bluuebunny/crossref_metadata_2025 huggingface dataset:
The Multilingual Naming Test (MINT) as a Measure of Picture Naming Ability in Alzheimer’s Disease
Authors: Stasenko Alena , Jacobs Diane M. , Salmon David P. , Gollan Tamar H.
Published: June 2019

Objective:

The present study investigated the ability of the Multilingual Naming Test (MINT), a picture naming test recently added to the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set neuropsychological test battery, to detect naming impairment (i.e., dysnomia) across stages of Alzheimer’s disease (AD).

Method:

Data from the initial administration of the MINT were obtained on NACC participants who were cognitively normal (N= 3,981) or diagnosed with mild cognitive impairment (N= 852) or dementia (N= 1,148) with presumed etiology of AD. Dementia severity was rated using the Clinical Dementia Rating (CDR) scale.

Results:

Cross-sectional multiple regression analyses revealed significant effects of diagnostic group, sex, education, age, and race on naming scores. Planned comparisons collapsing across age and education groups revealed significant group differences in naming scores across levels of dementia severity. ROC curve analyses showed good diagnostic accuracy of MINT scores for distinguishing cognitively normal controls from AD dementia, but not from MCI. Within the cognitively normal group, there was a robust interaction between age and education such that naming scores exhibited the most precipitous drop across age groups for the least educated participants. Additionally, education effects were stronger in African-Americans than in Whites (a race-by-education interaction), and race effects were stronger in older than in younger age groups (a race-by-age interaction).

Conclusions:

The MINT successfully detects naming deficits at different levels of cognitive impairment in patients with MCI or AD dementia, but comparison to age, sex, race, and education-corrected norms to determine impairment is essential.
Economics of climate change: introducing the Basic Climate Economic (BCE) model
Authors: Bretschger Lucas , Karydas Christos
Published: June 2019

Environmental economics models are often too complex to be communicated in an illustrative manner. For this reason, this paper develops the Basic Climate Economic (BCE) model that features core elements of macroeconomic and climate economic modelling, while allowing for an illustrative examination of the development path. The BCE model incorporates fossil stock depletion, pollution stock accumulation, endogenous growth, and climate-induced capital depreciation. We first use graphical analysis to show the effects of climate change and climate policy on economic development. Intuition for the different model mechanisms, the functional forms, and the effects of different climate policies is provided. We then show the model equations in mathematical terms to derive closed-form solutions and to run model simulations relating to the graphical part. Finally, we compare our setup to other models of climate economics.
How Intelligence Affects Fertility 30 Years On: Retherford and Sewell Revisited — With Polygenic Scores and Numbers of Grandchildren
Authors: Woodley of Menie Michael A. , Rindermann Heiner , Pallesen Jonatan , Sarraf Matthew A.
Published: June 2019

Using newly available polygenic scores for educational attainment and cognitive ability, this paper investigates the possible presence and causes of a negative association between IQ and fertility in the Wisconsin Longitudinal Study sample, an issue that Retherford and Sewell first addressed 30 years ago. The effect of the polygenic score on the sample’s reproductive characteristics was indirect: a latent cognitive ability measure, comprised of both educational attainment and IQ, wholly mediated the relationship. Age at first birth mediated the negative effect of cognitive ability on sample fertility, which had a direct (positive) effect on the number of grandchildren. Significantly greater impacts of cognitive ability on the sample’s fertility characteristics were found among the female subsample. This indicates that, in this sample, having a genetic disposition toward higher cognitive ability does not directly reduce number of offspring; instead, higher cognitive ability is a risk factor for prolonging reproductive debut, which, especially for women, reduces the fertility window and, thus, the number of children and grandchildren that can be produced. By estimating the effect of the sample’s reproductive characteristics on the strength of polygenic selection, it was found that the genetic variance component of IQ should be declining at a rate between −.208 (95% CI [−.020, −.383]) and −.424 (95% CI [−.041, −.766]) points per decade, depending on whether GCTA-GREML or classical behavior genetic estimates of IQ heritability are used to correct for ‘missing’ heritability.
Genetic Contributions to Health Literacy
Authors: Fawns-Ritchie Chloe , Davies Gail , Hagenaars Saskia P. , Deary Ian J.
Published: June 2019

