Pathogenicity of viral nervous necrosis virus for Guppy fish, Poecilia reticulata

The pathogenicity of a Nervous Necrosis Virus isolate obtained from naturally infected Golden grey mullet (Liza auratus) suffering serious mortalities in Iranian coastline water of the Caspian Sea was investigated for first time. An experimental infection has been performed using three groups, two experimental groups and one control group of Guppy (Poecilia reticulata) with mean weight 0.47±0.09 g, at temperature 25ºC. The infectious dosage (50 ml) with TCID50/ml= 10^4.25 for 2 hours in group 1 and 4 hours in group 2 developed the disease with immersion method. Clear clinical signs associated with significant mortality were observed since 15 dpi. Cumulative mortalities rose to 100% at 30 dpi. While in the control group no mortality was recorded. Virus was re-isolated on SSN-1 cell line that showing typical CPE developed after inoculation with tissues filtrate from dead fish. Histopathological examination of exposed fish, showed clear vacuolization in the granular layer of the retina and cerebellum. TEM micrographs revealed intracytoplasmic vacuoles in the retina of infected Guppy. IHC revealed the presence of viral antigens in the brain and retina. These results confirmed the pathogenicity of the NNV isolate obtained from Golden grey mullet suffering high mortality with regard to suggest that the same agent isolated from golden grey mullet is very likely the cause of the mortality observed in the same species

Synergy between industry and agriculture: techno-economic and life cycle assessments of waste recovery for crop growth in glasshouses

Controlled-environment agriculture in agro-industrial systems, where carbon dioxide, heat, and other wastes are recovered or recycled, has potential to be an environmentally friendly approach with economic feasibility. However, such approaches need careful exploration to ensure that environmental and economic benefits are maximised. Techno-economic, and life cycle assessments were applied to evaluate the synergy of producing crops (tomato and hemp) and recovering industrial wastes (e.g., heat and carbon dioxide) in glasshouses with robust uncertainty and sensitivity analyses. For each crop, two scenarios were compared, linear scenarios evaluated the use of raw materials with no waste recovery whereas circular scenarios captured industry flows and reused or recycled them in the glasshouse- avoiding raw materials consumption. Circular practices had a net benefit on the global warming potential for both crops, capturing up to 50,000 kg/y of CO2 in crops biomass and providing competitive product prices. The analysis showed that circular operational conditions can reduce, by almost half, the break-even product selling prices and sequester up to, approximately, 500 kg CO2eq./m2 of glasshouse if compared to linear systems. Future investments in this outstanding strategy to supply the United Kingdom's market demand of tomatoes could lead to a low-cost product and negative CO2eq. emissions by mitigating the importation of these products. Alongside, other impact categories scores may not be as favourable as the global warming potential, due to high impact of the waste management phase, chemical fertilisers, and pesticides utilisation

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models.Kptn−/− mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants.Molecular and structural analysis of Kptn−/− mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1.By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.Genetics of disease, diagnosis and treatmen

Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns Findings From the Pregnancy and Childhood Epigenetics Consortium

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development

Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium.

Development Psychopathology in context: famil