141 research outputs found
Application of the New Generation-Skipping Tax to Life Insurance Proceeds: A Headache for Everyone Involved
NF-Y activates genes of metabolic pathways altered in cancer cells
The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells
ICTV Virus Taxonomy Profile: Herpesviridae 2021
Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125–241 kbp contain 70–170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae
First complete genome sequence of infectious laryngotracheitis virus
BACKGROUND: Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that causes acute respiratory disease in chickens worldwide. To date, only one complete genomic sequence of ILTV has been reported. This sequence was generated by concatenating partial sequences from six different ILTV strains. Thus, the full genomic sequence of a single (individual) strain of ILTV has not been determined previously. This study aimed to use high throughput sequencing technology to determine the complete genomic sequence of a live attenuated vaccine strain of ILTV. RESULTS: The complete genomic sequence of the Serva vaccine strain of ILTV was determined, annotated and compared to the concatenated ILTV reference sequence. The genome size of the Serva strain was 152,628 bp, with a G + C content of 48%. A total of 80 predicted open reading frames were identified. The Serva strain had 96.5% DNA sequence identity with the concatenated ILTV sequence. Notably, the concatenated ILTV sequence was found to lack four large regions of sequence, including 528 bp and 594 bp of sequence in the UL29 and UL36 genes, respectively, and two copies of a 1,563 bp sequence in the repeat regions. Considerable differences in the size of the predicted translation products of 4 other genes (UL54, UL30, UL37 and UL38) were also identified. More than 530 single-nucleotide polymorphisms (SNPs) were identified. Most SNPs were located within three genomic regions, corresponding to sequence from the SA-2 ILTV vaccine strain in the concatenated ILTV sequence. CONCLUSIONS: This is the first complete genomic sequence of an individual ILTV strain. This sequence will facilitate future comparative genomic studies of ILTV by providing an appropriate reference sequence for the sequence analysis of other ILTV strains
Equine Transport and Changes in Equid Herpesvirus' Status
The risk of respiratory disease in the transported horse can increase as a consequence of immunosuppression and stress associated primarily with opportunistic bacterial proliferation and viral reactivation. This study examines the ecology of equid herpesviruses (EHV) in these horses, exploring reactivation and changes in infection and shedding associated with transport, and any potential contributions to transport-related respiratory disease. Twelve horses were subjected to an 8-h road-transport event. Antibodies to EHV-1 and EHV-4 were detected by ELISA in serum collected prior to, immediately after and 2 weeks post transport. Respiratory tract endoscopy and tracheal washes were collected prior to and 5 days after transportation. Nasal swabs collected prior to, immediately after, 1 and 5 days following transport were screened for EHV-1,-2,-4,-5 using qPCR. Six horses had persistent neutrophilic airway infiltrates post transportation, indicative of subclinical respiratory disease. No horses were qPCR positive for either of the alphaherpesviruses (i.e., EHV-1/-4) nor did any seroconvert to either virus. Four out of nine horses positive for either EHV-2 or EHV-5 on qPCR prior to transport developed neutrophilic airway inflammation. Five horses showed increasingly positive readings on qPCR (i.e., reduced Cq) for EHV-2 after transportation and seven out of eleven horses positive for EHV-2 after transport shared strains of high sequence similarity with other horses in the study. One EHV-2 virus detected in one horse after transport was genetically different which may be due to reactivation. The clinical significance of EHV-2 and EHV-5 remains in question. However these results indicate that transportation may lead to increased shedding, transmission and reactivation of EHV-2 and EHV-5 but not EHV-1/-4. Unlike previous work focusing on the role of alphaherpesviruses, this research suggests that investigation of the gammaherpesviruses (i.e., EHV-2/-5) in transport-related disease should not be dismissed, particularly given that these viruses can encode suppressive immunomodulators that may affect host health
Community health workers can improve child growth of antenatally-depressed, South African mothers: a cluster randomized controlled trial
Whole-genome sequencing reveals host factors underlying critical COVID-19
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
Low genetic diversity among historical and contemporary clinical isolates of felid herpesvirus 1
Robust estimation of bacterial cell count from optical density
Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
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