69 research outputs found
Alignment of Business Strategies and Human Resource Strategies in Banking Industry
The present study aimed to "align business strategies with HRM strategies in the banking industry." By reviewing theoretical basis, previous studies and existing documents, business strategies available in the three positions of the Delta model were identified in the banking industry, and they were mitigated and interpreted using banking experts' opinions. Then, using the matching alignment approach from among the Venkaterman approach models , and by the use of alignment model of reference strategic points, adaptation is made between the strategies available in each position and the strategies of the Bamberger and Meshoulam model, which itself was used as the model for determining the human resource strategy in this study. Thus, appropriate human resource strategies were identified for each business strategy in the three positions. The sampling method was a combination of non-probability sampling methods of snowball and judgment. These methods were chosen because of the specific information each step requires, the lack of familiarity of the researcher with experts in the related areas and the limited number of these people
A mammalian methylation array for profiling methylation levels at conserved sequences
Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures up to 36k CpGs per species that are well conserved across many mammalian species. We designed a set of probes that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development of epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others
DNA methylation predicts age and provides insight into exceptional longevity of bats
This work was supported by a Paul G. Allen Frontiers Group grant to S.H., the University of Maryland, College of Computer, Mathematical and Natural Sciences to G.S.W., an Irish Research Council Consolidator Laureate Award to E.C.T., a UKRI Future Leaders Fellowship (MR/T021985/1) to S.C.V. and a Discovery Grant from the Natural Sciences and Engineering Research Council (NSERC) of Canada to P.A.F. S.C.V. and P.D. were supported by a Max Planck Research Group awarded to S.C.V. by the Max Planck Gesellschaft, and S.C.V. and E.Z.L. were supported by a Human Frontiers Science Program Grant (RGP0058/2016) awarded to S.C.V. L.J.G. was supported by an NSERC PGS-D scholarship.Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.Publisher PDFPeer reviewe
DNA methylation networks underlying mammalian traits
INTRODUCTION: Comparative epigenomics is an emerging field that combines epigenetic signatures with phylogenetic relationships to elucidate species characteristics such as maximum life span. For this study, we generated cytosine DNA methylation (DNAm) profiles (n = 15,456) from 348mammalian species using amethylation array platform that targets highly conserved cytosines.
RATIONALE: Nature has evolved mammalian species of greatly differing life spans. To resolve the relationship ofDNAmwith maximum life span and phylogeny, we performed a largescale cross-species unsupervised analysis. Comparative studies in many species enables the identification of epigenetic correlates of maximum life span and other traits.
RESULTS: We first tested whether DNAm levels in highly conserved cytosines captured phylogenetic relationships among species. We constructed phyloepigenetic trees that paralleled the traditional phylogeny. To avoid potential confounding by different tissue types, we generated tissue-specific phyloepigenetic trees. The high phyloepigenetic-phylogenetic congruence is due to differences in methylation levels and is not confounded by sequence conservation. We then interrogated the extent to which DNA methylation associates with specific biological traits. We used an unsupervised weighted correlation network analysis (WGCNA) to identify clusters of highly correlated CpGs (comethylation modules). WGCNA identified 55 distinct comethylation modules, of which 30 were significantly associated with traits including maximum life span, adult weight, age, sex, human mortality risk, or perturbations that modulate murine life span. Both the epigenome-wide association analysis (EWAS) and eigengene-based analysis identified methylation signatures of maximum life span, and most of these were independent of aging, presumably set at birth, and could be stable predictors of life span at any point in life. Several CpGs that are more highly methylated in long-lived species are located near HOXL subclass homeoboxes and other genes that play a role in morphogenesis and development. Some of these life span–related CpGs are located next to genes that are also implicated in our analysis of upstream regulators (e.g., ASCL1 and SMAD6). CpGs with methylation levels that are inversely related to life span are enriched in transcriptional start site (TSS1) and promoter flanking (PromF4, PromF5) associated chromatin states. Genes located in chromatin state TSS1 are constitutively active and enriched for nucleic acid metabolic processes. This suggests that long-living species evolved mechanisms that maintain low methylation levels in these chromatin states that would favor higher expression levels of genes essential for an organism’s survival. The upstreamregulator analysis of the EWAS of life span identified the pluripotency transcription factors OCT4, SOX2, and NANOG. Other factors, such as POLII, CTCF, RAD21, YY1, and TAF1, showed the strongest enrichment for negatively life span–related CpGs.
