bluuebunny/crossref_metadata_2025 huggingface dataset:
Reallocation to lateral and early-emerging axial roots allows maize (Zea mays L.) with reduced nodal root number to more efficiently forage for nitrate
Authors: Guo Haichao , York Larry M.
Published: January 2019

Previous simulations indicated reduced nodal root number (NRN) was promising for maize (Zea maysL.) breeding, and were partially confirmed using variation in NRN among inbreds. However, the exact mechanism was unknown, therefore manipulative experiments were conducted in hydroponics and tall solid-media mesocosms with treatments involving no nodal root excision (0% NRE) or excising either 33% or 67% of the nodal roots (NR) as they emerged under high or low levels of nitrogen (N). Reduced NRN was hypothesized to increase elongation of all remaining root classes, increase N acquisition under low N, and increase shoot mass. In both experiments, plants with 67% NRE had 12% and 19% less root fraction of total biomass, 61% and 91% greater lateral-to-axial root length ratio regardless of N levels; and 61% and 182% greater biomass of embryonic roots under low N, compared to 0% NRE for hydroponics and mesocosms studies, respectively. In hydroponics, regardless of NRE level, specific root respiration under high N was 2.6 times of low N, and was greatest at depth. Under low N in mesocosms, plants with 67% NRE had 52% greater shoot biomass, 450% greater root length at depth, and 232% greater deep-injected15N content in the shoot relative to 0% NRE, however biomass in hydroponics did not differ based on NRE. These results reveal the mechanism by which plants with fewer nodal roots increase N capture and shoot mass by reallocation of biomass to lateral, embryonic, and first whorl nodal roots that increases foraging efficiency in solid media.

Reallocating root biomass from nodal roots to lateral and early-emerging axial roots allows grasses to capture more nitrogen under limiting conditions, including by increasing foraging at depth.
Single-molecule long-read sequencing reveals the chromatin basis of gene expression
Authors: Wang Yunhao , Wang Anqi , Liu Zujun , Thurman Andrew , Powers Linda S. , Zou Meng , Hefel Adam , Li Yunyi , Zabner Joseph , Au Kin Fai
Published: January 2019

Genome-wide chromatin accessibility and nucleosome occupancy profiles have been widely investigated, while the long-range dynamics remains poorly studied at the single-cell level. Here we present a new experimental approach MeSMLR-seq (methyltransferase treatment followed by single-molecule long-read sequencing) for long-range mapping of nucleosomes and chromatin accessibility at single DNA molecules, and thus achieve comprehensive-coverage characterization of the corresponding heterogeneity. We applied MeSMLR-seq to haploid yeast, where single DNA molecules represent single cells, and thus we could investigate the combinatorics of many (up to 356) nucleosomes at long range in single cells. We illustrated the differential organization principles of nucleosomes surrounding transcription start site for silently- and actively-transcribed genes, at the single-cell level and in the long-range scale. The heterogeneous patterns of chromatin statuses spanning multiple genes were phased. Together with single-cell RNA-seq data, we quantitatively revealed how chromatin accessibility correlated with gene transcription positively in a highly-heterogeneous scenario. Moreover, we quantified the openness of promoters and investigated the coupled chromatin changes of adjacent genes at single DNA molecules during transcription reprogramming.
Accumulation of Rare Coding Variants in Genes Implicated in Risk of Human Cleft Lip with or without Cleft Palate
Authors: Marini Nicholas J. , Asrani Kripa , Yang Wei , Rine Jasper , Shaw Gary M
Published: January 2019

Cleft lip with/without cleft palate (CLP) is a common craniofacial malformation with complex etiologies, reflecting both genetic and environmental factors. Most of the suspected genetic risk for CLP has yet to be identified. To further classify risk loci and estimate the contribution of rare variants, we sequenced the exons in 49 candidate genes in 323 CLP cases and 211 non-malformed controls. Our findings indicated that rare, protein-altering variants displayed markedly higher burdens in CLP cases at relevant loci. First, putative loss-of-function mutations (nonsense, frameshift) were significantly enriched among cases: 13 of 323 cases (~4%) harbored such alleles within these 49 genes, versus one such change in controls (p= 0.01). Second, in gene-level analyses, the burden of rare alleles showed greater case-association for several genes previously implicated in cleft risk. For example,BHMTdisplayed a 10-fold increase in protein-altering variants in CLP cases (p= 0.03), including multiple case occurrences of a rare frameshift mutation (K400fs). Other loci with greater rare, coding allele burdens in cases were in signaling pathways relevant to craniofacial development (WNT9B,BMP4,BMPR1B) as well as the methionine cycle (MTRR). We conclude that rare coding variants may confer risk for isolated CLP.
Multi-omic analysis of CIC’s functional networks reveals novel interaction partners and a potential role in mitotic fidelity
Authors: Takemon Yuka , LeBlanc Véronique G. , Song Jungeun , Chan Susanna Y. , Lee Stephen Dongsoo , Trinh Diane L. , Ahmad Shiekh Tanveer , Brothers William R. , Corbett Richard D. , Gagliardi Alessia , Moradian Annie , Cairncross J Gregory , Yip Stephen , Aparicio Samuel A.J.R. , Chan Jennifer A. , Hughes Christopher S. , Morin Gregg B. , Gorski Sharon M. , Chittaranjan Suganthi , Marra Marco A.
Published: January 2019

CICencodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CIC’s interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, and also observed novel interactions between CIC and cell cycle regulators and RNA processing factors. We found that CIC loss is associated with an increased frequency of mitotic defects in human cell lines and anin vivomouse model and with dysregulated expression of mitotic regulators. We also observed aberrant splicing in CIC-deficient cell lines predominantly at 3’ and 5’ untranslated regions of genes, including genes involved in MAPK signalling, DNA repair, and cell cycle regulation. Our study thus characterises the complexity of CIC’s functional network and describes the effect of its loss on cell cycle regulation, mitotic integrity, and transcriptional splicing, thereby expanding our understanding of CIC’s potential roles in cancers. In addition, our work exemplifies how multi-omic, network-based analyses can be used to uncover novel insights into the interconnected functions of pleiotropic genes/proteins across cellular contexts.

Simple summary

Capicua (CIC) is a gene that is frequently mutated in several cancer types, including stomach cancers and certain subtypes of brain tumours and sarcomas. CIC, the protein encoded by theCICgene, has been shown to play a multitude of roles in both normal and cancer cell functions; however, most studies exploring these roles focus on a single aspect of CIC function and may therefore overlook complex interconnected activities in which CIC is involved. In this study, we have used multiple complementary approaches to obtain a broader view of CIC’s complex functional networks. We observed novel interactions (genetic or physical) between CIC and genes/proteins involved in various aspects of cellular function, including regulation of cell division and processing of RNA molecules. Altogether, our work characterises the complexity of CIC’s functional network and expands our understanding of its potential roles in cancer.
Sample preparation protocol enabling nano-to-mesoscopic mapping of cellular connectomes and their habitats in human tissues and organs
Authors: Ngo Lucy , Nathanson Anton D. , Garbowski Tomasz , Knothe Ulf , Zeidler Dirk , Tate Melissa L. Knothe
Published: January 2019

Multibeam scanning electron microscopy (multiSEM) provides a technical platform for seamless nano-to-mesoscale mapping of cells in human tissues and organs, which is a major new initiative of the U.S. National Institutes of Health. Developed for rapid throughput imaging of minute defects on semiconductor wafers, multiSEM has recently been adapted for imaging of human organs, their constituent tissues, and their respective cellular inhabitants. Through integration of geospatial approaches, statistical and network modelling, advances in computing and the management of immense datasets, as well as recent developments in machine learning that enable the automation of big data analyses, multiSEM and other cross-cutting imaging technologies have the potential to exert a profound impact on elucidation of disease mechanisms, translating to improvements in human health. Here we provide a protocol for acquisition and preparation of sample specimen sizes of diagnostic relevance for human anatomy and physiology. We discuss challenges and opportunities to integrate this approach with multibeam scanning electron microscopy work flows as well as multiple imaging modalities for mapping of organ and tissue structure and function.
A sensory ecological perspective on mate sampling strategies: simulation models and an empirical test
Authors: Nandi Diptarup , Suswaram Megha , Balakrishnan Rohini
Published: January 2019

Long-range communication signals play a central role in mate search and mate choice across a wide range of taxa. Among the different aspects of mate choice, the strategy an individual employ to search for potential mates (mate sampling) has been less explored despite its significance. Although analytical models of mate sampling have demonstrated significant differences in individual fitness returns for different sampling strategies, these models have rarely incorporated relevant information on the ecology of signalers and sensory physiology of receivers, both of which can profoundly influence which sampling strategy is optimal. In this study, we used simulation models to compare the costs and benefits of different female mate sampling strategies in an acoustically communicating field cricket (Plebeiogryllus guttiventris) by incorporating information on relative spacing of callers in natural choruses, their signal intensity and the effect of signal intensity on female phonotaxis behaviour. Mating with the louder caller that the female first approaches emerged as the optimal strategy, thus reflecting the importance of physiological mechanisms of sound signal localization (passive attraction) over active sampling. When tested empirically in the field, female behaviour was consistent with passive attraction.
The influence of object-colour knowledge on emerging object representations in the brain
Authors: Teichmann Lina , Quek Genevieve L. , Robinson Amanda K. , Grootswagers Tijl , Carlson Thomas A. , Rich Anina N.
Published: January 2019

The ability to rapidly and accurately recognise complex objects is a crucial function of the human visual system. To recognise an object, we need to bind incoming visual features such as colour and form together into cohesive neural representations and integrate these with our pre-existing knowledge about the world. For some objects, typical colour is a central feature for recognition; for example, a banana is typically yellow. Here, we applied multivariate pattern analysis on time-resolved neuroimaging (magnetoencephalography) data to examine how object-colour knowledge affects emerging object representations over time. Our results from 20 participants (11 female) show that the typicality of object-colour combinations influences object representations, although not at the initial stages of object and colour processing. We find evidence that colour decoding peaks later for atypical object-colour combinations in comparison to typical object-colour combinations, illustrating the interplay between processing incoming object features and stored object-knowledge. Taken together, these results provide new insights into the integration of incoming visual information with existing conceptual object knowledge.

