Researchers have worked for many decades to master the rules of biomolecular design that would allow artificial biopolymer complexes to self-assemble and function similarly to the diverse biochemical ...constructs displayed in natural biological systems. The rules of nucleic acid assembly (dominated by Watson–Crick base-pairing) have been less difficult to understand and manipulate than the more complicated rules of protein folding. Therefore, nucleic acid nanotechnology has advanced more quickly than de novo protein design, and recent years have seen amazing progress in DNA and RNA design. By combining structural motifs with aptamers that act as affinity handles and add powerful molecular recognition capabilities, nucleic acid-based self-assemblies represent a diverse toolbox for use by bioengineers to create molecules with potentially revolutionary biological activities. In this review, we focus on the development of self-assembling nucleic acid nanostructures that are functionalized with nucleic acid aptamers and their great potential in wide ranging application areas.
Abstract
Research in the past decade has demonstrated that a single reference genome is not representative of a species’ diversity. MaizeGDB introduces a pan-genomic approach to hosting genomic data, ...leveraging the large number of diverse maize genomes and their associated datasets to quickly and efficiently connect genomes, gene models, expression, epigenome, sequence variation, structural variation, transposable elements, and diversity data across genomes so that researchers can easily track the structural and functional differences of a locus and its orthologs across maize. We believe our framework is unique and provides a template for any genomic database poised to host large-scale pan-genomic data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Since its 2015 update, MaizeGDB, the Maize Genetics and Genomics database, has expanded to support the sequenced genomes of many maize inbred lines in addition to the B73 reference genome ...assembly. Curation and development efforts have targeted high quality datasets and tools to support maize trait analysis, germplasm analysis, genetic studies, and breeding. MaizeGDB hosts a wide range of data including recent support of new data types including genome metadata, RNA-seq, proteomics, synteny, and large-scale diversity. To improve access and visualization of data types several new tools have been implemented to: access large-scale maize diversity data (SNPversity), download and compare gene expression data (qTeller), visualize pedigree data (Pedigree Viewer), link genes with phenotype images (MaizeDIG), and enable flexible user-specified queries to the MaizeGDB database (MaizeMine). MaizeGDB also continues to be the community hub for maize research, coordinating activities and providing technical support to the maize research community. Here we report the changes MaizeGDB has made within the last three years to keep pace with recent software and research advances, as well as the pan-genomic landscape that cheaper and better sequencing technologies have made possible. MaizeGDB is accessible online at https://www.maizegdb.org.
The ability to rapidly adapt cellular bioenergetic capabilities to meet rapidly changing environmental conditions is mandatory for normal cellular function and for cancer progression. Any loss of ...this adaptive response has the potential to compromise cellular function and render the cell more susceptible to external stressors such as oxidative stress, radiation, chemotherapeutic drugs, and hypoxia. Mitochondria play a vital role in bioenergetic and biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cell. Increased demand is met by mitochondrial biogenesis and fusion of individual mitochondria into dynamic networks, whereas a decrease in demand results in the removal of superfluous mitochondria through fission and mitophagy. Effective communication between nucleus and mitochondria (mito-nuclear cross talk), involving the generation of different mitochondrial stress signals as well as the nuclear stress response pathways to deal with these stressors, maintains bioenergetic homeostasis under most conditions. However, when mitochondrial DNA (mtDNA) mutations accumulate and mito-nuclear cross talk falters, mitochondria fail to deliver critical functional outputs. Mutations in mtDNA have been implicated in neuromuscular and neurodegenerative mitochondriopathies and complex diseases such as diabetes, cardiovascular diseases, gastrointestinal disorders, skin disorders, aging, and cancer. In some cases, drastic measures such as acquisition of new mitochondria from donor cells occurs to ensure cell survival. This review starts with a brief discussion of the evolutionary origin of mitochondria and summarizes how mutations in mtDNA lead to mitochondriopathies and other degenerative diseases. Mito-nuclear cross talk, including various stress signals generated by mitochondria and corresponding stress response pathways activated by the nucleus are summarized. We also introduce and discuss a small family of recently discovered hormone-like mitopeptides that modulate body metabolism. Under conditions of severe mitochondrial stress, mitochondria have been shown to traffic between cells, replacing mitochondria in cells with damaged and malfunctional mtDNA. Understanding the processes involved in cellular bioenergetics and metabolic adaptation has the potential to generate new knowledge that will lead to improved treatment of many of the metabolic, degenerative, and age-related inflammatory diseases that characterize modern societies.
