bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pisces Plume and the Magellanic wake
Authors: Belokurov Vasily , Deason Alis J , Erkal Denis , Koposov Sergey E , Carballo-Bello Julio A , Smith Martin C , Jethwa Prashin , Navarrete Camila
Published: June 2019

Using RR Lyrae stars in the Gaia Data Release 2 and Pan-STARRS1 we study the properties of the Pisces overdensity, a diffuse substructure in the outer halo of the Milky Way. We show that along the line of sight, Pisces appears as a broad and long plume of stars stretching from 40 to 110 kpc with a steep distance gradient. On the sky Pisces’s elongated shape is aligned with the Magellanic Stream. Using follow-up VLT FORS2 spectroscopy, we have measured the velocity distribution of the Pisces candidate member stars and have shown it to be as broad as that of the Galactic halo but offset to negative velocities. Using a suite of numerical simulations, we demonstrate that the structure has many properties in common with the predicted behaviour of the Magellanic wake, i.e. the Galactic halo overdensity induced by the infall of the Magellanic Clouds.
Prolactin decreases LPS-induced inflammatory cytokines by inhibiting TLR-4/NFκB signaling in the human placenta
Authors: Olmos-Ortiz A , Déciga-García M , Preciado-Martínez E , Bermejo-Martínez L , Flores-Espinosa P , Mancilla-Herrera I , Irles C , Helguera-Repetto A C , Quesada-Reyna B , Goffin V , Díaz L , Zaga-Clavellina V
Published: June 2019

Prolactin (PRL) plays an important role in trophoblast growth, placental angiogenesis and immunomodulation within the feto-maternal interface, where different cell types secrete PRL and express its receptor. During pregnancy, inflammatory signalling is a deleterious event that has been associated with poor fetal outcomes. The placenta is highly responsive to the inflammatory stimulus; however, the actions of PRL in placental immunity and inflammation remain largely unknown. The aim of this study was to evaluate PRL effects on the TLR4/NFkB signalling cascade and associated inflammatory targets in cultured explants from healthy term human placentas. An in utero inflammatory scenario was mimicked using lipopolysaccharides (LPS) from Escherichia coli. PRL significantly reduced LPS-dependent TNF-α, IL-1β and IL-6 secretion and intracellular levels. Mechanistically, PRL prevented LPS-mediated upregulation of TLR-4 expression and NFκB phosphorylation. In conclusion, PRL limited inflammatory responses to LPS in the human placenta, suggesting that this hormone could be critical in inhibiting exacerbated immune responses to infections that could threaten pregnancy outcome. This is the first evidence of a mechanism for anti-inflammatory activity of PRL in the human placenta, acting as a negative regulator of TLR-4/NFkB signaling.
The Effect of a 30-Min Water-Pipe Smoking Session on Cognitive Measures and Cardio-Pulmonary Parameters
Authors: Toukan Yazeed , Hakim Fahed , Bentur Yedidia , Aharon-Peretz Judith , Elemy Ameer , Gur Michal , Hanna Moneera , Fisher Tali , Scherb Inna , Bentur Lea
Published: June 2019

Introduction

One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion.

Methods

A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes.

Results

Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25–75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively).

Conclusions

One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS.

Implications

One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.
The relative incidence of cardiogenic and septic shock in neonates
Authors: Chan Ka Hong , Sanatani Shubhayan , Potts James E , Harris Kevin C
Published: June 2019

Objective

To evaluate the relative incidence of cardiogenic and septic shock in term neonates and identify findings that help differentiate the two entities.

Study Design

We conducted a retrospective chart review of term neonates presenting to British Columbia Children’s Hospital (BCCH) with decompensated shock of an undiagnosed etiology between January 1, 2008 and January 1, 2013. Charts were reviewed to determine the underlying diagnoses of all neonates meeting our inclusion criteria. Patients were categorized as having septic, cardiogenic, or other etiologies of shock. We then evaluated potential demographic, clinical, and biochemical parameters that could help differentiate between septic and cardiogenic shock.

Results

Cardiogenic shock was more common than septic shock (relative risk=1.53). A history of cyanosis was suggestive of cardiogenic shock (positive likelihood ratio, LR+=3.2 and negative likelihood ratio, LR−=0.4). Presence of a murmur or gallop (LR+=5.4, LR−=0.3), or decreased femoral pulses (LR+=5.1, LR−=0.5) on physical exam were also suggestive of cardiogenic shock as was cardiomegaly on chest x-ray (LR+=4.9, LR−=0.5). Notably, temperature instability (LR+=0.7, LR−=1.8) and white blood cell count elevation or depression (LR+=0.8, LR−=1.1) were all poor predictors of septic shock.