Significance Statement

To recognise objects, we have to be able to bind object features such as colour and shape into one coherent representation and compare it to stored object knowledge. The magnetoencephalography data presented here provide novel insights about the integration of incoming visual information with our knowledge about the world. Using colour as a model to understand the interaction between seeing and knowing, we show that there is a unique pattern of brain activity for congruently coloured objects (e.g., a yellow banana) relative to incongruently coloured objects (e.g., a red banana). This effect of object-colour knowledge only occurs after single object features are processed, demonstrating that conceptual knowledge is accessed relatively late in the visual processing hierarchy.
Complementary roles for ventral pallidum cell types and their projections in relapse
Authors: Prasad Asheeta A. , Xie Caroline , Chaichim Chanchanok , Killcross Simon , Power John M. , McNally Gavan P.
Published: January 2019

Ventral pallidum (VP) is a key node in the neural circuits controlling relapse to drug seeking but how this role relates to different VP cell types and their projections is poorly understood. Using male rats, we show how different forms of relapse to alcohol-seeking are assembled from VP cell types and their projections to lateral hypothalamus (LH) and ventral tegmental area (VTA). First, we used RNAScope in situ hybridization to characterize activity of different VP cell types during relapse to alcohol-seeking provoked by renewal (context-induced reinstatement). We found that VP Gad1 and parvalbumin (PV), but not vGlut2, neurons show relapse-associated changes in c-Fos expression. Next, we used retrograde tracing, chemogenetic, optogenetic, and electrophysiological approaches to study the roles of VPGad1 and VPPV neurons in relapse. We show that VPGad1 neurons contribute to contextual control over relapse (renewal), but not to relapse during reacquisition, via projections to LH where they converge with ventral striatal inputs onto LHGad1 neurons. This convergence of striatopallidal inputs at the level of individual LHGad1 neurons may be critical to balancing propensity for relapse versus abstinence. In contrast, VPPV neurons contribute to relapse during both renewal and reacquisition via projections to VTA but not LH. These findings show complementary roles for different VP cell types and their projections in relapse. VPGad1 neurons control relapse during renewal via projections to LH whereas VPPV neurons control relapse during both renewal and reacquisition via projections to VTA. Targeting these different pathways may provide tailored interventions for different forms of relapse.
Heterologous expression of Stlac2, a laccase isozyme of Setosphearia turcica, and the ability of decolorization of malachite green
Authors: Liu Ning , Shen Shen , Jia Hui , Yang Beibei , Guo Xiaoyue , Si Helong , Cao Zhiyan , Dong Jingao
Published: January 2019

Laccases can catalyze monoelectronic oxidation and have shown to have an increasing value in industrial application. In this study, as identified by Native-PAGE and ESI-MS/MS, ascomycetous fungus Setosphaeria turcica produced three laccase isozymes: Stlac1, Stlac2, and Stlac6. Stlac2 was heterologously expressed in both eukaryotic and prokaryotic expression systems. The eukaryotic recombinant Stlac2 expressed in Pichia pastoris was inactive, and also showed a higher molecular weight than predicted because of glycosylation. The depression of laccase activity was attributable to the incorrect glycosylation at Asn97. Stlac2 expressed in Escherichia coli and after being renaturated from the inclusion body, the recombinant Stlac2 exhibited activity of 28.23 U/mg with 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as the substrate. The highest activity was observed at pH of 4.5 and the temperature of 60 °C. The activity of recombinant Stlac2 was inhibited by 10 mM Na+, Mg2+, Ca2+, Mn2+, and increased by 10 mM of Fe3+ with a relatively activity of 315% compared with no addition. Cu2+ did not affect enzyme activity. Recombinant Stlac2 was capable of decolorizing 67.08% of 20 mg/L malachite green in 15 min without any mediators. It is suggested that Stlac2 has potential industrial applications.

Importance

Setosphaeria turcica, an ascomycetous fungus causes northern corn leaf blight, product three laccase isozymes identified by Native-PAGE and ESI-MS/MS. The major expression laccase gene StLAC2 was expression in both eukaryotic and prokaryotic expression systems, which found incorrect glycosylation at Asn97 may result in the depression of laccase activity. The heterologous laccase Stlac2 decolorize organic dye malachite green, which had a potential industrial application.
GIGI2: A Fast Approach for Parallel Genotype Imputation in Large Pedigrees
Authors: Ullah Ehsan , Kunji Khalid , Wijsman Ellen M. , Saad Mohamad
Published: January 2019

Motivation

Imputation of untyped SNPs has become important in Genome-wide Association Studies (GWAS). There has also been a trend towards analyzing rare variants, driven by the decrease of genome sequencing costs. Rare variants are enriched in pedigrees that have many cases or extreme phenotypes. This is especially the case for large pedigrees, which makes family-based designs ideal to detect rare variants associated with complex traits. The costs of performing relatively large family-based GWAS can be significantly reduced by fully sequencing only a fraction of the pedigree and performing imputation on the remaining subjects. The program GIGI can efficiently perform imputation in large pedigrees but can be time consuming. Here, we implement GIGI’s imputation approach in a new program, GIGI2, which performs imputation with computational time reduced by at least 25x on one thread and 120x on eight threads. The memory usage of GIGI2 is reduced by at least 30x. This reduction is achieved by implementing better memory layout and a better algorithm for solving the Identity by Descent graphs, as well as with additional features, including multithreading. We also make GIGI2 available as a webserver based on the same framework as the Michigan Imputation Server.

