Contributors:Benslimane Yahya, Bertomeu Thierry, Coulombe-Huntington Jasmin, McQuaid Mary, Maria SO, Papadopoli David, Avizonis Daina, De Sa Tavares Russo Mariana, Huard Caroline, ivan topisirovic, Wurtele Hugo, Tyers Mike, Harrington Lea
Resveratrol is a natural product associated with wide-ranging effects in animal and cellular models including lifespan extension. To identify the genetic target of resveratrol in human cells, we conducted genome-wide CRISPR-Cas9 screens to pinpoint genes that confer sensitivity or resistance to resveratrol. An extensive network of DNA damage response and replicative stress genes exhibited genetic interactions with resveratrol and its analog pterostilbene. These genetic profiles showed similarity to the response to hydroxyurea, an inhibitor of ribonucleotide reductase that causes replicative stress. Resveratrol, pterostilbene and hydroxyurea caused similar depletion of nucleotide pools, inhibition of replication fork progression and induction of replicative stress. The ability of resveratrol to inhibit cell proliferation and S phase transit was independent of the histone deacetylase Sirtuin 1, which has been implicated in lifespan extension by resveratrol. These results establish that a primary impact of resveratrol on human cell proliferation is the induction of low-level replicative stress.
Contributors:Callahan Owen, Eichhubl Peter, Davatzes Nicholas
Files and tables in support of the manuscript “Mineral precipitation as a mechanism of fault core growth” submitted to the Journal of Structural Geology. Table S1 contains structural measurements from Dixie Comstock, Nevada, USA. Map S1 is a .kmz file that can be downloaded and opened with Google Earth that includes a geologic map of the Dixie Comstock area, approximate locations for several other figures from the submitted text, sample locations, and scanline locations presented in Table S2. Unedited versions of all photographs used in the figures are also included.
This data set contains aligned concatenated protein gene sequences of 183 Clonorchis sinensis (phylum Platyhelminthes; class Trematoda; family Opisthorchiidae) specimens. The alignment includes polymorphic positions represented by IUPAC ambiguity characters; this polymorphism likely represents heteroplasmy as a result of multiple, distinct mitochondrial genomes being present within an individual worm. Sequence names correspond to specimen nos.
To make the EGFRvIII mutant cell line in H9, gene editing was performed using CRISRP-CAS9 with two sgRNAs.
This is the sequencing data for EGFR site for mutant cell line.
Off-target position of each sgRNA and deep sequencing raw data
VCF file containing filtered mutated sites in SARS-CoV-2 genomes obtained from GISAID EpiCoV, separated by individual mutations. The columns correspond to viral genome accession ID, nucleotide position in the genome, mutation ID (left blank in all rows), reference nucleotide, identified mutation, quality, filter, and information columns (all left blank), format (GT in all rows), column corresponding to reference genome (all 0, referring to reference nucleotide column), and columns corresponding to isolate genomes, with each row identifying the nucleotide in the POS column, and whether it is non-mutant (0), or the mutant indicated in the identified mutation column (1). The file is tab delimited, with 22546 rows including the names, and 30690 columns.
The file was generated to test the hypothesis whether the five most common mutations in the SARS-CoV-2 genome replication complex proteins, nsps 7, 8, 12, and 14, significantly affect the mutation density of the virus over time and whether these affect the synonymous and nonsynonymous mutation densities differently. We discovered that mutations in nsp14, an exonuclease with error correcting capabilities, are most likely to be correlated with increased mutational load across the genome compared to wildtype SARS-CoV-2. These results were obtained by identifying the frequency of mutations across all isolates in genomic regions of interest, analyzing which of the twenty mutations (five per nsp) have a statistically meaningful relationship with the mutation density in the M and E genes (chosen due to being under little selective pressure), and identifying the synonymous and nonsynonymous genomic SNV density for isolates with any of the statistically meaningful mutations, as well as isolates with none of the identified mutations.
Background. Whilst cannabis commercialization is occurring rapidly guided by highly individualistic public narratives, evidence that all congenital anomalies (CA) increase alongside cannabis use in Canada, a link with 21 CA’s in Hawaii, and rising CA’s in Colorado indicate that transgenerational effects can be significant and impact public health. It was therefore important to study Northern New South Wales (NNSW) a known cannabis use centre.
Methods. Design: Cohort. 2008-2015. Setting: NNSW and Queensland (QLD), Australia. Participants. Whole populations. Exposures. Tobacco, Risky Alcohol, Annual cannabis. Source: National Drug Strategy Household Surveys 2010, 2013. Main Outcomes. CA Rates. NNSW-QLD comparisons. Geospatial and causal regression.
Results. Cardiovascular, respiratory and gastrointestinal anomalies rose with falling tobacco and alcohol but rising cannabis use rates across Queensland. Maternal age NNSW-QLD was not different (2008-2015: 4,265/22,084 v. 96,473/490,514 >35 years, Chi.Sq.=1.687, P=0.194). A higher rate of NNSW cannabis-related than cannabis-unrelated defects occurred (prevalence ratio (PR)=2.13, 95%C.I. 1.80-2.52, P=3.24x10-19). CA’s rose more potently with rising cannabis than with rising tobacco or alcohol use. Exomphalos and gastroschisis had the highest NNSW:QLD PR (6.29(2.94-13.48) and 5.85(3.54-9.67)) and attributable fraction in the exposed (84.11%(65.95-92.58%) and 82.91%(71.75-89.66%), P=2.83x10-8 and P=5.62x10-15). In multivariable geospatial models cannabis was significantly linked with cardiovascular (atrial septal defect, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus), genetic (chromosomal defects, Downs syndrome), gastrointestinal (small intestinal atresia), body wall (gastroschisis, diaphragmatic hernia) and other (hypospadias) (AVTPCDSGDH) CA’s. In linear modelling cannabis use was significantly linked with anal stenosis, congenital hydrocephalus and Turner syndrome (ACT) and was significantly linked in borderline significant models (model P1.3 ranging up to 3.8x1030 making uncontrolled confounding unlikley.
Conclusions. These results suggest that population level CA’s react more strongly to small rises in cannabis use than tobacco or alcohol; cardiovascular, chromosomal, body wall and gastrointestinal CA’s rise significantly with small increases in cannabis use; and that cannabis is a bivariate correlate of AVTPCDSGDH and ACT anomalies and is robust to adjustment for other substances.