advance our understanding about how childhood experience and functional constraints shape the functional organization of the human brain.
Bacterial outer membrane vesicles provide an alternative pathway for trafficking of type III secreted effectors into epithelial cells
Authors: Sirisaengtaksin Natalie , O’Donoghue Eloise J. , Jabbari Sara , Roe Andrew J. , Krachler Anne Marie
Published: September 2018

Outer membrane vesicles (OMVs) are proteo-liposomes universally shed by Gram-negative bacteria. Their secretion is significantly enhanced by the transition into the intra-host milieu and OMVs have been shown to play critical roles during pathogenesis. EnterohemorrhagicEscherichia coliO157 (EHEC), causes diarrheal disease in humans, and soluble toxins including Shiga-like toxins that contribute to disease severity and clinical complications including hemolytic uremic syndrome, have been shown to be OMV associated. In addition to Shiga-like toxins, EHEC produces a type III secretion system (T3SS), and T3SS effectors are associated with colonization and disease severityin vivo. Here, we show that type III secreted substrates including translocators and effectors are incorporated into OMVs independent of type III secretion activity. EHEC strains with non-functional type III secretion systems shed more OMVs and vesicles enter host cells with accelerated kinetics compared to vesicles shed from wild type EHEC. The T3SS effector translocated intimin receptor (Tir) is trafficked from OMVs into host cells and localizes to the membrane. However, its clustering on the host membrane and co-localization with bacterial pedestals is intimin-dependent. We further show that OMV-delivered Tir can cross-complement an effector-deficient EHEC strain, demonstrating that OMV-associated effectors reach the host cell in a biologically intact form. Finally, we observe that the non-LEE encoded E3 ubiquitin ligase effector NleL is also trafficked to host cells via OMVs, where it ubiquitinylates its target kinase JNK. Together, these data demonstrate that trafficking of OMV-associated effectors is a novel and T3SS-independent pathway for the delivery of active effectors to host cells.
Hierarchical Reconstruction of High-Resolution 3D Models of Human Chromosomes
Authors: Trieu Tuan , Oluwadare Oluwatosin , Cheng Jianlin
Published: September 2018

Eukaryotic chromosomes are often composed of components organized into multiple scales, such as nucleosomes, chromatin fibers, topologically associated domains (TAD), chromosome compartments, and chromosome territories. Therefore, reconstructing detailed 3D models of chromosomes in high resolution is useful for advancing genome research. However, the task of constructing quality highresolution 3D models is still challenging with existing methods. Hence, we designed a hierarchical algorithm, called Hierarchical3DGenome, to reconstruct 3D chromosome models at high resolution (<=5 Kilobase (KB)). The algorithm first reconstructs high-resolution 3D models at TAD level. The TAD models are then assembled to form complete high-resolution chromosomal models. The assembly of TAD models is guided by a complete low-resolution chromosome model. The algorithm is successfully used to reconstruct 3D chromosome models at 5KB resolution for the human B-cell (GM12878). These high-resolution models satisfy Hi-C chromosomal contacts well and are consistent with models built at lower (i.e. 1MB) resolution, and with the data of fluorescent in situ hybridization experiments. The Java source code of Hierarchical3DGenome and its user manual are available here https://github.com/BDM-Lab/Hierarchical3DGenome.
Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies
Authors: Park By Sangeun , Park Sei-Kyoung , Watanabe Naruaki , Hashimoto Tadafumi , Iwatsubo Takeshi , Shelkovnikova Tatyana A. , Liebman Susan W.
Published: September 2018

Proteins associated with familial neurodegenerative disease often aggregate in patients’ neurons. Several such proteins, e.g. TDP-43, aggregate and are toxic when expressed in yeast. Deletion of the ATXN2 ortholog,PBP1,reduces yeast TDP-43 toxicity, which led to identification of ATXN2 as an amyotrophic lateral sclerosis (ALS) risk factor and therapeutic target. Likewise, new yeast neurodegenerative disease models could facilitate identification of other risk factors and targets. Mutations inSS18L1,encoding the calcium-responsive transactivator (CREST) chromatin-remodeling protein, are associated with ALS. We show that CREST is toxic in yeast and forms nuclear and occasionally cytoplasmic foci that stain with Thioflavin-T, a dye indicative of amyloid-like protein. Like the yeast chromatin-remodeling factor SWI1, CREST inhibits silencing ofFLOgenes. Toxicity of CREST is enhanced by the [PIN+] prion and reduced by deletion of theHSP104chaperone required for the propagation of many yeast prions. Likewise, deletion ofPBP1reduced CREST toxicity and aggregation. In accord with the yeast data, we show that the Drosophila ortholog of human ATXN2, dAtx2, is a potent enhancer of CREST toxicity. Downregulation of dAtx2 in flies overexpressing CREST in retinal ganglion cells was sufficient to largely rescue the severe degenerative phenotype induced by human CREST. Overexpression caused considerable co-localization of CREST and PBP1/ATXN2 in cytoplasmic foci in both yeast and mammalian cells. Thus, co-aggregation of CREST and PBP1/ATXN2 may serve as one of the mechanisms of PBP1/ATXN2-mediated toxicity. These results extend the spectrum of ALS associated proteins whose toxicity is regulated byPBP1/ATXN2, suggesting that therapies targeting ATXN2 may be effective for a wide range of neurodegenerative diseases.