Availability

GIGI2 is freely available online at https://cse-git.qcri.org/eullah/GIGI2 and the websever is at https://imputation.qcri.org/

Contact

msaad@hbku.edu.qa
SPIKEPIPE: A metagenomic pipeline for the accurate quantification of eukaryotic species occurrences and abundances using DNA barcodes or mitogenomes
Authors: Ji Yinqiu , Huotari Tea , Roslin Tomas , Schmidt Niels Martin , Wang Jiaxin , Yu Douglas W. , Ovaskainen Otso
Published: January 2019

The accurate quantification of eukaryotic species abundances from bulk samples remains a key challenge for community description and environmental biomonitoring. We resolve this challenge by combining shotgun sequencing, mapping to reference DNA barcodes or to mitogenomes, and three correction factors: (1) a percent-coverage threshold to filter out false positives, (2) an internal-standard DNA spike-in to correct for stochasticity during sequencing, and (3) technical replicates to correct for stochasticity across sequencing runs. This pipeline achieves a strikingly high accuracy of intraspecific abundance estimates from samples of known composition (mapping to barcodes R2=0.93, mitogenomes R2=0.95) and a high repeatability across environmental-sample replicates (barcodes R2=0.94, mitogenomes R2=0.93). As proof of concept, we sequence arthropod samples from the High Arctic systematically collected over 17 years, detecting changes in species richness, abundance, and phenology using either barcodes or mitogenomes. SPIKEPIPE provides cost-efficient and reliable quantification of eukaryotic communities, with direct application to environmental biomonitoring.

Statement of authorship

NMS has been involved in running the BioBasis sampling program for more than twenty years. TR, NMS, DWY, and OO conceived the study and its design. TH led the work in generating all the DNA samples and YJ led the work in assembling and annotating the mitogenomes for the mitochondrial genome reference database. TH led the work in generating the mock communities and bulk samples, with contributions from YJ and JW. YJ and DWY developed the molecular and bioinformatic methods. OO led the modelling of the data. TR and OO wrote the first draft of the manuscript, and all authors contributed substantially to its further improvement.

Data accessibility statement

Should the manuscript be accepted, the data supporting the results will be archived in an appropriate public repository (Dryad), and the data DOI will be included at the end of the article. The bioinformatic and R scripts and associated data tables will also be made available on github.com.
Bayesian Tip-dated Phylogenetics: Topological Effects, Stratigraphic Fit and the Early Evolution of Mammals
Authors: King Benedict , Beck Robin
Published: January 2019

The incorporation of stratigraphic data into phylogenetic analysis has a long history of debate, but is not currently standard practice for palaeontologists. Bayesian tip-dating (or morphological clock) phylogenetic methods have returned these arguments to the spotlight, but how tip-dating affects the recovery of evolutionary relationships has yet to be fully explored. Here we show, through analysis of several datasets with multiple phylogenetic methods, that topologies produced by tip-dating are outliers when compared to topologies produced by parsimony and undated Bayesian methods, which retrieve broadly similar trees. Unsurprisingly, trees recovered by tip-dating have better fit to stratigraphy than trees recovered by other methods, due to trees with better stratigraphic fit being assigned a higher prior probability. Differences in stratigraphic fit and tree topology between tip-dating and other methods appear to be concentrated in parts of the tree with weaker character signal and a stronger influence of the prior, as shown by successive deletion of the most incomplete taxa from a sauropod dataset. Tip-dating applied to Mesozoic mammals firmly rejects a monophyletic Allotheria, and strongly supports diphyly of haramiyidans, with the late TriassicHaramiyaviaandThomasiaforming a clade with tritylodontids, which is distant from the middle Jurassic euharamiyidans. This result is not sensitive to the controversial age of the eutherianJuramaia. A Test of the age ofJuramaiausing a less restrictive prior reveals strong support from the data for an Early Cretaceous age. Our results suggest that tip-dating incorporates stratigraphic data in an intuitive way, with good stratigraphic fit a prior expectation that can be overturned by strong evidence from character data.
Imaging Single–Cell Blood Flow in the Smallest to Largest Vessels in the Living Retina
Authors: Joseph Aby , Guevara–Torres Andrés , Schallek Jesse B.
Published: January 2019

Impact Statement

Using a specialized camera that corrects for eye blur, millions of single blood cells are imaged and their speed measured, as they travel through the largest-to-smallest vessels of the retina.