Conclusion

Cardiogenic shock is a more common cause of decompensated shock than septic shock. A history of cyanosis, murmur or gallop, or decreased femoral pulses on exam and cardiomegaly on chest x-ray are useful indicators of cardiogenic shock. In evaluating the neonate with decompensated shock, early consideration for Cardiology consultation and interventions to treat the underlying condition is warranted.
Zooplankton metabolism in South African estuaries: does habitat type influence ecological strategies?
Authors: Tagliarolo M , Porri F , Garvie C D , Lechman K , Scharler U M
Published: June 2019

Zooplankton community composition, biomass and metabolism can vary drastically over space and time in subtropical estuaries. Changing environmental conditions can affect communities differently, depending on the characteristics of the species involved. In the present study, we compared the rates of oxygen consumption of the dominant zooplankton taxa living in permanently open and in temporally open/closed estuaries. The metabolic response was tested at four temperatures experienced by the animals in their natural environment. Zooplankton from the temporally open/closed estuary showed low activation energies and low rate of metabolism at the highest temperature tested. Animals from the permanently open estuary had higher respiration rates at increased temperatures than those from the open/closed counterpart, with one taxon showing a particularly strong response to temperature increase. Results suggest that the metabolism of zooplankton in subtropical estuaries can be influenced by the environmental conditions experienced and those characteristics need to be accounted for in the development of bioenergetics budgets of species and ecosystems.
Long-term safety and limited organ damage in patients with systemic lupus erythematosus treated with belimumab: a Phase III study extension
Authors: van Vollenhoven Ronald F , Navarra Sandra V , Levy Roger A , Thomas Mathew , Heath Amy , Lustine Todd , Adamkovic Anthony , Fettiplace James , Wang Mei-Lun , Ji Beulah , Roth David
Published: June 2019

Objective

This extension study of the Phase III, randomized, placebo-controlled Belimumab International SLE Study (BLISS)-52 and BLISS-76 studies allowed non-US patients with SLE to continue belimumab treatment, in order to evaluate its long-term safety and tolerability including organ damage accrual.

Methods

In this multicentre, long-term extension study (GlaxoSmithKline Study BEL112234) patients received i.v. belimumab every 4 weeks plus standard therapy. Adverse events (AEs) were assessed monthly and safety-associated laboratory parameters were assessed at regular intervals. Organ damage (SLICC/ACR Damage Index) was assessed every 48 weeks. The study continued until belimumab was commercially available, with a subsequent 8-week follow-up period.

Results

A total of 738 patients entered the extension study and 735/738 (99.6%) received one or more doses of belimumab. Annual incidence of AEs, including serious and severe AEs, remained stable or declined over time. Sixty-nine (9.4%) patients experienced an AE resulting in discontinuation of belimumab or withdrawal from the study. Eleven deaths occurred (and two during post-treatment follow-up), including one (cardiogenic shock) considered possibly related to belimumab. Laboratory parameters generally remained stable. The mean (s.d.) SLICC/ACR Damage Index score was 0.6 (1.02) at baseline (prior to the first dose of belimumab) and remained stable. At study year 8, 57/65 (87.7%) patients had no change in SLICC/ACR Damage Index score from baseline, indicating low organ damage accrual.

Conclusion

Belimumab displayed a stable safety profile with no new safety signals. There was minimal organ damage progression over 8 years.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT00424476 (BLISS-52), NCT00410384 (BLISS-76), NCT00732940 (BEL112232), NCT00712933 (BEL112234).
Cardiovascular risk factors associated with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Study
Authors: Yates Max , Luben Robert , Hayat Shabina , Mackie Sarah L , Watts Richard A , Khaw Kay-Tee , Wareham Nick J , MacGregor Alex J
Published: June 2019

Objectives

PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA.

Methods

Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards.

Results

In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets.

Conclusion

PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.
Efficacy and safety of tocilizumab in a real-life observational cohort of patients with polyarticular juvenile idiopathic arthritis
Authors: Grönlund Minna-Maija , Remes-Pakarinen Terhi , Kröger Liisa , Markula-Patjas Kati , Backström Maria , Putto-Laurila Anne , Aalto Kristiina , Vähäsalo Paula
Published: June 2019

Objectives

To evaluate the patterns of usage, efficacy and safety of tocilizumab in polyarticular JIA.

Methods

An observational study of 56 consecutive polyarticular JIA patients was conducted using patient charts and electronic JIA databases. Efficacy was assessed by tocilizumab survival, rates of low disease activity (LDA) and of inactive disease by 10-joint Juvenile Arthritis Disease Activity Score (JADAS-10), and of clinically inactive disease according to Wallace’s preliminary criteria. Efficacy and rate of adverse events (AEs) were evaluated during a 24-month period after tocilizumab commencement.