Author summary

Mutations in the calcium-responsive transactivator (CREST) protein have been shown to cause amyotrophic lateral sclerosis (ALS). Here we show that the human CREST protein expressed in yeast forms largely nuclear aggregates and is toxic. We also show that the HSP104 chaperone required for propagation of yeast prions is likewise required for CREST toxicity. Furthermore deletion of HSP104 affects CREST aggregation. ATXN2, previously shown to modify ALS toxicity caused by mutations in the TDP-43 encoding gene, also modifies toxicity of CREST expressed in either yeast or flies. In addition, deletion of the yeast ATXN2 ortholog reduces CREST aggregation. These results extend the spectrum of ALS associated proteins whose toxicity is regulated byATXN2, suggesting that therapies targeting ATXN2 may be effective for a wide range of neurodegenerative diseases.
Rapid development of an infant-derived HIV-1 broadly neutralizing antibody lineage
Authors: Simonich Cassandra A , Doepker Laura , Ralph Duncan , Williams James A , Dhar Amrit , Yaffe Zak , Gentles Lauren , Small Christopher T , Oliver Brian , Vigdorovich Vladimir , Prasad Vidya Mangala , Nduati Ruth , Sather D Noah , Lee Kelly K , Frederick A Matsen , Overbaugh Julie
Published: September 2018

HIV-infected infants develop broadly neutralizing plasma responses with more rapid kinetics than adults, suggesting the ontogeny of infant responses could better inform a path to achievable vaccine targets. We developed computational methods to reconstruct the developmental lineage of BF520.1, the first example of a HIV-specific broadly neutralizing antibody (bnAb) from an infant. The BF520.1 inferred naïve precursor binds HIV Env and a bnAb evolved within six months of infection and required only 3% mutation. Mutagenesis and structural analyses revealed that for this infant bnAb, substitutions in the kappa chain were critical for activity, particularly in CDRL1. Overall, the developmental pathway of this infant antibody includes features distinct from adult antibodies, including several that may be amenable to better vaccine responses.
Microbial metabolite deoxycholic acid controlsClostridium perfringens-induced chicken necrotic enteritis through attenuating cyclooxygenase signaling
Authors: Wang Hong , Latorre Juan D. , Bansal Mohit , Abraha Mussie , Al-Rubaye Bilal , Tellez Guillermo , Hargis Billy , Sun Xiaolun
Published: September 2018

Clostridium perfringens-induced necrotic enteritis (NE) has reemerged as a prevalent chicken disease worldwide due to reduced usage of prophylactic antibiotics. The lack of antimicrobial alternative strategies to control NE is mainly due to limited insight into the disease pathogenesis. The aim of this study is to investigate the role of microbiota metabolic product secondary bile acid deoxycholic acid (DCA) on preventing NE.C. perfringensgrowth was inhibited by 82.8% in 50 μM DCA Tryptic Soy Broth. SequentialEimeria maximaandC. perfringenschallenges induced acute NE showed as severe intestinal inflammation and body weight (BW) loss in broiler chickens, while 1.5 g/kg DCA diet dramatically reduced the disease. At the cellular level, DCA alleviated NE-associated ileal epithelial death and reduced lamina propria cell apoptosis. Interestingly, DCA reducedC. perfringensinvasion into ileum without altering the bacterial ileal luminal colonization. Molecular analysis showed that DCA reduced inflammatory mediators ofInfγ,Litaf, andMmp9mRNA accumulation in ileal tissue. Mechanism studies revealed thatC. perfringensinduced elevated expression of inflammatory mediators ofInfγ,Litaf,Mmp9,andPtgs2(Cyclooxygenase- 2 (COX-2) gene) in chicken splenocytes. Blocking COX signaling by pharmacological inhibitor aspirin attenuated INFγ-induced inflammatory response in the splenocytes. Consistent with thein vitroassay, chickens fed 0.12 g/kg aspirin diet protected the birds against NE-induced ileal inflammation, intestinal cell apoptosis, and BW loss. In conclusion, microbial metabolic product DCA prevents NE-induced ileal inflammation and BW loss through attenuating inflammatory response. These novel findings offer new strategies againstC. perfringens-induced diseases.