Higher health literacy is associated with higher cognitive function and better health. Despite its wide use in medical research, no study has investigated the genetic contributions to health literacy. Using 5783 English Longitudinal Study of Ageing (ELSA) participants (mean age = 65.49,SD= 9.55) who had genotyping data and had completed a health literacy test at wave 2 (2004–2005), we carried out a genome-wide association study (GWAS) of health literacy. We estimated the proportion of variance in health literacy explained by all common single nucleotide polymorphisms (SNPs). Polygenic profile scores were calculated using summary statistics from GWAS of 21 cognitive and health measures. Logistic regression was used to test whether polygenic scores for cognitive and health-related traits were associated with having adequate, compared to limited, health literacy. No SNPs achieved genome-wide significance for association with health literacy. The proportion of variance in health literacy accounted for by common SNPs was 8.5% (SE= 7.2%). Greater odds of having adequate health literacy were associated with a 1 standard deviation higher polygenic score for general cognitive ability [OR= 1.34, 95% CI (1.26, 1.42)], verbal-numerical reasoning [OR= 1.30, 95% CI (1.23, 1.39)], and years of schooling [OR= 1.29, 95% CI (1.21, 1.36)]. Reduced odds of having adequate health literacy were associated with higher polygenic profiles for poorer self-rated health [OR= 0.92, 95% CI (0.87, 0.98)] and schizophrenia [OR= 0.91, 95% CI (0.85, 0.96)). The well-documented associations between health literacy, cognitive function and health may partly be due to shared genetic etiology. Larger studies are required to obtain accurate estimates of SNP-based heritability and to discover specific health literacy-associated genetic variants.
Single‐Site IPS Power Spectra Analysis for Space Weather Products Using Cross‐Correlation Function Results From EISCAT and MERLIN IPS Data
Authors: Chang O. , Bisi M. M. , Aguilar‐Rodriguez E. , Fallows R. A. , Gonzalez‐Esparza J. A. , Chashei I. , Tyul'bashev S.
Published: June 2019

Interplanetary scintillation (IPS) manifests itself as a variation in the radio signal received from a distant, compact radio source on the sky. The intensity fluctuations of the radio waves are caused by density inhomogeneities in the outflowing solar plasma across the heliosphere. IPS allows us to infer solar wind speed and density variations along the line of sight. There are two types of techniques in the literature to infer solar wind speed using IPS data sets: single‐site analysis (SSA), where the power spectra from single time series are analyzed to obtain solar wind parameters, and multisite analysis, where the cross‐correlation function of data from two or more widely separated sites is used. The selection of the analysis technique depends on the number of sites available to each IPS system. In order to combine and complement solar wind speed determinations from different instruments, it is important to validate results and methodologies of the two techniques. In this paper, we analyzed previously well‐studied European Incoherent SCATter (EISCAT) and Multi‐Element Radio‐Linked Interferometer Network (MERLIN) observations of IPS with well‐known results from the cross‐correlation function methodology. We applied the SSA technique to each of the individual EISCAT and MERLIN IPS power spectra. This work shows the capabilities of the SSA to describe complex events and seeks to obtain improved parameter fits using the SSA methodology.
Louise H. Kellogg (1959–2019)
Authors: Romanowicz Barbara , Billen Magali
Published: June 2019

Louise Kellogg, an influential solid Earth geodynamicist and leader of the geoscience community, passed away in April.
Whistler Waves in the Plasmasphere Boundary Layer: Nonlinear Parametric Excitation
Authors: Mishin Evgeny , Sotnikov Vladimir , Gershenzon Naum , Sharma Amit
Published: June 2019

We present the initial results of numerical simulations of nonlinear coupling between quasi‐electrostatic lower hybrid oblique resonance and fast magnetosonic waves, which was suggested to explain the observations of Very Low Frequency (VLF) electromagnetic emissions at frequencies well above the lower hybrid resonance frequency in the turbulent plasmasphere boundary layer. These emissions represent a distinctive subset of the substorm/storm‐related VLF whistler activity contributing to the alteration of the outer radiation belt boundary. As the turbulent plasmasphere boundary layer is interior to the plasma sheet inner boundary and thus devoid of substorm‐injected kiloelectron volt electrons, the “standard” whistler generation mechanism must be excluded. The simulations show that the parametric coupling of lower hybrid oblique resonance and magnetosonic waves creates VLF electromagnetic emissions with the spectral characteristics consistent with the observations.
Wave Field Propagation in Extended Highly Anisotropic Media
Authors: Rino Charles , Carrano Charles , Groves Keith
Published: June 2019

The theory propagation in the Earth's ionosphere is well established. However, with the advent of Global Navigation Satellite System measurements, new demands are being placed on satellite system performance evaluation and diagnostic measurements. Propagation simulations are essential for system performance evaluation and they provide guidelines for interpreting diagnostic measurements. This paper presents simulations of propagation in extended highly anisotropic media obtained with split‐step integration of the parabolic wave equation. This requires three‐dimensional realizations of the electron density structure. A new configuration‐space model is used to generate realizations as summations of striations, which are local to field lines with defined scales and peak densities. The scale and peak densities can be selected to generate specified power law spectral density functions. An analytic three‐dimensional expectation spectral density function provides a parameterized ionospheric structure model. The simulations results show that replacing the extended structure with an equivalent phase screen placed at the center of the structured region provides statistically equivalent realizations of observation‐plane measurements at propagation distances greater than the layer extent. The equivalence is independent of the propagation direction relative to the magnetic field direction, although there is some variation for the extreme propagation disturbances caused by field‐aligned propagation. We also investigate the interpretation of in situ and path‐integrated diagnostic measurements and two‐dimensional propagation models, which are being used to model diagnostic measurements directly.
Live imaging screen reveals that TYRO3 and GAK ensure accurate spindle positioning in human cells
Authors: Wolf Benita , Busso Coralie , Gönczy Pierre
Published: June 2019