CONCLUSION: The phyloepigenetic trees indicate that divergence of DNA methylation profiles closely parallels that of genetics through evolution. Our results demonstrate that DNA methylation is subjected to evolutionary pressures and selection. The publicly available data from ourMammalian Methylation Consortium are a rich source of information for different fields such as evolutionary biology, developmental biology, and aging
Antiviral activity and mechanism of action of edible bird’s nest against influenza A virus strain A/Puerto Rico/8/1934 (H1N1)
Influenza infection is still a high-risk disease affecting human and different animal
species by causative agent influenza A virus (IAV). Currently there is neither effective
vaccine nor efficient drug to control this infection. Edible Bird’s Nest (EBN) as a
popular traditional Chinese medicine (TCM) is believed to have health enhancing
effects like anti-tumor and immunomodulatory activities. These natural extracts also
have shown antiviral properties against influenza viruses; however, the molecular
mechanism of action of these compounds still is not well characterized. Hence, the first
aim of this study was to highlight the inhibitory effects of EBNs against influenza A
virus (IAV) infection. Accordingly, house EBNs were collected from Teluk Intan and
cave nests from Gua Madai in Malaysia and the extractions were prepared based on the
established methods with two different enzymatic treatments. The median cytotoxic
concentration (CC50) of the EBN extracts were determined on Madin-Darby canine
kidney (MDCK) cell line using microculture tetrazolium (MTT) assay and later on the
best exposure way and median inhibitory concentration (IC50) of the EBNs were shown
against IAV strain A/Puerto Rico/8/1934 (H1N1). The results showed that post
inoculation of the EBNs had the highest antiviral effect against IAV. The CC50 of these
compounds ranged from 27.5-32 mg/ml with IC50 of 2.5-4.9 mg/ml against IAV and
EBNs from Gua Madai had higher selectivity index compared to Teluk Intan. The
second aim of this study was to understand the mechanism of action of these natural
compounds against different molecular processes of IAV life cycle. These processes
included effect of EBN on four viral proteins, virus host immune interactions through
cytokines, early endosomes formation and their trafficking, and lastly autophagy
process during IAV infection. Consequently, four viral genes and six cytokines were
selected to be analyzed by RT-qPCR and ELISA to elucidate the effect of EBNs on the
virus and immune system. Later, Western blotting on three GTPases proteins, and
immunofluorescent labeling of actin cytoskleton and lysosomes were done to
investigate the effects of EBNs on endocytosis, actin cytoskeleton and macroautophagy
processes during influenza virus life cycle. Regarding the effect of EBNs on viral genes
and cytokines, the results showed that depends on the EBN composition, EBNs could
significantly decrease the extracellular NA and NS1 copy number (p<0.05) of the virus along with high immunomodulatory effects against IAV. EBNs showed antiinflammatory
effects through decrease of CCL2 and IL-6, and increase of IL-27. In
addition, these compounds might affect the virus by increase of TNF-α and activation
of NF-κB. Immunofluorescent staining and Western blot results revealed the effects of
EBNs on endocytosis, actin filament polymerization and macroautophagy pathways
against IAV. EBNs could affect the trafficking of early endosomes by significant
(p<0.05) decrease in GTPase proteins like RAB5 and RhoA, also ameliorating the actin
filaments distress. These natural mixtures could efficiently inhibit the autophagy
process involved in IAV life cycle by decrease (p<0.05) in LC3-II protein and
augmentation of lysosome activity. In conclusion, EBNs can inhibit influenza infection
by affecting critical steps of the virus life cycle. EBNs from different locations would
show different mechanisms against IAV. Hence, after screening for the composition,
these natural remedies have the potential to be used as an alternative antiviral agent
against future influenza disasters. Further in vitro and in vivo studies are required to
detect the bioactive agents and investigate the clinical applications of this natural
medicine against influenza
Gene annotations for the Horvath37K_DNAMethylation array for 10 bat genomes
We used sequences and annotations for ten bat genomes (see Table 1 below), which include six recently published reference assemblies, to locate each 50 bp probe on the array. The alignment was done using the QUASR package (Gaidatzis et al., 2015) with the assumption for bisulfite conversion treatment of the genomic DNA. For each species’ genome sequence, QUASR creates an in-silico-bisulfite-treated version of the genome. The set of nucleotide sequences of the designed probes, which includes degenerate base positions due to the bisulfite conversion, was expanded into a larger set of nucleotide sequences representing every possible combination of degenerate bases. We then ran QUASR (a wrapper for Bowtie2) with parameters -k 2 --strata --best -v 3 and bisulfite = "undir” to align the enlarged set of probe sequences to each prepared genome. From these files, we collected only alignments where the entire length of the probe perfectly matched to the genome sequence (i.e. the CIGAR string 50M and flag XM=0).
Following the alignment, the CpGs were annotated based on the distance to the closest transcriptional start site using the Chipseeker package (Yu et al., 2015). A gff file with these was created using these positions, sorted by scaffold and position, and compared to the location of each probe in BAM format. We report probes whose variants only mapped to one unique locus in a particular genome. Genomic location of each CpG is categorized as intergenic, 3’ UTR, 5’ UTR, promoter region (minus 10 kb to plus 1000 bp from the nearest TSS), exon, or intron.
Gaidatzis, D., Lerch, A., Hahne, F., and Stadler, M.B. (2015). QuasR: quantification and annotation of short reads in R. Bioinformatics 31, 1130-1132.
Yu, G., Wang, L.G., and He, Q.Y. (2015). ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics 31, 2382-2383.
Table 1. Bat genome assemblies and sources used for identifying location of CpG sites and number of sites mapped per genome.
Species, Assembly and annotation, Source, CpGs mapped
Molossus molossus, HLmolMol2, MPI*, 33557
Myotis myotis, HLmyoMyo6, MPI*, 32687
Phyllostomus discolor, HLphyDis3, MPI*, 33615
Rhinolophus ferrumequinum, HLrhiFer5, MPI*, 34411
Pipistrellus kuhlii, HLpipKuh2, MPI*, 31074
Rousettus aegyptiacus, HLrouAeg4, MPI*, 34308
Desmodus rotundus, GCF 002940915.1, ASM294091v2, NCBI, 32930
Eptesicus fuscus, GCF 000308155.1, EptFus1.0, NCBI, 32218
Myotis lucifugus, GCF 000147115.1, Myoluc2.0, NCBI, 29810
Pteropus vampyrus, pteVam1.100, ENSEMBL, 24681
MPI* (downloaded from https://bds.mpi-cbg.de/hillerlab/Bat1KPilotProject/)This submission contain gene annotations for an Illumina microarray (HorvathMammalMethylChip40) for 10 species of bats. The array design is available from the Gene Expression Omnibus (GEO) at NCBI as platform GPL28271. This array was used to generate DNA methylation data for nearly 700 known-aged individuals representing 26 species of bats. The resulting data were then used to predict age and species lifespan, and identify genomic regions that influence both of those traits.Paul G. Allen Frontiers Grou
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