scholarly journals Comparative Nutrigenomics Analysis of the Pig, Mouse and Human (P15-004-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Harry Dawson ◽  
Celine Chen ◽  
Thomas Wang ◽  
Joseph Urban
Keyword(s):  
Large Scale ◽  
Great Majority ◽  
Cell Types ◽  
Nutrient Sensing ◽  
Orthologous Genes ◽  
Funding Sources ◽  
Large Scale Analysis ◽  
Genes Encoding ◽  
Superfamily Analysis ◽  
Unique Genes

Abstract Objectives The seminal work of Miller and Ullrey examined the suitability of the pig as a model for human nutrition concluded “With the possible exception of nonhuman primates, it is apparent that the omnivorous pig is one of the best models for study of nutrition issues in the omnivorous human.” To date, a cross-species, large-scale analysis of genes related to nutrition and metabolism has not been reported. Our goal was to systematically review similarities and differences in nutrition-related physiology, and where different, to explore possible etiologies behind each phenomena using comparative genomics. Methods A broad literature and laboratory-based analysis was conducted comparing 1532 genes associated with porcine, murine, and human macro and micronutrient metabolism, including metalloproteins. Four questions were addressed. Are genes in specific pathways conserved? Are the genes/proteins structurally and functionally similar? Are the genes expressed in similar cell types? Are the genes regulated in a similar manner to stimuli? Results Pigs have roughly 4-fold fewer unique genes (66) than the mouse (240) and human (209). The great majority of these unique genes were zinc-containing members of the KRAB-A box Transcription Factor Superfamily. Analysis of 142 non-orthologous genes revealed that these genes were 10 times more likely to be present in only pigs and humans (120) than only in mice and humans (17). Genes involved in vitamin A and lipid metabolism were more highly conserved between pigs and humans. Notable, differences were found between humans and pigs in regard to genes encoding digestive enzymes and nutrient sensing genes. In some cases, mechanistic data were obtained to explain for previously described differences in physiology. For example, the lack of porcine salivary lipase and amylase activities is likely related to the absence of these genes in the pig. Analysis of 888 orthologous genes indicated a greater pig-human protein similarity for almost every gene examined. Conclusions Overall, the genomic and physiological parameters examined were more similar between pigs and humans than mice and humans. This supports the proposition that evaluating nutrition in pigs provides data that is more physiologically relevant to humans. Funding Sources Supported by USDA/ARS Project Plan 1235-51,000-055-00D.

scholarly journals FILER: large-scale, harmonized FunctIonaL gEnomics Repository

2021 ◽  
Author(s):  
Pavel P. Kuksa ◽  
Prabhakaran Gangadharan ◽  
Zivadin Katanic ◽  
Lauren Kleidermacher ◽  
Alexandre Amlie-Wolf ◽  
...  
Keyword(s):  
Functional Genomics ◽  
Large Scale ◽  
Cell Types ◽  
Data Sources ◽  
Reproducible Research ◽  
Functional Genomic ◽  
Data Types ◽  
Link Type ◽  
Annotation Data ◽  
Large Scale Analysis

AbstractMotivationQuerying massive collections of functional genomic and annotation data, linking and summarizing the query results across data sources and data types are important steps in high-throughput genomic and genetic analytical workflows. However, accomplishing these steps is difficult because of the heterogeneity and breadth of data sources, experimental assays, biological conditions (e.g., tissues, cell types), data types, and file formats.ResultsFunctIonaL gEnomics Repository (FILER) is a large-scale, harmonized functional genomics data catalog uniquely providing: 1) streamlined access to >50,000 harmonized, annotated functional genomic and annotation datasets across >20 integrated data sources, >1,100 biological conditions/tissues/cell types, and >20 experimental assays; 2) a scalable, indexing-based genomic querying interface; 3) ability for users to analyze and annotate their own experimental data against reference datasets. This rich resource spans >17 Billion genomic records for both GRCh37/hg19 and GRCh38/hg38 genome builds. FILER scales well with the experimental (query) data size and the number of reference datasets and data sources. When evaluated on large-scale analysis tasks, FILER demonstrated great efficiency as the observed running time for querying 1000x more genomic intervals (106 vs. 103) against all 7×109 hg19 FILER records increased sub-linearly by only a factor of 15x. Together, these features facilitate reproducible research and streamline querying, integrating, and utilizing large-scale functional genomics and annotation data.Availability and implementationFILER can be 1) freely accessed at https://lisanwanglab.org/FILER,2) deployed on cloud or local servers (https://bitbucket.org/wanglab-upenn/FILER), and 3) integrated with other pipelines using provided scripts.