Results

Tocilizumab was started on average as third-line biological agent (median, range first- to fourth-line) at a median disease duration of 5.2 years (interquartile range 3.0–7.7). Survival rates were 82% at 12 months and 64% at 24 months. The reasons for discontinuation were inadequate treatment effect in 50%, AE plus inadequate treatment effect in 37.5% and AE alone in 12.5%. LDA (JADAS-10 ⩽3.9) was reached in 58% at 12 months and in 84% at 24 months, inactive disease (JADAS-10 ⩽0.7) in 19% and 44%, and clinically inactive disease in 28% and 46%, respectively. The rate of AEs was 200.9/100 patient years and of serious AEs 12.9/100 patient years.

Conclusion

Survival of tocilizumab was high and a large proportion of the treatment-resistant patients reached LDA at 12 months of treatment. The LDA rate continued to increase throughout 24 months. The rates of AEs and serious AEs were higher than in register studies but lower than in the originator study of tocilizumab.
GAMMA DOSE RATES IN THE HIGH BACKGROUND RADIATION AREA OF MANGALORE REGION, INDIA
Authors: Al-Azmi Darwish , Kumara Sudeep , Mohan M P , Karunakara N
Published: June 2019

Elevated levels of natural background radiation due to scattered patches of monazite sand around the beaches of Mangalore, India, have been reported earlier. A comparative study of gamma dose rates was performed in both normal background and high natural background radiation areas around Mangalore using different types of portable gamma dosimeters. In addition to this, gamma-ray energy spectra were acquired, in situ, using a NaI(Tl) based portable gamma spectrometer. Soil and sand samples were collected for laboratory analysis with HPGe detectors. Measurements were carried out during the years 2016–18 revealed that in majority of the locations the gamma dose rates were similar to the normal background regions, whereas, in certain locations the dose rates were higher with values up to 530 nSv/h.
Restricted generalizability of city innovation policies: The case of E-hailing in China
Authors: Sharif Naubahar , Xing Jack Linzhou
Published: June 2019

Electronic-hailing (e-hailing) has experienced explosive growth in China. The Chinese government’s e-hailing policies illustrate its central–regional policy mix. This study analyzes e-hailing policies in four Chinese cities—Xi’an, Chengdu, Beijing, and Guangzhou—and compares these policies with goals in four policy areas. We show that local Chinese governments’ attitudes toward e-hailing are varied, contradictory, and in some cases even not in accordance with central government policies. Our insights demonstrate the limited generalizability of the policymaking experiments we studied. It would be difficult to infer broad policy implications from the experience any of the four cities has had with e-hailing, because China’s regionally decentralized innovation system and policy experiment process address the unique needs and contexts of regional governments on a case-by-case basis.
Bioavailability of l-lysine sulfate relative to l-lysine HCl for growing–finishing pigs
Authors: Li Qingyun , Gould Stacie A , Htoo John Khun Kyaw , González-Vega J Caroline , Patience John F
Published: June 2019

The objective of this study was to evaluate the relative bioavailability (RBV) of l-Lys sulfate in comparison to l-Lys HCl based on the growth performance response from approximately 26 to 48 kg and from approximately 68 to 114 kg. The effect of Lys source on blood urea nitrogen (BUN), digestibility of dry matter (DM) and sulfur (S), as well as carcass characteristics was determined. A total of 280 growing pigs (25.9 ± 0.25 kg BW) were randomly assigned to one of seven dietary treatments in 56 pens, with five pigs per pen. The diets included a Lys-deficient basal diet (65% of requirement) and the basal diet supplemented with three graded levels of Lys (75%, 85%, and 95% of requirement), as either l-Lys HCl (78.8% Lys purity) or l-Lys sulfate (54.6% Lys purity). The experiment lasted for 112 d, with four dietary phases: Phase 1 lasted for 4 wk (BW: 25.9 to 47.5 kg), Phase 2 lasted for 3 wk (common commercial diet as washout period), Phase 3 lasted for 5 wk (BW: 67.5 to 98.2 kg), and Phase 4 lasted for 3 or 4 wk to reach an average market weight of 114.2 kg. Fresh fecal samples of pigs fed the highest levels of Lys (both Lys sources) were collected on 7 to 10 days after the beginning of Phase 3 for digestibility assay. Blood samples were collected on day 21 and day 81 to determine BUN. Carcass data were collected at a commercial packing plant. Data were analyzed using PROC GLM of SAS (9.4) according to a completely randomized design with pen as the experimental unit. The RBV of l-Lys sulfate was determined using the multiple regression slope-ratio method. Increasing levels of Lys, independent of source, increased (P < 0.05) BW, ADG, and feed efficiency during Phases 1, 3, and 4; market BW increased linearly (P < 0.01) and backfat and BUN decreased linearly (P < 0.01). Lysine source had no impact on growth performance, carcass characteristics, BUN, or digestibility of S and DM. The RBV of l-Lys sulfate compared with l-Lys HCl was also not different based upon ADG or G:F during Phase 1, 3, or 4. These data suggest that the bioavailability of Lys in l-Lys sulfate and l-Lys HCl is at least equivalent for growing–finishing pigs.
Dietary fatty acids promote sleep through a taste-independent mechanism
Authors: Sah Pamboro Estelle Laure , Brown Elizabeth B. , Keene Alex C.
Published: June 2019