Tissue light scatter limits the visualization of the microvascular network deep inside the living mammal. The transparency of the mammalian eye provides a noninvasive view of the microvessels of the retina, a part of the central nervous system. Despite its clarity, imperfections in the optics of the eye blur microscopic retinal capillaries, and single blood cells flowing within. This limits early evaluation of microvascular diseases that originate in capillaries. To break this barrier, we use adaptive optics to noninvasively measure single–cell blood flow, in one of the most widely used research animals: the C57BL/6J mouse. Flow ranged four orders of magnitude (0.0002–1.55 µL min−1) across the full spectrum of retinal vessel diameters (3.2–45.8 µm), without requiring surgery or contrast dye. Here we describe the data collection approach using adaptive optics and provide an analysis pipeline that can measure millions of blood cell speeds automatically.
ABCDE approach to victims by lifeguards: how do they manage a critical patient? A cross sectional simulation study
Authors: Fernández-Méndez Felipe , Otero-Agra Martín , Abelairas-Gómez Cristian , Saez-Gallego Nieves Maria , Rodríguez-Núñez Antonio , Barcala-Furelos Roberto
Published: January 2019

Introduction

Decision-making in emergencies is a multifactorial process based on the rescuer, patient, setting and resources. The eye-tracking system is a proven method for assessing decision-making process that has been used in different fields of science. Our aim was to evaluate the lifeguards' capacity to perform the ABCDE (Airway-Breathing-Circulation-Dissability-Exposure) approach when facing a simulated critically ill-drowned victim.

Methods

A cross sectional simulation study was designed to assess the skills and sequence of the ABCDE approach by 20 professional lifeguards. They had to assess a victim and act according to his/her clinical status following the ABCDE primary assessment approach. Two kind of variables were recorder: those related to quality of each step of the ABCDE approach; visual behaviour using a portable eye-movement system. The eye-tracking system was the Mobile Eye system (Bedford, USA).

Results

None of the study participants was able to complete correctly the ABCDE approach. Lifeguards spent more time in the Circulation step: Airway (15.5±11.1 s), Breathing (25.1±21.1 s), Circulation (44.6±29.5 s), Disability (38.5±0.7 s). Participants spent more time in viewpoints considered as important (65.5±17.4 s) compared with secondary ones (34.6±17.4 s, p = 0.008). This also was represented in the percentage of visual fixations (fixations in important viewpoints: 63.36±15.06; fixation in secondary viewpoints: 36.64±15.06).

Conclusion

Professional lifeguards failed to fully perform the ABCDE sequence. Evaluation by experts with the help of eye-tracking technology detected lifeguards' limitations in the assessment and treatment of an eventual critically ill victim. Such deficits should be considered in the design and implementation of lifeguards’ training programmes.
Mating Induces Switch From Hormone-Dependent to – Independent Steroid Receptor-Mediated Growth in Drosophila Prostate-Like Cells
Authors: Leiblich Aaron , Hellberg Josephine E. E. U. , Sekar Aashika , Gandy Carina , Redhai Siamak , Wainwright Mark , Marie Pauline , Goberdhan Deborah C. I. , Hamdy Freddie C. , Wilson Clive
Published: January 2019

Male reproductive glands like the mammalian prostate and the paired Drosophila melanogaster accessory glands secrete seminal fluid components that enhance fecundity. In humans, the prostate grows throughout adult life, stimulated by environmentally regulated endocrine and local androgens. We previously showed that in each fly accessory gland, secondary cells (SCs) and their nuclei also grow in adults, a process enhanced by mating and controlled by bone morphogenetic protein (BMP) signalling. Here we demonstrate that BMP-mediated SC growth is dependent on the receptor for the developmental steroid, ecdysone, whose concentration reflects socio-sexual experience in adults. BMP signalling regulates ecdysone receptor (EcR) levels post-transcriptionally, partly via EcR’s N-terminus. Nuclear growth in virgin males is ecdysone-dependent. However, mating activates genome endoreplication to drive additional BMP-mediated nuclear growth via a cell type-specific form of hormone-independent EcR signalling. In virgin males with low ecdysone levels, this mechanism ensures resources are conserved. However, by switching to hormone-independence after mating, this control is overridden to hyper-activate growth of secretory secondary cells. Our data suggest parallels between this physiological, behaviour-induced switch and altered pathological signalling associated with prostate cancer progression.
Computational vaccinology approach: Designing an efficient multi-epitope peptide vaccine againstCryptococcus neoformans var. grubii’sheat shock 70KDa protein
Authors: Elhassan Reham M. , Alsony Nagla M. , Othman Khadeejah M. , Izz-Aldin Duaa T. , Alhaj Tamadour A. , Ali Abdelrahman A. , Abashir Lena A. , Ahmed Omar H. , Hassan Mohammed A.
Published: January 2019

Introduction

Cryptococcosis is a ubiquitous opportunistic fungal disease caused by Cryptococcus neoformans var. grubii. It has high global morbidity and mortality among HIV patients and none-HIV carriers with 99% and 95% respectively. Furthermore, the increasing prevalence of undesired toxicity profile of antifungal, multi-drug resistant organism, and the scarcity of FDA authorized vaccines, where the hallmark in the present days. This study was undertaken to design a reliable multi-epitope peptide vaccine against highly conserved immunodominant heat shock 70KDa protein of Cryptococcus neoformans var. grubii that covers a considerable digit of the world population through implementing computational vaccinology approach.