Significance Statement

Widespread antimicrobial resistance has become a serious challenge to both agricultural and healthcare industries. Withdrawing antimicrobials without effective alternatives exacerbates chicken productivity loss at billions of dollars every year, caused by intestinal diseases, such as coccidiosis-andC. perfringens-induced necrotic enteritis. This study revealed that microbial metabolic product secondary bile acid DCA preventsC. perfringens-induced intestinal disease in chickens through modulating inflammatory COX signaling pathways. Therefore, microbiome and its downstream targets of host inflammatory responses could be used to control NE. These findings have opened new avenues for developing novel antimicrobial free alternatives to prevent or treatC. perfringens-induced diseases.
RstA is a Major Regulator ofClostridioides difficileToxin Production and Motility
Authors: Edwards Adrianne N. , Anjuwon-Foster Brandon R. , McBride Shonna M.
Published: September 2018

Clostridioides difficileinfection (CDI) is a toxin-mediated disease. Several factors have been identified that influence the production of the two majorC. difficiletoxins, TcdA and TcdB, but prior published evidence suggested that additional unknown factors were involved in toxin regulation. Previously, we identified aC. difficileregulator, RstA, that promotes sporulation and represses motility and toxin production. We observed that the predicted DNA-binding domain of RstA was required for RstA-dependent repression of toxin genes, motility genes andrstAtranscription. In this study, we further investigated the regulation of toxin and motility gene expression by RstA. DNA pulldown assays confirmed that RstA directly binds therstApromoter via the predicted DNA-binding domain. Through mutational analysis of therstApromoter, we identified several nucleotides that are important for RstA-dependent transcriptional regulation. Further, we observed that RstA directly binds and regulates the promoters of the toxin genes,tcdAandtcdB, as well as the promoters for thesigDandtcdRgenes, which encode regulators of toxin gene expression. Complementation analyses with theClostridium perfringensRstA ortholog and a multi-species chimeric RstA protein revealed that theC. difficileC-terminal domain is required for RstA DNA-binding activity, suggesting that species-specific signaling controls RstA function. Our data demonstrate that RstA is a transcriptional repressor that autoregulates its own expression and directly inhibits transcription of the two toxin genes and two positive toxin regulators, thereby acting at multiple regulatory points to control toxin production.

IMPORTANCE

Clostridioides difficileis an anaerobic, gastrointestinal pathogen of humans and other mammals.C. difficileproduces two major toxins, TcdA and TcdB, which cause the symptoms of the disease, and forms dormant endospores to survive the aerobic environment outside of the host. A recently discovered regulatory factor, RstA, inhibits toxin production and positively influences spore formation. Herein, we determine that RstA directly represses toxin gene expression and gene expression of two toxin gene activators, TcdR and SigD, creating a complex regulatory network to tightly control toxin production. In addition, the ability for RstA to bind DNA and repress toxin production requires the species-specific domain predicted to respond to small quorum-sensing peptides. This study provides a novel regulatory link betweenC. difficilesporulation and toxin production. Further, our data suggest thatC. difficiletoxin production is regulated through a direct sensing mechanism.
Cre-dependent optogenetic transgenic mice without early age-related hearing loss
Authors: Lyngholm Daniel , Sakata Shuzo
Published: September 2018

With the advent of recent genetic technologies for mice, it is now feasible to investigate the circuit mechanisms of brain functions in an unprecedented manner. Although transgenic mice are commonly used on C57BL/6J (C57) background, hearing research has typically relied on different genetic backgrounds, such as CBA/Ca or CBA due to the genetic defect of C57 mice for early age-related hearing loss. This limits the utilization of available genetic resources for hearing research. Here we report congenic (>F10) Cre-dependent channelrhodopsin2 (ChR2) mice on CBA/Ca background. By crossing this line with Cre-driver mice on C57 background, F1 hybrids restored the hearing deficit of C57 mice. We also found a linear relationship between aging and hearing loss, with progression rates varied depending on genetic backgrounds (3.39 dB/month for C57; 0.82 dB/month for F1 hybrid). We further demonstrate that this approach allows to express ChR2 in a specific type of inhibitory neurons in the auditory cortex and that they can be identified within a simultaneously recorded population of neurons in awake mice. Thus, our Cre-dependent optogenetic transgenic mice on CBA/Ca background are a valuable tool to investigate the circuit mechanisms of hearing across lifespan.
Subcellular localization of microcystin in the liver and the gonad of medaka fish acutely exposed to microcystin-LR
Authors: Qiao Qin , Djediat Chakib , Huet Hélène , Duval Charlotte , Manach Séverine Le , Bernard Cécile , Edery Marc , Marie Benjamin
Published: September 2018

