bluuebunny/crossref_metadata_2025 huggingface dataset:
Porous substrate affects a subsequent attachment ability of the beetleHarmonia axyridis(Coleoptera, Coccinellidae)
Authors: Gorb Elena V. , Lemke Wiebke , Gorb Stanislav N.
Published: January 2019

According to literature data, porous substrates can cause a reduction of insect attachment ability. We carried out traction experiments with adult ladybird beetlesHarmonia axyridison the smooth solid glass sample and rough porous Al2O3membrane to prove the primary effect of absorption of the insect pad secretion by porous media, rather than surface roughness, on the attachment force on the porous sample. With each insect individual, a set of five experiments was conducted: (1) on glass; (2) on the porous membrane; (3–5) on glass immediately after the test on the porous surface, then after 30 min and 1 h of recovery time. On the porous substrate, the forces, being similar in females and males, were greatly reduced compared to those measured on glass. A significant difference between the force values obtained in the first (before the test on the porous sample) and second (immediately after the experiment on the porous sample) tests on glass was observed. After 30 min recovery time, beetles completely regained their attachment ability. Females produced significantly lower forces than males in all experiments on glass: the differences are probably caused by the sexual dimorphism in the microstructure of their adhesive pads. The obtained results are of fundamental importance for further application in biomimetics of novel insect-repelling surfaces and in plant protection by using porous materials.
New theropod (Tetanurae: Avetheropoda) material from the ‘mid’-Cretaceous Griman Greek Formation at Lightning Ridge, New South Wales, Australia
Authors: Birch Sienna A. , Smith Elizabeth T. , Bell Phil R.
Published: January 2019

The limited fossil record of Australian Cretaceous theropods is dominated by megaraptorids, reported from associated and isolated material from the Early Cretaceous of Victoria and the ‘Mid’-Cretaceous of central-north New South Wales and central Queensland. Here, we report on new postcranial theropod material from the early Late Cretaceous Griman Creek Formation at Lightning Ridge. Among this new material is an associated set consisting of two anterior caudal vertebrae and a pubic peduncle of the ilium, to which a morphologically similar partial vertebral centra from a separate locality is tentatively referred. These elements display a combination of characteristics that are present in megaraptorid and carcharodontosaurid theropods, including camellate internal organization of the vertebral centra, ventrally keeled anterior caudal centra and a pubic peduncle of the ilium with a ventral surface approximately twice as long anteroposteriorly as mediolaterally wide. Unfortunately, a lack of unambiguous synapomorphies precludes accurate taxonomic placement; however, avetheropodan affinities are inferred. This new material represents the second instance of a medium-sized theropod from this interval, and only the third known example of associated preservation in an Australian theropod. Additional isolated theropod material is also described, including an avetheropodan femoral head that shows similarities to
Allosaurus
and
Australovenator
, and a mid-caudal vertebral centrum bearing pneumatic foraminae and extensive camellae that is referrable to Megaraptora and represents the first axial skeletal element of a megaraptorid described from Lightning Ridge.
Distinct effects of short-term reconstructed topsoil on soya bean and corn rhizosphere bacterial abundance and communities in Chinese Mollisol
Authors: Yu Zhenhua , Jin Jian , Li Yansheng , Yang Yue , Zhao Yue , Liu Changkai , Liu Xiaobing
Published: January 2019

Eroded black soils (classified as Mollisols) lead to a thinner topsoil layer, reduced organic carbon storage and declined crop productivity. Understanding the changes in soil microbial communities owing to soil erosion is of vital importance as soil microbial communities are sensitive indicators of soil condition and are essential in soil nutrient cycling. This study used the reconstructed facility with 10, 20 and 30 cm topsoil thickness under no-till soya bean–corn rotation in black soil region of Northeast China. Illumina MiSeq sequencing targeting 16S rRNA,
q
PCR and soil respiration measurement were performed to assess the changes in soya bean and corn rhizosphere bacterial communities, as well as their abundance and activities due to the topsoil thickness. The results showed that soil bacterial communities from both soya bean and corn were more sensitive to topsoil removal than to soil biogeochemical characteristics. Topsoil depths significantly influenced both soya bean and corn bacterial communities, while they only significantly influenced the bacterial abundance and respiration in corn. We also found that the topsoil depths significantly induced the changes in phyla and genera from both soya bean and corn rhizosphere bacterial community, which aid further understandings on how topsoil layer influences the global nutrient cycling of Mollisols by influencing the change in microbial communities.
Unscrambling variation in avian eggshell colour and patterning in a continent-wide study
Authors: L'Herpiniere Kiara L. , O'Neill Louis G. , Russell Andrew F. , Duursma Daisy Englert , Griffith Simon C.
Published: January 2019

The evolutionary drivers underlying marked variation in the pigmentation of eggs within many avian species remains unclear. The leading hypotheses proposed to explain such variation advocate the roles of genetic differences, signalling and/or structural integrity. One means of testing among these hypotheses is to capitalize on museum collections of eggs obtained throughout a broad geographical range of a species to ensure sufficient variation in predictors pertaining to each hypothesis. Here, we measured coloration and patterning in eggs from 272 clutches of Australian magpies (
Cracticus tibicen
) collected across most of their geographical range of
ca
7 million km
2
; encompassing eight subspecies, variation in environmental parameters, and the presence/absence of a brood parasite. We found considerable variation in background colour, as well as in the extent and distribution of patterning across eggs. There was little evidence that this variation was explained by subspecies or the contemporary presence of a brood parasite. However, measures of maximum temperature, leaf area index and soil calcium all contributed to variation in egg appearance, although their explanatory power was relatively low. Our results suggest that multiple factors combine to influence egg appearance in this species, and that even in species with highly variable eggs, coloration is not readily explained.
Green's function for anisotropic dispersive poroelastic media based on the Radon transform and eigenvector diagonalization
Authors: Zhan Qiwei , Zhuang Mingwei , Fang Yuan , Liu Jian-Guo , Liu Qing Huo
Published: January 2019

