bluuebunny/crossref_metadata_2025 huggingface dataset:
The Politics of A Modest Proposal: Swift and the Irish Crisis of the Late 1720s
Authors: McBride Ian
Published: April 2019

Swift’s Modest Proposal (1729) is widely regarded as the most brilliant satire in the English language, but its political context has never been properly explored. Some literary scholars have presented the tract as a parody of political economy; others have concentrated on the imputation of cannibalism, the distinguishing mark of the savage, which Swift redirects away from the natives towards the English settlers and their descendants. But nobody has convincingly related A Modest Proposal to the Irish parliamentary debates and pamphlet discussions of the late 1720s, when three successive harvest failures led to food riots in southern ports, large-scale emigration from the north, and thousands of deaths. Nor has anyone seriously investigated Swift’s hatred of the Irish landlord class, which provides A Modest Proposal with its most powerful, animating grievance. During the 1720s disputes over estate management, leasing practices and the relative merits of tillage and pastoral agriculture reflected the spiralling sense that the colonial mission of Ireland’s Protestant elite was on the point of collapse. Swift joined other patriotic commentators in deploring the conversion of arable land to pasture and the resultant expulsion of communities of villagers. Political economists marshalled statistics to demonstrate that human tenants could be as profitable as livestock. A dramatic deterioration in relations between Ireland’s clerical intelligentsia and the landed elite encouraged a distinct strain of social criticism among Anglican clergymen, who blamed landowners for depopulating the countryside ‐ something that Swift repeatedly associated with those barbarous man-eaters of ancient times, the Scythians. For a century and a half the cultivation of Irish soil had been a barometer of the civilising process; consequently the figure of the grazier had become for Swift the epitome of Irish perversity and self-destruction.
Supplemental oxygen therapy recommendations in patients with sickle cell disease during air travel: A cross-sectional survey of North American health care providers
Authors: Padda Amarjot , Corriveau-Bourque Catherine , Belletrutti Mark , Bruce Aisha A K
Published: April 2019

Introduction

Air travel may expose patients with sickle cell disease (SCD) to an increased risk of disease-related complications. Several factors are felt to contribute including prolonged hypoxia, dehydration, temperature changes, and stress. The Canadian Paediatric Society (CPS) position statement, published in 2007, recommends that SCD patients use supplemental oxygen on flights. While the National Heart, Lung and Blood Institute (NHLBI) recommend that SCD patients dress warmly, stay hydrated, and move about the cabin. Other guidelines do not make specific recommendations.

Methods

A cross-sectional online survey was circulated through the Canadian Hemoglobinopathy Association (CanHaem) and American Society of Pediatric Hematology and Oncology (ASPHO) listservs to North American health care practitioners (HCPs). Participants were asked to share their air travel recommendations for patients with SCD. Similarly, a patient survey regarding experiences with air travel was circulated through the Sickle Cell Disease Association of Canada (SCDAC) and the Sickle Cell Foundation of Alberta (SCFOA) listservs and discussion boards.

Results

Although air travel is perceived to be a risk factor for sickling complications, only 18% of HCPs recommend supplemental oxygen. Most HCPs advise patients to increase hydration, carry analgesics, and wear warm clothes to prevent sickling complications. The patient survey was limited by a low response rate.

Conclusion

The majority of HCPs are not routinely recommending prophylactic oxygen to patients with SCD during air travel.
Identification of Differentially Expressed miRNAs between a Wheat K-type Cytoplasmic Male Sterility Line and Its Near-Isogenic Restorer Line
Authors: Li Hongxia , Guo Jinglei , Zhang Chengyang , Zheng Weijun , Song Yulong , Wang Yu
Published: April 2019

K-type cytoplasmic male sterility (KCMS) lines were ideal material for three-line hybrid wheat system due to the major role in hybrid wheat production. In this study, the morphology of developing microspore and mature pollen was compared between a KCMS line and its near-isogenic restorer line (KCMS-NIL). The most striking difference is that the microspore was unable to develop into tricellular pollen in the KCMS line. MicroRNA plays vital roles in flowering and gametophyte development. Small RNA sequencing identified a total of 274 known and 401 novel miRNAs differentially expressed between two lines or two developmental stages. Most of miRNAs with high abundance were differentially expressed at the uninucleate stage, and their expression level recovered or remained at the binucleate stage. Further degradome sequencing identified target genes which were mainly enriched in transcription regulation, phytohormone signaling and RNA degradation pathways. Combining with the transcriptome data, a correlation was found between the abnormal anther development, such as postmeiotic mitosis cessation, deformative pollen wall and the chromosome condensation of the vegetative cell, and the alterations in the related miRNA and their targets expression profiles. According to the correlation and pathway analysis, we propose a hypothetic miRNA-mediated network for the control of KCMS restoration.
Iron Biofortification of Staple Crops: Lessons and Challenges in Plant Genetics
Authors: Connorton James M , Balk Janneke
Published: April 2019