Materials and Methods

A total of 38 Sequences of Cryptococcus neoformans var. grubii’s heat shock 70KDa protein were retrieved from NCBI protein database. Different prediction tools were used to analyze the aforementioned protein at Immune Epitope Database (IEDB) to discriminate the most promising T-cell and B-cell epitopes. Then the proposed epitopes were subjected to Population coverage analysis tool to compute global population’s coverage. Finally, the projected epitopes were ranked based on their scores and binding modes through using Moe 2007 program.

Outstanding Results and Conclusion

Our prime vaccine candidate was a putative ten promising epitopes (ANYVQASEK, NYVQASEK, KSVEKPAS, TPQQPPAQ, YVYDTRGKL, FYRQGAFEL, FTQLVAAYL, FFGGKVLNF, FDYALVQHF, and FINAQLVDV). Together, these epitopes are forecasted to trigger T lymphocytes, B lymphocytes, and immunological memory with overall population coverage above 90%. Accordingly, our in silico vaccine is expected to be the future multi-epitope peptide vaccine against Cryptococcus neoformans var. grubii’s heat shock 70KDa protein that covers a significant figure of the entire world citizens. Therefore, there is a definite need for experimental validation for the carefully chosen vaccine candidates in vitro and in vivo to fortify their antigenic and immunogenic potentials. Additionally, further computational studies are needed to be conducted in pathogens-derived Heat shock 70KDa protein family, as it believed to find universal epitopes that might be overlapped with other pathogens-derived Hsp70.
Controlling gene activation by enhancers through a drug-inducible topological insulator
Authors: Tsujimura Taro , Takase Osamu , Yoshikawa Masahiro , Sano Etsuko , Hayashi Matsuhiko , Hoshi Kazuto , Takato Tsuyoshi , Toyoda Atsushi , Okano Hideyuki , Hishikawa Keiichi
Published: January 2019

While regulation of gene-enhancer interaction is better understood, its application remains limited. Here, we reconstituted arrays of CTCF binding sites and devised a synthetic topological insulator with tetO for chromatin-engineering (STITCH). By coupling STITCH with tetR linked to the KRAB domain to induce heterochromatin and disable the insulation, we developed a drug-inducible system to control gene activation by enhancers. We applied this to dissect MYC regulation in human pluripotent stem cells. Insertion of STITCH between MYC and the enhancer down-regulated MYC and affected its target transcriptome. Progressive mutagenesis of STITCH led to preferential escalation of the gene-enhancer interaction, corroborating the strong insulation ability of STITCH. The STITCH insertion altered epigenetic states around MYC. Time-course analysis by drug induction uncovered deposition and removal of H3K27me3 repressive marks follows and reflects, but does not precede and determine, the expression change. Thus the tool provided important insights in gene regulation, demonstrating its potency.
The determinants of genetic diversity in butterflies – Lewontin’s paradox revisited
Authors: Mackintosh Alexander , Laetsch Dominik R. , Hayward Alexander , Waterfall Martin , Vila Roger , Lohse Konrad
Published: January 2019

Under the neutral theory genetic diversity is expected to be a simple function of population size. However, comparative studies have consistently failed to find any strong correlation between measures of census population size and genetic diversity. Instead, a recent comparative study across several animal phyla identified propagule size as the strongest predictor of genetic diversity, suggesting that r-strategists that produce many offspring but invest little in each, have greater long-term effective population sizes. We present a comparison of genome-wide levels of genetic diversity across 38 species of European butterflies (Papilionoidea). We show that across butterflies, genetic diversity varies over an order of magnitude and that this variation cannot be explained by differences in abundance, fecundity, host plant use or geographic range. Instead, we find that genetic diversity is negatively correlated with body size and positively with the length of the genetic map. This suggests that variation in genetic diversity is determined both by fluctuation inNeand the effect of selection on linked neutral sites.
HOPS: Automated detection and authentication of pathogen DNA in archaeological remains
Authors: Hübler Ron , Key Felix M. , Warinner Christina , Bos Kirsten I. , Krause Johannes , Herbig Alexander
Published: January 2019

High-throughput DNA sequencing enables large-scale metagenomic analyses of complex biological systems. Such analyses are not restricted to present day environmental or clinical samples, but can also be fruitfully applied to molecular data from archaeological remains (ancient DNA), and a focus on ancient bacteria can provide valuable information on the long-term evolutionary relationship between hosts and their pathogens. Here we present HOPS (HeuristicOperations forPathogenScreening), an automated bacterial screening pipeline for ancient DNA sequence data that provides straightforward and reproducible information on species identification and authenticity. HOPS provides a versatile and fast pipeline for high-throughput screening of bacterial DNA from archaeological material to identify candidates for subsequent genomic-level analyses.
PGxCorpus: a Manually Annotated Corpus for Pharmacogenomics
Authors: Legrand Joël , Gogdemir Romain , Bousquet Cédric , Dalleau Kevin , Devignes Marie-Dominique , Digan William , Lee Chia-Ju , Ndiaye Ndeye-Coumba , Petitpain Nadine , Ringot Patrice , Smaïl-Tabbone Malika , Toussaint Yannick , Coulet Adrien
Published: January 2019