Consumption of foods that are high in fat contributes to obesity and metabolism-related disorders that are increasing in prevalence and present an enormous health burden throughout the world. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable taste of dietary fatty acids promotes food consumption, activates reward centers in mammals, and underlies hedonic feeding. Despite a central role of dietary fats in the regulation of food intake and the etiology of metabolic diseases, little is known about how fat consumption regulates sleep. The fruit fly,Drosophila melanogaster, provides a powerful model system for the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented fatty acids into the diet ofDrosophilaand measured their effects on sleep and activity. We found that feeding flies a diet of hexanoic acid, a medium-chain fatty acid that is a by-product of yeast fermentation, promotes sleep by increasing the number of sleep episodes. This increase in sleep is dose-dependent and independent of the light-dark cues. Diets consisting of other fatty acids, including medium- and long-chain fatty acids, also increase sleep, suggesting many fatty acid types promote sleep. To assess whether dietary fatty acids regulate sleep through the taste system, we assessed sleep in flies with a mutation in the hexanoic acid receptorIonotropic receptor 56d, which is required for fatty acid taste perception. We found that these flies also increase their sleep when fed a hexanoic acid diet, suggesting the sleep promoting effect of hexanoic acid is not dependent on sensory perception. Overall, these results define a role for fatty acids in sleep regulation, providing a foundation to investigate the molecular and neural basis for fatty acid-dependent modulation of sleep duration.
PRC2 activates interferon-stimulated genes indirectly by repressing miRNAs in glioblastoma
Authors: Shivram Haridha , Le Steven V. , Iyer Vishwanath R.
Published: June 2019

Polycomb repressive complex 2 (PRC2) is a chromatin binding complex that represses gene expression by methylating histone H3 at K27 to establish repressed chromatin domains. PRC2 can either regulate genes directly through the methyltransferase activity of its component EZH2 or indirectly by regulating other gene regulators. Gene expression analysis of glioblastoma (GBM) cells lacking EZH2 showed that PRC2 regulates hundreds of interferon-stimulated genes (ISGs). We found that PRC2 directly represses several ISGs and also indirectly activates a distinct set of ISGs. Assessment of EZH2 binding proximal to miRNAs showed that PRC2 directly represses miRNAs encoded in the chromosome 14 imprinted DLK1-DIO3 locus. We found that repression of this locus by PRC2 occurs in immortalized GBM-derived cell lines as well as in primary bulk tumors from GBM and anaplastic astrocytoma patients. Through repression of these miRNAs and several other miRNAs, PRC2 activates a set of ISGs that are targeted by these miRNAs. This PRC2-miRNA-ISG network is likely to be important in regulating gene expression programs in GBM.
A twisted visual field map in the primate cortex predicted by topographic continuity
Authors: Yu Hsin-Hao , Rowley Declan P. , Price Nicholas S.C. , Rosa Marcello G.P. , Zavitz Elizabeth
Published: June 2019

Adjacent neurons in visual cortex have overlapping receptive fields within and across area boundaries, an arrangement which is theorized to minimize wiring cost. This constraint is thought to create retinotopic maps of opposing field sign (mirror and non-mirror representations of the visual field) in adjacent visual areas, a concept which has become central in current attempts to subdivide the cortex. We modelled a realistic developmental scenario in which adjacent areas do not mature simultaneously, but need to maintain topographic continuity across their borders. This showed that the same mechanism that is hypothesized to maintain topographic continuity within each area can lead to a more complex type of retinotopic map, consisting of sectors with opposing field sign within a same area. Using fully quantitative electrode array recordings, we then demonstrate that this type of map exists in the primate extrastriate cortex.
The long non-coding RNAGHSROSreprograms prostate cancer cell lines toward a more aggressive phenotype
Authors: Thomas Patrick B. , Jeffery Penny L. , Gahete Manuel D. , Whiteside Eliza J. , Walpole Carina , Maugham Michelle L. , Jovanovic Lidija , Gunter Jennifer H. , Williams Elizabeth D. , Nelson Colleen C. , Herington Adrian C. , Luque Raúl M. , Veedu Rakesh N. , Chopin Lisa K. , Seim Inge
Published: June 2019