scholarly journals Disruption of protease A and B orthologous genes in the basidiomycetous yeast Pseudozyma antarctica GB-4(0) yields a stable extracellular biodegradable plastic-degrading enzyme

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247462
Author(s):  
Natsuki Omae ◽  
Yuka Sameshima-Yamashita ◽  
Kazunori Ushimaru ◽  
Hideaki Koike ◽  
Hiroko Kitamoto ◽  
...  
Keyword(s):  
Large Scale ◽  
Amino Acid Sequences ◽  
Biodegradable Plastic ◽  
Orthologous Genes ◽  
Degrading Enzyme ◽  
Pseudozyma Antarctica ◽  
Overexpression Strain ◽  
Genes Encoding ◽  
Large Scale Cultivation ◽  
And Storage

The yeast Pseudozyma antarctica (currently designated Moesziomyces antarcticus) secretes a xylose-induced biodegradable plastic-degrading enzyme (PaE). To suppress degradation of PaE during production and storage, we targeted the inhibition of proteolytic enzyme activity in P. antarctica. Proteases A and B act as upper regulators in the proteolytic network of the model yeast, Saccharomyces cerevisiae. We searched for orthologous genes encoding proteases A and B in the genome of P. antarctica GB-4(0) based on the predicted amino acid sequences. We found two gene candidates, PaPRO1 and PaPRO2, with conserved catalytically important domains and signal peptides indicative of vacuolar protease function. We then prepared gene-deletion mutants of strain GB-4(0), ΔPaPRO1 and ΔPaPRO2, and evaluated PaE stability in culture by immunoblotting analysis. Both mutants exhibited sufficient production of PaE without degradation fragments, while the parent strain exhibited the degradation fragments. Therefore, we concluded that the protease A and B orthologous genes are related to the degradation of PaE. To produce a large quantity of PaE, we made a PaPRO2 deletion mutant of a PaE-overexpression strain named XG8 by introducing a PaE high-production cassette into the strain GB-4(0). The ΔPaPRO2 mutant of XG8 was able to produce PaE without the degradation fragments during large-scale cultivation in a 3-L jar fermenter for 3 days at 30°C. After terminating the agitation, the PaE activity in the XG8 ΔPaPRO2 mutant culture was maintained for the subsequent 48 h incubation at 25°C regardless of remaining cells, while activity in the XG8 control was reduced to 55.1%. The gene-deleted mutants will be useful for the development of industrial processes of PaE production and storage.

scholarly journals Contribution of Ionotropic Glutamatergic Receptors to Excitability and Attentional Signals in Macaque Frontal Eye Field

2021 ◽  
Author(s):  
Miguel Dasilva ◽  
Christian Brandt ◽  
Marc Alwin Gieselmann ◽  
Claudia Distler ◽  
Alexander Thiele
Keyword(s):  
Attentional Control ◽  
Large Scale ◽  
Neuronal Excitability ◽  
Cell Types ◽  
Receptor Activation ◽  
Frontal Eye Field ◽  
Control Signals ◽  
Cognitive Operations ◽  
Eye Field ◽  
Large Scale Networks