Proper spindle positioning is crucial for spatial cell division control. Spindle positioning in human cells relies on a ternary complex comprising Gαi1–3, LGN and NuMA, which anchors dynein at the cell cortex, thus enabling pulling forces to be exerted on astral microtubules. We develop a live imaging siRNA-based screen using stereotyped fibronectin micropatterns to uncover components modulating spindle positioning in human cells, testing 1280 genes, including all kinases and phosphatases. We thus discover 16 components whose inactivation dramatically perturbs spindle positioning, including tyrosine receptor kinase 3 (TYRO3) and cyclin G associated kinase (GAK). TYRO3 depletion results in excess NuMA and dynein at the cortex during metaphase, similar to the effect of blocking the TYRO3 downstream target phosphatidylinositol 3-kinase (PI3K). Furthermore, depletion of GAK leads to impaired astral microtubules, similar to the effect of downregulating the GAK-interactor Clathrin. Overall, our work uncovers components and mechanisms governing spindle positioning in human cells.
Does splitting sleep improve long-term memory in chronically sleep deprived adolescents?
Authors: Cousins James N. , van Rijn Elaine , Ong Ju Lynn , Wong Kian F. , Chee Michael W. L.
Published: June 2019

Sleep aids the encoding and consolidation of declarative memories, but many adolescents do not obtain the recommended amount of sleep each night. After a normal night of sleep, there is abundant evidence that a daytime nap enhances the consolidation of material learned before sleep and also improves the encoding of new information upon waking. However, it remains unclear how learning is affected when sleep is split between nocturnal and daytime nap periods during a typical school week of restricted sleep. We compared long-term memory in 58 adolescents who underwent two simulated school weeks of suboptimal continuous (6.5 h nocturnal sleep opportunity) or split sleep (5 h nocturnal sleep +1.5 h daytime nap at 14:00). In the first week, participants encoded pictures in the late afternoon on Day 5 and were tested after 2-nights of recovery sleep. On 3 consecutive days in the second week, participants learned about six species of amphibians in the morning, and six different amphibians in the late afternoon. Testing was performed in the evening following a night of recovery sleep. In the first week, the split sleep group recognized more pictures. In the second week, they remembered more facts about species learned in the afternoon. Groups did not differ for species learned in the morning. This suggests that under conditions of sleep restriction, a split sleep schedule benefits learning after a nap opportunity without impairing morning learning, despite less preceding nocturnal sleep. While not replacing adequate nocturnal sleep, a split sleep schedule may be beneficial for chronically sleep restricted learners.
Rational design using sequence information only produces a peptide that binds to the intrinsically disordered region of p53
Authors: Kamagata Kiyoto , Mano Eriko , Itoh Yuji , Wakamoto Takuro , Kitahara Ryo , Kanbayashi Saori , Takahashi Hiroto , Murata Agato , Kameda Tomoshi
Published: June 2019

Intrinsically disordered regions (IDRs) of proteins are involved in many diseases. The rational drug design against disease-mediating proteins is often based on the 3D structure; however, the flexible structure of IDRs hinders the use of such structure-based design methods. Here, we developed a rational design method to obtain a peptide that can bind an IDR using only sequence information based on the statistical contact energy of amino acid pairs. We applied the method to the disordered C-terminal domain of the tumor suppressor p53. Titration experiments revealed that one of the designed peptides, DP6, has a druggable affinity of ~1 μM to the p53 C-terminal domain. NMR spectroscopy and molecular dynamics simulation revealed that DP6 selectively binds to the vicinity of the target sequence in the C-terminal domain of p53. DP6 inhibits the nonspecific DNA binding of a tetrameric form of the p53 C-terminal domain, but does not significantly affect the specific DNA binding of a tetrameric form of the p53 core domain. Single-molecule measurements revealed that DP6 retards the 1D sliding of p53 along DNA, implying modulation of the target searching of p53. Statistical potential-based design may be useful in designing peptides that target IDRs for therapeutic purposes.
Accelerated diversifications in three diverse families of morphologically complex lichen-forming fungi link to major historical events
Authors: Huang Jen-Pan , Kraichak Ekaphan , Leavitt Steven D. , Nelsen Matthew P. , Lumbsch H. Thorsten
Published: June 2019

Historical mass extinction events had major impacts on biodiversity patterns. The most recent and intensively studied event is the Cretaceous – Paleogene (K-Pg) boundary (ca. 66 million years ago [MYA]). However, the factors that may have impacted diversification dynamics vary across lineages. We investigated the macroevolutionary dynamics with a specific focus on the impact of major historical events such as the K-Pg mass extinction event on two major subclasses – Lecanoromycetidae and Ostropomycetidae – of lichen-forming fungi and tested whether variation in the rate of diversification can be associated with the evolution of a specific trait state - macrolichen. Our results reveal accelerated diversification events in three families of morphologically complex lichen-forming fungi – Cladoniaceae, Parmeliaceae, and Peltigeraceae – which are from the subclass Lecanoromycetidae and mostly composed of macrolichens, those that form three dimensional structures. Our RTT plot result for the subclass Lecanoromycetidae also reveals accelerated diversification. Changes in diversification rates occurred around the transition between Mesozoic and Cenozoic eras and was likely related to the K-Pg mass extinction event. The phylogenetic positions for rate increases estimated based on marginal shift probability are, however, scattered from 100 to 40 MYA preventing us from making explicit inference. Although we reveal that the phenotypic state of macrolichens is associated with a higher diversification rate than microlichens, we also show that the evolution of macrolichens predated the K-Pg event. Furthermore, the association between macrolichens and increased diversification is not universal and can be explained, in part, by phylogenetic relatedness. By investigating the macroevolutionary dynamics of lichen-forming fungi our study provides a new empirical system suitable to test the effect of major historical event on shaping biodiversity patterns and to investigate why changes in biodiversity patterns are not in concordance across clades. Our results imply that multiple historical events during the transition from Mesozoic to Cenozoic eras, including the K-Pg mass extinction event, impacted the evolutionary dynamics in lichen-forming fungi. However, future studies focusing on individual lichen-forming fungal families are required to ascertain whether diversification rates are associated with growth form and certain geological events.
Hypergravity disrupts murine intestinal microbiota
Authors: Alauzet Corentine , Cunat Lisiane , Wack Maxime , Lozniewski Alain , Busby Hélène , Agrinier Nelly , Cailliez-Grimal Catherine , Frippiat Jean-Pol
Published: June 2019