Among the diverse toxic components produced by cyanobacteria, microcystins (MCs) are one of the most toxic and notorious cyanotoxin groups. Besides their potent hepatotoxicity, MCs have been revealed to induce potential reproductive toxicity in various animal studies. However, little is still known regarding the distribution of MCs in the reproductive organ, which could directly affect reproductive cells. In order to respond to this question, an acute study was conducted in adult medaka fish (model animal) gavaged with 10 µg.g-1 body weight of pure MC-LR. The histological and immunohistochemical examinations reveal an intense distribution of MC-LR within hepatocytes along with a severe liver lesion in the toxin-treated female and male fish. Besides being accumulated in the hepatocytes, MC-LR was also found in the connective tissue of the ovary and the testis, as well as in oocytes and degenerative spermatocyte-like structures. Both liver and gonad play important roles in the reproductive process of oviparous vertebrates. This observation constitutes the first observation of the presence of MC-LR in the reproductive cell of a vertebrate model with in vivo study. Our results, which provide intracellular localization of MC-LR in the gonad, advance our understanding of the potential reproductive toxicity of MC-LR in fish.
Mapping the Substrate Recognition Pathway in Cytochrome P450
Authors: Ahalawat Navjeet , Mondal Jagannath
Published: September 2018

Cytochrome P450s are ubiquitous metalloenzymes involved in the metabolism and detoxification of foreign components via catalysis of the hydroxylation reactions of a vast array of organic substrates. However, despite the breadth of cytochrome P450 mediated reactions, a long-standing question is: How does the substrate, in the first place, access the catalytic center of cytochrome P450? The prevalence of conflicting crystallographic evidences of both closed and open catalytic center in the substrate-free and substrate-bound cytochrome P450 has given rise to a notion of conformational heterogeneity, which makes the plausible mechanism of substrate recognition by cytochrome P450 puzzling from structural point of view. Here we report multi-microsecond-long unbiased molecular dynamics simulations, which are able to capture the spontaneous process of binding of substrate from bulk solvent to the occluded catalytic center of an archetypal system cytochrome P450cam, at an atomistic precision. In all binding trajectories, the substrate enters through a single channel, where it makes its first contact with the protein-surface and subsequently dwells in a highly long-lived intermediate state, before sliding into the catalytic center of P450cam. The simulated substrate-bound pose and crystallographic pose are in excellent agreement. Contrary to the prevalent hypotheses, our results indicate that a large-scale opening of F/G loop of P450cam is not required for passage of substrate to the catalytic center. Rather, we find that a substrate-induced side-chain displacement of Phe87 residue, coupled with a complex array of dynamical interconversions of multiple metastable substrate conformations along the entry channel, drives the substrate recognition in P450cam. By reconciling multiple precedent investigations, this work put forward an unambiguous view of the substrate recognition mechanism in deep buried cavity of cytochrome P450.
Effects of exposure to sublethal concentrations of methoxyfenozide on honey bee colony activity and thermoregulation
Authors: Meikle William G. , Corby-Harris Vanessa , Carroll Mark J. , Weiss Milagra , Snyder Lucy A. , Meador Charlotte A.D. , Beren Eli , Brown Nicholas
Published: September 2018

Methoxyfenozide is an insect growth regulator (IGR) commonly used in agricultural to simultaneously control pests and preserve beneficial insect populations; however, its impact on honey bees in not fully understood. We conducted field and laboratory experiments to investigate bee health in response to field-relevant doses of this pesticide. Significant effects were observed in honey bee colony flight activity and thermoregulation after being treated with methoxyfenozide. Data collected indicated that hives fed 500 ppb methoxyfenozide treated pollen patty had: 1) a significantly reduced rate of daily hive weight loss due to forager departure at the start of the colony’s daily activity; 2) the end of the colony’s daily activity delayed by 17-21 minutes compared to Control; and 3) higher temperature variability during the winter. Colonies in the 125 ppb treatment group had fewer differences with the Control group, but did show a delay in the foraging end time by 30-46 minutes compared to the Control. Bee colony metrics of adult bee mass and brood surface area, and individual bee measurements of head weight, newly-emerged bee weight, and hypopharyngeal gland size were not significantly affected by the methoxyfenozide exposure levels of our experiments. An experiment conducted using the same treatment groups in the spring resulted in fewer differences among groups than did the experiments conducted in the fall. Analyses of methoxyfenozide concentrations in the treatment patty, wax, and bee bread showed that: 1) observed methoxyfenozide concentrations were about 18-60% lower than the calculated concentrations; 2) no residues were observed in wax in any treatment; and 3) methoxyfenozide was detected in stored bee bread in the 500 ppb treatment, at concentrations about 1-2.5% of the observed concentration for that treatment. These results suggest that there may be significant effects on honey bee colony behavior (and possibly health) in the field that are difficult to detect through traditional hive inspections and individual metrics.
Implementation of a practical and effective control program for Taenia solium in the Banke District of Nepal
Authors: Poudel Ishab , Sah Keshav , Subedi Suyog , Singh Dinesh Kumar , Kushwaha Peetambar , Colston Angela , Gauci Charles G. , Donadeu Meritxell , Lightowlers Marshall W.
Published: September 2018

