Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response

We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-cell response specific for the DEN-2 virus prM and E proteins. This response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-cell response

Maternal metabolic factors during pregnancy predict early childhood growth trajectories and obesity risk: the CANDLE Study.

BackgroundWe investigated the individual and additive effects of three modifiable maternal metabolic factors, including pre-pregnancy overweight/obesity, gestational weight gain (GWG), and gestational diabetes mellitus (GDM), on early childhood growth trajectories and obesity risk.MethodsA total of 1425 mother-offspring dyads (953 black and 472 white) from a longitudinal birth cohort were included in this study. Latent class growth modeling was performed to identify the trajectories of body mass index (BMI) from birth to 4 years in children. Poisson regression models were used to examine the associations between the maternal metabolic risk factors and child BMI trajectories and obesity risk at 4 years.ResultsWe identified three discrete BMI trajectory groups, characterized as rising-high-BMI (12.6%), moderate-BMI (61.0%), or low-BMI (26.4%) growth. Both maternal pre-pregnancy obesity (adjusted relative risk [adjRR] = 1.96; 95% confidence interval [CI]: 1.36-2.83) and excessive GWG (adjRR = 1.71, 95% CI: 1.13-2.58) were significantly associated with the rising-high-BMI trajectory, as manifested by rapid weight gain during infancy and a stable but high BMI until 4 years. All three maternal metabolic indices were significantly associated with childhood obesity at age 4 years (adjRR for pre-pregnancy obesity = 2.24, 95% CI: 1.62-3.10; adjRR for excessive GWG = 1.46, 95% CI: 1.01-2.09; and adjRR for GDM = 2.14, 95% = 1.47-3.12). In addition, risk of rising-high BMI trajectory or obesity at age 4 years was stronger among mothers with more than one metabolic risk factor. We did not observe any difference in these associations by race.ConclusionMaternal pre-pregnancy obesity, excessive GWG, and GDM individually and jointly predict rapid growth and obesity at age 4 years in offspring, regardless of race. Interventions targeting maternal obesity and metabolism may prevent or slow the rate of development of childhood obesity

The first mitochondrial 5-methylcytosine map in a non-model teleost (Oreochromis niloticus) reveals extensive strand-specific and non-CpG methylation

DNA methylation is one of the main epigenetic mechanisms that regulate gene expression in a manner that depends on the genomic context and varies considerably across taxa. This DNA modification was first found in nuclear genomes of eukaryote several decades ago and it has also been described in mitochondrial DNA. It has recently been shown that mitochondrial DNA is extensively methylated in mammals and other vertebrates. Our current knowledge of mitochondrial DNA methylation in fish is very limited, especially in non-model teleosts. In this study, using whole-genome bisulfite sequencing, we determined methylation patterns within non-CpG (CH) and CpG (CG) contexts in the mitochondrial genome of Nile tilapia, a non-model teleost of high economic importance. Our results demonstrate the presence of mitochondrial DNA methylation in this species predominantly within a non-CpG context, similarly to mammals. We found a strand-specific distribution of methylation, in which highly methylated cytosines were located on the minus strand. The D-loop region had the highest mean methylation level among all mitochondrial loci. Our data provide new insights into the potential role of epigenetic mechanisms in regulating metabolic flexibility of mitochondria in fish, with implications in various biological processes, such as growth and development.publishedVersio