During spaceflight, organisms are subjected to various physical stressors including modification of gravity (G) that, associated with lifestyle, could lead to impaired immunity, intestinal dysbiosis and thus potentially predispose astronauts to illness. Whether space travel affects microbiota homeostasis has not been thoroughly investigated. The aim of this study was to evaluate changes in intestinal microbiota and mucosa in a ground-based murine model consisting in a 21-days confinement of mice in a centrifuge running at 2 or 3G. Results revealed an increased α-diversity and a significant change in intracaecal β-diversity observed only at 3G, with profiles characterized by a decrease of theFirmicutes/Bacteroidetesratio. Compared to 1G microbiota, 12.1% of the taxa were significantly impacted in 3G microbiota, most of them (78%) being enriched. This study shows a G-level-dependent disruption of intracaecal microbiota, without alteration of mucosal integrity. These first data reinforce those recently obtained with in-flight experimentations or microgravity models, and emphasize the critical need for further studies exploring the impact of spaceflight on intestinal microbiota in order to optimize long-term space travel conditions.
Macrophage migration inhibitory factor regulates TLR4 expression and modulates TCR/CD3-mediated activation in CD4+ T lymphocytes
Authors: Alibashe-Ahmed Mohamed , Roger Thierry , Serre-Beinier Veronique , Berishvili Ekaterine , Reith Walter , Bosco Domenico , Berney Thierry
Published: June 2019

Toll-like receptor 4 (TLR4) is involved in CD4+ T lymphocyte-mediated pathologies. Here, we demonstrate that CD4+ T lymphocytes express functional TLR4 that contributes to their activation, proliferation and cytokine secretion. In addition, we demonstrate that TLR4-induced responses are mediated by macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine. We also demonstrate that MIF regulates suboptimal TCR/CD3-mediated activation of T lymphocytes. On one hand, MIF prevents excessive TCR/CD3-mediated activation of CD4+ T lymphocytes under suboptimal stimulation conditions and, on the other hand, MIF enables activated CD4+ T lymphocytes to sense their microenvironment and adapt their effector response through TLR4. Therefore, MIF appears to be a major regulator of the activation of CD4+ T lymphocytes and the intensity of their effector response. TLR4-mediated activation is thus an important process for T cell-mediated immunity.
Effect of cold provocation on vessel density in eyes with primary open angle glaucoma: An optical coherence tomography angiography study
Authors: Chou Wei-Yi , Liu Catherine Jui-Ling , Chen Mei-Ju , Chiou Shih-Hwa , Chen Wei-Ta , Ko Yu-Chieh
Published: June 2019

The cold pressor test (CPT) induces a cardiovascular response, which may affect ocular blood flow and neuronal function. This study assessed whether optical coherence tomography angiography (OCT-A) can be used to evaluate CPT-induced changes in healthy eyes and in eyes with primary open-angle glaucoma (POAG). Twenty-two healthy subjects and 23 subjects with POAG and retinal fibre layer defects in only one hemifield were included in this study. The CPT was performed by submerging a subject’s hand in cold water (0–4 °C) for 1 minute. The results showed that baseline peripapillary and macular vessel density (VD) measurements were significantly lower in subjects with POAG than in controls (all P < 0.05). Post-CPT VD measurements did not significantly differ from baseline in either healthy or glaucomatous eyes. Additionally, CPT-induced changes in VD did not differ among normal eyes, damaged and undamaged glaucomatous hemifields. Changes in VD were also not significantly influenced by self-reported history of cold extremities. In conclusion, the CPT does not induce significant VD changes, as measured by OCT-A, in the peripapillary or macular areas of either healthy eyes or eyes with POAG. The VD, an all-or-nothing flow measure, may not be sensitive enough for evaluating cold-induced ocular haemodynamic changes.
Modulation of viscoelastic fluid response to external body force
Authors: Zhang Meng , Zhang Wu , Wu Zhengwei , Shen Yinan , Wu Huayin , Cheng Jianping , Zhang Hongna , Li Fengchen , Cai Weihua
Published: June 2019

