Dissecting the Transcriptional Regulatory Properties of Human Chromosome 16 Highly Conserved Non-Coding Regions

Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs) have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions

Height-diameter allometry and above ground biomass in tropical montane forests: Insights from the Albertine Rift in Africa

Tropical montane forests provide an important natural laboratory to test ecological theory. While it is well-known that some aspects of forest structure change with altitude, little is known on the effects of altitude on above ground biomass (AGB), particularly with regard to changing height-diameter allometry. To address this we investigate (1) the effects of altitude on height-diameter allometry, (2) how different height-diameter allometric models affect above ground biomass estimates; and (3) how other forest structural, taxonomic and environmental attributes affect above ground biomass using 30 permanent sample plots (1-ha; all trees ≥ 10 cm diameter measured) established between 1250 and 2600 m asl in Kahuzi Biega National Park in eastern Democratic Republic of Congo. Forest structure and species composition differed with increasing altitude, with four forest types identified. Different height-diameter allometric models performed better with the different forest types, as trees got smaller with increasing altitude. Above ground biomass ranged from 168 to 290 Mg ha-1, but there were no significant differences in AGB between forests types, as tree size decreased but stem density increased with increasing altitude. Forest structure had greater effects on above ground biomass than forest diversity. Soil attributes (K and acidity, pH) also significantly affected above ground biomass. Results show how forest structural, taxonomic and environmental attributes affect above ground biomass in African tropical montane forests. They particularly highlight that the use of regional height-diameter models introduces significant biases in above ground biomass estimates, and that different height-diameter models might be preferred for different forest types, and these should be considered in future studies

Defective proliferation and osteogenic potential with altered immunoregulatory phenotype of native bone marrow-multipotential stromal cells in atrophic fracture non-union

Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271highCD45low cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271highCD45low cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing

Influence of latitude on the light availability for intercrops in an agroforestry alley-cropping system

Light competition by trees is often regarded as a major limiting factor for crops in alley-cropping agroforestry. Northern latitude farmers are usually reluctant to adopt agroforestry as they fear that light competition will be fiercer in their conditions. We questioned the light availability for crops in alley-cropping at different latitudes from the tropic circle to the polar circle with a process-based 3D model of alley-cropping agroforestry. Two tree densities and two tree line orientations were considered. The effect of the latitude was evaluated with same-sized trees. The relative irradiance of the crops was computed for the whole year or at specific times of the year when crops need more light. The heterogeneity of crop irradiance across the alley was also computed. Surprisingly, crop relative irradiance of summer crops at high latitudes is high, at odds with farmers’ fears. Best designs were highlighted for improving the crop irradiance: North–South tree lines are recommended at high latitudes and East–West tree lines at low latitudes. At medium latitudes, North–South tree lines should be preferred to achieve an homogeneous irradiance of the crop in the alley. If we assume that trees at northern latitudes grow slower when compared to southern latitudes, then alley-cropping agroforestry is highly advisable even at high latitudes with summer crops

5-year follow-up of spinal and sacroiliac MRI abnormalities in early axial spondyloarthritis: data from the DESIR cohort

Objective To study changes on MRI of the spine and sacroiliac joint (SIJ) in early axial spondyloarthritis (axSpA) over time.Methods In the Devenir des Spondyloarthropathies Indifferenciees Recentes cohort, MRI-spine and MRI-SI J at baseline and 2 and 5 years were scored by central readers for bone marrow oedema (BME), fatty lesions, erosions, sclerosis, ankylosis and spinal bone spurs. The average mean number of lesions was reported or the agreement of >= 2 out of 3 readers for binary outcomes. Net progression was calculated by subtracting the patients that 'improved' from those that 'worsened' divided by the total number of patients.Results Over 5 years, in 155 patients with axSpA (mean age 33.5 (SD 8.9) years, symptom duration 1.4 (0.8) years, 63% human leucocyte antigen+, 14% modified New York+), BME on MRI-SI J decreased by a mean Spondyloarthritis Research Consortium of Canada score of 1.4 (SD 6.5) (p=0.009). The largest BME decrease was observed in patients using biological disease-modifying antirheumatic drugs at 5 years. Spinal BME increased by 0.3 (4.6) (p=0.41). Fatty lesions and/or erosions on MRI-SIJ increased by a mean of 1.0 (SD 2.6) (p= 5 fatty lesions and/or erosions. At 5 years, 0.7% less patients had >= 5 spinal BME lesions and 0.7% less patients had >= 5 spinal fatty lesions.Conclusion Over 5 years, BME on MRI-SI J decreased and spinal BME remained similar, but numerically, little progression of structural lesions on MRI of the SIJ and spine was seen.Pathophysiology and treatment of rheumatic disease