Taenia solium is a zoonotic cestode parasite which causes human neurocysticercosis. Pigs transmit the parasite by acting as the intermediate host. An intervention was implemented in pigs to control transmission of T. solium in Dalit communities of Banke District, Nepal. Every 3 months, pigs were vaccinated with the TSOL18 recombinant vaccine (Cysvax™, IIL, India)) and, at the same time, given an oral treatment with 30mg/kg oxfendazole (Paranthic 10%™, MCI, Morocco). The prevalence of porcine cysticercosis was determined in both an intervention area as well as a similar no intervention control area, among randomly selected, slaughter-age pigs. Post mortem assessments were undertaken both at the start and at the end of the intervention. Participants conducting the post mortem assessments were blinded as to the source of the animals being assessed. At the start of the intervention the prevalence of porcine cysticercosis was 23.6% and 34.5% in the control and intervention areas, respectively. Following the intervention, the prevalence of cysticercosis in pigs from the control area was 16.7% (no significant change), whereas no infection was detected after complete slicing of all muscle tissue and brain in animals from the intervention area (P=0.004). These findings are discussed in relation to the feasibility and sustainability of T. solium control. The 3-monthly vaccination and drug treatment intervention in pigs used here is suggested as an effective and practical method for reducing T. solium transmission, thereby reducing the incidence of human neurocysticercosis.

Author summary

Neurocysticercosis is a disease caused by a parasitic infection of the brain. The parasite responsible, Taenia solium, is transmitted by pigs where human sanitation is poor and pigs roam freely. Neurocysticercosis is responsible for many cases of epilepsy in people living in poor, developing countries. The feasibility and sustainability of implementing control measures have been major impediments to reducing the incidence of neurocysticercosis. Recently, two new commercial products have become available for pigs which together offer the possibility of interrupting the parasite’s transmission the TSOL18 vaccine (Cysvax™, IIL, India) and an oxfendazole formulation (Paranthic 10%™, MCI, Morocco) licensed for use in pigs for the treatment of cysticercosis. Here we describe the impact of implementing vaccination plus drug treatment of pigs in the Banke district of Nepal. The intervention eliminated the risk of transmission of T. solium by the animals vaccinated and treated during the trial. Application of the vaccination and drug treatment program used here, possibly with strategic use of anthelmintics also in the human population, is an effective option for reducing the incidence of neurocysticercosis in Nepal and elsewhere.
Molecular organization of integrin-based adhesion complexes in mouse Embryonic Stem Cells
Authors: Xia Shumin , Yim Evelyn K. F. , Kanchanawong Pakorn
Published: September 2018

The mechanical microenvironment serves as an important factor influencing stem cell differentiation. Mechanobiological responses depend strongly on actomyosin contractility and integrin-based cell-extracellular matrix (ECM) interactions mediated by adhesive structures such as focal adhesions (FAs). While the roles of FAs in mechanobiology have been intensively studied in many mesenchymal and migratory cell types, recently it has been recognized that certain pluripotent stem cells (PSCs) exhibited significantly attenuated FA-mediated mechanobiological responses. FAs in such PSCs are sparsely distributed and much less prominent in comparison to “classical” FAs of typical adherent cells. Despite these differences, insights into how FAs in PSCs are structurally organized to perform their functions are still elusive. Using mouse embryonic stem cells (mESCs) to study PSC-ECM interactions, here we surveyed the molecular composition and nanostructural organization of FAs. We found that despite being small in size, mESC FAs appeared to be compositionally mature, containing markers such as vinculin, zyxin, and α-actinin, and dependent on myosin II contractility. Using super-resolution microscopy, we revealed that mESC FAs were organized into a conserved multilayer nanoscale architecture. However, the nanodomain organization was compressed in mESCs, with the force transduction layer spanning ∼ 10 nm, significantly more compact than in FAs of other cell types. Furthermore, we found that the position and orientation of vinculin, a key mechanotransduction protein, were modulated in an ECM-dependent manner. Our analysis also revealed that while most core FA genes were expressed, the expression of LIM domain proteins was comparatively lower in PSCs. Altogether our results suggest that while core structural and mechanosensitive elements are operational in mESC FAs, their structural organization and regulatory aspects may diverge significantly from “classical” FAs, which may account for the attenuated mechanobiological responses of these cell types.
Arginine culture generates triacylglycerol by triggering nitrogen starvation responses during robust growth inChlamydomonas
Authors: Munz Jacob , Xiong Yuan , Hwan Kim Jaoon Young , Sung Young Joon , Seo Seungbeom , Hong Ran Ha , Kariyawasam Thamali , Shelley Nolan , Lee Jenny , Sim Sang Jun , Jin EonSeon , Lee Jae-Hyeok
Published: September 2018

