Maturation of Gut Microbiota and Circulating Regulatory T Cells and Development of IgE Sensitization in Early Life

Recent studies suggest that the cross-talk between the gut microbiota and human immune system during the first year of life is an important regulator of the later development of atopic diseases. We explored the changes in the gut microbiota, blood regulatory T cells, and atopic sensitization in a birth-cohort of Estonian and Finnish children followed from 3 to 36 months of age. We describe here an infant Treg phenotype characterized by high Treg frequency, the maturation of Treg population characterized by a decrease in their frequency accompanied with an increase in the highly activated Treg cells. These changes in Treg population associated first with the relative abundance of Bifidobacterium longum followed by increasing colonization with butyrate producing bacteria. High bifidobacterial abundance in the neonatal microbiota appeared to be protective, while colonization with Bacteroides and E. coli was associated with later risk of allergy. Estonian children with lower risk of IgE mediated allergic diseases than Finnish children showed an earlier maturation of the gut microbiota, detected as earlier switch to an increasing abundance of butyrate-producing bacteria, combined with an earlier maturation of Treg cell phenotype and total IgE production. The children with established allergic diseases by age 3 showed a decreased abundance of butyrate producing Faecalibacterium. These results suggest that as well as the maintenance of a bifidobacterial dominated gut microbiota is important during the first weeks of life, the overtake by butyrate producing bacteria seems to be a beneficial shift, which should not be postponed

Genetic analyses reveal independent domestication origins of Eurasian reindeer

Although there is little doubt that the domestication of mammals was instrumental for the modernization of human societies, even basic features of the path towards domestication remain largely unresolved for many species. Reindeer are considered to be in the early phase of domestication with wild and domestic herds still coexisting widely across Eurasia. This provides a unique model system for understanding how the early domestication process may have taken place. We analysed mitochondrial sequences and nuclear microsatellites in domestic and wild herds throughout Eurasia to address the origin of reindeer herding and domestication history. Our data demonstrate independent origins of domestic reindeer in Russia and Fennoscandia. This implies that the Saami people of Fennoscandia domesticated their own reindeer independently of the indigenous cultures in western Russia. We also found that augmentation of local reindeer herds by crossing with wild animals has been common. However, some wild reindeer populations have not contributed to the domestic gene pool, suggesting variation in domestication potential among populations. These differences may explain why geographically isolated indigenous groups have been able to make the technological shift from mobile hunting to large-scale reindeer pastoralism independently

Evaluation of articular cartilage with quantitative MRI in an equine model of post-traumatic osteoarthritis.

Chondral lesions lead to degenerative changes in the surrounding cartilage tissue, increasing the risk of developing post-traumatic osteoarthritis (PTOA). This study aimed to investigate the feasibility of quantitative magnetic resonance imaging (qMRI) for evaluation of articular cartilage in PTOA. Articular explants containing surgically induced and repaired chondral lesions were obtained from the stifle joints of seven Shetland ponies (14 samples). Three age-matched nonoperated ponies served as controls (six samples). The samples were imaged at 9.4 T. The measured qMRI parameters included T(1) , T(2) , continuous-wave T(1ρ) (CWT(1ρ) ), adiabatic T(1ρ) (AdT(1ρ) ), and T(2ρ) (AdT(2ρ) ) and relaxation along a fictitious field (T(RAFF) ). For reference, cartilage equilibrium and dynamic moduli, proteoglycan content and collagen fiber orientation were determined. Mean values and profiles from full-thickness cartilage regions of interest, at increasing distances from the lesions, were used to compare experimental against control and to correlate qMRI with the references. Significant alterations were detected by qMRI parameters, including prolonged T(1) , CWT(1ρ) , and AdT(1ρ) in the regions adjacent to the lesions. The changes were confirmed by the reference methods. CWT(1ρ) was more strongly associated with the reference measurements and prolonged in the affected regions at lower spin-locking amplitudes. Moderate to strong correlations were found between all qMRI parameters and the reference parameters (ρ = -0.531 to -0.757). T(1) , low spin-lock amplitude CWT(1ρ) , and AdT(1ρ) were most responsive to changes in visually intact cartilage adjacent to the lesions. In the context of PTOA, these findings highlight the potential of T(1) , CWT(1ρ) , and AdT(1ρ) in evaluation of compositional and structural changes in cartilage

Whole-Genome Sequencing Identifies STAT4 as a Putative Susceptibility Gene in Classic Kaposi Sarcoma

Background. Classic Kaposi sarcoma (cKS) is an inflammatory tumor caused by human herpesvirus 8 (HHV-8) commonly observed in elderly men of Mediterranean origin. We studied a Finnish family of 5 affected individuals in 2 generations. Except for atypical mycobacterial infection of the index case, the affected individuals did not have notable histories of infection. Methods. We performed genome and exome sequencing and mapped shared chromosomal regions to identify genetic predisposition in the family. Results. We identified 12 protein-coding candidate variants that segregated in the 3 affected cousins from whom we had samples. The affected mother of the index case was an obligatory carrier. Among the 12 candidates was a rare heterozygous substitution rs141331848 (c.1337C>T, p.Thr446Ile) in the DNA-binding domain of STAT4. The variant was not present in 242 Finnish control genomes or 180 additional regional controls. Activated T-helper cells from the HHV-8-negative variant carriers showed reduced interferon \u3b3 production, compared with age and sex matched wild-type individuals. We screened STAT4 in additional 18 familial KS cases and the variant site from 56 sporadic KS cases but detected no pathogenic mutations. Conclusions. Our data suggest that STAT4 is a potential cKS-predisposition gene, but further functional and genetic validation is needed