Plants are the ultimate source of iron in our diet, either directly as staple crops and vegetables or indirectly via animal fodder. Increasing the iron concentration of edible parts of plants, known as biofortification, is seen as a sustainable approach to alleviate iron deficiency which is a major global health issue. Advances in sequencing and gene technology are accelerating both forward and reverse genetic approaches. In this review, we summarize recent progress in iron biofortification using conventional plant breeding or transgenics. Interestingly, some of the gene targets already used for transgenic approaches are also identified as genetic factors for high iron in genome-wide association studies. Several quantitative trait loci and transgenes increase both iron and zinc, due to overlap in transporters and chelators for these two mineral micronutrients. Research efforts are predominantly aimed at increasing the total concentration of iron but enhancing its bioavailability is also addressed. In particular, increased biosynthesis of the metal chelator nicotianamine increases iron and zinc levels and improves bioavailability. The achievements to date are very promising in being able to provide sufficient iron in diets with less reliance on meat to feed a growing world population.
In vitro and in vivo proves of concept for the use of a chemically cross-linked poly(ester-urethane-urea) scaffold as an easy handling elastomeric biomaterial for bone regeneration
Authors: Rohman Géraldine , Changotade Sylvie , Frasca Sophie , Ramtani Salah , Consalus Anne , Langueh Credson , Collombet Jean-Marc , Lutomski Didier
Published: April 2019

Bone loss can occur as a result of various pathologies, traumas and injuries and poor bone healing leads to functionally debilitating condition, loss of self-sufficiency and deterioration in life quality. Given the increasing incidence of facial trauma and the emergence of new procedural techniques, advanced scaffolds are currently developed as substitutes for bone tissue engineering. In this study, we investigated the capability of a chemically cross-linked ε-caprolactone-based poly(ester-urethane-urea) (PCLU) scaffold to support bone regeneration. In vitro assays demonstrated that PCLU scaffolds could be colonized by cells through direct cell seeding and cell migration from outside to scaffold inside. Moreover, PCLU scaffolds could provide a suitable environment for stem cells proliferation in a 3D spatial arrangement, and allowed osteogenic differentiation under appropriate induction. In vivo results revealed the osteogenic properties of PCLU scaffolds through a drilled-hole femoral bone defect repair improvement in rats. Using histology and microtomography analysis, we showed that PCLU scaffolds fit well the bone cavity and were eventually entrapped between the newly formed trabeculae. Finally, no sign of inflammation or rejection was noticed. We envision that PCLU scaffolds can provide the clinicians with a substitute having appropriate characteristics for the treatment of bone defects.
Fast and cloning-free CRISPR/Cas9-mediated genomic editing in mammalian cells
Authors: Manna Paul T. , Davis Luther J. , Robinson Margaret S.
Published: April 2019

CHoP-In (CRISPR/Cas9-mediated, Homology-independent, PCR-product Integration) is a fast and cloning-free strategy for genomic editing of mammalian cells. The desired integration fragment is produced as a PCR product, flanked by the Cas9 recognition sequences of the target locus. When co-transfected with the cognate Cas9/guide RNA, double strand breaks are introduced at the target genomic locus and at both ends of the PCR product. This allows incorporation into the genomic locus via hon-homologous end joining. The approach is versatile, allowing N-terminal, C-terminal or internal tag integration and gives predictable genomic integrations, as demonstrated for a selection of key membrane trafficking proteins. The lack of any donor vectors offers advantages over existing methods in terms of both speed and hands-on time. As such this approach will be a useful addition to the genome editing toolkit of those working in mammalian cell systems.
The Community Simulator: A Python package for microbial ecology
Authors: Marsland Robert , Mehta Pankaj , Cui Wenping , Goldford Joshua
Published: April 2019

Natural microbial communities contain hundreds to thousands of interacting species. For this reason, computational simulations are playing an increasingly important role in microbial ecology. In this manuscript, we present a new open-source, freely available Python package called Community Simulator for simulating microbial population dynamics in a reproducible, transparent and scalable way. The Community Simulator includes five major elements: tools for preparing the initial states and environmental conditions for a set of samples, automatic generation of dynamical equations based on a dictionary of modeling assumptions, random parameter sampling with tunable levels of metabolic and taxonomic structure, parallel integration of the dynamical equations, and support for metacommunity dynamics with migration between samples. To significantly speed up simulations using Community Simulator, our Python package implements a new Expectation-Maximization (EM) algorithm for finding equilibrium states of community dynamics that exploits a recently discovered duality between ecological dynamics and convex optimization. We present data showing that this EM algorithm improves performance by between one and two orders compared to direct numerical integration of the corresponding ordinary differential equations. We conclude by listing several recent applications of the Community Simulator to problems in microbial ecology, and discussing possible extensions of the package for directly analyzing microbiome compositional data.
A comparison between power spectral density and network metrics: an EEG study
Authors: Demuru Matteo , La Cava Simone Maurizio , Pani Sara Maria , Fraschini Matteo
Published: April 2019