Under nitrogen (N) starvation, microalgae increase carbon storage in the form of lipid droplets while also downregulating photosynthesis and eventually terminating growth. To improve lipid yield, we asked whether lipid droplets and N starvation responses can be induced without limiting growth or photosynthesis. In the chlorophyteChlamydomonas reinhardtii, gametogenesis is induced either by N starvation or by growth with arginine as the sole N source. We showed that arginine cultures supported robust phototrophic growth, constitutively turned on N starvation-induced genes, and increased lipid droplets. The lipids accumulated in arginine cultures exhibited strong enrichment of saturated and monounsaturated fatty acids, a preferred characteristic of biodiesel precursors. The diatomPhaeodactylum tricornutumalso accumulated lipid droplets in arginine culture without growth impairment. We document a system wherein N starvation responses are induced without compromising photosynthesis or growth, thereby suited to the producing valuable chemicals and biofuel precursors without requiring stressors in microalgae.
Predicting mRNA abundance directly from genomic sequence using deep convolutional neural networks
Authors: Agarwal Vikram , Shendure Jay
Published: September 2018

Algorithms that accurately predict gene structure from primary sequence alone were transformative for annotating the human genome. Can we also predict the expression levels of genes based solely on genome sequence? Here we sought to apply deep convolutional neural networks towards this goal. Surprisingly, a model that includes only promoter sequences and features associated with mRNA stability explains 59% and 71% of variation in steady-state mRNA levels in human and mouse, respectively. This model, which we call Xpresso, more than doubles the accuracy of alternative sequence-based models, and isolates rules as predictive as models relying on ChIP-seq data. Xpresso recapitulates genome-wide patterns of transcriptional activity and predicts the influence of enhancers, heterochromatic domains, and microRNAs. Model interpretation reveals that promoter-proximal CpG dinucleotides strongly predict transcriptional activity. Looking forward, we propose the accurate prediction of cell type-specific gene expression based solely on primary sequence as a grand challenge for the field.
Probing the intrinsic and extrinsic origins of piezoelectricity in lead zirconate titanate single crystals
Authors: Zhang Nan , Gorfman Semën , Choe Hyeokmin , Vergentev Tikhon , Dyadkin Vadim , Yokota Hiroko , Chernyshov Dmitry , Wang Bixia , Glazer Anthony Michael , Ren Wei , Ye Zuo-Guang
Published: September 2018

The physical origin of the piezoelectric effect has been the focus of much research work. While it is commonly accepted that the origins of piezoelectricity may be intrinsic (related to the change of lattice parameters) and extrinsic (related to the movement of domain walls), their separation is often a challenging experimental task. Here in situ high-resolution synchrotron X-ray diffraction has been combined with a new data analysis technique to characterize the change of the lattice parameters and domain microstructure of a PbZr1−x
Ti
x
O3 (x = 0.45) crystal under an external electric field. It is shown how `effective piezoelectric coefficients' evolve upon the transition from purely `intrinsic' effects to `extrinsic' ones due to domain-wall motion. This technique and corresponding data analysis can be applied to broader classes of materials and provide important insights into the microscopic origin of their physical properties.
Synthesis of ReItricarbonyl complexes with various sulfur- and oxygen-donating ligands: crystal structures of two ReIdinuclear structures bridged by S atoms
Authors: Nkoe Pheello I. , Visser Hendrik G. , Swart Chantel , Brink Alice , Schutte-Smith Marietjie
Published: September 2018

The synthesis and characterization of two dinuclear complexes, namelyfac-hexacarbonyl-1κ3C,2κ3C-(pyridine-1κN)[μ-2,2′-sulfanediyldi(ethanethiolato)-1κ2S1,S3:2κ3S1,S2,S3]dirhenium(I), [Re2(C4H8S3)(C5H5N)(CO)6], (1), and tetraethylammoniumfac-tris(μ-2-methoxybenzenethiolato-κ2S:S)bis[tricarbonylrhenium(I)], (C8H20N)[Re2(C7H7OS)3(CO)6], (2), together with two mononuclear complexes, namely (2,2′-bithiophene-5-carboxylic acid-κ2S,S′)bromidotricarbonylrhenium(I), (3), and bromidotricarbonyl(methyl benzo[b]thiophene-2-carboxylate-κ2O,S)rhenium(I), (4), are reported. Crystals of (1) and (2) were characterized by X-ray diffraction. The crystal structure of (1) revealed two Re—S—Re bridges. The thioether S atom only bonds to one of the ReImetal centres, while the geometry of the second ReImetal centre is completed by a pyridine ligand. The structure of (2) is characterized by three S-atom bridges and an Re...Re nonbonding distance of 3.4879 (5) Å, which is shorter than the distance found for (1) [3.7996 (6)/3.7963 (6) Å], but still clearly a nonbonding distance. Complex (1) is stabilized by six intermolecular hydrogen-bond interactions and an O...O interaction, while (2) is stabilized by two intermolecular hydrogen-bond interactions and two O...π interactions.
Different coordination modes of trans-2-{[(2-methoxyphenyl)imino]methyl}phenoxide in rare-earth complexes: influence of the metal cation radius and the number of ligands on steric congestion and ligand coordination modes
Authors: Roitershtein Dmitrii M. , Minashina Kseniya I. , Minyaev Mikhail E. , Ananyev Ivan V. , Lyssenko Konstantin A. , Tavtorkin Alexander N. , Nifant'ev Ilya E.
Published: September 2018

