bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of chloroplast microsatellite markers for identification of Glycyrrhiza species
Authors: Lee Kyung Jun , Raveendar Sebastin , Choi Ji Seon , Gil Jinsu , Lee Jeong Hoon , So Yoon-Sup , Chung Jong-Wook
Published: October 2018

Licorice (Glycyrrhiza glabra) is an important medicinal herb and has long been used in traditional medicine for the treatment of several diseases worldwide. Understanding the genetic diversity within Glycyrrhiza species is important for the efficient conservation of these medicinal herbs. In this study, we have developed 20 polymorphic chloroplast microsatellite (cpSSR) markers using the chloroplast genome of G. lepidota. The cpSSR markers were tested on a total of 27 Glycyrrhiza individual plants. The number of alleles per locus ranged from two to eight among the Glycyrrhiza accessions. Overall, the Shannon index (I) for each cpSSR ranged from 0.315 to 1.694, the diversity indices (h) were 0.140–0.793 and the unbiased diversity indices (uh) were 0.145–0.825. In addition, the cpSSR markers were successfully divided and classified the 27 Glycyrrhiza individuals into four groups. The cpSSR markers developed in this study could be used in the assessment of genetic diversity and rapid identification of Glycyrrhiza species.
The impact of Recovery Colleges on mental health staff, services and society
Authors: Crowther A. , Taylor A. , Toney R. , Meddings S. , Whale T. , Jennings H. , Pollock K. , Bates P. , Henderson C. , Waring J. , Slade M.
Published: October 2018

Aims

Recovery Colleges are opening internationally. The evaluation focus has been on outcomes for Recovery College students who use mental health services. However, benefits may also arise for: staff who attend or co-deliver courses; the mental health and social care service hosting the Recovery College; and wider society. A theory-based change model characterising how Recovery Colleges impact at these higher levels is needed for formal evaluation of their impact, and to inform future Recovery College development. The aim of this study was to develop a stratified theory identifying candidate mechanisms of action and outcomes (impact) for Recovery Colleges at staff, services and societal levels.

Methods

Inductive thematic analysis of 44 publications identified in a systematised review was supplemented by collaborative analysis involving a lived experience advisory panel to develop a preliminary theoretical framework. This was refined through semi-structured interviews with 33 Recovery College stakeholders (service user students, peer/non-peer trainers, managers, community partners, clinicians) in three sites in England.

Results

Candidate mechanisms of action and outcomes were identified at staff, services and societal levels. At the staff level, experiencing new relationships may change attitudes and associated professional practice. Identified outcomes for staff included: experiencing and valuing co-production; changed perceptions of service users; and increased passion and job motivation. At the services level, Recovery Colleges often develop somewhat separately from their host system, reducing the reach of the college into the host organisation but allowing development of an alternative culture giving experiential learning opportunities to staff around co-production and the role of a peer workforce. At the societal level, partnering with community-based agencies gave other members of the public opportunities for learning alongside people with mental health problems and enabled community agencies to work with people they might not have otherwise. Recovery Colleges also gave opportunities to beneficially impact on community attitudes.

Conclusions

This study is the first to characterise the mechanisms of action and impact of Recovery Colleges on mental health staff, mental health and social care services, and wider society. The findings suggest that a certain distance is needed in the relationship between the Recovery College and its host organisation if a genuine cultural alternative is to be created. Different strategies are needed depending on what level of impact is intended, and this study can inform decision-making about mechanisms to prioritise. Future research into Recovery Colleges should include contextual evaluation of these higher level impacts, and investigate effectiveness and harms.
An Improved High‐Spatial‐Resolution Aerosol Retrieval Algorithm for MODIS Images Over Land
Authors: Wei Jing , Sun Lin , Peng Yiran , Wang Lunche , Zhang Zhaoyang , Bilal Muhammad , Ma Yanci
Published: October 2018

MODerate resolution Imaging Spectroradiometer (MODIS) data can play an important role in aerosol retrieval at the global scale due to their short revisit period and long‐term observations. The operational MODIS aerosol optical depth (AOD) products are severely limited in air quality studies at the city or local scales due to their coarse spatial resolutions. Therefore, an improved aerosol retrieval algorithm for MODIS images at 1‐km spatial resolution is proposed in this paper. This algorithm is based on the high‐resolution aerosol retrieval algorithm with a priori land surface reflectance database support (HARLS), which was developed over bright urban areas and was subsequently modified and validated over land. For this study, an eight‐day surface reflectance database and a seasonal aerosol‐type database over land are constructed using the MODIS surface reflectance and aerosol products. Four typical regions (in Europe, North America, Beijing‐Tianjin‐Hebei, and the Sahara) with different underlying surfaces and aerosol types are selected to perform the aerosol retrieval experiments. The AOD retrievals are validated against the AERosol RObotic NETwork (AERONET) version 2 level 2.0 AOD measurements and compared with the operational MODIS AOD product at 3‐km resolution (MOD04_3K). The results show that AOD retrievals adequately match with AERONET AOD measurements, with 79.56%, 72.69%, 74.71%, and 61.01% of the collections falling within the MOD04_3K expected error over land [±(0.05 + 20%)] for each of the above‐listed regions, respectively. The Improved HARLS (I‐HARLS) algorithm performs well overall under different surface conditions, but the data quality gradually decreases with the increase in surface reflectance. Moreover, the I‐HARLS algorithm is robust with less bias and can provide more detailed aerosol spatial distributions than those provided by the MOD04_3K AOD product. These results suggest that the I‐HARLS algorithm can be used for air‐pollution‐ and climate‐related studies at medium or small scales.
Foreland Basin Record of Uplift and Exhumation of the Eastern Cordillera, Northwest Argentina
Authors: Rahl Jeffrey M. , Harbor David J. , Galli Claudia I. , O'Sullivan Paul
Published: October 2018