Power spectral density (PSD) and network analysis performed on functional correlation (FC) patterns represent two common approaches used to characterize Electroencephalographic (EEG) data. Despite the two approaches are widely used, their possible association may need more attention. To investigate this question, we performed a comparison between PSD and some widely used nodal network metrics (namely strength, clustering coefficient and betweenness centrality), using two different publicly available resting-state EEG datasets, both at scalp and source levels, employing four different FC methods (PLV, PLI, AEC and AECC). Here we show that the two approaches may provide similar information and that their correlation depends on the method used to estimate FC. In particular, our results show a strong correlation between PSD and nodal network metrics derived from FC methods (PLV and AEC) that do not limit the effects of volume conduction/signal leakage. The correlations are less relevant for more conservative FC methods (AECC). These findings suggest that the results derived from the two different approaches may be not independent and should not be treated as distinct analyses. We conclude that it may represent good practice to report the findings from the two approaches in conjunction to have a more comprehensive view of the results.
Explicit control of step timing during split-belt walking reveals interdependent recalibration of movements in space and time
Authors: Gonzalez-Rubio Marcela , Velasquez Nicolas F. , Torres-Oviedo Gelsy
Published: April 2019

Split-belt treadmills that move the legs at different speeds are thought to update internal representations of the environment, such that this novel condition generates a new locomotor pattern with distinct spatio-temporal features compared to those of regular walking. It is unclear the degree to which such recalibration of movements in the spatial and temporal domains is interdependent. In this study, we explicitly altered subjects’ limb motion in either space or time during split-belt walking to determine its impact on the adaptation of the other domain. Interestingly, we observed that motor adaptation in the spatial domain was susceptible to altering the temporal domain, whereas motor adaptation in the temporal domain was resilient to modifying the spatial domain. This nonreciprocal relation suggests a hierarchical organization such that the control of timing in locomotion has an effect on the control of limb position. This is of translational interest because clinical populations often have a greater deficit in one domain compared to the other. Our results suggest that explicit changes to temporal deficits cannot occur without modifying the spatial control of the limb.
Demographic Model for Inheritable Cardiac Disease
Authors: Burghardt Thomas P.
Published: April 2019

The cardiac muscle proteins, generating and regulating energy transduction during a heartbeat, assemble in the sarcomere into a cyclical machine repetitively translating actin relative to myosin filaments. Myosin is the motor transducing ATP free energy into actin movement against resisting force. Cardiac myosin binding protein C (mybpc3) regulates shortening velocity probably by transient N-terminus binding to actin while its C-terminus strongly binds the myosin filament. Inheritable heart disease associated mutants frequently modify these proteins involving them in disease mechanisms. Nonsynonymous single nucleotide polymorphisms (SNPs) cause single residue substitutions with independent characteristics (sequence location, residue substitution, human demographic, and allele frequency) hypothesized to decide dependent phenotype and pathogenicity characteristics in a feed-forward Neural network model. Trial models train and validate on a dynamic worldwide SNP database for cardiac muscle proteins then predict phenotype and pathogenicity for any single residue substitution in myosin, mybpc3, or actin. A separate Bayesian model formulates conditional probabilities for phenotype or pathogenicity given independent SNP characteristics. Neural/Bayes forecasting tests SNP pathogenicity vs (in)dependent SNP characteristics to assess individualized disease risk and in particular to elucidate gender and human subpopulation bias in disease. Evident subpopulation bias in myosin SNP pathogenicities imply myosin normally engages other sarcomere proteins functionally. Consistent with this observation, mybpc3 forms a third actomyosin interaction competing with myosin essential light chain N-terminus suggesting a novel strain-dependent mechanism adapting myosin force-velocity to load dynamics. The working models, and the integral myosin/mybpc3 motor concept, portends the wider considerations involved in understanding heart disease as a systemic maladaptation.
Predicting the conservation status of Europe’s Data Deficient sharks and rays
Authors: Walls Rachel H.L. , Dulvy Nicholas K.
Published: April 2019

Shark and ray biodiversity is threatened primarily by overfishing and the globalisation of trade, and Europe has been one of the most documented heavily fished regions for a relatively long time. Yet, we have little idea of the conservation status of the hundreds of Data Deficient shark and ray species. It is important to derive some insight into the status of these species, both to understand global extinction rates and also to ensure that any threatened Data Deficient species are not overlooked in conservation planning. Here, we developed a biological and ecological trait model to predict the categorical conservation status of 26 Northeast Atlantic and 15 Mediterranean Sea Data Deficient sharks and rays. We first developed an explanatory model based on all speciesevaluatedon the International Union for Conservation of Nature (IUCN) Red List of Threatened SpeciesTM, using maximum body size, median depth (as a proxy for fisheries exposure), and reproductive mode, and thenpredictedthe status of all Data Deficient species. Almost half of Northeast Atlantic (46%,n=12 of 26), and two-thirds of Mediterranean (67%,n=10 of 15) Data Deficient species are predicted to be in one of the three IUCN threatened categories. Northeast Atlantic Data Deficient species arepredictedto be 1.2 times more threatened thanevaluatedspecies (38%,n=36 of 94), whereas threat levels in the Mediterranean Sea are relative for each (66%,n=38 of 58). This case study is intended for extrapolation to the global shark and ray dataset upon completion of the global IUCN Red List assessment. Trait-based, categorical prediction of conservation status is a cost-effective approach towards incorporating Data Deficient species into (i) estimates of lineage-wide extinction rates, (ii) revised protected species lists, and (iii) Red List Indices, thus preventing poorly known species from reaching extinction unnoticed.
A Simulation Study of mRNA Diffusion and Mitochondrial Localization
Authors: Horton Paul
Published: April 2019

Background

We have observed a negative correlation between rapid translation initiation of mRNA and their localization at mitochondria. One potential explanation of this anti-correlation is that mRNA which initiate translation away from mitochondria experience a significant drop in mobility and thus remain there. To explore this possibility, we conducted an initial simulation of diffusion and compared those results to gene-specific experimental measurements of mRNA mitochondrial localization.