A simple and effective synthetic route to homo- and heteroleptic rare-earth (Ln = Y, La and Nd) complexes with a tridentate Schiff base anion has been demonstrated using exchange reactions of rare-earth chlorides with in-situ-generated sodium (E)-2-{[(2-methoxyphenyl)imino]methyl}phenoxide in different molar ratios in absolute methanol. Five crystal structures have been determined and studied, namely tris(2-{[(2-methoxyphenyl)imino]methyl}phenolato-κ3
O
1,N,O
2)lanthanum, [La(C14H12NO2)3], (1), tris(2-{[(2-methoxyphenyl)imino]methyl}phenolato-κ3
O
1,N,O
2)neodymium tetrahydrofuran disolvate, [La(C14H12NO2)3]·2C4H8O, (2)·2THF, tris(2-{[(2-methoxyphenyl)imino]methyl}phenolato)-κ3
O
1,N,O
2;κ3
O
1,N,O
2;κ2
N,O
1-yttrium, [Y(C14H12NO2)3], (3), dichlorido-1κCl,2κCl-μ-methanolato-1:2κ2
O:O-methanol-2κO-(μ-2-{[(2-methoxyphenyl)imino]methyl}phenolato-1κ3
O
1,N,O
2:2κO
1)bis(2-{[(2-methoxyphenyl)imino]methyl}phenolato)-1κ3
O
1,N,O
2;2κ3
O
1,N,O
2-diyttrium–tetrahydrofuran–methanol (1/1/1), [Y2(C14H12NO2)3(CH3O)Cl2(CH4O)]·CH4O·C4H8O, (4)·MeOH·THF, and bis(μ-2-{[(2-methoxyphenyl)imino]methyl}phenolato-1κ3
O
1,N,O
2:2κO
1)bis(2-{[(2-methoxyphenyl)imino]methyl}phenolato-2κ3
O
1,N,O
2)sodiumyttrium chloroform disolvate, [NaY(C14H12NO2)4]·2CHCl3, (5)·2CHCl3. Structural peculiarities of homoleptic tris(iminophenoxide)s (1)–(3), binuclear tris(iminophenoxide) (4) and homoleptic ate tetrakis(iminophenoxide) (5) are discussed. The nonflat Schiff base ligand displays μ2-κ3
O
1,N,O
2:κO
1 bridging, and κ3
O
1,N,O
2 and κ2
N,O
1 terminal coordination modes, depending on steric congestion, which in turn depends on the ionic radii of the rare-earth metals and the number of coordinated ligands. It has been demonstrated that interligand dihedral angles of the phenoxide ligand are convenient for comparing steric hindrance in complexes. (4)·MeOH has a flat Y2O2 rhomboid core and exhibits both inter- and intramolecular MeO—H...Cl hydrogen bonding. Catalytic systems based on complexes (1)–(3) and (5) have demonstrated medium catalytic performance in acrylonitrile polymerization, providing polyacrylonitrile samples with narrow polydispersity.
A new two-dimensional CoII coordination polymer based on bis[4-(2-methyl-1H-imidazol-1-yl)phenyl] ether and biphenyl-4,4′-diyldicarboxylic acid: synthesis, crystal structure and photocatalytic degradation activity
Authors: Chen Ning-Ning , Ni Jian-Ling , Wang Jun
Published: September 2018

A novel two-dimensional CoII coordination framework, namely poly[(μ2-biphenyl-4,4′-diyldicarboxylato-κ2
O
4:O
4′){μ2-bis[4-(2-methyl-1H-imidazol-1-yl)phenyl] ether-κ2
N
3:N
3′}cobalt(II)], [Co(C14H8O4)(C20H18N4O)]
n
, has been prepared and characterized by IR, elemental analysis, thermal analysis and single-crystal X-ray diffraction. The crystal structure reveals that the compound has an achiral two-dimensional layered structure based on opposite-handed helical chains. In addition, it exhibits significant photocatalytic degradation activity for the degradation of methylene blue.
A new one-dimensional CdII coordination polymer incorporating 2,2′-(1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylate)
Authors: Liu Yan-Ju , Cheng Di , Li Ya-Xue , Zhang Jun-Di , Yang Huai-Xia
Published: September 2018