It is now appreciated that long non-coding RNAs (lncRNAs) are important players in the orchestration of cancer progression. In this study we characterizedGHSROS, a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets. Consistently, transcriptome data revealed thatGHSROSalters the expression of cancer-associated genes. Functional analysesin vitroshowed thatGHSROSmediates tumor growth, migration, and survival and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation ofGHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell linesin vitrowas recapitulated in a subcutaneous xenograft model. Conversely,in vitroantisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably,GHSROSmodulates the expression of PPP2R2C, the loss of which may drive androgen receptor pathway-independent prostate tumor progression in a subset of prostate cancers. Collectively, our findings suggest thatGHSROScan reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.
Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics
Authors: Morrison Jean , Knoblauch Nicholas , Marcus Joseph , Stephens Matthew , He Xin
Published: June 2019

Mendelian randomization (MR) is a valuable tool for detecting evidence of causal relationships using genetic variant associations. Opportunities to apply MR are growing rapidly with the number of genome-wide association studies (GWAS) with publicly available results. However, existing MR methods rely on strong assumptions that are often violated, leading to false positives. Many methods have been proposed loosening these assumptions. However, it has remained challenging to account for correlated pleiotropy, which arises when variants affect both traits through a heritable shared factor. We propose a new MR method, Causal Analysis Using Summary Effect Estimates (CAUSE), that accounts for correlated and uncorrelated horizontal pleiotropic effects. We demonstrate in simulations that CAUSE is more robust to correlated pleiotropy than other methods. Applied to traits studied in recent GWAS, we find that CAUSE detects causal relationships with strong literature support and avoids identifying most unlikely relationships. Our results suggest that many pairs of traits identified as causal using alternative methods may be false positives due to horizontal pleiotropy.
Generating high-quality libraries for DIA-MS with empirically-corrected peptide predictions
Authors: Searle Brian C. , Swearingen Kristian E. , Barnes Christopher A. , Schmidt Tobias , Gessulat Siegfried , Kuster Bernhard , Wilhelm Mathias
Published: June 2019

Data-independent acquisition approaches typically rely on sample-specific spectrum libraries requiring offline fractionation and tens to hundreds of injections. We demonstrate a new library generation workflow that leverages fragmentation and retention time prediction to build libraries containing every peptide in a proteome, and then refines those libraries with empirical data. Our method specifically enables rapid library generation for non-model organisms, which we demonstrate using the malaria parasite Plasmodium falciparum, and non-canonical databases, which we show by detecting missense variants in HeLa.
Biodiversity of Magnetotactic Bacteria in the Freshwater Lake Beloe Bordukovskoe, Russia
Authors: Koziaeva V. V. , Alekseeva L. M. , Uzun M. M. , Leão P. , Sukhacheva M. V. , Patutina E. O. , Kolganova T. V. , Grouzdev D. S.
Published: June 2019

According to 16S rRNA gene- or genome-based phylogeny, magnetotactic bacteria (MTB) belong to diverse taxonomic groups. Here we analyzed the diversity of MTB in a sample taken from the freshwater lake Beloe Bordukovskoe near Moscow, Russia, by using molecular identification based on sequencing of the 16S rRNA gene andmamK, a specific marker gene for these bacteria. A protein encoded by themamKgene is involved in magnetosome chain arrangement inside the cell. As a result, six operational taxonomic units (OTUs) of MTB were identified. Among them, OTUs affiliated with the phylumNitrospiraewere predominant. ‘Ca. Etaproteobacteria’ andAlphaproteobacteriarepresented the minor groups of MTB. We also identified a novel MTB belonging to the familySyntrophaceaeof theDeltaproteobacteriaclass. Using a combination of fluorescence and transmission electron microscopy, the bacteria belonging to these new MTB groups were visualized. Electron microscopy revealed thatSyntrophaceaeMTB were rod-shaped and synthesized elongated magnetosomes, arranged as a disorganized cluster. Among theNitrospiraegroup, two groups with vibrioid cell shape and one group of ovoid-shaped bacteria were identified, all of which had elongated magnetosome crystals consisting of magnetite.
The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic
Authors: Liang Zhaoduan , Qin Lili , Chen Lei , Li Wenhui , Chen Chao , Huang Yaling , Zhang Le , Liu Songming , Qiu Si , Ge Yuping , Peng Wenting , Lin Xinxin , Dong Xuan , Zhang Xiuqing , Li Bo
Published: June 2019

Colorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world, as the result of the traditional treatments. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to individual treatment, resulting from the unique neoantigens. Many shared oncogenic mutations are detected, but whether the common neoantigens can be identified in CRC is unknown. Using the somatic mutations data from 321 CRC patients combined with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*11:01 restricted common neoantigens with high binding affinity (IC50<50 nM) and presentation score (>0.9). Except the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens were proved to be naturally processed and presented on constructed K562 cell surface by mass spectroscopy (MS), and 11 out of 25 common neoantigens specifically induced in vitro pre-stimulated cytotoxic lymphocyte (CTL) to secrete IFN-γ. However, only 2 out of 25 common neoantigens were simultaneously presented and immunogenic. Moreover, using cell-sorting technology combined with single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were clarified. Therefore, common neoantigens with presentation and immunogenicity could be found in CRC, which would be developed as the universal targets for CRC immunotherapy.
Determining the scale at which variation in WUE traits changes population yields
Authors: McGale Erica , Valim Henrique , Mittal Deepika , Jimenez Jesús Morales , Halitschke Rayko , Schuman Meredith C. , Baldwin Ian T.
Published: June 2019

Functional variation is known to influence population yield, but the scale at which this happens is still unknown. Relevant signals might only reach immediate neighbors of a phenotypically diverse plant (neighbor-scale) or conversely may distribute across the population (population-scale). We useNicotiana attenuatasilenced in mitogen-activated protein kinase 4 (irMPK4), plants with low water-use efficiency (WUE), to study the scale at which water-use traits alter intraspecific population yields. In the field and glasshouse, populations with low percentages of irMPK4 plants planted among isogenic control plants produced maximum overall growth and yield. Through paired-plant and local-plant-configuration analyses, we determined that this occurred at the population scale. However, we find that this effect was not due to irMPK4’s WUE phenotype. With micro-grafting, we additionally show thatMPK4-deficiency may mediate the response at the population-scale: shoot-expressedMPK4is required forN. attenuatato change yield in response to a neighbor.
Antibody Complementarity Determining Region Design Using High-Capacity Machine Learning
Authors: Liu Ge , Zeng Haoyang , Mueller Jonas , Carter Brandon , Wang Ziheng , Schilz Jonas , Horny Geraldine , Birnbaum Michael E. , Ewert Stefan , Gifford David K.
Published: June 2019

The precise targeting of antibodies and other protein therapeutics is required for their proper function and the elimination of deleterious off-target effects. Often the molecular structure of a therapeutic target is unknown and randomized methods are used to design antibodies without a model that relates antibody sequence to desired properties. Here we present a machine learning method that can design human Immunoglobulin G (IgG) antibodies with target affinities that are superior to candidates from phage display panning experiments within a limited design budget. We also demonstrate that machine learning can improve target-specificity by the modular composition of models from different experimental campaigns, enabling a new integrative approach to improving target specificity. Our results suggest a new path for the discovery of therapeutic molecules by demonstrating that predictive and differentiable models of antibody binding can be learned from high-throughput experimental data without the need for target structural data.

Significance

Antibody based therapeutics must meet both affinity and specificity metrics, and existing in vitro methods for meeting these metrics are based upon randomization and empirical testing. We demonstrate that with sufficient target-specific training data machine learning can suggest novel antibody variable domain sequences that are superior to those observed during training. Our machine learning method does not require any target structural information. We further show that data from disparate antibody campaigns can be combined by machine learning to improve antibody specificity.
TREM-1 activation is a key regulator in driving severe pathogenesis of enterovirus 71 infection
Authors: Amrun Siti Naqiah , Tan Jeslin J.L. , Rickett Natasha Y. , Cox Jonathan A. , Lee Bernett , Griffiths Michael J. , Solomon Tom , Perera David , Ooi Mong How , Hiscox Julian A. , Ng Lisa F.P.
Published: June 2019

Hand, foot and mouth disease (HFMD), caused by enterovirus 71 (EV71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterized in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signaling. Depletion of TREM-1 in EV71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes, and reduced viral loads for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV71 infections in primary human cells, and the involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration
Authors: Loreto Andrea , Hill Ciaran S. , Hewitt Victoria L. , Orsomando Giuseppe , Angeletti Carlo , Gilley Jonathan , Lucci Cristiano , Sanchez-Martinez Alvaro , Whitworth Alexander J. , Conforti Laura , Dajas-Bailador Federico , Coleman Michael P.
Published: June 2019

Wallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these proteins led to the identification of non-axotomy insults causing axon degeneration by a Wallerian-like mechanism, including several involving mitochondrial impairment. Mitochondrial dysfunction is heavily implicated in Parkinson’s disease, Charcot-Marie-Tooth disease, hereditary spastic paraplegia and other axonal disorders. However, whether and how mitochondrial impairment activates Wallerian degeneration has remained unclear. Here, we show that disruption of mitochondrial membrane potential leads to axonal NMNAT2 depletion in mouse sympathetic neurons, increasing the substrate-to-product ratio (NMN/NAD) of this NAD-synthesising enzyme, a metabolic fingerprint of Wallerian degeneration. The mechanism appears to involve both impaired NMNAT2 synthesis and reduced axonal transport. Expression of WLDS and Sarm1 deletion both protect axons after mitochondrial uncoupling. Blocking the pathway also confers neuroprotection and increases the lifespan of flies with Pink1 loss-of-function mutation, which causes severe mitochondrial defects. These data indicate that mitochondrial impairment replicates all the major steps of Wallerian degeneration, placing it upstream of NMNAT2 loss, with the potential to contribute to axon pathology in mitochondrial disorders.
A solvable model of entrainment ranges for the circadian rhythm under light/dark cycles
Authors: Takakura Ren , Ichikawa Masatoshi , Oyama Tokitaka
Published: June 2019

A continuous model for entrainment of the circadian clock responding to light/dark cycles is analytically studied. The circadian rhythm is entrained to light/dark cycles in a certain range of periods including the 24 hour period. Entrainment ranges vary among organisms; plants show much larger ranges than mammals. To analyze entrainment manners, we exploit a simplified model in which the angular velocity of the circadian rhythm is modulated by a sinusoidal function of phase difference between the circadian rhythm and reference phases. This model contains only one parameter called entrainment strength (K). For light and dark states, we set two reference phases. Using this model, we characterized the entrainment manners of circadian rhythms under non-24 hour light/dark cycles. The conditions of the K value for the entrainment were analytically calculated and a phase diagram showing entrainment/non-entrainment boundaries was drawn. In the diagram we found a region where disordered orbitals emerge. Then, critical values for the entrainment and the disordered irregular motion of the oscillation were derived. Simulation results near a critical value were comparable with the experimental results of the entrainment manners of plant circadian rhythms, suggesting the compatibility of self-oscillation and a strong light/dark response in plants. The diagram clearly represents an overview of the relationship between entrainment strengths and entrainment manners of circadian rhythms in general, and enables us to uniformly compare strengths of periodic stimuli in the environment and degrees of responsiveness for the stimuli among various circadian rhythms.
World Heritage Site as the place for education: the case of the Gango-ji Temple in Japan
Authors: Serizawa Satohiro , Sunami Soichiro
Published: June 2019

Purpose

The purpose of this paper is to investigate educational functions of the World Heritage Site by examining the case of cultural tourism in a Japanese Buddhist temple.

Design/methodology/approach

Japan accepted the World Heritage Convention in 1992. “Historic Monuments of Ancient Nara” were decided to be listed on the World Cultural Heritage in 1998. It was composed of buildings, monuments and related cultural landscape, including five Buddhist temples and one Shinto shrine. Among them, the Gango-ji, focused in this paper, is one of the oldest Buddhist temples in Japan.

Findings

It has been keeping many cultural properties related to the folk religious practice and providing many activities for the local community. The material culture of folk-belief is now preserved in a building in the temple yard. And there is an exhibition room. The main hall and the exhibition room are the important facilities for social education, where the visitors can watch and touch the real materials. According to the staffs of the temple, the tourists had better stay in the main hall after 1 h study at the exhibition room.

Originality/value

Heritage is a process of the contemporary people engaging in the usage of past as resources. The buildings as the tangible heritage used by the present community are combined with the actions as the intangible heritage of the people who preserve the heritage. The temporal tourists are also permitted to enjoy the process as participants. They can learn many things through their experiences at the heritage site.
Comorbid mental health disorders in children and young people with intellectual disabilities and autism spectrum disorders
Authors: Gobrial Ereny
Published: June 2019

Purpose

Children and young people with comorbid intellectual disabilities (ID) and autism spectrum disorders (ASD) are more likely to exhibit comorbid mental health disorders (MHD) and other significant behaviours (SB) in addition to the core symptoms of ASD. The purpose of this paper is to identify the prevalence of comorbid MHD and behaviours in children and young people with ID and ASD in Egypt.

Design/methodology/approach

The Reiss scale for children’s dual diagnosis was administered by parents and teachers of 222 Egyptian children and young people with mild/moderate ID and ASD to screen for MHD and SB. The mean age of children and young people was 12.3 years (SD = 3.64), with 75.6 per cent male.

Findings

The results revealed that 62.2 per cent of children and young people with ID and ASD had high rates of comorbid MHD and behaviour disorders were shown in 64.4 per cent of the participated children and young people. The results identified anger, anxiety and psychosis being the most frequently diagnosed disorders while crying spells and pica were the most SB. No differences were found between the male and female with ID and ASD in the current study.