A compact Green's function for general dispersive anisotropic poroelastic media in a full-frequency regime is presented for the first time. First, starting in a frequency domain, the anisotropic dispersion is exactly incorporated into the constitutive relationship, thus avoiding fractional derivatives in a time domain. Then, based on the Radon transform, the original three-dimensional differential equation is effectively reduced to a one-dimensional system in space. Furthermore, inspired by the strategy adopted in the characteristic analysis of hyperbolic equations, the eigenvector diagonalization method is applied to decouple the one-dimensional vector problem into several independent scalar equations. Consequently, the fundamental solutions are easily obtained. A further derivation shows that Green's function can be decomposed into circumferential and spherical integrals, corresponding to static and transient responses, respectively. The procedures shown in this study are also compatible with other pertinent multi-physics coupling problems, such as piezoelectric, magneto-electro-elastic and thermo-elastic materials. Finally, the verifications and validations with existing analytical solutions and numerical solvers corroborate the correctness of the proposed Green's function.
Critical curvature localization in graphene. II. Non-local flexoelectricity–dielectricity coupling
Authors: Kothari Mrityunjay , Cha Moon-Hyun , Lefevre Victor , Kim Kyung-Suk
Published: January 2019

As a sequel of part I (Kothari
et al.
2018
Proc. R. Soc. A
474
, 20180054), we present a general thermodynamic framework of flexoelectric constitutive laws for multi-layered graphene (MLG), and apply these laws to explain the role of crinkles in peculiar molecular adsorption characteristics of highly oriented pyrolytic graphite (HOPG) surfaces. The thermodynamically consistent constitutive laws lead to a non-local interaction model of polarization induced by electromechanical deformation with flexoelectricity–dielectricity coupling. The non-local model predicts curvature and polarization localization along crinkle valleys and ridges very close to those calculated by density functional theory (DFT). Our analysis reveals that the non-local model can be reduced to a simplified uc-local or e-local model (Kothari
et al.
2018
Proc. R. Soc. A
474
, 20180054) only when the curvature distribution is uniform or highly localized. For the non-local model, we calibrated and formulated the layer-number-dependent dielectric and intrinsic flexoelectric coefficients of MLGs. In addition, we also obtained layer-number dependent flexoelectric coefficients for uc-local and e-local models. Our DFT analysis shows that polarization-induced adsorption of neutral molecules at crinkle ridges depends on the molecular weight of the molecule. Furthermore, our detailed study of polarization localization in graphene crinkles enables us to understand previously unexplained self-organized adsorption of C
60
buckyballs in a linear array on an HOPG surface.
Direct transmission by injection affects competition among RNA viruses in honeybees
Authors: Remnant Emily J. , Mather Niklas , Gillard Thomas L. , Yagound Boris , Beekman Madeleine
Published: January 2019

The arrival of the ectoparasitic mite
Varroa destructor
on the western honeybee
Apis mellifera
saw a change in the diversity and prevalence of honeybee RNA viruses. One virus in particular, deformed wing virus (DWV) has become closely associated with
V. destructor
, leading many to conclude that
V. destructor
has affected viral virulence by changing the mode of transmission. While DWV is normally transmitted via feeding and faeces,
V. destructor
transmits viruses by direct injection. This change could have resulted in higher viral prevalence causing increased damage to the bees. Here we test the effect of a change in the mode of transmission on the composition and levels of honeybee RNA viruses in the absence of
V. destructor
. We find a rapid increase in levels of two viruses, sacbrood virus (SBV) and black queen cell virus (BQCV) after direct injection of viral extracts into honeybee pupae. In pupae injected with high levels of DWV extracted from symptomatic adult bees, DWV levels rapidly decline in the presence of SBV and BQCV. Further, we observe high mortality in honeybee pupae when injected with SBV and BQCV, whereas injecting pupae with high levels of DWV results in near 100% survival. Our results suggest a different explanation for the observed association between
V. destructor
and DWV. Instead of
V. destructor
causing an increase in DWV virulence, we hypothesize that direct virus inoculation, such as that mediated by a vector, quickly eliminates the most virulent honeybee viruses resulting in an association with less virulent viruses such as DWV.
Marinilabilia rubra sp. nov., isolated from a marine solar saltern
Authors: Zhang Rui , Wang Shuo , Wang Chong , Wang Guang-Yu , Du Zong-Jun
Published: January 2019

A novel cherry-red-pigmented, Gram-stain-negative, gliding, facultatively anaerobic and rod-shaped bacterium, designated strain WTE16T, was isolated from a sediment sample taken from a marine solar saltern of Wendeng, China (36° 59′ 56.49′′ N 122° 1′ 38.84′′ E). The novel isolate was able to grow at 20–40 °C (optimum 33 °C), at pH 6.0–9.0 (optimum pH 7.0) and with 1.0–12.0 % (w/v) NaCl (optimum 3.0–5.0 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that the most closely related validly published species is