The style, tempo, and timing of orogenic plateaus such as the Altiplano‐Puna in South America are actively debated. Foreland basin strata in northwestern Argentina preserve a record of the eastward propagation, uplift, and erosion of the eastern margin of the high topography of the Puna plateau and Eastern Cordillera. Herein, we present new sedimentologic and geochronologic data from the Neogene foreland basin strata and modern fluvial sediments at 23°S to reveal the timing of growth and erosion of the modern plateau margin. Traditional sedimentologic approaches, including conglomeratic clast counts and sandstone point‐counts, combined with detrital zircon U‐Pb age distributions preserve robust signatures that track changes in sediment provenance over the past 12 Ma. Growth of the modern plateau edge commenced between 12 and 7 Ma and erected a topographic barrier that cut off the supply of sediment from more westerly sources. Erosion of this rising block has progressively dissected a cover of early Paleozoic sediments of the Mesón and Santa Victoria Groups, leading to deep incision into the pre‐Cambrian metasediments of the Puncoviscana Formation that continues today. Detrital apatite and zircon fission track data from the both the Neogene strata and modern streams document erosion of the frontal block at a rate of about 0.6 mm/a.
Seasonal Evolution of Stratosphere‐Troposphere Coupling in the Southern Hemisphere and Implications for the Predictability of Surface Climate
Authors: Lim E.‐P. , Hendon H. H. , Thompson D. W. J.
Published: October 2018

Stratosphere‐troposphere coupling in the Southern Hemisphere (SH) polar vortex is an important dynamical process that provides predictability of the tropospheric Southern Annular Mode (SAM) and its associated surface impacts. SH stratosphere‐troposphere coupling is explored by height‐time domain empirical orthogonal function (EOF) analysis applied to the zonal mean‐zonal wind anomalies averaged over the Antarctic circumpolar region (55–65°S; U55–65°S). The leading EOF explains 42% of the height‐time variance of U55–65°S and depicts the variations of the vortex that is tightly tied to the seasonal breakdown of the vortex during late spring. The leading EOF pattern, defined here as the stratosphere‐troposphere coupled mode, is characterized by variations in U55–65°S that develop in early winter near the stratopause, change sign from late winter to early spring, gain maximum amplitude during October in the upper stratosphere, and then extend downward to the surface from October to January. This stratosphere‐troposphere coupling during the spring months appears to be preconditioned by anomalies in upward propagating planetary wave activity and a meridional shift of the vortex as high as the stratopause and as early as June. Interannual variations of the stratosphere‐troposphere coupled mode are highly correlated with those of the tropospheric SAM, Antarctic stratospheric ozone concentration, Antarctic sea ice concentrations in the South Pacific and the Weddell Sea, and SH regional climate during late spring–early summer. Anomalies in the upper stratospheric flow as early as June are thus a potentially important source of predictability for the tropospheric SAM and its associated impacts on surface climate in spring and summer.
Smoking and the Risk of Non-Alcoholic Fatty Liver Disease: A Cohort Study
Authors: Jung Hyun-Suk , Chang Yoosoo , Kwon Min-Jung , Sung Eunju , Yun Kyung Eun , Cho Yong Kyun , Shin Hocheol , Ryu Seungho
Published: October 2018

OBJECTIVES:

The role of smoking in the development of non-alcoholic fatty liver disease (NAFLD) remains controversial. We assessed the risk of incident NAFLD according to smoking status and urinary cotinine levels.

METHODS:

We performed a cohort study of 199,468 Korean adults without NAFLD at baseline who were followed annually or biennially for a median of 4.1 years. The presence of fatty liver was determined using ultrasound. NAFLD severity was assessed using NAFLD fibrosis score (NFS), a non-invasive fibrosis marker.

RESULTS:

During 1,070,991 person-years of follow-up, 45,409 participants developed NAFLD. Self-reported current smoking, pack-years, and urinary cotinine level were significantly associated with increased risk for NAFLD. For men, the multivariable-adjusted hazard ratios (aHR) (95% confidence intervals (CI)) for incident NAFLD comparing 10–19.9, and ≥20 pack-years to 0 pack-years were 1.25 (1.21– 1.29), and 1.36 (1.30–1.42), respectively; for women, aHR (95% CI) for NAFLD comparing 5–9.9, and ≥10 pack-years to 0 pack-years were 1.25 (1.04–1.50), and 1.46 (1.17–1.81), respectively. Smoking pack-years were also associated with increased risk for NAFLD plus intermediate or high fibrosis score. For men, the aHR (95% CI) for NAFLD plus intermediate or high NFS comparing ≥20 pack-years to 0 pack-years was 1.29 (1.18–1.42); for women, the aHR (95% CI) comparing ≥10 pack-years to 0 pack-years was 1.75 (1.12–2.73).