Transient flow responses of viscoelastic fluids to different external body forces are studied. As a non-Newtonian fluid, the viscoelastic fluid exhibits significant elastic response which does not raise in Newtonian fluid. Here, we investigate the transient response of a viscoelastic Poiseuille flow in a two-dimensional channel driven by external body forces in different forms. The velocity response is derived using the Oldroyd-B constitutive model in OpenFOAM. Responses in various forms like damped harmonic oscillation and periodic oscillation are induced and modulated depending on the fluid intrinsic properties like the viscosity and the elasticity. The external body forces like constant force, step force and square wave force are applied at the inlet of the channel. Through both time domain and frequency domain analysis on the fluid velocity response, it is revealed that the oscillation damping originates from the fluid viscosity while the oscillation frequency is dependent on the fluid elasticity. The velocity response of the applied square waves with different periods shows more flexible modulation signal types than constant force and step force. An innovative way is also developed to characterize the relaxation time of the viscoelastic fluid by modulating the frequency of the square wave force.
Circulatory miR-223-3p Discriminates Between Parkinson’s and Alzheimer’s Patients
Authors: Mancuso Roberta , Agostini Simone , Hernis Ambra , Zanzottera Milena , Bianchi Anna , Clerici Mario
Published: June 2019

MiR-223-3p is involved in the regulation of a broad range of cellular processes and in many types of pathological processes as cancer, autoimmune and inflammatory diseases. MiR-223-3p has been indicated as negative regulator of NLRP3 protein, a key protein of inflammasome. The chronic inflammasome activation, an underlying feature of neurodegenerative disorders, is induced by misfolded protein aggregates, including amyloid-beta and alpha-synuclein, resulting in pro-inflammatory cytokines secretion and propagating of neuroinflammation. The aim of the study was to analyze whether circulatory miR-223-3p could be used as biomarker in neurodegeneration and to clarify its possible relationship with inflammasome activation. miR-223-3p concentration was evaluated in serum of Alzheimer’s (AD) and Parkinson’s disease (PD) or mild cognitive impairment (MCI) patients and healthy controls (HC). Compared to HC, miR-223-3p serum concentration was reduced in MCI and AD, but up-regulated in PD (p < 0.0001), and it decreased progressively from MCI to moderate (p < 0.0001) to severe AD (p = 0.0016). Receiver operating characteristic analysis showed that miR-223-3p concentration discriminates between AD, PD and MCI vs. HC, as well as between AD and PD. miR-223-3p serum concentration discriminates between AD/MCI and PD, suggesting that this molecule could be a potential non-invasive biomarker for differential diagnosis and prognosis of these neurodegenerative conditions.
Species identification of Bombyx mori and Antheraea pernyi silk via immunology and proteomics
Authors: Gu Jincui , Li Qingqing , Chen Boyi , Xu Chengfeng , Zheng Hailing , Zhou Yang , Peng Zhiqin , Hu Zhiwen , Wang Bing
Published: June 2019

In recent years, increasing attention has been paid to the origin, transmission and communication of silk. However, this is still an unsolved mystery in archaeology. The identification of silk-producing species, especially silk produced by Bombyx mori (B. mori) and Antheraea pernyi (A. pernyi), is of key significance to address this challenge. In this study, two innovative methods, i.e. immunology and proteomics, were proposed and successfully established for the species identification of silks. ELISAs result demonstrated that the two prepared antibodies exhibited high sensitivity and specificity in distinguishing B. mori and A. pernyi silk. No cross-reactivity with each other was observed. Moreover, biomarkers were obtained for Bombyx and Antheraea through proteomic analysis. It was also confirmed that the biomarkers were suitable for identifying the species that produced a given silk sample. Compared with conventional methods for distinguishing silk species, immunological and proteomics techniques used in tandem can provide intact information and have the potential to provide accurate and reliable information for species identification.
Interleukin-18 as a drug repositioning opportunity for inflammatory bowel disease: A Mendelian randomization study
Authors: Mokry Lauren E. , Zhou Sirui , Guo Cong , Scott Robert A. , Devey Luke , Langenberg Claudia , Wareham Nick , Waterworth Dawn , Cardon Lon , Sanseau Philippe , Davey Smith George , Richards J. Brent
Published: June 2019

Support from human genetics increases the probability of success in drug development. However, few examples exist of successful genomically-driven drug repositioning. Given that a Mendelian form of severe enterocolitis is due to up-regulation of the interleukin-18 (IL18) signaling pathway, and pharmacologic inhibition of IL18 has been shown to reverse this enterocolitis, we undertook a Mendelian randomization study to test the causal effect of elevated IL18 levels on inflammatory bowel disease susceptibility (IBD) in 12,882 cases and 21,770 controls. Mendelian randomization is an established method to assess the role of biomarkers in disease etiology in a manner that minimizes confounding and prevents reverse causation. Using three SNPs that explained almost 7% of the variance in IL18 level, we found that each genetically predicted standard deviation increase in IL18 was associated with an increase in IBD susceptibility (odds ratio = 1.22, 95% CI = 1.11–1.34, P-value = 6 × 10−5). This association was further validated in 25,042 IBD cases and 34,915 controls (odds ratio = 1.13, 95% CI = 1.05–1.20). Recently, an anti-IL18 monoclonal antibody, which decreased free IL18 levels, was found to be safe, yet ineffective in a phase II trial for type 2 diabetes. Taken together, these genomic findings implicated IBD as an alternative indication for anti-IL18 therapy, which should be tested in randomized controlled trials.
Experimental study of the influence of mode excitation on mode instability in high power fiber amplifier
Authors: Chu Qiuhui , Tao Rumao , Li Chengyu , Lin Honghuan , Wang Yuying , Guo Chao , Wang Jianjun , Jing Feng , Tang Chuanxiang
Published: June 2019