Marinilabilia salmonicolor

JCM 21150T (96.0 % similarity). Average nucleotide identity, average amino acid identity, percentage of conserved proteins and digital DNA–DNA hybridization values between strain WTE16T and

Marinilabilia salmonicolor

JCM 21150T were 73.8 %, 73.5 %, 63.4 % and 19.5–24.2 %, respectively. The genomic DNA G+C content of strain WTE16T was 40.8 mol%. Chemotaxonomic analysis showed that the sole respiratory quinone was menaquinone 7 (MK-7), and the major fatty acids included iso-C15 : 0 and anteiso-C15 : 0. The polar lipid profile of strain WTE16T included phosphatidylethanolamine, three unidentified phospholipids and three unidentified lipids. On the basis of its phylogenetic, phenotypic, chemotaxonomic, genotypic and genomic characteristics, strain WTE16T is suggested to represent a novel species of the genus

Marinilabilia

, for which the name

Marinilabilia
rubra sp. nov. is proposed. The type strain is WTE16T (=KCTC 62599T=MCCC 1H00311T).
PerMemDB: a database for eukaryotic peripheral membrane proteins
Authors: Nastou Katerina C. , Tsaousis Georgios N. , Hamodrakas Stavros J. , Iconomidou Vassiliki A.
Published: January 2019

The majority of all proteins in cells interact with membranes either permanently or temporarily. Peripheral membrane proteins form transient complexes with membrane proteins and/or lipids, via non-covalent interactions and are of outmost importance, due to numerous cellular functions in which they participate. In an effort to collect data regarding this heterogeneous group of proteins we designed and constructed a database, called PerMemDB. PerMemDB is currently the most complete and comprehensive repository of data for eukaryotic peripheral membrane proteins deposited in UniProt or predicted with the use of MBPpred – a computational method that specializes in the detection of proteins that interact non-covalently with membrane lipids, via membrane binding domains. The first version of the database contains 241173 peripheral membrane proteins from 1216 organisms. All entries have cross-references to other databases, literature references and annotation regarding their interactions with other proteins. Moreover, additional sequence annotation of the characteristic domains that allow these proteins to interact with membranes is available, due to the application of MBPpred. Through the web interface of PerMemDB, users can browse the contents of the database, submit advanced text searches and BLAST queries against the protein sequences deposited in PerMemDB. We expect this repository to serve as a source of information for the development of prediction algorithms regarding peripheral membrane proteins, in addition to proteome-wide analyses.

Availability

http://bioinformatics.biol.uoa.gr/permemdb

Contact

veconom@biol.uoa.gr

Supplementary information

http://83.212.109.111:8085/assets/Nastou_Supplement.xlsx
Integrating multi-network topology for gene function prediction using deep neural networks
Authors: Xue Hansheng , Peng Jiajie , Shang Xuequn
Published: January 2019

Motivation

The emerging of abundant biological networks, which benefit from the development of advanced high-throughput techniques, contribute to describing and modeling complex internal interactions among biological entities such as genes and proteins. Multiple networks provide rich information for inferring the function of genes or proteins. To extract functional patterns of genes based on multiple heterogeneous networks, network embedding-based methods, aiming to capture non-linear and low-dimensional feature representation based on network biology, have recently achieved remarkable performance in gene function prediction. However, existing methods mainly do not consider the shared information among different networks during the feature learning process. Thus, we propose a novel multi-networks embedding-based function prediction method based on semi-supervised autoencoder and feature convolution neural network, namedDeepMNE-CNN, which captures complex topological structures of multi-networks and takes the correlation among multi-networks into account.

Results

We design a novel semi-supervised autoencoder method to integrate multiple networks and generate a low-dimensional feature representation. Then we utilize a convolutional neural network based on the integrated feature embedding to annotate unlabeled gene functions. We test our method on both yeast and human dataset and compare with four state-of-the-art methods. The results demonstrate the superior performance of our method over four state-of-the-art algorithms. From the future explorations, we find that semi-supervised autoencoder based multi-networks integration method and CNN-based feature learning methods both contribute to the task of function prediction.

Availability

DeepMNE-CNNis freely available athttps://github.com/xuehansheng/DeepMNE-CNN
Gene Info: Easy retrieval of gene product information on any website
Authors: Knight James D.R. , Samavarchi-Tehrani Payman , Gingras Anne-Claude
Published: January 2019

Viewing information about gene products is a constant part of the molecular biologist’s life. While there are many high quality and well-designed resources to fulfill this need, they require the user to navigate to these resources, execute a search, select the desired result and then view its information. This can be a repetitive, time-consuming and even disruptive process, for example when exploring the results of large scale genomics or proteomics screens or reading an online article.
Heterogeneity in surface sensing produces a division of labor inPseudomonas aeruginosapopulations
Authors: Armbruster Catherine R. , Lee Calvin K. , Parker-Gilham Jessica , Anda Jaime de , Xia Aiguo , Tseng Boo Shan , Hoffman Lucas R. , Jin Fan , Harwood Caroline S. , Wong Gerard C. L. , Parsek Matthew R.
Published: January 2019