CONCLUSIONS:

In a large cohort of young and middle-aged men and women, current smoking, pack-years, and urinary cotinine levels were positively associated with the risk of incident NAFLD, suggesting that smoking contributes to the development of NAFLD.
Phylogenetic imprint of woody plants on the soil mycobiome in natural mountain forests of eastern China
Authors: Yang Teng , Tedersoo Leho , Soltis Pamela S , Soltis Douglas E , Gilbert Jack A , Sun Miao , Shi Yu , Wang Hongfei , Li Yuntao , Zhang Jian , Chen Zhiduan , Lin Hanyang , Zhao Yunpeng , Fu Chengxin , Chu Haiyan
Published: October 2018

Recent studies have detected strong phylogenetic signals in tree–fungus associations for diseased leaves and mycorrhizal symbioses. However, the extent of plant phylogenetic constraints on the free-living soil mycobiome remains unknown, especially at broad geographic scales. Here, 343 soil samples were collected adjacent to individual tree trunks, representing 58 woody plant species located in five mountain forests of eastern China. Integrating plant species identity and phylogenetic information, we aimed to unravel the relative contributions of phylogenetic relationships among tree species, abiotic environmental filtering, and geographic isolation to the geographic distribution of soil mycobiome. We found that the community dissimilarities of total fungi and each dominant guild (viz. saprotrophs, plant pathogens, and ectomycorrhizal fungi) significantly increased with increasing plant phylogenetic distance. Plant phylogenetic eigenvectors explained 11.4% of the variation in community composition, whereas environmental and spatial factors explained 24.1% and 7.2% of the variation, respectively. The communities of ectomycorrhizal fungi and plant pathogens were relatively more strongly affected by plant phylogeny than those of saprotrophs (13.7% and 10.4% vs. 8.5%). Overall, our results demonstrate how plant phylogeny, environment, and geographic space contribute to forest soil fungal distributions and suggest that the influence of plant phylogeny on fungal association may differ by guilds.
Achieving a multi-strain symbiosis: strain behavior and infection dynamics
Authors: Bongrand Clotilde , Ruby Edward G
Published: October 2018

Strain diversity, while now recognized as a key driver underlying partner dynamics in symbioses, is usually difficult to experimentally manipulate and image in hosts with complex microbiota. To address this problem, we have used the luminous marine bacterium Vibrio fischeri, which establishes a symbiosis within the crypts of the nascent light organ of the squid Euprymna scolopes. Competition assays in newly hatched juvenile squid have shown that symbiotic V. fischeri are either niche-sharing “S strains”, which share the light organ when co-inoculated with other S strains, or niche-dominant “D strains”, which are typically found alone in the light organ after a co-colonization. To understand this D strain advantage, we determined the minimum time that different V. fischeri strains needed to initiate colonization and used confocal microscopy to localize the symbionts along their infection track. Further, we determined whether symbiont-induced host morphogenic events also occurred earlier during a D strain colonization. We conclude that D strains colonized more quickly than S strains. Nevertheless, light-organ populations in field-caught adult squid often contain both D and S strains. We determined experimentally that this symbiont population heterogeneity might be achieved in nature by a serial encounter of different strains in the environment.
Music improves social communication and auditory–motor connectivity in children with autism
Authors: Sharda Megha , Tuerk Carola , Chowdhury Rakhee , Jamey Kevin , Foster Nicholas , Custo-Blanch Melanie , Tan Melissa , Nadig Aparna , Hyde Krista
Published: October 2018

Music has been identified as a strength in people with Autism Spectrum Disorder; however, there is currently no neuroscientific evidence supporting its benefits. Given its universal appeal, intrinsic reward value and ability to modify brain and behaviour, music may be a potential therapeutic aid in autism. Here we evaluated the neurobehavioural outcomes of a music intervention, compared to a non-music control intervention, on social communication and brain connectivity in school-age children (ISRCTN26821793). Fifty-one children aged 6–12 years with autism were randomized to receive 8–12 weeks of music (n = 26) or non-music intervention (n = 25). The music intervention involved use of improvisational approaches through song and rhythm to target social communication. The non-music control was a structurally matched behavioural intervention implemented in a non-musical context. Groups were assessed before and after intervention on social communication and resting-state functional connectivity of fronto-temporal brain networks. Communication scores were higher in the music group post-intervention (difference score = 4.84, P = .01). Associated post-intervention resting-state brain functional connectivity was greater in music vs. non-music groups between auditory and subcortical regions (z = 3.94, P < .0001) and auditory and fronto-motor regions (z = 3.16, P < .0001). Post-intervention brain connectivity was lower between auditory and visual regions in the music compared to the non-music groups, known to be over-connected in autism (z = 4.01, P < .00001). Post-intervention brain connectivity in the music group was related to communication improvement (z = 3.57, P < .0001). This study provides the first evidence that 8–12 weeks of individual music intervention can indeed improve social communication and functional brain connectivity, lending support to further investigations of neurobiologically motivated models of music interventions in autism.
Nimbolide, a neem limonoid inhibits cytoprotective autophagy to activate apoptosis via modulation of the PI3K/Akt/GSK-3β signalling pathway in oral cancer
Authors: Sophia Josephraj , Kowshik Jaganathan , Dwivedi Anju , Bhutia Sujit K , Manavathi Bramanandam , Mishra Rajakishore , Nagini Siddavaram
Published: October 2018