Methods

Here, we conduct a follow-up simulation study to complement the initial one. In particular we attempt a more quantitative analysis, deriving linear scale estimates of mitochondrial localization probability from sequencing based measurements. We compare this data to simulated mitochondrial localization probabilities under a variety of simulation parameter settings.

Conclusions

We conclude that if a change in mRNA mobility after translation initiation is a significant factor in explaining the negative correlation between mRNA localization and translation initiation efficiency, then 1) the effective diffusion coefficient of mRNA must be strongly reduced upon translation initiation (e.g. 20x) and 2) mRNA molecules which have not yet initiated translation when approaching a mitochondrial surface must have a non-zero probability of anchoring there.
Logic-based Analysis of Gene Expression Data Predicts Pathway Crosstalk between TNF, TGFB1 and EGF in Basal-like Breast Cancer
Authors: Jo Kyuri , Buitrago Beatriz Santos , Kim Minsu , Rhee Sungmin , Talcott Carolyn , Kim Sun
Published: April 2019

For breast cancer, clinically important subtypes are well characterised at the molecular level in terms of gene expression profiles. In addition, signaling pathways in breast cancer have been extensively studied as therapeutic targets due to their roles in tumor growth and metastasis. However, it is challenging to put signaling pathways and gene expression profiles together to characterise biological mechanisms of breast cancer subtypes since many signaling events result from post-translational modifications, rather than gene expression differences.

We present a logic-based approach to explain the differences in gene expression profiles among breast cancer subtypes using Pathway Logic and transcriptional network information. Pathway Logic is a rewriting-logic-based formal system for modeling biological pathways including post-translational modifications. Proposed method demonstrated its utility by constructing subtype-specific path from key receptors (TNFR, TGFBR1 and EGFR) to key transcription factor (TF) regulators (RELA, ATF2, SMAD3 and ELK1) and identifying potential pathway crosstalk via TFs in basal-specific paths, which could provide a novel insight on aggressive breast cancer subtypes.

Availability

Analysis result is available athttp://epigenomics.snu.ac.kr/PL/
The Chinese chestnut genome: a reference for species restoration
Authors: Staton Margaret , Addo-Quaye Charles , Cannon Nathaniel , Sun Yongshuai , Zhebentyayeva Tetyana , Huff Matthew , Fan Shenghua , Bellis Emily , Islam-Faridi Nurul , Yu Jiali , Henry Nathan , Conrad Anna , Drautz-Moses Daniela I. , Zhu Xingfu , Lu Zhiqiang , Noorai Rooksana E. , Ficklin Stephen , Saski Chris , Mandal Mihir , Wagner Tyler K , Zembower Nicole , Bodénès Catherine , Holliday Jason , Westbrook Jared , Lasky Jesse , Georgi Laura , Hebard Fred V , Nelson C. Dana , Schuster Stephan C , Abbott Albert G , Carlson JE
Published: April 2019

Forest tree species are increasingly subject to severe mortalities from exotic pests, diseases, and invasive organisms, accelerated by climate change. Forest health issues are threatening multiple species and ecosystem sustainability globally. While sources of resistance may be available in related species, or among surviving trees, introgression of resistance genes into threatened tree species in reasonable time frames requires genome-wide breeding tools. Asian species of chestnut (Castaneaspp.) are being employed as donors of disease resistance genes to restore native chestnut species in North America and Europe. To aid in the restoration of threatened chestnut species, we present the assembly of a reference genome with chromosome-scale sequences for Chinese chestnut (C. mollissima), the disease-resistance donor for American chestnut restoration. We also demonstrate the value of the genome as a platform for research and species restoration, including new insights into the evolution of blight resistance in Asian chestnut species, the locations in the genome of ecologically important signatures of selection differentiating American chestnut from Chinese chestnut, the identification of candidate genes for disease resistance, and preliminary comparisons of genome organization with related species.
The statistical structure of the hippocampal code for space as a function of time, context, and value
Authors: Lee Jae Sung , Briguglio John , Romani Sandro , Lee Albert K.
Published: April 2019

Hippocampal activity represents many behaviorally important variables, including context, an animal’s location within a given environmental context, time, and reward. Here we used longitudinal calcium imaging in mice, multiple large virtual environments, and differing reward contingencies to derive a unified probabilistic model of hippocampal CA1 representations centered on a single feature – the field propensity. Each cell’s propensity governs how many place fields it has per unit space, predicts its reward-related activity, and is preserved across distinct environments and over months. The propensity is broadly distributed—with many low, and some very high, propensity cells —and thus strongly shapes hippocampal representations. The result is a range of spatial codes, from sparse to dense. Propensity varied ~10-fold between adjacent cells in a salt-and-pepper fashion, indicating substantial functional differences within a presumed cell type. The stability of each cell’s propensity across conditions suggests this fundamental property has anatomical, transcriptional, and/or developmental origins.
DeepGOPlus: Improved protein function prediction from sequence
Authors: Kulmanov Maxat , Hoehndorf Robert
Published: April 2019

Protein function prediction is one of the major tasks of bioinformatics that can help in wide range of biological problems such as understanding disease mechanisms or finding drug targets. Many methods are available for predicting protein functions from sequence based features, protein–protein interaction networks, protein structure or literature. However, other than sequence, most of the features are difficult to obtain or not available for many proteins thereby limiting their scope. Furthermore, the performance of sequence-based function prediction methods is often lower than methods that incorporate multiple features and predicting protein functions may require a lot of time.