Mode instability with different mode excitation has been investigated by off-splicing the fusion point in a 4 kW-level monolithic fiber laser system, which reveals that the fiber systems exciting more high order mode content exhibits lower beam quality but higher mode instability threshold. The static-to-dynamic mode degradation and dynamic-only mode degradation have also been observed in the same high power fiber amplifier by varying the mode excitation, which implicates that the mode excitation plays an important role in mode characteristics in high power fiber lasers. By employing a seed with near fundamental mode beam quality, only dynamic mode degradation-mode instability sets in with negligible static beam quality degradation. Then the fusion point in the seed laser is offset spliced to excite high order mode. As the output power of the main amplifier scales, the beam quality degrades with the beam profile being static, and then the dynamic mode instability sets in, the power threshold of which is higher than that with good beam quality seed. We consider that the static mode degradation is caused by the presence of incoherent supposition of fundamental and high order mode, which leads to that the measured dynamic mode instability threshold is higher.
Complex general stress response regulation in Sphingomonas melonis Fr1 revealed by transcriptional analyses
Authors: Gottschlich Lisa , Geiser Petra , Bortfeld-Miller Miriam , Field Christopher M. , Vorholt Julia A.
Published: June 2019

The general stress response (GSR) represents an important trait to survive in the environment by leading to multiple stress resistance. In alphaproteobacteria, the GSR is under the transcriptional control of the alternative sigma factor EcfG. Here we performed transcriptome analyses to investigate the genes controlled by EcfG of Sphingomonas melonis Fr1 and the plasticity of this regulation under stress conditions. We found that EcfG regulates genes for proteins that are typically associated with stress responses. Moreover, EcfG controls regulatory proteins, which likely fine-tune the GSR. Among these, we identified a novel negative GSR feedback regulator, termed NepR2, on the basis of gene reporter assays, phenotypic analyses, and biochemical assays. Transcriptional profiling of signaling components upstream of EcfG under complex stress conditions showed an overall congruence with EcfG-regulated genes. Interestingly however, we found that the GSR is transcriptionally linked to the regulation of motility and biofilm formation via the single domain response regulator SdrG and GSR-activating histidine kinases. Altogether, our findings indicate that the GSR in S. melonis Fr1 underlies a complex regulation to optimize resource allocation and resilience in stressful and changing environments.
High-throughput sequencing and analysis of microbial communities in the mangrove swamps along the coast of Beibu Gulf in Guangxi, China
Authors: Gong Bin , Cao Hongming , Peng Chunyan , Perčulija Vanja , Tong Guixiang , Fang Huaiyi , Wei Xinxian , Ouyang Songying
Published: June 2019

Mangrove swamp is one of the world’s richest and most productive marine ecosystems. This ecosystem also has a great ecological importance, but is highly susceptible to anthropogenic disturbances. The balance of mangrove ecosystem depends largely on the microbial communities in mangrove sediments. Thus, understanding how the mangrove microbial communities respond to spatial differences is essential for more accurate assessment of mangrove ecosystem health. To this end, we performed the first medium-distance (150 km) research on the biogeographic distribution of mangrove microbial communities. The hypervariable regions of 16S rRNA gene was sequenced by Illumina to compare the microbial communities in mangrove sediments collected from six locations (i.e. Zhenzhu harbor, Yuzhouping, Maowei Sea, Qinzhou harbor, Beihai city and Shankou) along the coastline of Beibu Gulf in Guangxi province, China. Collectively, Proteobacteria, Bacteroidetes, Chloroflexi, Actinobacteria, Parvarchaeota, Acidobacteria and Cyanobacteria were the predominant phyla in the mangrove sediments of this area. At genus level, the heat map of microbial communities reflected similarities between study sites and was in agreement with their biogeographic characteristics. Interestingly, the genera Desulfococcus, Arcobacter, Nitrosopumilus and Sulfurimonas showed differences in abundance between study sites. Furthermore, the principal component analysis (PCA) and unweighted UniFrac cluster tree of beta diversity were used to study the biogeographic diversity of the microbial communities. Relatively broader variation of microbial communities was found in Beihai city and Qinzhou harbour, suggesting that environmental condition and historical events may play an important role in shaping the bacterial communities as well. This is the first report on medium-distance range distribution of bacteria in the mangrove swamp ecosystem. Our data is valuable for monitoring and evaluation of the impact of human activity on mangrove habitats from the perspective of microbiome.
VK210 and VK247 genotypes of Plasmodium vivax in anopheline mosquitoes from Brazilian Amazon
Authors: Santos Erian de Almeida , Sucupira Izis Mônica Carvalho , de Oliveira Martins Bruno Matheus , de Paula Souza e Guimarães Ricardo José , Catete Clístenes Pamplona , de Souza Raimundo Tadeu Lessa , Santos Ana Cecília Feio dos , Póvoa Marinete Marins
Published: June 2019