Key message
High-density haplotype analysis revealed significant haplotype sharing between ex-PVPs registered from 1976 to 1992 and key maize founders, and uncovered similarities and differences in ...haplotype sharing patterns by company and heterotic group.
Proprietary inbreds developed by the private seed industry have been the major source for driving genetic gain in successful North American maize hybrids for decades. Much of the history of industry germplasm can be traced back to key founder lines, some of which were pivotal in the development of prominent heterotic groups. Previous studies have summarized pedigree-based relationships, genetic diversity and population structure among commercial inbreds with expired Plant Variety Protection (ex-PVP). However, less is known about the extent of haplotype sharing between historical founders and ex-PVPs. A better understanding of the relationships between founders and ex-PVPs provides insight into the haplotype and heterotic group structure among industry germplasm. We performed high-density haplotype analysis with 11.3 million SNPs on 212 maize inbreds, which included 157 ex-PVPs registered 1976–1992 and 55 public lines relevant to PVPs. Among these lines were 12 key founders identified in literature review: 207, A632, B14, B37, B73, LH123HT, LH82, Mo17, Oh43, OH7, PHG39 and Wf9. Our results revealed that, on average, 81.6% of an ex-PVP’s genome is shared with at least 1 of these 12 founder lines and more than half when limited to B73, Mo17 and 207. Quantifiable similarities and contrasts among heterotic groups and major US seed industry companies were also observed. The results from this study provide high-resolution haplotype data on ex-PVP germplasm, confirm founder relationship trends observed in previous studies, uncover region-specific haplotype structure differences and demonstrate how haplotype sharing analysis can be used as a tool to explore germplasm diversity.
•5FU increases mortality and symptom severity despite anti-tumor effects.•Colon inflammation is elevated with 5FU and this is further exacerbated with cancer.•5FU and cancer lead to dissimilarity and ...alterations in gut bacterial taxonomy.•5FU reduces grip strength and run-to-fatigue performance in cancer mice.•A 5FU altered microbiome influences the immune milieu and functional parameters.
Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10–15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations.
With the advances in the high throughput next generation sequencing technologies, genome-wide association studies (GWAS) have identified a large set of variants associated with complex phenotypic ...traits at a very fine scale. Despite the progress in GWAS, identification of genotype-phenotype relationship remains challenging in maize due to its nature with dozens of variants controlling the same trait. As the causal variations results in the change in expression, gene expression analyses carry a pivotal role in unraveling the transcriptional regulatory mechanisms behind the phenotypes.
To address these challenges, we incorporated the gene expression and GWAS-driven traits to extend the knowledge of genotype-phenotype relationships and transcriptional regulatory mechanisms behind the phenotypes. We constructed a large collection of gene co-expression networks and identified more than 2 million co-expressing gene pairs in the GWAS-driven pan-network which contains all the gene-pairs in individual genomes of the nested association mapping (NAM) population. We defined four sub-categories for the pan-network: (1) core-network contains the highest represented ~ 1% of the gene-pairs, (2) near-core network contains the next highest represented 1-5% of the gene-pairs, (3) private-network contains ~ 50% of the gene pairs that are unique to individual genomes, and (4) the dispensable-network contains the remaining 50-95% of the gene-pairs in the maize pan-genome. Strikingly, the private-network contained almost all the genes in the pan-network but lacked half of the interactions. We performed gene ontology (GO) enrichment analysis for the pan-, core-, and private- networks and compared the contributions of variants overlapping with genes and promoters to the GWAS-driven pan-network.