Of late, nimbolide, a limonoid from the neem tree (Azadirachta indica) has gained increasing research attention owing to its potent antiproliferative and apoptosis-inducing effects. The present study was designed to investigate the effect of nimbolide on autophagy and the time point at which the phosphorylation status of GSK-3β and PI3K dictate the choice between autophagy and apoptosis in SCC131 and SCC4 oral cancer cells. Additionally, we analysed changes in the expression of proteins involved in autophagy and apoptosis after therapeutic intervention with nimbolide in a hamster model of oral oncogenesis. Furthermore, we also demonstrate changes in the expression of key genes involved in apoptosis and autophagy during the stepwise evolution of hamster and human OSCCs. Nimbolide-induced stereotypical changes in oral cancer cells characteristic of both apoptosis and autophagy. Time-course experiments revealed that nimbolide induces autophagy as an early event and then switches over to apoptosis. Nimbolide negatively regulates PI3K/Akt signalling with consequent increase in p-GSK-3βTyr216, the active form of GSK-3β that inhibits autophagy. Downregulation of HOTAIR, a competing endogenous RNA that sponges miR-126 may be a major contributor to the inactivation of PI3K/Akt/GSK3 signalling by nimbolide. Analysis of key markers of apoptosis and autophagy as well as p-AktSer473 during sequential progression of hamster and human OSCC revealed a gradual evolution to a pro-autophagic and antiapoptotic phenotype that could confer a survival advantage to tumors. In summary, the results of the present study provide insights into the molecular mechanisms by which nimbolide augments apoptosis by overcoming the shielding effects of cytoprotective autophagy through modulation of the phosphorylation status of Akt and GSK-3β as well as the ncRNAs miR-126 and HOTAIR. Development of phytochemicals such as nimbolide that target the complex interaction between proteins and ncRNAs that regulate the autophagy/apoptosis flux is of paramount importance in cancer prevention and therapeutics.
Seeded X-ray free-electron laser generating radiation with laser statistical properties
Authors: Gorobtsov Oleg Yu. , Mercurio Giuseppe , Capotondi Flavio , Skopintsev Petr , Lazarev Sergey , Zaluzhnyy Ivan A. , Danailov Miltcho B. , Dell’Angela Martina , Manfredda Michele , Pedersoli Emanuele , Giannessi Luca , Kiskinova Maya , Prince Kevin C. , Wurth Wilfried , Vartanyants Ivan A.
Published: October 2018

The invention of optical lasers led to a revolution in the field of optics and to the creation of such fields of research as quantum optics. The reason was their unique statistical and coherence properties. The emerging, short-wavelength free-electron lasers (FELs) are sources of very bright coherent extreme-ultraviolet and X-ray radiation with pulse durations on the order of femtoseconds, and are presently considered to be laser sources at these energies. FELs are highly spatially coherent to the first-order but in spite of their name, behave statistically as chaotic sources. Here, we demonstrate experimentally, by combining Hanbury Brown and Twiss interferometry with spectral measurements that the seeded XUV FERMI FEL-2 source does indeed behave statistically as a laser. The results may be useful for quantum optics experiments and for the design and operation of next generation FEL sources.
Pressure-induced emission of cesium lead halide perovskite nanocrystals
Authors: Ma Zhiwei , Liu Zhun , Lu Siyu , Wang Lingrui , Feng Xiaolei , Yang Dongwen , Wang Kai , Xiao Guanjun , Zhang Lijun , Redfern Simon A. T. , Zou Bo
Published: October 2018

Metal halide perovskites (MHPs) are of great interest for optoelectronics because of their high quantum efficiency in solar cells and light-emitting devices. However, exploring an effective strategy to further improve their optical activities remains a considerable challenge. Here, we report that nanocrystals (NCs) of the initially nonfluorescent zero-dimensional (0D) cesium lead halide perovskite Cs4PbBr6 exhibit a distinct emission under a high pressure of 3.01 GPa. Subsequently, the emission intensity of Cs4PbBr6 NCs experiences a significant increase upon further compression. Joint experimental and theoretical analyses indicate that such pressure-induced emission (PIE) may be ascribed to the enhanced optical activity and the increased binding energy of self-trapped excitons upon compression. This phenomenon is a result of the large distortion of [PbBr6]4− octahedral motifs resulting from a structural phase transition. Our findings demonstrate that high pressure can be a robust tool to boost the photoluminescence efficiency and provide insights into the relationship between the structure and optical properties of 0D MHPs under extreme conditions.
Molecular definition of group 1 innate lymphoid cells in the mouse uterus
Authors: Filipovic Iva , Chiossone Laura , Vacca Paola , Hamilton Russell S. , Ingegnere Tiziano , Doisne Jean-Marc , Hawkes Delia A. , Mingari Maria Cristina , Sharkey Andrew M. , Moretta Lorenzo , Colucci Francesco
Published: October 2018

Determining the function of uterine lymphocytes is challenging because of the dynamic changes in response to sex hormones and, during pregnancy, to the invading foetal trophoblast cells. Here we provide a genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (ILCs) at mid-gestation. Tissue-resident Eomes+CD49a+NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and have gene signatures associated with TGF-β responses and interactions with trophoblast, epithelial, endothelial, smooth muscle cells, leucocytes and extracellular matrix. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. Eomes−CD49a+ILC1s dominate before puberty, and specifically expand in second pregnancies when the expression of the memory cell marker CXCR6 is upregulated. These results identify trNK cells as the cellular hub of uterine group 1 ILCs, and mark CXCR6+ILC1s as potential memory cells of pregnancy.
IL-6 and the dysregulation of immune, bone, muscle, and metabolic homeostasis during spaceflight
Authors: Smith John Kelly
Published: October 2018