Imidazole-4,5-dicarboxylic acid (H3IDC) and its derivatives are widely used in the preparation of new coordination polymers owing to their versatile bridging coordination modes and potential hydrogen-bonding donors and acceptors. A new one-dimensional coordination polymer, namely catena-poly[[diaquacadmium(II)]-μ3-2,2′-(1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylato)], [Cd(C16H6N4O8)0.5(H2O)2]
n
or [Cd(H2Phbidc)1/2(H2O)2]
n
, has been synthesized by the reaction of Cd(OAc)2·2H2O (OAc is acetate) with 2,2′-(1,2-phenylene)bis(1H-imidazole-4,5-dicarboxylic acid) (H6Phbidc) under solvothermal conditions. In the polymer, one type of Cd ion (Cd1) is six-coordinated by two N atoms and two O atoms from one H2Phbidc4− ligand and by two O atoms from two water molecules, forming a significantly distorted octahedral CdN2O4 coordination geometry. In contrast, the other type of Cd ion (Cd2) is six-coordinated by two N atoms and two O atoms from two symmetry-related H2Phbidc4− ligands and by two O atoms from two symmetry-related water molecules, leading to a more regular octahedral coordination geometry. The Cd1 and Cd2 ions are linked by H2Phbidc4− ligands into a one-dimensional chain which runs parallel to the b axis. In the crystal, the one-dimensional chains are connected through hydrogen bonds, generating a two-dimensional layered structure parallel to the ab plane. Adjacent layers are further linked by hydrogen bonds, forming a three-dimensional structure in the solid state.
Electrodeposition of Pr-Mg-Ni ternary alloy films from the choline chloride-urea ionic liquid and their corrosion properties
Authors: Li Miao , Chen Bi Qing , He Min , Xiong Tongtong , Gao Lixia
Published: September 2018

Purpose

This paper aims to obtain rare earth magnesium alloy with good adhesion and corrosion resistance.

Design/methodology/approach

In 353 K oil bath, cyclic voltammetry was used to study the electrochemical behavior of Pr(III), Mg(II) and Ni(II) in choline chloride-urea ionic liquid. The constant potential method was adopted for electrodeposition of Pr-Mg-Ni ternary alloy films. The content of Pr in the Pr-Mg-Ni alloy films changes with respect to the deposition potential, deposition time and concentration ratio of Pr3+:Mg2+:Ni2+. Response surface methodology was applied to optimize the conditions for obtaining high-quality deposition films.

Findings

The results showed that the reaction of Ni(II) to Ni is irreversible; this result can be verified by Tafel polarization curve and chronocoulometry curve. Its transfer coefficient on the platinum electrode of 0.32 and diffusion coefficient is 1.0510−6 cm2.s−1. Mg(II) and Pr(III) cannot solely be reduced to their elemental form, but they can be induced via codeposition by Ni(II). The result shows that under a voltage of −1.00 V, the alloy coating with even structure is obtained when the concentration ratio of Pr3+:Mg2+:Ni2+ is 1:1:1 and the deposition time is 20 min. Scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy and other analyses revealed that the alloy coating is amorphous. Polarization curves of the cathode are tested, which manifest the lowest corrosion current density, stating which has good corrosion performance in alkaline solution and NaCl solution; this can be attributed to its dense film structure and good combination with the substrate.

Originality/value

It provides some technology for the production of corrosion-resistant materials.
Flexural performance of TRC-strengthened RC beam under chloride environment
Authors: Shi-ping Yin , Yulin Yu , Xi Yunping
Published: September 2018

Purpose

Textile reinforced concrete (TRC) has excellent bearing capacity and anti-crack and corrosion resistance capacity, which are suitable for strengthening concrete structure under harsh environments.

Design/methodology/approach

In this thesis, flexural properties of RC beams strengthened with TRC under chloride wet–dry cycles were studied and the effects of the concentration of the salt solution, number of wet–dry cycles, bending stress level and TRC form were considered. Four-point bend loading mode was adopted for the step-loading procedure.

Findings

As the number of wet–dry cycles was relatively few, the trend of the yield and ultimate load with the increasing concentration of salt solution and wet–dry cycles were not obvious. However, the beams under high sustained bending stress level (0.5) had a decrease in the bearing capacity and an increase in mid-span deflection because of the larger degree of the corrosion of steel bars and the weaker bond capacity between the steel bar and concrete. Besides, there was little difference between the precast TRC plate and the casting TRC on beams in terms of the capacity of anti-crack, bearing and deflection.

Research limitations/implications

In this paper, preliminary work has been carried out, but some of the factors were not comprehensive considered, which are inevitable. As the time of dry–wet cycles was short and TRC layer had good anti-crack and anti-permeability performance, smaller chloride ions’ penetration resulted in the corrosion ratio of steel bars to be lower.

Practical implications

It should be noted that under high corrosion rates of the reinforcement, the whole TRC strengthening layer might be spalled off if only the strengthening form at the beam bottom is used, and thus the U-type strengthening form could be considered, which means that the beam is strengthened at both the bottom and side surfaces.

Originality/value

This research only considers the flexural performance of the beams strengthened with TRC in conventional environment, and there is little research on the TRC-strengthened beam under corrosion environment. On the basis of previous research, this paper carried out the experimental study on beams strengthened with TRC under chloride wet–dry cycle environment, and the effects of the concentration of the salt solution, number of wet–dry cycles, bending stress level and TRC form were considered.