The second messenger signaling molecule cyclic diguanylate monophosphate (c-di-GMP) drives the transition from planktonic to biofilm growth in many bacterial species.Pseudomonas aeruginosahas two surface sensing systems that produce c-di-GMP in response to surface adherence. The current thinking in the field is that once cells attach to a surface, they uniformly respond with elevated c-di-GMP. Here, we describe how the Wsp system generates heterogeneity in surface sensing, resulting in two physiologically distinct subpopulations of cells. One subpopulation has elevated c-di-GMP and produces biofilm matrix, serving as the founders of initial microcolonies. The other subpopulation has low c-di-GMP and engages in surface motility, allowing for exploration of the surface. We also show that this heterogeneity strongly correlates to surface behavior for descendent cells. Together, our results suggest that after surface attachment,P. aeruginosaengages in a division of labor that persists across generations, accelerating early biofilm formation and surface exploration.
Probabilistic Harmonization and Annotation of Single-cell Transcriptomics Data with Deep Generative Models
Authors: Xu Chenling , Lopez Romain , Mehlman Edouard , Regier Jeffrey , Jordan Michael I. , Yosef Nir
Published: January 2019

As single-cell transcriptomics becomes a mainstream technology, the natural next step is to integrate the accumulating data in order to achieve a common ontology of cell types and states. However, owing to various nuisance factors of variation, it is not straightforward how to compare gene expression levels across data sets and how to automatically assign cell type labels in a new data set based on existing annotations. In this manuscript, we demonstrate that our previously developed method, scVI, provides an effective and fully probabilistic approach for joint representation and analysis of cohorts of single-cell RNA-seq data sets, while accounting for uncertainty caused by biological and measurement noise. We also introduce single-cell ANnotation using Variational Inference (scANVI), a semi-supervised variant of scVI designed to leverage any available cell state annotations — for instance when only one data set in a cohort is annotated, or when only a few cells in a single data set can be labeled using marker genes. We demonstrate that scVI and scANVI compare favorably to the existing methods for data integration and cell state annotation in terms of accuracy, scalability, and adaptability to challenging settings such as a hierarchical structure of cell state labels. We further show that different from existing methods, scVI and scANVI represent the integrated datasets with a single generative model that can be directly used for any probabilistic decision making task, using differential expression as our case study. scVI and scANVI are available as open source software and can be readily used to facilitate cell state annotation and help ensure consistency and reproducibility across studies.
Length of uninterrupted CAG repeats, independent of polyglutamine size, results in increased somatic instability and hastened age of onset in Huntington disease
Authors: Wright Galen E.B. , Collins Jennifer A. , Kay Chris , McDonald Cassandra , Dolzhenko Egor , Xia Qingwen , Bečanović Kristina , Semaka Alicia , Nguyen Charlotte M. , Trost Brett , Richards Fiona , Bijlsma Emilia K. , Squitieri Ferdinando , Scherer Stephen W. , Eberle Michael A. , Yuen Ryan K.C. , Hayden Michael R.
Published: January 2019

Huntington disease (HD) is an autosomal dominant neurological disorder that is caused by a CAG repeat expansion, translated into polyglutamine, in the huntingtin (HTT)gene. Although the length of this repeat polymorphism is inversely correlated with age of onset (AOO), it does not fully explain the variability in AOO. Genomic studies have provided evidence for the involvement of DNA repair in modifying this trait, potentially through somatic repeat instability. We therefore assessed genetic variants within the 12bp interrupting sequence between the pathogenic CAG repeat and the polymorphic proline (CCG) tract in theHTTgene and identified variants that result in complete loss of interruption (LOI) between the adjacent CAG/CCG repeats. Analysis of multiple HD pedigrees showed that this variant is associated with dramatically earlier AOO and is particularly relevant to HD patients with reduced penetrance alleles. On average AOO of HD is hastened by an average of 25 years in LOI carriers. This finding indicates that the number of uninterrupted CAG repeats is the most significant contributor to AOO of HD and is more impactful than polyglutamine length, which is not altered in these patients. We show that the LOI variant is associated with increases in both somatic and germline repeat instability, demonstrating a potential mechanism for this effect. Screening individuals from the general population (n=2,674 alleles) suggests that the variant occurs only in expanded CAG repeat alleles. Identification of this modifier has important clinical implications for disease management of HD families, especially for those in the reduced penetrance ranges.
An allele-specific functional SNP associated with two autoimmune diseases modulatesIRF5expression by long-range chromatin loop formation
Authors: Thynn Hlaing Nwe , Chen Xiao-Feng , Hu Wei-Xin , Duan Yuan-Yuan , Zhu Dong-Li , Chen Hao , Wang Nai-Ning , Chen Huan-Huan , Rong Yu , Lu Bing-Jie , Yang Man , Jiang Feng , Dong Shan-Shan , Guo Yan , Yang Tie-Lin
Published: January 2019