Plasmodium vivax sporozoites are differenced by circumsporozoite protein. Studies on the circulation of P. vivax VK210 and P. vivax VK247 in anopheline mosquitoes are important to verify the adaptability of these parasites on mosquitoes in different locations and periods. This study aimed to describe and compare the distribution of these genotypes in anopheline mosquitoes from four states of the Brazilian Amazon. Epidemiological databases about CSP infections on mosquitoes from Pará (2000–2015), Amapá (2000–2010), Roraima (2000–2003 and 2009–2011) and Acre States (2012–2015) were used for analysis. A total of 895 specimens were found infected mainly by P. vivax VK210. We showed that the distribution of P. vivax VK247 changed over time in the main malaria vectors on the Brazilian Amazon. We note that A. darlingi was abundant in certain localities while A. albitarsis s.l. in anothers, which highlights the importance of entomological studies for the control of human malaria.
Skeletal muscle in MuRF1 null mice is not spared in low-gravity conditions, indicating atrophy proceeds by unique mechanisms in space
Authors: Cadena Samuel M. , Zhang Yunyu , Fang Jian , Brachat Sophie , Kuss Pia , Giorgetti Elisa , Stodieck Louis S. , Kneissel Michaela , Glass David J.
Published: June 2019

Microgravity exposure is associated with loss of muscle mass and strength. The E3 ubiquitin ligase MuRF1 plays an integral role in degrading the contractile apparatus of skeletal muscle; MuRF1 null (KO) mice have shown protection in ground-based models of muscle atrophy. In contrast, MuRF1 KO mice subjected to 21 days of microgravity on the International Space Station (ISS) were not protected from muscle atrophy. In a time course experiment microgravity-induced muscle loss on the ISS showed MuRF1 gene expression was not upregulated. A comparison of the soleus transcriptome profiles between spaceflight and a publicly available data set for hindlimb suspension, a claimed surrogate model of microgravity, showed only marginal commonalities between the models. These findings demonstrate spaceflight induced atrophy is unique, and that understanding of effects of space requires study situated beyond the Earth’s mesosphere.
Probing spatial inhomogeneity of cholinergic changes in cortical state in rat
Authors: Nur Tazima , Gautam Shree Hari , Stenken Julie A. , Shew Woodrow L.
Published: June 2019

Acetylcholine (ACh) plays an essential role in cortical information processing. Cholinergic changes in cortical state can fundamentally change how the neurons encode sensory input and motor output. Traditionally, ACh distribution in cortex and associated changes in cortical state have been assumed to be spatially diffuse. However, recent studies demonstrate a more spatially inhomogeneous structure of cholinergic projections to cortex. Moreover, many experimental manipulations of ACh have been done at a single spatial location, which inevitably results in spatially non-uniform ACh distribution. Such non-uniform application of ACh across the spatial extent of a cortical microcircuit could have important impacts on how the firing of groups of neurons is coordinated, but this remains largely unknown. Here we describe a method for applying ACh at different spatial locations within a single cortical circuit and measuring the resulting differences in population neural activity. We use two microdialysis probes implanted at opposite ends of a microelectrode array in barrel cortex of anesthetized rats. As a demonstration of the method, we applied ACh or neostigmine in different spatial locations via the microdialysis probes while we concomitantly recorded neural activity at 32 locations with the microelectrode array. First, we show that cholinergic changes in cortical state can vary dramatically depending on where the ACh was applied. Second, we show that cholinergic changes in cortical state can vary dramatically depending on where the state-change is measured. These results suggests that previous work with single-site recordings or single-site ACh application should be interpreted with some caution, since the results could change for different spatial locations.
Sponge diversity in Eastern Tropical Pacific coral reefs: an interoceanic comparison
Authors: Carballo José Luis , Cruz-Barraza José Antonio , Vega Cristina , Nava Héctor , Chávez-Fuentes María del Carmen
Published: June 2019

Sponges are an important component of coral reef communities. The present study is the first devoted exclusively to coral reef sponges from Eastern Tropical Pacific (ETP). Eighty-seven species were found, with assemblages dominated by very small cryptic patches and boring sponges such as Cliona vermifera; the most common species in ETP reefs. We compared the sponge patterns from ETP reefs, Caribbean reefs (CR) and West Pacific reefs (WPR), and all have in common that very few species dominate the sponge assemblages. However, they are massive or large sun exposed sponges in CR and WPR, and small encrusting and boring cryptic species in ETP. At a similar depth, CR and WPR had seven times more individuals per m2, and between four (CR) and five times (WPR) more species per m2 than ETP. Perturbation, at local and large scale, rather than biological factors, seems to explain the low prevalence and characteristics of sponge assemblages in ETP reefs, which are very frequently located in shallow water where excessive turbulence, abrasion and high levels of damaging light occur. Other factors such as the recurrence of large-scale phenomena (mainly El Niño events), age of the reef (younger in ETP), isolation (higher in ETP), difficulty to gain recruits from distant areas (higher in ETP), are responsible for shaping ETP sponge communities. Such great differences in sponge fauna between the three basins might have consequences for coral reef structure and dynamics.
Rats deficient in α-galactosidase A develop ocular manifestations of Fabry disease
Authors: Miller James J. , Aoki Kazuhiro , Reid Christopher A. , Tiemeyer Michael , Dahms Nancy M. , Kassem Iris S.
Published: June 2019