We developed a novel method for predicting protein functions from sequence alone which combines deep convolutional neural network (CNN) model with sequence similarity based predictions. Our CNN model scans the sequence for motifs which are predictive for protein functions and combines this with functions of similar proteins. We evaluate the performance of DeepGOPlus on the CAFA3 dataset and significantly improve the performance of predictions of biological processes and cellular components with Fmax of 0.47 and 0.70, respectively, using only the amino acid sequence of proteins as input. DeepGOPlus can annotate around 40 protein sequences per second, thereby making fast and accurate function predictions available for a wide range of proteins.
The rice leaf microbiome has a conserved community structure controlled by complex host-microbe interactions
Authors: Roman-Reyna Veronica , Pinili Dale , Borja Frances Nikki , Quibod Ian Lorenzo , Groen Simon C. , Mulyaningsih Enung S , Rachmat Agus , Slamet-Loedin Inez H. , Alexandrov Nikolai , Mauleon Ramil , Oliva Ricardo
Published: April 2019

Understanding the factors that influence the outcome of crop interactions with microbes is key to managing crop diseases and improving yield. While the composition, structure and functional profile of crop microbial communities are shaped by complex interactions between the host, microbes and the environment, the relative contribution of each of these factors is mostly unknown. Here, we profiled the community composition of bacteria across leaves of 3,024 rice (Oryza sativa) accessions from field trials in China and the Philippines using metagenomics. Despite significant differences in diversity between environments, the structure and metabolic profiles of the microbiome appear to be conserved, suggesting that microbiomes converge onto core functions. Furthermore, co-occurrence analysis identified microbial hubs that regulate the network structure of the microbiome. We identified rice genomic regions controlling the abundance of these hubs, enriched for processes involved in stress responses and carbohydrate metabolism. We functionally validated the importance of these processes, finding that abundance of hub taxa was different in rice mutants with altered cellulose and salicylate accumulation, two major metabolites at the host-microbe interactions interface. By identifying key host genomic regions, host traits and hub microbes that govern microbiome composition, our study opens the door to designing future cropping systems.
Degradation levels of continuous speech affect neural speech tracking and alpha power differently
Authors: Hauswald Anne , Keitel Anne , Chen Ya-Ping , Rösch Sebastian , Weisz Nathan
Published: April 2019

Understanding degraded speech, e.g. following a hearing damage, can pose a challenge. Previous attempts to quantify speech intelligibility in neural terms have usually focused on one of two measures, namely low-frequency speech-brain synchronization or alpha power modulations. However, reports have been mixed concerning the modulation of these measures, an issue aggravated by the fact that they have normally been studied separately. Using a parametric speech degradation approach, we present MEG studies that overcome this shortcoming. In a first study, participants listened to unimodal auditory speech with three different levels of degradation (original, 7-channel and 3-channel vocoding). Intelligibility declined with declining clarity, implemented by fewer vocoding channels but was still intelligible to some extent even for the lowest clarity level used (3-channel vocoding). Low- frequency (1-7 Hz) speech tracking suggested a u-shaped relationship with strongest effects for the medium degraded speech (7-channel) in bilateral auditory and left frontal regions. To follow up on this finding, we implemented three additional vocoding levels (5-channel, 2- channel, 1-channel) in a second MEG study. Using this wider range of degradation, the speech-brain synchronization showed a similar pattern for the degradation levels used in the first study but further shows that when speech becomes unintelligible, synchronization declines again. The relationship differed for alpha power, which continued to decrease across vocoding levels reaching a floor effect for 5-channel vocoding. Predicting subjective intelligibility based on models either combining both measures or each measure alone, showed superiority of the combined model. Our findings underline that speech tracking and alpha power are modified differently by the degree of degradation of continuous speech but together contribute to the subjective understanding of speech.
Effects of sugars and lipids on the growth and development ofCaenorhabditis elegans
Authors: Wang Xiong , Zhang Lin , Zhang Lei , Wang Wenli , Wei Sihan , Wang Jie , Che Huilian , Zhang Yali
Published: April 2019

Excessive intake of carbohydrates and fats causes over-nutrition, leading to a variety of diseases and complications. Here, we characterized the effects of different types of sugar and lipids on the growth and development ofCaenorhabditis elegans. We measured the lifespan, reproductive capacity, and length of nematodes after sugars and lipids treatment alone and co-treatment of sugars and lipids. Furthermore, by using transcriptome sequencing technology, we studied the mechanisms underlying the damaged caused by high-sucrose and high-stearic acid onC. elegans. The results showed that a certain concentration of sugar and lipid promoted the growth and development of nematodes. However, excessive sugars and lipids shortened the lifespan and length of nematodes and destroyed their reproductive capacity. Based on the results of the orthogonal test, we selected 400 mmol/L sucrose and 500 μg/mL stearic acid to model a high-sugar and high-lipid diet forC. elegans. High-sugar and high-lipid intake altered the expression of genes involved in biofilm synthesis, genes that catalyze the synthesis and degradation of endogenous substances, and genes involved in innate immunity, resulting in physiological damage.
The PPR-related splicing cofactor MSP1/EMB1025 protein, encoded by At4g20090, encode an essential protein that is required for the splicing ofnad1intron 1 and for the biogenesis of complex I in Arabidopsis mitochondria
Authors: Best Corinne , Zmudjak Michal , Ostersetzer-Biran Oren
Published: April 2019