Research limitations/implications

Mental health assessment of children and young people with ID and ASD will help to highlight the needs of these vulnerable children and develop the appropriate services.

Originality/value

The findings highlight the prevalence of MHD in children and young people with ID and ASD in Egypt. This has implications on the assessment of comorbid disorders and services needed for children with ID and ASD in Egypt.
Can plate colour promote appetite and joy while dining? An investigative study in Chinese fine dining restaurants
Authors: Chen Yen-Cheng , Tsui Pei-ling , Lee Ching-Sung , Chen Guan-lin
Published: June 2019

Purpose

This study used the colours of plates as atmospheric stimulus factors in the Mehrabian–Russell model of environmental influence, which served as the study’s basic background theory, to explore how plate colour affects consumer appetite preference and dining emotions in Chinese fine dining restaurants. The paper aims to discuss this issue.

Design/methodology/approach

The study used quantitative surveys and employed purposeful sampling and rolling snowball surveys of consumers in Chinese fine dining restaurants in Taipei; 581 effective surveys were collected from the test subjects. The research tools included a plate colour appetite preference scale and a dining emotion scale.

Findings

There were significant differences in age and gender in terms of appetite preference and plate colour. The plate colours with the highest appetite preference were gold, white and black. There were significant differences in plate colour appetite preference in terms of dining mood, with white and gold plates eliciting positive dining moods.

Originality/value

Most academic papers have focused on studying plates in Western dining, while very few studies have focused on the colour of Chinese dining plates. The greatest contribution and value of this study is its discovery of the colour combination of dining plates that can elicit appetite preferences and positive dining emotions among diners in Chinese fine dining restaurants. This information can be used to stimulate positive dining emotions among consumers and help restaurateurs improve the level of dining aesthetics.
The health-taste trade-off in consumer decision making for functional snacks
Authors: Papoutsi Georgia S. , Klonaris Stathis , Drichoutis Andreas
Published: June 2019

Purpose

The purpose of this paper is twofold: first, to evaluate the claim that consumers are willing to compromise on taste in order to obtain the potential health benefits from functional snacks; and second, to investigate the effect of expectations for the snacks, blind tasting and product information on hedonic judgments and willingness to pay (WTP).

Design/methodology/approach

A sample of 160 subjects was recruited to participate in a lab experiment that combined hedonic evaluations and a series of non-hypothetical second-price Vickrey auctions, under blind or informed tasting conditions. Participants were also asked to complete a questionnaire about consumer preferences, purchasing habits and demographics.

Findings

Results indicate that tasting and information have economically and statistically significant effects on overall food assessment with respect to prior product expectations. Provision of information regarding functional food components shortly before consumption makes consumers less strict on their taste evaluation and increases their WTP. This indicates that consumers are willing to partly sacrifice the pleasure of taste in order to improve the healthfulness of their diet. When information is provided after taste, it only exerts influence with respect to the carob-based snack. Furthermore, blind tasting has a negative effect on liking, irrespective of the product being evaluated. Finally, the econometric results reveal that older respondents tend to bid higher for functional snacks.

Originality/value

This study contributes to the existing literature not only on the basis of the novelty of results but also on the methodological front, since it showcases the combined use of hedonic tests and auctions with real monetary incentives as a state of the art technique on eliciting consumers’ overall assessment for functional snacks. It also highlights important elements in the toolkit that marketers can use to influence products’ perceived health benefits, and thus consumption choices.
Indoor and outdoor physical surroundings and guests’ emotional well-being
Authors: Han Heesup , Moon Hyoungeun , Hyun Sunghyup Sean
Published: June 2019

Purpose

This paper aims to examine the relationship of internal/external physical environments and emotional well-being and to explore the possible influence of such an association with guest satisfaction and retention considering the moderating role of price perception in the luxury resort hotel context.

Design/methodology/approach

A total of 603 responses were gathered from a field survey at luxury resort hotels. The data were analyzed using quantitative data analyses to achieve research objectives.

Findings

The results from the structural model assessment revealed that both internal and external physical environments elicited emotional well-being, which in turn leads to the increased guest satisfaction and retention. More specifically, internal atmospherics had a stronger impact on triggering subsequent variables compared to external environment factors. The outcomes also indicated the significant mediating role of emotional well-being and satisfaction. Emotional well-being was found to mediate the effect of internal and external physical environments on guest satisfaction, while guest satisfaction mediated the effect of emotional well-being on guest retention. Moreover, price perception significantly moderated the guest satisfaction–guest retention association. Overall, the proposed conceptual framework satisfactorily accounted for variance in guest retention.

Originality/value

The findings help practitioners in luxury resort hotels to develop ways to boost guests’ post-purchase behaviors by using internal/external atmospherics and emotional well-being.