Hjort i Hedmark: Resultater fra GPS-merking 2002–2011

Prosjektet Hjort i Hedmark var en del av samarbeidsprosjektet HjortAreal, som undersøkte hjortens arealbruk, økologisk bærekraft og hjort som næring i Møre & Romsdal og Sør-Trøndelag, Sogn i Hordaland, Buskerud, Haugalandet i Rogaland/Hordaland og Hedmark. Studieområdet i Hedmark hadde en unik posisjon i prosjektet fordi det representerte et ytterpunkt i forhold til klima, landskapsstruktur og tetthet av elg (Alces alces). Vi undersøkte Hedmarkshjortens trekkmønster og habitatbruk og da spesielt bruken av innmark og foringsplasser. Hjortemerking med GPS radiosendere begynte i Hedmark i 2002 og ble avsluttet vinteren 2011. Det ble totalt merket 51 hinder og vi fikk bra nok data fra 48 hinder. Sammenlignet med de andre studieområdene i HjortAreal-prosjektet var andelen trekkdyr høyest i Hedmark, der hele 96 % av hjortehindene var trekkdyr, og kun 4 % stasjonære. Også trekkavstandene var lengst i Hedmark. Hjorten trakk i gjennomsnitt 36.7 ± 7.5 km (2 SE) og tre av hjortene hadde sine respektive sommerområder rundt 100 km i luftlinje fra merkeplassen. Trekktidene er nokså sammenlignbare over hele Sør-Norge, med vårtrekket i løpet av april-mai og høsttrekket i august-september. Det var stor variasjon på størrelse av både vinter- og sommerområde. Gjennomsnittlig var vinterområde og sommerområde på henholdsvis 18.8 km2¬ (minst – størst 1.9–83.0 km2) og 22.9 km2 (1.7–98.0 km2). Avhengig av hvor hindene hadde sine vinterområder trakk de enten til høyereliggende eller lavereliggende sommerområde, eller vinter- og sommerområdene overlappet hverandre. Hjortens områdebruk ble styrt av menneskeskapte matressurser. Hele 10.5 % av posisjonene var knyttet til menneskeskapte konsentrasjoner av mat, enten de var innen 100 m av nærmeste foringsplass (3.1 %), eller på innmark (7.4 %). I månedsskifte februar-mars var en tredjedel av alle GPS-posisjonene knyttet til foringsplasser. Når bruken av foringsplasser avtok utover vinteren, fikk innmark mer og mer betydning. Innmarksarealet dekket gjennomsnittlig 3.4 ± 1.3 % (2 SE) av sommerleveområdene, og tilgangen varierte sterkt mellom hindene og områdene. Hindene oppholdt seg lenger enn forventet på innmark nattestid mens de brukte mindre tid enn forventet på innmark på dagtid. Samtlige foringsplasser i hoveddalføret langs Glomma i Stor-Elvdal og Rendalen kommuner hadde spor etter hjort, men ingen av foringsplassene hadde høye tettheter av både elg og hjort. Vi kan kun spekulere hvorvidt foring av elg har vært en medvirkende årsak for den nylige økningen i hjortebestanden i Hedmark. Vi har diskutert både plantefenologi-, konkurranse-, sosial barriere- og antipredator-hypotesen som en forklaring for Hedmarkhjortens trekkatferd med lange avstander og stor andel av trekkende dyr. Det kan tenkes et samspill av flere av disse hypotesene som grunnlag for at andel trekkdyr er høyest og trekkrutene er lengst i Hedmark sammenlignet med de andre studieområdene. Som delvis trekkende art kan hjorten utfordre forvaltningen. Fordi hjorten stort sett er tilbake på vinterområdene til jaktstart, kan kommune eller jaktvald være tilstrekkelig forvaltningsenhet, men ved en mer helthetlig forvaltning som tar hensyn til biologisk mangfold, vern av kalvingsområder og tiltak mot viltulykker, bør den romlige forvaltningsenheten være på regionalt nivå