Group II introns are particularly plentiful within plant mitochondrial genomes (mtDNAs), where they interrupt the coding-regions of many organellar genes, especialy within complex I (CI) subunits. Their splicing is essential for the biogenesis of the respiratory system and is facilitated by various protein-cofactors that belong to a diverse set of RNA-binding cofactors. These including maturases, which co-evolved with their host-introns, and varioustrans-acting factors, such as members of the pentatricopeptide-repeat (PPR) protein family. The genomes of angiosperms contain hundreds ofPPR-related genes that are postulated to reside within the organelles and affect diverse posttranscriptional steps, such as editing, RNA-stability and processing or translation. Here, we report the characterization of MSP1 (Mitochondria Splicing PPR-factor 1; also denoted as EMB1025), which plays a key role in the processing ofnad1pre-RNAs in Arabidopsis mitochondria. Mutations inMSP1gene-locus (At4g20090) result in early embryonic arrest. To analyze the putative roles of MSP1 in organellar RNA-metabolism we used a modified embryo-rescue method, which allowed us to obtain sufficient plant tissue for the analysis of the RNA and protein profiles associated withmsp1mutants. Our data indicate that MSP1 is essential for thetrans-splicing ofnad1intron 1 in Arabidopsis mitochondria. Accordingly,msp1mutants show CI biogenesis defects and reduced respiratory-mediated functions. These results provide with important insights into the roles of nuclear-encoded factors during early plant development, and contribute to our limited understanding of the importance of RNA-maturation and splicing in plant mitochondria during early embryogenesis.
Multifaceted Changes in Synaptic Composition and Astrocytic Involvement in a Mouse Model of Fragile X Syndrome
Authors: Simhal Anish K. , Zuo Yi , Perez Marc M. , Madison Daniel V. , Sapiro Guillermo , Micheva Kristina D.
Published: April 2019

Fragile X Syndrome (FXS), a common inheritable form of intellectual disability, is known to alter neocortical circuits. However, its impact on the diverse synapse types comprising these circuits, or on the involvement of astrocytes, is not well known. We used immunofluorescent array tomography to quantify different synaptic populations and their association with astrocytes in layers 1 through 4 of the adult somatosensory cortex of a FXS mouse model, the FMR1 knockout mouse. The collected multi-channel data contained approximately 1.6 million synapses which were analyzed using a probabilistic synapse detector. Our study reveals complex, synapse-type and layer specific changes in the neocortical circuitry of FMR1 knockout mice. In layers 1 and 2/3, there is a significant decrease in the density of excitatory glutamatergic synapses, both VGluT1 and VGluT2 type, and their association with astrocytes, while the changes in inhibitory GABAergic synapses are less pronounced. Meanwhile in layer 4, there is a significant increase in the density of small VGluT1 synapses, with no changes in the astrocytic association of synapses. The ability to dissect the circuit deficits by synapse type and astrocytic involvement, will be crucial for understanding how these changes affect circuit function, and ultimately define targets for therapeutic intervention.
Multilayered N-glycoproteomics reveals impaired N-glycosylation promoting Alzheimer’s disease
Authors: Fang Pan , Xie Juan-Juan , Sang Shao-Ming , Zhang Lei , Liu Ming-Qi , Yang Lu-Jie , Xu Yi-Teng , Yan Guo-Quan , Yao Jun , Gao Xing , Qian Wen-Jing , Wang Zhong-Feng , Zhang Yang , Yang Peng-Yuan , Shen Hua-Li
Published: April 2019

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases that currently lacks clear pathogenesis and effective treatment. Protein glycosylation is ubiquitous in brain tissue and site-specific analysis of N-glycoproteome, which is technically challenging, can advance our understanding of the glycoproteins’ role in AD. In this study, we profiled the multilayered variations in proteins, N-glycosites, N-glycans, and in particular site-specific N-glycopeptides in the APP/PS1 and wild type mouse brain through combining pGlyco 2.0 strategy with other quantitative N-glycoproteomic strategies. The comprehensive brain N-glycoproteome landscape was constructed, and rich details of the heterogeneous site-specific protein N-glycosylations were exhibited. Quantitative analyses explored generally downregulated N-glycosylation involving proteins such as glutamate receptors, as well as fucosylated and oligo-mannose type glycans in APP/PS1 mice versus wild type mice. Moreover, our preliminary functional study revealed that N-glycosylation was crucial for the membrane localization of NCAM1 and for maintaining the excitability and viability of neuron cells. Our work offered a panoramic view of the N-glycoproteomes in Alzheimer’s disease and revealed that generally impaired N-glycosylation promotes Alzheimer’s disease progression.
Catestatin improves insulin sensitivity in diet-induced obese mice: in vivo and in silico validation
Authors: Dasgupta Abhijit , Bandyopadhyay Keya , Ray Indrani , Bandyopadhyay Gautam K. , Chowdhury Nirmalya , De Rajat K. , Mahata Sushil K.
Published: April 2019