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of α-galactosidase A. Ocular findings, such as cornea verticillata, cataracts, and retinal vascular tortuosity, serve as important diagnostic markers. We aimed to evaluate ocular phenotypes in α-galactosidase A-deficient (Fabry) rats and hypothesized that these rats would manifest ocular signs similar to those observed in patients. Slit lamp biomicroscopy was used to evaluate the cornea and lens, and retinal vasculature was examined by fluorescein angiography in WT and Fabry rats. Mass spectrometry was used to characterize and quantify ocular glycosphingolipids, and histology and electron microscopy revealed the location of the glycosphingolipid storage. We found that Fabry rats developed corneal and lenticular opacities to a statistically greater degree than WT rats. Retinal vascular morphology did not appear grossly different, but there was vascular leakage in at least one Fabry rat. Fabry rat eyes accumulated substrates of α-galactosidase A, and these α-galactosyl glycoconjugates were found in corneal keratocytes, lens fibers, and retinal vascular endothelial cells. Electron-dense lamellar inclusions were observed in keratocytes. Because Fabry rats recapitulate many ocular phenotypes observed in patients, they can be used to study disease pathogenesis and determine whether ocular findings serve as noninvasive indicators of therapeutic efficacy.
Intracellular Zn2+ transients modulate global gene expression in dissociated rat hippocampal neurons
Authors: Sanford Lynn , Carpenter Margaret C. , Palmer Amy E.
Published: June 2019

Zinc (Zn2+) is an integral component of many proteins and has been shown to act in a regulatory capacity in different mammalian systems, including as a neurotransmitter in neurons throughout the brain. While Zn2+ plays an important role in modulating neuronal potentiation and synaptic plasticity, little is known about the signaling mechanisms of this regulation. In dissociated rat hippocampal neuron cultures, we used fluorescent Zn2+ sensors to rigorously define resting Zn2+ levels and stimulation-dependent intracellular Zn2+ dynamics, and we performed RNA-Seq to characterize Zn2+-dependent transcriptional effects upon stimulation. We found that relatively small changes in cytosolic Zn2+ during stimulation altered expression levels of 931 genes, and these Zn2+ dynamics induced transcription of many genes implicated in neurite expansion and synaptic growth. Additionally, while we were unable to verify the presence of synaptic Zn2+ in these cultures, we did detect the synaptic vesicle Zn2+ transporter ZnT3 and found it to be substantially upregulated by cytosolic Zn2+ increases. These results provide the first global sequencing-based examination of Zn2+-dependent changes in transcription and identify genes that may mediate Zn2+-dependent processes and functions.
Conventional and Specific-Pathogen Free Rats Respond Differently to Anesthesia and Surgical Trauma
Authors: Letson Hayley L. , Morris Jodie , Biros Erik , Dobson Geoffrey P.
Published: June 2019

Specific-pathogen free (SPF) animals were introduced in the 1960s to minimize disease and infection as variables in biomedical research. Our aim was to examine differences in physiological response in rat colonies bred and housed in a conventional versus SPF facility, and implications for research. Sprague-Dawley rats were anesthetized and catheterized for blood and pressure monitoring, and electrocardiogram (ECG) leads implanted. Hematology was assessed, and coagulation profile using rotational thromboelastometry. Health screening was outsourced to Cerberus Sciences. SPF rats had significantly lower pulse pressure (38% decrease), arrhythmias and prolonged QTc (27% increase) compared to conventional rats. No arrhythmias were found in conventional rats. SPF rats had significantly higher white cell, monocyte, neutrophil and lymphocyte counts, and were hyperfibrinolytic, indicated by EXTEM maximum lysis >15%. Independent assessment revealed similar pathogen exclusion between colonies, with the exception of Proteus in SPF animals. Returning to a conventional facility restored normal host physiology. We conclude that SPF animals displayed an abnormal hemodynamic, hematological and hemostatic phenotype in response to anesthesia and surgery, and provide a number of recommendations to help standardize research outcomes and translation.
Cell population heterogeneity driven by stochastic partition and growth optimality
Authors: Fernandez-de-Cossio-Diaz Jorge , Mulet Roberto , Vazquez Alexei
Published: June 2019

A fundamental question in biology is how cell populations evolve into different subtypes based on homogeneous processes at the single cell level. Here we show that population bimodality can emerge even when biological processes are homogenous at the cell level and the environment is kept constant. Our model is based on the stochastic partitioning of a cell component with an optimal copy number. We show that the existence of unimodal or bimodal distributions depends on the variance of partition errors and the growth rate tolerance around the optimal copy number. In particular, our theory provides a consistent explanation for the maintenance of aneuploid states in a population. The proposed model can also be relevant for other cell components such as mitochondria and plasmids, whose abundances affect the growth rate and are subject to stochastic partition at cell division.