We have previously reported that exercise-related secretion of IL-6 by peripheral blood mononuclear cells is proportionate to body weight, suggesting that IL-6 is gravisensitive and that suboptimal production of this key cytokine may contribute to homeostatic dysregulations that occur during spaceflight. This review details what is known about the role of this key cytokine in innate and adaptive immunity, hematopoiesis, and in bone, muscle and metabolic homeostasis on Earth and in the microgravity of space and suggests an experimental approach to confirm or disavow the role of IL-6 in space-related dysregulations.
Molecular and Metabolic Markers of Fructose Induced Hepatic Insulin Resistance in Developing and Adult Rats are Distinct and Aegle marmelos is an Effective Modulator
Authors: Nair Jayachandran , Velpandian Thirumurthy , Das Ujjalkumar Subhash , Sharma Prateek , Nag Tapas , Mathur Sandeep R. , Mathur Rajani
Published: October 2018

The time course of pathogenesis of fructose mediated hepatic insulin resistance (HepIR) is not well-delineated and we chronicle it here from post-weaning to adulthood stages. Weaned rats were provided for either 4 or 8 weeks, i.e., upto adolescence or adulthood, chow + drinking water, chow + fructose, 15% or chow + fructose, 15% + hydroalcoholic extract of leaves of Aegle marmelos (AM-HM, 500 mg/kg/d, po) and assessed for feed intake, fructose intake, body weight, fasting blood sugar, oral glucose tolerance test, HOMA-IR, insulin tolerance test and lipid profile. Activities of enzymes (glucose-6-phosphatase, hexokinase, phosphofructokinase, aldehyde dehydrogenase), hormones (leptin, ghrelin, insulin), insulin signaling molecules (Akt-PI3k, AMPK, JNK) hallmarks of inflammation (TNF-α), angiogenesis (VEGF), hypoxia (HIF-1), lipogenesis (mTOR) and regulatory nuclear transcription factors of de novo lipogenesis and hepatic insulin resistance gene (SREBP-1, FoxO1) that together govern the hepatic fructose metabolism, were also studied. The effect of fructose-rich environment on metabolic milieu of hepatocytes was confirmed using (human hepatocellular carcinoma) HepG2 cells. Using in vitro model, fructose uptake and glucose output from isolated murine hepatocytes were measured to establish the HepIR under fructose environment and delineate the effect of AM-HM. The leaves from the plant Aegle marmelos (L) Correa were extracted, fractionated and validated for rutin content using LC-MS/MS. The rutin content of extract was quantified and correlated with oral pharmacokinetic parameters in rat. The outcomes of the study suggest that the molecular and metabolic markers of fructose induced HepIR in developing and adult rats are distinct. Further, AM-HM exerts a multi-pronged attack by raising insulin secretion, augmenting insulin action, improving downstream signaling of insulin, reducing overall requirement of insulin and modulating hepatic expression of glucose transporter (Glut2). The butanol fraction of AM-HM holds promise for future development.
Metabolic Biomarkers of Monochorionic Twins Complicated With Selective Intrauterine Growth Restriction in Cord Plasma and Placental Tissue
Authors: Wang Lianlian , Han Ting-Li , Luo Xiaofang , Li Siming , Young Tim , Chen Chang , Wen Li , Xu Ping , Zheng Yangxi , Saffery Richard , Baker Philip N. , Tong Chao , Qi Hongbo
Published: October 2018

The selective intrauterine growth restriction (sIUGR) of monochorionic diamniotic (MCDC) twins causes phenotypic growth discordance, which is correlated with metabolomic pertubations. A global, untargeted identification of the metabolic fingerprint may help elucidate the etiology of sIUGR. Umbilical cord blood and placentas collected from 15 pairs of sIUGR monochorionic twins, 24 pairs of uncomplicated twins, and 14 singletons diagnosed with intrauterine growth restriction (IUGR) were subjected to gas chromatography-mass spectrometry based metabolomic analyses. Supervised multivariate regression analysis and pathway analysis were performed to compare control twins with sIUGR twins. A generalized estimating equation (GEE) model was utilized to explore metabolic differences within sIUGR co-twins. Linear logistic regression was applied to screen metabolites that significantly differed in concentration between control twins and sIUGR twins or IUGR singletons. Umbilical cord blood demonstrated better global metabolomic separation of sIUGR and control twins compared to the placenta. Disrupted amino acid and fatty acid metabolism as well as high levels of exposure to environmental xenobiotics were associated with sIUGR. The metabolic abnormalities in MCDA twins suggested that in utero growth discordance is caused by intrauterine and extrauterine environmental factors, rather than genetics. Thus, this study provides new therapeutic targets and strategies for sIUGR management and prevention.
Author Correction: Immune regulation by oral tolerance induces alternate activation of macrophages and reduces markers of plaque destabilization in Apobtm2Sgy/Ldlrtm1Her/J mice
Authors: Thota Lakshmi Narasimha , Ponnusamy Thiruvelselvan , Philip Sheena , Lu Xinjie , Mundkur Lakshmi
Published: October 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper
Transcranial stimulation of the frontal lobes increases propensity of mind-wandering without changing meta-awareness
Authors: Axelrod Vadim , Zhu Xingxing , Qiu Jiang
Published: October 2018