Pharmacogenomics (PGx) studies how individual gene variations impact drug response phenotypes, which makes knowledge related to PGx a key component towards precision medicine. A significant part of the state-of-the-art knowledge in PGx is accumulated in scientific publications, where it is hardly usable to humans or software. Natural language processing techniques have been developed and are indeed employed for guiding experts curating this amount of knowledge. But, existing works are limited by the absence of high quality annotated corpora focusing on the domain. This absence restricts in particular the use of supervised machine learning approaches. This article introduces PGxCorpus, a manually annotated corpus, designed for the automatic extraction of PGx relationships from text. It comprises 945 sentences from 911 PubMed abstracts, annotated with PGx entities of interest (mainly genes variations, gene, drugs and phenotypes), and relationships between those. We present in this article the method used to annotate consistently texts, and a baseline experiment that illustrates how this resource may be leveraged to synthesize and summarize PGx knowledge.
Three stages in the development of the cyst wall of the eye pathogen Acanthamoeba castellanii
Authors: Magistrado-Coxen Pamela , Aqeel Yousuf , Lopez A , Samuelson John
Published: January 2019

When deprived of nutrients, trophozoites of the eye pathogen Acanthamoeba castellanii make a cyst wall, which contains cellulose and has two layers connected by cone-shaped ostioles. We recently showed chitin is also present and identified three sets of lectins, which localize to the ectocyst layer (Jonah lectin) or the endocyst layer and ostioles (Luke and Leo lectins). To determine how the cyst wall is made, we examined encysting protists using structured illumination microscopy, probes for glycopolymers, and tags for lectins. In the first stage (3 to 9 hr), cellulose, chitin, and a Jonah lectin were each made in dozens of encystation-specific vesicles. In the second stage (12 to 18 hr), a primordial wall contained both glycopolymers and Jonah lectin, while small, flat ostioles were outlined by a Luke lectin. In the third stage (24 to 36 hr), an ectocyst layer enriched in Jonah lectin was connected to an endocyst layer enriched in Luke and Leo lectins by large, conical ostioles. Jonah and Luke lectins localized to the same places in mature cyst walls (72 hr) independent of the timing of expression. The Jonah lectin and the glycopolymer bound by the lectin were accessible in the ectocyst layer of mature walls. In contrast, Luke and Leo lectins and glycopolymers bound by the lectins were mostly inaccessible in the endocyst layer and ostioles. These results show that cyst wall formation is a tightly choreographed event, in which glycopolymers and lectins combine to form a mature wall with a protected endocyst layer.

Importance

While the cyst wall of Acanthamoeba castellanii, cause of eye infections, contains cellulose like plants and chitin like fungi, it is a temporary, protective structure, analogous to spore coats of bacteria. We showed here that, unlike plants and fungi, A. castellanii makes cellulose and chitin in encystation-specific vesicles. The outer and inner layers of cyst walls, which resemble the primary and secondary walls of plant cells, respectively, are connected by unique structures (ostioles) that synchronously develop from small, flat circles to large, conical structures. Cyst wall proteins, which are lectins that bind cellulose and chitin, localize to inner or outer layers independent of the timing of expression. Because of its abundance and accessibility in the outer layer, the Jonah lectin is an excellent target for diagnostic antibodies. A description of the sequence of events during cyst wall development is a starting point for mechanistic studies of its assembly.
Spectral tuning of adaptation supports coding of sensory context in auditory cortex
Authors: Espejo Mateo Lopez , Schwartz Zachary P. , David Stephen V.
Published: January 2019

Perception of vocalizations and other behaviorally relevant sounds requires integrating acoustic information over hundreds of milliseconds, but the latency of sound-evoked activity in auditory cortex typically has much shorter latency. It has been observed that the acoustic context, i.e., sound history, can modulate sound evoked activity. Contextual effects are attributed to modulatory phenomena, such as stimulus-specific adaption and contrast gain control. However, an encoding model that links context to natural sound processing has yet to be established. We tested whether a model in which spectrally tuned inputs undergo adaptation mimicking short-term synaptic plasticity can account for contextual effects during natural sound processing. Single-unit activity was recorded from primary auditory cortex of awake ferrets during presentation of noise with natural temporal dynamics and fully natural sounds. Encoding properties were characterized by a standard linear-nonlinear spectro-temporal receptive field model (LN STRF) and STRF variants that incorporated STP-like adaptation. In two models, STP was applied either globally across all spectral channels or locally to subsets of channels. For most neurons, STRFs incorporating locally tuned STP predicted neural activity as well or better than the LN and global STP STRF. The strength of nonlinear adaptation varied across neurons. Within neurons, adaptation was generally stronger for activation with excitatory than inhibitory gain. Neurons showing improved STP model performance also tended to undergo stimulus-specific adaptation, suggesting a common mechanism for these phenomena. When STP STRFs were compared between passive and active behavior conditions, response gain often changed, but average STP parameters were stable. Thus, spectrally and temporally heterogeneous adaptation, subserved by a mechanism with STP-like dynamics, may support representation of the diverse spectro-temporal patterns that comprise natural sounds.