Obesity is characterized by a state of chronic, unresolved inflammation in insulin-targeted tissues. Obesity-induced inflammation accumulates proinflammatory macrophages in adipose tissue and liver. Proinflammatory cytokines released from tissue macrophages inhibits insulin sensitivity. Chromogranin A (CgA) peptide catestatin (CST: hCgA352-372) improves obesity-induced hepatic insulin resistance by reducing inflammation and inhibiting proinflammatory macrophage infiltration. Obesity leads to inflammation-induced endoplasmic reticulum (ER) stress and insulin resistance. We reasoned that the anti-inflammatory effects of CST would alleviate ER stress. CST decreased obesity-induced ER dilation in hepatocytes and macrophages. CST reduced phosphorylation of UPR signaling molecules and increased phosphorylation of insulin signaling molecules. We developed an in silico state space model mimicking dynamics of integrated ER stress and insulin pathways. Proportional-Integral-Derivative (PID) controllers helped in checking whether the reduction of phosphorylated PERK resulting in attenuation of ER stress, resembling CST effect, could enhance insulin sensitivity. The simulation results showed CST not only decreased ER stress but also enhanced insulin sensitivity. Simulation results also revealed that enhancement of AKT phosphorylation overcame effects of high ER stress to achieve insulin sensitivity.
Methylation content sensitive enzyme ddRAD (MCSeEd): a reference-free, whole genome profiling system to address cytosine/ adenine methylation changes
Authors: Marconi Gianpiero , Capomaccio Stefano , Comino Cinzia , Acquadro Alberto , Portis Ezio , Porceddu Andrea , Albertini Emidio
Published: April 2019

Methods for investigating DNA methylation nowadays either require a reference genome and high coverage, or investigate only CG methylation. Moreover, no large-scale analysis can be performed for N6-methyladenosine (6mA). Here we describe the methylation content sensitive enzyme double-digest restriction-site-associated DNA (ddRAD) technique (MCSeEd), a reduced-representation, reference-free, cost-effective approach for characterizing whole genome methylation patterns across different methylation contexts (e.g., CG, CHG, CHH, 6mA). MCSeEd can also detect genetic variations among hundreds of samples. MCSeEd is based on parallel restrictions carried out by combinations of methylation insensitive and sensitive endonucleases, followed by next-generation sequencing. Moreover, we present a robust bioinformatic pipeline (available athttps://bitbucket.org/capemaster/mcseed/src/master/) for differential methylation analysis combined with single nucleotide polymorphism calling without or with a reference genome.
Perception of aversive stimuli of different gustatory modalities in an haematophagous insect,Rhodnius prolixus
Authors: Masagué Santiago , Cano Agustina , Asparch Yamila , Barrozo Romina B. , Minoli Sebastian
Published: April 2019

Sensory aversion is an essential link for avoiding potential dangers. Here, we studied the chemical perception of aversive compounds of different gustatory modalities (salty and bitter) in the haematophagous kissing bug,Rhodnius prolixus. Over a walking arena, insects preferred a substrate embedded with 0.3 M NaCl or KCl rather than with distilled water. Same salts were avoided when prepared at 1 M. When NaCl and KCl were confronted, no preferences were evinced by insects. A pre-exposure to amiloride interfered with the repellency of NaCl and KCl equally, suggesting that amiloride-sensitive receptors are involved in the detection of both salts. Discriminative experiments were then performed to determine ifR. prolixuscan distinguish between these salts. An aversive operant conditioning involving either NaCl or KCl modulated the repellency of the conditioned salt, but also of the novel salt. A chemical pre-exposure to the salts did not to modify their repellency levels. When we crossed gustatory modalities by confronting NaCl to caffeine (i.e.a bitter stimulus) no innate preferences were evinced. Aversive operant conditionings with either NaCl or Caf rendered unspecific changes in the repellency of both compounds. A chemical pre-exposure to Caf modulated the response to Caf but not to NaCl, suggesting the existence of two independent neural pathways for the detection of salts and bitter compounds. Overall results suggest thatR. prolixuscannot distinguish between NaCl and KCl but can distinguish between NaCl and Caf and generalizes the response between these two aversive stimuli of different gustatory modality.

Summary statement

Kissing-bugs use contact chemo-perception to avoid aversive substrates. They can sensory distinguish between salty (sodium chloride) and bitter (caffeine) tastes, but not between different salts (sodium and potassium chloride).
Smear positive tuberculosis and genetic diversity ofM. tuberculosisisolates in individuals visiting health facilities in South Gondar Zone, northwest Ethiopia
Authors: Alelign Amir , Petros Beyene , Ameni Gobena
Published: April 2019

Background

Tuberculosis (TB), a bacterial infectious disease, persisted to be a public health concern in many developing countries. However, lack of enough data concerning the public health burden and potential risk factors for the disease hampered control programs in target areas. Therefore, the present study aimed in determining the prevalence of TB and genetic diversity ofM. tuberculosisisolates in South Gondar Zone, northwest Ethiopia.