Mind-wandering is omnipresent in our lives. The benefits of mind-wandering are not yet clear, but given how much time we spend mind-wandering, this mental function is likely to be important. Accordingly, it is essential to understand the neural and cognitive mechanisms of mind-wandering. In a recent study by the leading author of the present paper it was demonstrated that by applying transcranial direct current stimulation (tDCS) of the frontal lobes, but not sham or occipital cortex stimulation, it was possible to increase propensity of mind-wandering. The goal of the present study has been to replicate these previous findings and to extend them by examining whether changes in mind-wandering as a result of stimulation are associated with a change of meta-awareness of the attentional focus. By using a larger sample size and by conducting the experiment in a different country and language, we fully replicated the key original findings by showing that stimulation of the prefrontal cortex increased the level of mind-wandering. We also show that stimulation had no major effect on the level of meta-awareness of the attentional focus. Taken together, our results indicate that mind-wandering − probably the most internal and self-related mental function − can be modulated externally, that at least in some cases mind-wandering might not be regulated by meta-awareness, and that the frontal lobes might play a causal role in mind-wandering.
Dehydroabietic oximes halt pancreatic cancer cell growth in the G1 phase through induction of p27 and downregulation of cyclin D1
Authors: Kolsi Laura E. , Leal Ana S. , Yli-Kauhaluoma Jari , Liby Karen T. , Moreira Vânia M.
Published: October 2018

Low 5-year survival rates, increasing incidence, as well as the specific challenges of targeting pancreatic cancer, clearly support an urgent need for new multifunctional drugs for the prevention and treatment of this fatal disease. Natural products, such as abietane-type diterpenoids, are widely studied as promiscuous anticancer agents. In this study, dehydroabietic oximes were identified as potential compounds to target pancreatic cancer and cancer-related inflammation. The compounds inhibited the growth of human pancreatic cancer Aspc-1 cells with IC50 values in the low micromolar range and showed anti-inflammatory activity, measured as the inhibition of nitric oxide production, an important inflammatory mediator in the tumour microenvironment. Further studies revealed that the compounds were able to induce cancer cell differentiation and concomitantly downregulate cyclin D1 expression with upregulation of p27 levels, consistent with cell cycle arrest at the G1 phase. Moreover, a kinase profiling study showed that one of the compounds has isoform-selective, however modest, inhibitory activity on RSK2, an AGC kinase that has been implicated in cellular invasion and metastasis.
Extraordinary Mechanical Properties of Composite Silk Through Hereditable Transgenic Silkworm Expressing Recombinant Major Ampullate Spidroin
Authors: You Zhengying , Ye Xiaogang , Ye Lupeng , Qian Qiujie , Wu Meiyu , Song Jia , Che Jiaqian , Zhong Boxiong
Published: October 2018

Spider dragline silk is a remarkable material that shows excellent mechanical properties, diverse applications, biocompatibility and biodegradability. Transgenic silkworm technology was used to obtain four types of chimeric silkworm/spider (termed composite) silk fibres, including different lengths of recombinant Major ampullate Spidroin1 (re-MaSp1) or recombinant Major ampullate Spidroin2 (re-MaSp2) from the black widow spider, Latrodectus hesperus. The results showed that the overall mechanical properties of composite silk fibres improved as the re-MaSp1 chain length increased, and there were significant linear relationships between the mechanical properties and the re-MaSp1 chain length (p < 0.01). Additionally, a stronger tensile strength was observed for the composite silk fibres that included re-MaSp1, which only contained one type of repetitive motif, (GA)n/An, to provide tensile strength, compared with the silk fibres that includedre-MaSp2, which has the same protein chain length as re-MaSp1 but contains multiple types of repetitive motifs, GPGXX and (GA)n/An. Therefore, the results indicated that the nature of various repetitive motifs in the primary structure played an important role in imparting excellent mechanical properties to the protein-based silk fibres. A silk protein with a single type of repetitive motif and sufficiently long chains was determined to be an additional indispensable factor. Thus, this study forms a foundation for designing and optimizing the structure of re-silk protein using a heterologous expression system.
Lipopolysaccharide shock reveals the immune function of indoleamine 2,3-dioxygenase 2 through the regulation of IL-6/stat3 signalling
Authors: Yamamoto Yasuko , Yamasuge Wakana , Imai Shinjiro , Kunisawa Kazuo , Hoshi Masato , Fujigaki Hidetsugu , Mouri Akihiro , Nabeshima Toshitaka , Saito Kuniaki
Published: October 2018

Indoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified catalytic enzyme in the tryptophan-kynurenine pathway that is expressed primarily in monocytes and dendritic cells. To elucidate the biological role of Ido2 in immune function, we introduced lipopolysaccharide (LPS) endotoxin shock to Ido2 knockout (Ido2 KO) mice, which led to higher mortality than that in the wild type (WT) mice. LPS-treated Ido2 KO mice had increased production of inflammatory cytokines (including interleukin-6; IL-6) in serum and signal transducer and activator of transcription 3 (stat3) phosphorylation in the spleen. Moreover, the peritoneal macrophages of LPS-treated Ido2 KO mice produced more cytokines than did the WT mice. By contrast, the overexpression of Ido2 in the murine macrophage cell line (RAW) suppressed cytokine production and decreased stat3 expression. Finally, RAW cells overexpressing Ido2 did not alter nuclear factor κB (NF-κB) or stat1 expression, but IL-6 and stat3 expression decreased relative to the control cell line. These results reveal that Ido2 modulates IL-6/stat3 signalling and is induced by LPS, providing novel options for the treatment of immune disorders.
Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties
Authors: Leroux Louis-Philippe , Nasr Mohamad , Valanparambil Rajesh , Tam Mifong , Rosa Bruce A. , Siciliani Elizabeth , Hill Dolores E. , Zarlenga Dante S. , Jaramillo Maritza , Weinstock Joel V. , Geary Timothy G. , Stevenson Mary M. , Urban Joseph F. , Mitreva Makedonka , Jardim Armando
Published: October 2018