Abstract Top-down attention, controlled by frontal cortical areas, is a key component of cognitive operations. How different neurotransmitters and neuromodulators flexibly change the cellular and network interactions with attention demands remains poorly understood. While acetylcholine and dopamine are critically involved, glutamatergic receptors have been proposed to play important roles. To understand their contribution to attentional signals, we investigated how ionotropic glutamatergic receptors in the frontal eye field (FEF) of male macaques contribute to neuronal excitability and attentional control signals in different cell types. Broad-spiking and narrow-spiking cells both required N-methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation for normal excitability, thereby affecting ongoing or stimulus-driven activity. However, attentional control signals were not dependent on either glutamatergic receptor type in broad- or narrow-spiking cells. A further subdivision of cell types into different functional types using cluster-analysis based on spike waveforms and spiking characteristics did not change the conclusions. This can be explained by a model where local blockade of specific ionotropic receptors is compensated by cell embedding in large-scale networks. It sets the glutamatergic system apart from the cholinergic system in FEF and demonstrates that a reduction in excitability is not sufficient to induce a reduction in attentional control signals.

A large-scale analysis of HTTPS deployments: Challenges, solutions, and recommendations

2020 ◽  
pp. 1-26
Author(s):  
Qinwen Hu ◽  
Muhammad Rizwan Asghar ◽  
Nevil Brownlee
Keyword(s):  
Secure Communication ◽  
Large Scale ◽  
Transport Layer ◽  
Security Level ◽  
Secure Socket Layer ◽  
Security Issues ◽  
Large Scale Analysis ◽  
Government Websites ◽  
Encrypted Communication ◽  
Specific Implementation

HTTPS refers to an application-specific implementation that runs HyperText Transfer Protocol (HTTP) on top of Secure Socket Layer (SSL) or Transport Layer Security (TLS). HTTPS is used to provide encrypted communication and secure identification of web servers and clients, for different purposes such as online banking and e-commerce. However, many HTTPS vulnerabilities have been disclosed in recent years. Although many studies have pointed out that these vulnerabilities can lead to serious consequences, domain administrators seem to ignore them. In this study, we evaluate the HTTPS security level of Alexa’s top 1 million domains from two perspectives. First, we explore which popular sites are still affected by those well-known security issues. Our results show that less than 0.1% of HTTPS-enabled servers in the measured domains are still vulnerable to known attacks including Rivest Cipher 4 (RC4), Compression Ratio Info-Leak Mass Exploitation (CRIME), Padding Oracle On Downgraded Legacy Encryption (POODLE), Factoring RSA Export Keys (FREAK), Logjam, and Decrypting Rivest–Shamir–Adleman (RSA) using Obsolete and Weakened eNcryption (DROWN). Second, we assess the security level of the digital certificates used by each measured HTTPS domain. Our results highlight that less than 0.52% domains use the expired certificate, 0.42% HTTPS certificates contain different hostnames, and 2.59% HTTPS domains use a self-signed certificate. The domains we investigate in our study cover 5 regions (including ARIN, RIPE NCC, APNIC, LACNIC, and AFRINIC) and 61 different categories such as online shopping websites, banking websites, educational websites, and government websites. Although our results show that the problem still exists, we find that changes have been taking place when HTTPS vulnerabilities were discovered. Through this three-year study, we found that more attention has been paid to the use and configuration of HTTPS. For example, more and more domains begin to enable the HTTPS protocol to ensure a secure communication channel between users and websites. From the first measurement, we observed that many domains are still using TLS 1.0 and 1.1, SSL 2.0, and SSL 3.0 protocols to support user clients that use outdated systems. As the previous studies revealed security risks of using these protocols, in the subsequent studies, we found that the majority of domains updated their TLS protocol on time. Our 2020 results suggest that most HTTPS domains use the TLS 1.2 protocol and show that some HTTPS domains are still vulnerable to the existing known attacks. As academics and industry professionals continue to disclose attacks against HTTPS and recommend the secure configuration of HTTPS, we found that the number of vulnerable domain is gradually decreasing every year.

scholarly journals Transcriptional and morphological profiling of parvalbumin interneuron subpopulations in the mouse hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Que ◽  
David Lukacsovich ◽  
Wenshu Luo ◽  
Csaba Földy
Keyword(s):  
Large Scale ◽  
Cell Types ◽  
Rna Seq ◽  
Neuronal Identity ◽  
Parvalbumin Interneurons ◽  
Different Types ◽  
Parvalbumin Interneuron ◽  
Cam Profile ◽  
Developmental Domains

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.

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