Both Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc) are autoimmune diseases sharing similar genetic backgrounds. Genome-wide association studies (GWASs) have constantly disclosed numerous genetic variants conferring to both disease risks at 7q32.1, but the functional mechanisms underlying them are still largely unknown. Through combining fine-mapping and functional epigenomic analyses, we prioritized a potential independent functional SNP (rs13239597) withinTNPO3promoter region, residing in a putative enhancer element. Functional analysis integrating expression quantitative trait locus (eQTL) and high-throughput chromatin interaction (Hi-C) demonstrated thatIRF5is the distal target gene (~118kb) of rs13239597, which is a key regulator of pathogenic autoantibody dysregulation increased risk of both SLE and SSc. We experimentally validated the long-range chromatin interactions between rs13239597 andIRF5using chromosome conformation capture (3C) assay. We further demonstrated that rs13239597-A acted as an allele-specific enhancer regulatingIRF5expression, independently ofTNPO3by using dual-luciferase reporter assays and CRISPR-Cas9. Particularly, the transcription factor EVI1 could preferentially bind to rs13239597-A allele and increase the enhancer activity to regulateIRF5expression. Taken together, our results uncovered the mechanistic insight connecting between a noncoding functional variant with a distal immunologically pathogenic geneIRF5, which might obligate in understanding the complex genetic architectures of SLE and SSc pathogenesis.
Translational regulation of non-autonomous mitochondrial stress response promotes longevity
Authors: Lan Jianfeng , Rollins Jarod , Wu Di , Zang Xiao , Zou Lina , Wang Zi , Ye Chang , Wu Zixing , Kapahi Pankaj , Rogers Aric N. , Chen Di
Published: January 2019

Inhibition of mRNA translation delays aging, but the underlying mechanisms remain underexplored. Mutations in both DAF-2 (IGF-1 receptor) and RSKS-1 (ribosomal S6 kinase/S6K) cause synergistic lifespan extension inC. elegans. To understand the roles of S6K-mediated translational regulation in this process, we performed genome-wide translational profiling and genetic screens to identify genes that are not only regulated at the translational level in thedaf-2 rsks-1mutant, but also affect lifespan. Inhibition of CYC-2.1 (cytochrome c) in the germline significantly extends lifespan through non-autonomous activation of the mitochondrial unfolded protein response (UPRmt) and AMP-activated kinase (AMPK) in the metabolic tissue. Furthermore, the RNA-binding protein GLD-1-mediated translational repression of cytochrome c in the germline is important for the non-autonomous activation of UPRmtand synergistic longevity of thedaf-2 rsks-1mutant. Together, these results illustrate a translationally regulated non-autonomous mitochondrial stress response mechanism in the modulation of lifespan by insulin-like signaling and S6K.

Highlights

Longevity of thedaf-2 rsks-1mutant is mediated by translational repression of ribosomal proteins and CYC-2.1/cytochrome c.

Germline inhibition ofcyc-2.1non-autonomously activates UPRmtand AMPK to extend lifespan.

GLD-1 represses germlinecyc-2.1translation in thedaf-2 rsks-1mutant.

Translational regulation ofcyc-2.1and UPRmtcontribute to the synergistic longevity of thedaf-2 rsks-1mutant.
Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort
Authors: Khandaker Golam M , Zuber Verena , Rees Jessica MB , Carvalho Livia , Mason Amy M , Foley Christopher N , Gkatzionis Apostolos , Jones Peter B , Burgess Stephen
Published: January 2019

While comorbidity between coronary heart disease (CHD) and depression is evident, it is unclear whether the two diseases have shared underlying mechanisms. We performed a range of analyses in 367,703 unrelated middle-aged participants of European ancestry from UK Biobank, a population based cohort study, to assess whether comorbidity is primarily due to genetic or environmental factors, and to test whether cardiovascular risk factors and CHD are likely to be causally related to depression using Mendelian randomization. We showed family history of heart disease was associated with a 20% increase in depression risk (95% confidence interval [CI] 16% to 24%, p<0.0001), but a genetic risk score that is strongly associated with CHD risk was not associated with depression. An increase of one standard deviation in the CH D genetic risk score was associated with 71% higher CHD risk, but 1% higher depression risk (95% CI 0% to 3%; p=0.11). Mendelian randomization analyses suggested that triglycerides, interleukin-6 (IL-6), and C-reactive protein (CRP) are likely causal risk factors for depression. The odds ratio for depression per standard deviation increase in genetically-predicted triglycerides was 1.18 (95% CI 1.09 to 1.27; p=2×10-5); per unit increase in genetically-predicted log-transformed I L-6 was 0.74 (95% CI 0.62 to 0.89; p=0.0012); and per unit increase in genetically-predicted log-transformed CRP was 1.18 (95% CI 1.07 to 1.29; p=0.0009). Our analyses suggest that comorbidity between depression and CHD arises largely from shared environmental factors. I L-6, CRP and triglycerides, are likely to be causally linked with depression, so could be targets for treatment and prevention of depression.
Water and ion transport across the eversible vesicles in the collophore of a springtailOrchesella cincta
Authors: Konopová Barbora , Kolosov Dennis , O’Donnell Michael J.
Published: January 2019

Springtails (Collembola) are ancient close relatives of the insects. The eversible vesicles are their unique paired transporting organs, which consist of an epithelium located inside a tube-like structure on the first abdominal segment called the collophore. The vesicles can be protruded out of the collophore and several lines of evidence indicate that they have a vital function in water uptake and ion balance. However, the amount of water absorbed by the vesicles and which other ions apart from sodium are transported remain unknown. UsingOrchesella cinctaas a model, we developed protocols for two assays that enabled us to study water and ion movement across the eversible vesicles in whole living springtails. Using an inverse Ramsay assay we demonstrate that the eversible vesicles absorb water from a droplet applied onto their surface. Using the scanning ion-selective electrode technique (SIET) we show that the vesicles absorb Na+and Cl−from the bathing medium, secrete NH4+, and both absorb and secrete K+, H+is secreted at a low level in the anterior part and absorbed at the posterior. We did not detect transport of Ca2+at significant levels. The highest flux was the absorption of Cl−, and the magnitude of ion fluxes were significantly lower in fully hydrated springtails. Our data demonstrate that the eversible vesicles are a transporting epithelium functioning in osmo- and ionoregulation, nitrogenous waste excretion and likely acid-base balance.
Evolutionary Implications of Anoxygenic Phototrophy in the Bacterial PhylumCandidatusPalusbacterota (WPS-2)
Authors: Ward Lewis M. , Cardona Tanai , Holland-Moritz Hannah
Published: January 2019