Parasitic worms have a remarkable ability to modulate host immune responses through several mechanisms including excreted/secreted proteins (ESP), yet the exact nature of these proteins and their targets often remains elusive. Here, we performed mass spectrometry analyses of ESP (TsESP) from larval and adult stages of the pig whipwormTrichuris suis(Ts) and identified ~350 proteins. Transcriptomic analyses revealed large subsets of differentially expressed genes in the various life cycle stages of the parasite. Exposure of bone marrow-derived macrophages and dendritic cells to TsESP markedly diminished secretion of the pro-inflammatory cytokines TNFα and IL-12p70. Conversely, TsESP exposure strongly induced release of the anti-inflammatory cytokine IL-10, and also induced high levels of nitric oxide (NO) and upregulated arginase activity in macrophages. Interestingly, TsESP failed to directly induce CD4+CD25+FoxP3+regulatory T cells (Tregcells), while OVA-pulsed TsESP-treated dendritic cells suppressed antigen-specific OT-II CD4+T cell proliferation. Fractionation of TsESP identified a subset of proteins that promoted anti-inflammatory functions, an activity that was recapitulated using recombinantT. suistriosephosphate isomerase (TPI) and nucleoside diphosphate kinase (NDK). Our study helps illuminate the intricate balance that is characteristic of parasite-host interactions at the immunological interface, and further establishes the principle that specific parasite-derived proteins can modulate immune cell functions.
Complex hybridization patterns in European pond turtles (Emys orbicularis) in the Pyrenean Region
Authors: Pöschel Julia , Heltai Botond , Graciá Eva , Quintana Marc Franch , Velo-Antón Guillermo , Arribas Oscar , Valdeón Aitor , Wink Michael , Fritz Uwe , Vamberger Melita
Published: October 2018

Hybrid zones are natural laboratories allowing insights in genetic processes like lineage diversification, speciation and introgression. Using large sampling, 15 microsatellite loci and a mitochondrial marker, we examined the Pyrenean contact zone of three pond turtle taxa (Emys orbicularis orbicularis,E.o.galloitalica,E.o.occidentalis). The Pyrenees are a biogeographically important region separating many lineages endemic to the Iberian Peninsula from their Western European counterparts. We discovered limited admixture, reflecting a complex biogeographic scenario. Simulations using Approximate Bayesian Computing supported thatE.o.orbicularisinvaded the Iberian Peninsula in the Holocene, circumventing the Pyrenees along the Mediterranean coast, and hybridized in the northern peninsula with the local coastal subspeciesgalloitalica, and to a lesser extent, withoccidentalis. WhileE.o.occidentalis, and in particularE.o.orbicularis, expanded their ranges considerably during Holocene warming,E.o.galloitalicaremained largely confined to its former Iberian refuge. Admixture among the three taxa is surprisingly low, and a future taxonomic investigation that includes the unstudied subspecies ofE.orbicularisfrom North Africa, Eastern Europe and Asia has to determine whether their current status properly reflects their evolutionary divergence or whether certain taxa should be regarded as full species.
Non-invasive genotyping with a massively parallel sequencing panel for the detection of SNPs in HPA-axis genes
Authors: Gutleb D. R. , Ostner J. , Schülke O. , Wajjwalku W. , Sukmak M. , Roos C. , Noll A.
Published: October 2018

We designed a genotyping panel for the investigation of the genetic underpinnings of inter-individual differences in aggression and the physiological stress response. The panel builds on single nucleotide polymorphisms (SNPs) in genes involved in the three subsystems of the hypothalamic-pituitary-adrenal (HPA)-axis: the catecholamine, serotonin and corticoid metabolism. To promote the pipeline for use with wild animal populations, we used non-invasively collected faecal samples from a wild population of Assamese macaques (Macaca assamensis). We targeted loci of 46 previously reported SNPs in 21 candidate genes coding for elements of the HPA-axis and amplified and sequenced them using next-generation Illumina sequencing technology. We compared multiple bioinformatics pipelines for variant calling and variant effect prediction. Based on this strategy and the application of different quality thresholds, we identified up to 159 SNPs with different types of predicted functional effects among our natural study population. This study provides a massively parallel sequencing panel that will facilitate integrating large-scale SNP data into behavioural and physiological studies. Such a multi-faceted approach will promote understanding of flexibility and constraints of animal behaviour and hormone physiology.
Fibroblast Growth Factor Binding Protein 3 (FGFBP3) impacts carbohydrate and lipid metabolism
Authors: Tassi Elena , Garman Khalid A. , Schmidt Marcel O. , Ma Xiaoting , Kabbara Khaled W. , Uren Aykut , Tomita York , Goetz Regina , Mohammadi Moosa , Wilcox Christopher S. , Riegel Anna T. , Carlstrom Mattias , Wellstein Anton
Published: October 2018

Secreted FGF binding proteins (FGFBP) mobilize locally-acting paracrine FGFs from their extracellular storage. Here, we report that FGFBP3 (BP3) modulates fat and glucose metabolism in mouse models of metabolic syndrome. BP3 knockout mice exhibited altered lipid metabolism pathways with reduced hepatic and serum triglycerides. In obese mice the expression of exogenous BP3 reduced hyperglycemia, hepatosteatosis and weight gain, blunted de novo lipogenesis in liver and adipose tissues, increased circulating adiponectin and decreased NEFA. The BP3 protein interacts with endocrine FGFs through its C-terminus and thus enhances their signaling. We propose that BP3 may constitute a new therapeutic to reverse the pathology associated with metabolic syndrome that includes nonalcoholic fatty liver disease and type 2 diabetes mellitus.
Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson’s disease
Authors: Jeong Jin Seok , Piao Ying , Kang Sora , Son Minuk , Kang Young Cheol , Du Xiao Fei , Ryu Jayoung , Cho Young Woong , Jiang Hai-Hua , Oh Myung Sook , Hong Seon-Pyo , Oh Young J. , Pak Youngmi Kim
Published: October 2018