Hjortens trekkmønster skaper forvaltningsutfordringer i Hedmark

Jaktstatistikken fra Hedmark fylke tilsier at hjorten er tilbake for godt i Hedmark og befinner seg i en sterk vekstfase. Med det følger mange forvaltningsutfordringer. Vi har studert hjortens forflytningsmønster og trekkatferd ved å merke 51 hinder med GPS på fire merkeplasser i henholdsvis Rendalen, Stor-Elvdal, Åmot og Stange kommune. De aller fleste hindene oppholdt seg i et sommerområde som var atskilt fra vinterområdet. Avstanden mellom de to områdene var gjennomsnittlig lenger enn for hinder merket på Vest- og Sørlandet. For tre av hindene var avstanden rundt 100 km. På trekkruten var hindene innom forskjellige kommuner, og totalt ble vårt studieområde utvidet fra de fire vinterkommunene til 29 kommuner for hele året. Vi anbefaler derfor en mer regional forvaltning av hjorten enn dagens forvaltning på eiendoms- eller kommunenivå. Innmark og fôringsplasser ble flittig brukt av hindene, og da spesielt nattestid. Overvåkning av fôringsplasser for elg som opprinnelig ble etablert for å redusere trafikkulykker og beiteskader i skogen, viste at hjorten var til stede på samtlige plasser langs Glommas hoveddalføre i Stor-Elvdal og Rendalen kommuner. Mye tyder på at hjorten har tatt over flere plasser, og at elg og hjort til en viss grad unngikk hverandre i tid og rom. Det kan tenkes at hjorten kan minske den ønskede effekten av vinterfôring av elg. Hvis vinterfôring skal fortsette, anbefaler vi å legge ut flere siloballer samtidig per fôringsplass for å sikre elgens tilgang til fôr

Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics

Early nutritional programming affects liver transcriptome in diploid and triploid Atlantic salmon, Salmo salar

Background  To ensure sustainability of aquaculture, plant-based ingredients are being used in feeds to replace marine-derived products. However, plants contain secondary metabolites which can affect food intake and nutrient utilisation of fish. The application of nutritional stimuli during early development can induce long-term changes in animal physiology. Recently, we successfully used this approach to improve the utilisation of plant-based diets in diploid and triploid Atlantic salmon. In the present study we explored the molecular mechanisms occurring in the liver of salmon when challenged with a plant-based diet in order to determine the metabolic processes affected, and the effect of ploidy.  Results  Microarray analysis revealed that nutritional history had a major impact on the expression of genes. Key pathways of intermediary metabolism were up-regulated, including oxidative phosphorylation, pyruvate metabolism, TCA cycle, glycolysis and fatty acid metabolism. Other differentially expressed pathways affected by diet included protein processing in endoplasmic reticulum, RNA transport, endocytosis and purine metabolism. The interaction between diet and ploidy also had an effect on the hepatic transcriptome of salmon. The biological pathways with the highest number of genes affected by this interaction were related to gene transcription and translation, and cell processes such as proliferation, differentiation, communication and membrane trafficking.  Conclusions  The present study revealed that nutritional programming induced changes in a large number of metabolic processes in Atlantic salmon, which may be associated with the improved fish performance and nutrient utilisation demonstrated previously. In addition, differences between diploid and triploid salmon were found, supporting recent data that indicate nutritional requirements of triploid salmon may differ from those of their diploid counterparts

State transitions across the Strep A disease spectrum: scoping review and evidence gaps.

The spectrum of diseases caused by Streptococcus pyogenes (Strep A) ranges from superficial to serious life-threatening invasive infections. We conducted a scoping review of published articles between 1980 and 2021 to synthesize evidence of state transitions across the Strep A disease spectrum. We identified 175 articles reporting 262 distinct observations of Strep A disease state transitions. Among the included articles, the transition from an invasive or toxin-mediated disease state to another disease state (i.e., to recurrent ARF, RHD or death) was described 115 times (43.9% of all included transition pairs) while the transition to and from locally invasive category was the lowest (n = 7; 0.02%). Transitions from well to any other state was most frequently reported (49%) whereas a relatively higher number of studies (n = 71) reported transition from invasive disease to death. Transitions from any disease state to locally invasive, Strep A pharyngitis to invasive disease, and chronic kidney disease to death were lacking. Transitions related to severe invasive diseases were more frequently reported than superficial ones. Most evidence originated from high-income countries and there is a critical need for new studies in low- and middle-income countries to infer the state transitions across the Strep A disease spectrum in these high-burden settings