Genome-resolved environmental metagenomic sequencing has uncovered substantial previously unrecognized microbial diversity relevant for understanding the ecology and evolution of the biosphere, providing a more nuanced view of the distribution and ecological significance of traits including phototrophy across diverse niches. Recently, the capacity for bacteriochlorophyll-based anoxygenic photosynthesis has been found in the uncultured bacterial WPS-2 clade that are in close association with boreal moss. Here, we use phylogenomic analysis to investigate the diversity and evolution of phototrophic WPS-2. We demonstrate that phototrophic WPS-2 show significant genetic and metabolic divergence from other phototrophic and non-phototrophic lineages. The genomes of these organisms encode a completely new family of anoxygenic Type II photochemical reaction centers and other phototrophy-related proteins that are both phylogenetically and structurally distinct from those found in previously described phototrophs. We propose the nameCandidatusPalusbacterota for the phylum-level aerobic WPS-2 clade which contains phototrophic lineages, from the Latin for “bog bacteria”, distinguishing it from the anaerobic, non-phototrophic sister phylumCandidatusEremiobacterota for “desert bacteria”, typically found in dry environments.
DNA-guided DNA cleavage at moderate temperatures by Clostridium butyricum Argonaute
Authors: Hegge Jorrit W. , Swarts Daan C. , Chandradoss Stanley D. , Cui Tao Ju , Kneppers Jeroen , Jinek Martin , Joo Chirlmin , van der Oost John
Published: January 2019

Prokaryotic Argonaute proteins (pAgos) constitute a diverse group of endonucleases of which some mediate host defense by utilizing small interfering DNA guides (siDNA) to cleave complementary invading DNA. This activity can be repurposed for programmable DNA cleavage. However, currently characterized DNA-cleaving pAgos require elevated temperatures (≥65°C) for their activity, making them less suitable for applications that require moderate temperatures, such as genome editing. Here we report the functional and structural characterization of the siDNA-guided DNA-targeting pAgo from the mesophilic bacterium Clostridium butyricum (CbAgo). CbAgo displays a preference for siDNAs that have a deoxyadenosine at the 5’-end and thymidines in the sub-seed segment (siDNA nucleotides 2-4). Furthermore, CbAgo mediates DNA-guided DNA cleavage of AT-rich double stranded DNA at moderate temperatures (37°C). This study demonstrates that certain pAgos are capable of programmable DNA cleavage at moderate temperatures and thereby expands the scope of the potential pAgo–based applications.
Chemogenetic inhibition of the amygdala modulates emotional behavior expression in infant rhesus monkeys
Authors: Raper Jessica , Murphy Lauren , Richardson Rebecca , Romm Zoe , Kovacs-Balint Zsofia , Payne Christa , Galvan Adriana
Published: January 2019

Manipulation of neuronal activity during the early postnatal period in monkeys has been largely limited to permanent lesion studies, which can be impacted by developmental plasticity leading to reorganization and compensation from other brain structures that can interfere with the interpretations of results. Chemogenetic tools, such as DREADDs (designer receptors exclusively activated by designer drugs), can transiently and reversibly activate or inactivate brain structures, avoiding the pitfalls of permanent lesions to better address important developmental neuroscience questions. We demonstrate that inhibitory DREADDs in the amygdala can be used to manipulate socioemotional behavior in infant monkeys. Two infant rhesus monkeys (1 male, 1 female) received AAV5-hSyn-HA-hM4Di-IRES-mCitrine injections bilaterally in the amygdala at 9 months of age. DREADD activation after systemic administration of either clozapine-N-oxide or low dose clozapine resulted in decreased freezing and anxiety on the human intruder paradigm and changed the looking patterns on a socioemotional attention eyetracking task, compared to vehicle administration. The DREADD-induced behaviors were reminiscent of, but not identical to, those seen after permanent lesions of the amygdala in infant monkeys, such that early amygdala lesions produce a more extensive array of behavioral changes in response to the human intruder task that were not seen with DREADD-evoked inhibition of this region. Our results support the notion that early permanent damage leads to brain reorganization manifesting in a broader impact on behavior. The current study provides a proof-of-principle that DREADDs can be used in young infant monkeys to transiently and reversibly manipulate behavior.