Moutan cortex, Angelica Dahurica root, and Bupleurum root are traditional herbal medicines used in Asian countries to treat various diseases caused by oxidative stress or inflammation. Parkinson’s disease (PD) has been associated with mitochondrial dysfunction, but no effective treatment for mitochondrial dysfunction has yet been identified. In this study we investigated the neuroprotective effects of the triple herbal extract DA-9805 in experimental models of PD. DA-9805 was prepared by extracting three dried plant materials (Moutan cortex, Angelica Dahurica root, and Bupleurum root in a 1:1:1 mixture) with 90% ethanol on a stirring plate for 24 h at room temperature and fingerprinted using high-performance liquid chromatography. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), which both exert neurotoxic effects on dopaminergic neurons by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) complex I, were used to make experimental models of PD. In MPP+-treated SH-SY5Y cells, DA-9805 ameliorated the suppression of tyrosine hydroxylase expression and mitochondrial damage on OXPHOS complex 1 activity, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and oxygen consumption rate. In the MPTP-induced subacute PD model mice, oral administration of DA-9805 recovered dopamine content as well as bradykinesia, as determined by the rotarod test. DA-9805 protected against neuronal damage in the substantia nigra pars compacta (SNpc) and striatum. In both in vitro and in vivo models of PD, DA-9805 normalized the phosphorylation of AKT at S473 and T308 on the insulin signaling pathway and the expression of mitochondria-related genes. These results demonstrate that the triple herbal extract DA-9805 showed neuroprotective effects via alleviating mitochondria damage in experimental models of PD. We propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics for PD.
A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism
Authors: Mahaweni Niken M. , Olieslagers Timo I. , Rivas Ivan Olivares , Molenbroeck Stefan J. J. , Groeneweg Mathijs , Bos Gerard M. J. , Tilanus Marcel G. J. , Voorter Christina E. M. , Wieten Lotte
Published: October 2018

TheFCGR3Agene encodes for the receptor important for antibody-dependent natural killer cell-mediated cytotoxicity.FCGR3Agene polymorphisms could affect the success of monoclonal antibody therapy. Although polymorphisms, such as the FcγRIIIA-V158F and -48L/R/H, have been studied extensively, an overview of other polymorphisms within this gene is lacking. To provide an overview ofFCGR3Apolymorphisms, we analysed the 1000 Genomes project database and found a total of 234 polymorphisms within theFCGR3Agene, of which 69%, 16%, and 15% occur in the intron, UTR, and exon regions respectively. Additionally, only 16% of all polymorphisms had a minor allele frequency (MAF) > 0.01. To facilitate (full-length) analysis ofFCGR3Agene polymorphism, we developed aFCGR3Agene-specific amplification and sequencing protocol for Sanger sequencing and MinION (Nanopore Technologies). First, we used the Sanger sequencing protocol to study the presence of the V158F polymorphism in 76 individuals resulting in frequencies of 38% homozygous T/T, 7% homozygous G/G and 55% heterozygous. Next, we performed a pilot with both Sanger sequencing and MinION based sequencing of 14 DNA samples which showed a good concordance between Sanger- and MinION sequencing. Additionally, we detected 13 SNPs listed in the 1000 Genome Project, from which 11 had MAF > 0.01, and 10 SNPs were not listed in 1000 Genome Project. In summary, we demonstrated thatFCGR3Agene is more polymorphic than previously described. As most novel polymorphisms are located in non-coding regions, their functional relevance needs to be studied in future functional studies.
Deep sequencing and miRNA profiles in alcohol-induced neuroinflammation and the TLR4 response in mice cerebral cortex
Authors: Ureña-Peralta J. R. , Alfonso-Loeches S. , Cuesta-Diaz C. M. , García-García F. , Guerri C.
Published: October 2018

Alcohol abuse can induce brain injury and neurodegeneration, and recent evidence shows the participation of immune receptors toll-like in the neuroinflammation and brain damage. We evaluated the role of miRNAs as potential modulators of the neuroinflammation associated with alcohol abuse and the influence of the TLR4 response. Using mice cerebral cortex and next-generation sequencing (NGS), we identified miRNAs that were differentially expressed in the chronic alcohol-treated versus untreated WT or TLR4-KO mice. We observed a differentially expression of miR-183 Cluster (C) (miR-96/-182/-183), miR-200a and miR-200b, which were down-regulated, while mirR-125b was up-regulated in alcohol-treated WT versus (vs.) untreated mice. These miRNAs modulate targets genes related to the voltage-gated sodium channel, neuron hyperexcitability (Nav1.3, Trpv1, Smad3 and PP1-γ), as well as genes associated with innate immune TLR4 signaling response (Il1r1, Mapk14, Sirt1, Lrp6 and Bdnf). Functional enrichment of the miR-183C and miR-200a/b family target genes, revealed neuroinflammatory pathways networks involved in TLR4 signaling and alcohol abuse. The changes in the neuroinflammatory targets genes associated with alcohol abuse were mostly abolished in the TLR4-KO mice. Our results show the relationship between alcohol intake and miRNAs expression and open up new therapeutically targets to prevent deleterious effects of alcohol on the brain.