Author summary

Successfully discriminating between behaviorally relevant sounds such as vocalizations and environmental noise requires processing how acoustic information changes over many tens to hundreds of milliseconds. The sound-evoked activity measured for most auditory cortical neurons is relatively short (< 50 ms), so it is not clear how the auditory cortex encodes sound information over longer periods. In this study, we propose that nonlinear adaptation, mimicking the effects of short-term synaptic plasticity (STP), enables auditory neurons to encode longer and more complex spectro-temporal patterns. A model in which sound history is stored in the latent state of plastic synapses is able to describe responses of single cortical neurons to natural sounds better than a standard encoding model that does not include nonlinear adaptation. Moreover, STP-like adaptation can account for contextual effects on sound evoked activity that cannot be accounted for by standard encoding models.
Characterizing and comparing missense variants in monogenic disease and in cancer
Authors: Yin Yizhou , Moult John
Published: January 2019

In both monogenic disease and cancer a large fraction of causative mutations are missense, even though these are very different types of disease. Here we examine and compare a number of properties of these mutations in the two classes of disease to determine the extent to which the properties of the mutations are similar or different. Analysis of cancer mutations is complicated by the problem of distinguishing between drivers and passengers. After controlling for this factor in three different ways, we find the following: (1) A very high and similar fraction (~90%) of causal mutations in both diseases are at positions under strong selection pressure. (2) Mutations in structurally disordered regions play a minor role in monogenic disease (only about 10% of mutations are in those regions), but a larger role (about 25%) in cancer, largely because of the higher fraction of disordered regions in cancer driver proteins. (3) A large (~75%) and similar fraction of causal mutations in protein cores in both diseases act by significantly destabilizing three-dimensional structure, implying a large impact on protein function. (4) Cancer oncogene mutations tend to be on the protein surface whereas tumor suppressor and monogenic disease mutations are more common in the core. (5) A surprisingly high fraction (~50%) of mutations in cancer passenger genes are at positions under strong selection pressure.
Structural basis for transcription initiation by bacterial ECF σ factors
Authors: Li Lingting , Fang Chengli , Zhuang Ningning , Wang Tiantian , Zhang Yu
Published: January 2019

Bacterial RNA polymerase employs extra-cytoplasmic function (ECF) σ factors to regulate context-specific gene expression programs. Despite being the most abundant and divergent σ factor class, the structural basis of ECF σ factor-mediated transcription initiation remains unknown. Here, we determine a crystal structure of Mycobacterium tuberculosis (Mtb) RNAP holoenzyme comprising an RNAP core enzyme and the ECF σ factor σH (σH-RNAP) at 2.7 Å, and solve another crystal structure of a transcription initiation complex of Mtb σH-RNAP (σH-RPo) comprising promoter DNA and an RNA primer at 2.8 Å. The two structures together reveal the interactions between σH and RNAP that are essential for σH-RNAP holoenzyme assembly as well as the interactions between σH-RNAP and promoter DNA responsible for stringent promoter recognition and for promoter unwinding. Our study establishes that ECF σ factors and primary σ factors employ distinct mechanisms for promoter recognition and for promoter unwinding.
Dissociating neural activity associated with the subjective phenomenology of monocular stereopsis: an EEG study
Authors: Uji Makoto , Jentzsch Ines , Redburn James , Vishwanath Dhanraj
Published: January 2019

Abstracts

The subjective phenomenology associated with stereopsis, of solid tangible objects separated by a palpable negative space, is conventionally thought to be a by-product of the derivation of depth from binocular disparity. However, the same qualitative impression has been reported in the absence of disparity, e.g., when viewing pictorial images monocularly through an aperture. Here we aimed to explore if we could identify dissociable neural activity associated with the qualitative impression of stereopsis, in the absence of the processing of binocular disparities. We measured EEG activity while subjects viewed pictorial (non-stereoscopic) images of 2D and 3D geometric forms under four different viewing conditions (Binocular, Monocular, Binocular aperture, Monocular aperture). EEG activity was analysed by oscillatory source localization (beamformer technique) to examine power change in occipital and parietal regions across viewing and stimulus conditions in targeted frequency bands (alpha: 8-13Hz & gamma: 60-90Hz). We observed expected event-related gamma synchronization and alpha desynchronization in occipital cortex and predominant gamma synchronization in parietal cortex across viewing and stimulus conditions. However, only the viewing condition predicted to generate the strongest impression of stereopsis (monocular aperture) revealed significantly elevated gamma synchronization within the parietal cortex for the critical contrasts (3D vs. 2D form). These findings suggest dissociable neural processes specific to the qualitative impression of stereopsis as distinguished from disparity processing.