Gene co-expression networks revealed meaningful information about groups of co-regulated genes that play a central role in regulatory processes. Pan-network approach enabled us to visualize the global view of the gene regulatory network for the studied system that could not be well inferred by the core-network alone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objective was to examine the associations of peripartum concentrations of nonesterified fatty acids (NEFA), β-hydroxybutyrate (BHBA), and calcium with milk production in early lactation and ...pregnancy at the first artificial insemination (AI) across different management systems. Fifty-five Holstein freestall dairy herds located across the United States and Canada were visited weekly for blood sample collection from 2,365 cows. For each week of sampling (from wk −1 through wk 3 relative to calving) and for each metabolite, serum concentrations were dichotomized at various thresholds to identify the thresholds with the best negative associations with milk production and pregnancy at first AI. These thresholds were used to categorize the serum concentrations into higher and lower risk categories. Repeated-measures ANOVA and multivariable logistic regression were conducted for milk production and pregnancy at the first AI data, respectively, considering cow as the experimental unit and herd as a random effect. In the week before calving, serum NEFA ≥0.5mEq/L, BHBA ≥600μmol/L, and calcium ≤2.1mmol/L were associated with 1.6 to 3.2 kg/d milk loss across the first 4 Dairy Herd Improvement Association (DHIA) milk tests. High levels of NEFA and BHBA in wk 1 and 2 after calving (≥0.7 and ≥1.0mEq/L for NEFA, and ≥1,400 and ≥1,200μmol/L for BHBA), and low levels of calcium (≤2.1mmol/L) in wk 1, 2 and 3 after calving were associated with milk loss at the first DHIA milk test. Serum concentrations of NEFA and BHBA were not associated with pregnancy at first AI in any sampling week, whereas calcium <2.2 to 2.4mmol/L from wk 1 through wk 3 postpartum were associated with reduced pregnancy at first AI. In conclusion, high serum concentrations of NEFA, BHBA, and low concentrations of calcium around parturition were associated with early lactation milk loss, and low calcium concentration around parturition was associated with impaired early lactation reproduction.
We present regional sea-level projections and associated uncertainty estimates for the end of the 21 ˢᵗ century. We show regional projections of sea-level change resulting from changing ocean ...circulation, increased heat uptake and atmospheric pressure in CMIP5 climate models. These are combined with model- and observation-based regional contributions of land ice, groundwater depletion and glacial isostatic adjustment, including gravitational effects due to mass redistribution. A moderate and a warmer climate change scenario are considered, yielding a global mean sea-level rise of 0.54 ±0.19 m and 0.71 ±0.28 m respectively (mean ±1σ). Regionally however, changes reach up to 30 % higher in coastal regions along the North Atlantic Ocean and along the Antarctic Circumpolar Current, and up to 20 % higher in the subtropical and equatorial regions, confirming patterns found in previous studies. Only 50 % of the global mean value is projected for the subpolar North Atlantic Ocean, the Arctic Ocean and off the western Antarctic coast. Uncertainty estimates for each component demonstrate that the land ice contribution dominates the total uncertainty.
MaizeGDB is a highly curated, community-oriented database and informatics service to researchers focused on the crop plant and model organism Zea mays ssp. mays. Although some form of the maize ...community database has existed over the last 25 years, there have only been two major releases. In 1991, the original maize genetics database MaizeDB was created. In 2003, the combined contents of MaizeDB and the sequence data from ZmDB were made accessible as a single resource named MaizeGDB. Over the next decade, MaizeGDB became more sequence driven while still maintaining traditional maize genetics datasets. This enabled the project to meet the continued growing and evolving needs of the maize research community, yet the interface and underlying infrastructure remained unchanged. In 2015, the MaizeGDB team completed a multi-year effort to update the MaizeGDB resource by reorganizing existing data, upgrading hardware and infrastructure, creating new tools, incorporating new data types (including diversity data, expression data, gene models, and metabolic pathways), and developing and deploying a modern interface. In addition to coordinating a data resource, the MaizeGDB team coordinates activities and provides technical support to the maize research community. MaizeGDB is accessible online at http://www.maizegdb.org.
PDF