Methods

A cross-sectonal study was conducte between March 2015 and April 2017. Bacteriological examination, region of difference (RD) 9 based polymerase chain reaction (PCR) and spoligotyping were used to undertake the study.

Results

The overall prevalence of smear positive all forms TB was 6.3% (186/2953). Extra pulmonary TB (EPTB) was clinically characterized on about 62.4% (116/186) TB-positive cases. Some of the patients’ demographic characteristics such as [patients’ origin (chi-square (χ2) value; 62.8, p<0.001) were found to be significantly associated risk factors for the occurrence of TB in the study area. All the mycobacterial isolates were found to beM. tuberculosis.Among the 35 different spoligotype patterns identified, 22 patterns were shared types. The three dominantly identified families were T, CAS and Manu, each consisting of 46.9%, 24.0% and 10.4% of the isolates, respectively

Conclusion

The presented study revealed that TB continued to be a public health problem in South Gondar Zone which suggests a need of implementing effective disease control strategies.
Vitamin D deficiency during pregnancy and its associated factors among third trimester Malaysian pregnant women
Authors: Woon Fui Chee , Chin Yit Siew , Ismail Intan Hakimah , Batterham Marijka , Abdul Latiff Amir Hamzah , Gan Wan Ying , Appannah Geeta , Mohammed Hussien Siti Huzaifah , Edi Muliana , Tan Meng Lee , Chan Yoke Mun
Published: April 2019

Background

Despite perennial sunshine, vitamin D deficiency is prevalent among Malaysian especially pregnant women.

Objective

To determine the vitamin D status and its associated factors among third trimester pregnant women attending government health clinics in Selangor and Kuala Lumpur, Malaysia.

Methods

Information on socio-demographic characteristics, obstetrical history, vitamin D intake, supplement use, and sun exposure were obtained through face-to-face interviews. Serum 25-hydroxyvitamin D concentration was measured and classified as deficient (< 30 nmol/L), insufficient (30-50 nmol/L), and sufficient (≥ 50 nmol/L).

Results

Of the 535 pregnant women recruited, 42.6% were vitamin D deficient. They consumed an average of 8.7 ± 6.7 μg of vitamin D daily. A total of 80.4% of the vitamin D were obtained from the food sources, while 19.6% were from dietary supplements. Fish and fish products showed the highest contribution to vitamin D intake (35.8%). The multivariate generalized linear mixed models, with clinic as a random effect, indicates that higher intake of vitamin D is associated with lower risk of vitamin D deficiency among pregnant women (OR = 0.96; 95% CI = 0.93-0.99). Non-Malay pregnant women had lower odds of having vitamin D deficiency (OR = 0.13; 95% CI = 0.04-0.37) compared to Malays. No associations were found between age, educational level, monthly household income, work status, gravidity, parity, pre-pregnancy body mass index, total hours of sun exposure, total percentage of body surface area, and sun exposure index per day with vitamin D deficiency.

Conclusions

Vitamin D deficiency is prevalent among Malaysian pregnant women. Considering the possible adverse obstetric and fetal outcomes of vitamin D deficiency during pregnancy, antenatal screening of vitamin D levels and nutrition education should be emphasised by taking into consideration ethnic differences.
PanoView: An iterative clustering for single-cell RNA sequencing data
Authors: Hu Ming-Wen , Kim Dong Won , Liu Sheng , Zack Donald J , Blackshaw Seth , Qian Jiang
Published: April 2019

Single-cell RNA-sequencing (scRNA-seq) provides new opportunities to gain a mechanistic understanding of many biological processes. Current approaches for single cell clustering are often sensitive to the input parameters and have difficulty dealing with cell types with different densities. Here, we present Panoramic View (PanoView), an iterative method integrated with a novel density-based clustering, Ordering Local Maximum by Convex hull (OLMC), that uses a heuristic approach to estimate the required parameters based on the input data structures. In each iteration, PanoView will identify the most confident cell clusters and repeat the clustering with the remaining cells in a new PCA space. Without adjusting any parameter in PanoView, we demonstrated that PanoView was able to detect major and rare cell types simultaneously and outperformed other existing methods in both simulated datasets and published single-cell RNA-sequencing datasets. Finally, we conducted scRNA-Seq analysis of embryonic mouse hypothalamus, and PanoView was able to reveal known cell types and several rare cell subpopulations.

Author summary

One of the important tasks in analyzing single-cell transcriptomics data is to classify cell subpopulations. Most computational methods require users to input parameters and sometimes the proper parameters are not intuitive to users. Hence, a robust but easy-to-use method is of great interest. We proposed PanoView algorithm that utilizes an iterative approach to search cell clusters in an evolving three-dimension PCA space. The goal is to identify the cell cluster with the most confidence in each iteration and repeat the clustering algorithm with the remaining cells in a new PCA space. To cluster cells in a given PCA space, we also developed OLMC clustering to deal with clusters with varying densities. We examined the performance of PanoView in comparison to other existing methods using ten published single-cell datasets and simulated datasets as the ground truth. The results showed that PanoView is an easy-to-use and reliable tool and can be applied to diverse types of single-cell RNA-sequencing datasets.