Statement of Significance

Many neurodevelopmental disorders exhibit abnormal structural or functional amygdala development and alterations in socioemotional behavior. To date, developmental neuroscience studies have relied on permanent lesions techniques to investigate how atypical amygdala development impacts socioemotional behaviors, which may not adequately recapitulate the role of amygdala dysfunction in the manifestation of aberrant behavior. The present study sought to demonstrate that the DREADDs (designer receptors exclusively activated by designer drugs) chemogenetic tool could transiently inhibit amygdala activity in infant monkeys resulting in alterations in socioemotional behavior. This proof-of-principle study supports the use of chemogenetics for developmental neuroscience research, providing an opportunity to broaden our understanding of how changes in neuronal activity across early postnatal development influences behavior and clinical symptoms.
3D Ultrastructure of the Cochlear Outer Hair Cell Lateral Wall Revealed By Electron Tomography
Authors: Jeffrey Triffo William , Palsdottir Hildur , Gene Morgan David , McDonald Kent L. , Raphael Robert M. , Auer Manfred
Published: January 2019

Outer hair cells in the mammalian cochlea display a unique type of voltage-induced mechanical movement, termed electromotility, which amplifies auditory signals and contributes to the sensitivity and frequency selectivity of mammalian hearing. Electromotility occurs in the outer hair cell (OHC) lateral wall, and it is not fully understood how the supramolecular architecture of the lateral wall enables this unique form of cellular motility. Employing electron tomography of high-pressure frozen and freeze-substituted OHCs, we visualized the 3D structure and organization of the membrane and cytoskeletal components of the OHC lateral wall. The subsurface cisterna (SSC) is a highly prominent feature, and we report that the SSC membranes and lumen possess hexagonally ordered arrays of particles that endow the SSC with a previously unrealized anisotropic structural rigidity. We also find the SSC is tightly connected to adjacent actin filaments by short filamentous protein connections spaced at regular intervals. Pillar proteins that join the plasma membrane to the cytoskeleton appear as variable structures considerably thinner than actin filaments and significantly more flexible than actin-SSC links. The structurally rich organization and rigidity of the SSC coupled with apparently weaker mechanical connections between the plasma membrane and cytoskeleton reveal that the membrane-cytoskeletal architecture of the OHC lateral wall is more complex than previously appreciated. These observations are important for our understanding of OHC mechanics and need to be considered in computational models of OHC electromotility that incorporate subcellular features.
MTF1, a classic metal sensing transcription factor, promotes myogenesis in response to copper
Authors: Tavera-Montañez Cristina , Hainer Sarah J. , Cangussu Daniella , Gordon Shellaina J.V. , Xiao Yao , Reyes-Gutierrez Pablo , Imbalzano Anthony N. , Navea Juan G. , Fazzio Thomas G. , Padilla-Benavides Teresita
Published: January 2019

MTF1 is a conserved metal-binding transcription factor in eukaryotes that binds to conserved DNA sequence motifs, termed metal response elements (MREs). MTF1 responds to metal excess and deprivation, protects cells from oxidative and hypoxic stresses, and is required for embryonic development in vertebrates. We used multiple strategies to identify an unappreciated role for MTF1 and copper (Cu) in cell differentiation. Upon initiation of myogenesis from primary myoblasts, MTF1 expression increased, as did nuclear localization.Mtf1knockdown impaired differentiation, while addition of non-toxic concentrations of Cu+enhanced MTF1 expression and promoted myogenesis. Cu+bound stoichiometrically to a C-terminus tetra-cysteine of MTF1. MTF1 bound to chromatin at the promoter regions of myogenic genes and binding was stimulated by copper. MTF1 formed a complex with MyoD at myogenic promoters, the master transcriptional regulator of the myogenic lineage. These studies establish novel mechanisms by which copper and MTF1 regulate gene expression in myoblast differentiation.
The Metabolites NADP+ and NADPH are the Targets of the Circadian Protein Nocturnin (Curled)
Authors: Estrella Michael A. , Du Jin , Chen Li , Rath Sneha , Prangley Eliza , Chitrakar Alisha , Aoki Tsutomu , Schedl Paul , Rabinowitz Joshua , Korennykh Alexei
Published: January 2019

Nocturnin (NOCT) is a rhythmically expressed protein that regulates metabolism under the control of circadian clock. It has been proposed that NOCT deadenylates and regulates metabolic enzyme mRNAs. However, in contrast to other deadenylases, purified NOCT lacks the deadenylase activity. To identify the substrate of NOCT, we conducted a mass spectrometry screen and report that NOCT specifically and directly converts the dinucleotide NADP+ into NAD+ and NADPH into NADH. Further, we demonstrate that the Drosophila NOCT ortholog, Curled, has the same enzymatic activity. We obtained the 2.7 Å crystal structure of the human NOCT•NADPH complex, which revealed that NOCT recognizes the chemically unique ribose-phosphate backbone of the metabolite, placing the 2’-terminal phosphate productively for removal. We provide evidence for NOCT targeting to mitochondria and propose that NADP(H) regulation, which takes place at least in part in mitochondria, establishes the molecular link between circadian clock and metabolism.
Soybean Haplotype Map (GmHapMap): A Universal Resource for Soybean Translational and Functional Genomics
Authors: Torkamaneh Davoud , Laroche Jérôme , Valliyodan Babu , O’Donoughue Louise , Cober Elroy , Rajcan Istvan , Abdelnoor Ricardo Vilela , Sreedasyam Avinash , Schmutz Jeremy , Nguyen Henry T. , Belzile François
Published: January 2019

Here we describe the first worldwide haplotype map for soybean (GmHapMap) constructed using whole-genome sequence data for 1,007Glycine maxaccessions and yielding 15 million variants. The number of unique haplotypes plateaued within this collection (4.3 million tag SNPs) suggesting extensive coverage of diversity within the cultivated germplasm. We imputed GmHapMap variants onto 21,618 previously genotyped (50K array/210K GBS) accessions with up to 96% success for common alleles. A GWAS performed with imputed data enabled us to identify a causal SNP residing in theNPC1gene and to demonstrate its role in controlling seed oil content. We identified 405,101 haplotypes for the 55,589 genes and show that such haplotypes can help define alleles. Finally, we predicted 18,031 putative loss-of-function (LOF) mutations in 10,662 genes and illustrate how such a resource can be used to explore gene function. The GmHapMap provides a unique worldwide resource for soybean genomics and breeding.
A tunable microfluidic device enables cargo encapsulation by cell- or organelle-sized lipid vesicles comprising asymmetric lipid monolayers
Authors: Romanov Valentin , McCullough John , Sharma Abhimanyu , Vershinin Michael , Gale Bruce K. , Frost Adam
Published: January 2019

Cellular membranes play host to a wide variety of morphologically and chemically complex processes. Although model membranes, like liposomes, are already widely used to reconstitute and study these processes, better tools are needed for making model bilayers that faithfully mimic cellular membranes. Existing methods for fabricating cell-sized (μm) or organelle-sized (tens to hundreds of nm) lipid vesicles have distinctly different requirements. Of particular note for biology, it remains challenging for any technique to efficiently encapsulate fragile cargo molecules or to generate liposomes with stable, asymmetric lipid-leaflets within the bilayer. Here we describe a tunable microfluidic device and protocol for fabricating liposomes with desired diameters ranging from ~10 μm to ~100 nm. Lipid vesicle size is templated by the simple inclusion of a polycarbonate filter within the microfluidic system and tuned with flow rate. We show that the vesicles made with our device are stable, unilamellar, lipid asymmetric, and capable of supporting transmembrane protein assembly, peripheral membrane protein binding, as well as soluble cargo encapsulation (including designer nanocages for biotechnology applications). These fabricated vesicles provide a new platform for studying the biophysically rich processes found within lipid-lipid and lipid-protein systems typically associated with cellular membranes.
Saccharomyces cerevisiae strains display robust phenotypes in the presence of Dyskeratosis congenita mutations in the Cbf5 gene
Authors: Ogailan Abeer Abdullah , Rintala-Dempsey Anne C. , Kothe Ute
Published: January 2019

Dyskeratosis congenita is a rare, congenital disorder affecting the skin, nails and oral mucosa of patients that often progresses to bone marrow failure and an increased predisposition for a variety of carcinomas. Mutations in the human dyskerin gene have been identified as the most prevalent cause of the disease. Dyskerin is a pseudouridine synthase and the catalytic subunit of H/ACA ribonucleoproteins (RNPs) responsible for the modification of uridines to pseudouridine in ribosomal RNA (rRNA), but dyskerin also binds to the telomerase RNA component (TERC). Accordingly, Dyskeratosis congenita mutations have been reported to affect both telomerase function as well as ribosome biogenesis, but the relative contribution of each pathway to the diseases is under debate. As the yeast homolog of dyskerin, Cbf5, does not interact with telomerase RNA, Saccharomyces cerevisiae is an ideal model to identify the selective impact of Dyskeratosis congenita mutations on ribosome biogenesis. Therefore, chromosomal mutations in the yeast homologue of dyskerin, Cbf5, were introduced at positions corresponding to the mutations in human dyskerin that result in Dyskeratosis congenita. To determine if the mutations affect cellular fitness, we screened for growth defects in yeast. Growth curves at different temperatures and yeast spot assays under several stress conditions revealed that the mutations in cbf5 did not impair growth compared to wild type. These findings suggest that in the yeast cell, Dyskeratosis congenita mutations do not significantly affect ribosome biogenesis, and we discuss the implications for understanding the molecular cause of Dyskeratosis congenita.
Dosimetric Study of Breast Scar Marker in Different Radiotherapy Dose Calculation Algorithms
Authors: Abdullah S. S , Alsadig Ahmed , Sulieman A. , Mattar Isam H. , Ying C. K. , Gokula K. , Azahari A. N. , Abdul Aziz M. Z
Published: January 2019

The purpose to this work is to validate and benchmark the delivered dose accuracy during radiotherapy treatment (without marker at scar site) to the dose calculated by treatment planning that included a marker on scar site. Dose distributions in breast cancer 3-dimensional conformal treatment planning (3D CRT) calculated with Pencil Beam (PB) and Collapsed Cone (CC) algorithms of commercial treatment planning system (Monaco and Oncentra MasterPlan) was compared as photon beam through homogenous and heterogenous media (by placing marker on phantom surface) to evaluate the perturbation of photon beam. Radiochromic film dose distribution value was compared to the dose calculated by CC algorithm of Monaco and Oncentra MasterPlan (OMP) Treatment Planning Systems (TPS) and PB algorithm of OMP TPS. During Computed Tomography (CT) simulation procedure for breast case, a metal-based scar marker (wire) was used to localize the tumour bed during treatment planning procedure which the phantom was considered as heterogeneous medium. In homogenous medium, PB algorithm gave smaller dose deviation compared to CC algorithm. When wire was introduced to the surface of phantom, PB algorithm (6.0 cGy) gave higher dose deviation compared to CC algorithm (2.0 cGy). However, CC algorithm (plasticine: 7.0 cGy and cable: 7.3 cGy) shows higher dose deviation compared to PB algorithm (plasticine: 6.3 cGy and cable: 6.6 cGy) when Plasticine and Cable marker were introduced. The placement of marker in lateral orientation gave smaller perturbation to megavoltage photon beam compared to axial orientation in overall case. Moreover, wire and plasticine are suitable as a scar marker due to its tissue equivalent density with less perturbation to photon beam.