Multi-Parameter Analysis of Biobanked Human Bone Marrow Stromal Cells Shows Little Influence for Donor Age and Mild Comorbidities on Phenotypic and Functional Properties

Heterogeneous populations of human bone marrow-derived stromal cells (BMSC) are among the most frequently tested cellular therapeutics for treating degenerative and immune disorders, which occur predominantly in the aging population. Currently, it is unclear whether advanced donor age and commonly associated comorbidities affect the properties of ex vivo-expanded BMSCs. Thus, we stratified cells from adult and elderly donors from our biobank (n = 10 and n = 13, mean age 38 and 72 years, respectively) and compared their phenotypic and functional performance, using multiple assays typically employed as minimal criteria for defining multipotent mesenchymal stromal cells (MSCs). We found that BMSCs from both cohorts meet the standard criteria for MSC, exhibiting similar morphology, growth kinetics, gene expression profiles, and pro-angiogenic and immunosuppressive potential and the capacity to differentiate toward adipogenic, chondrogenic, and osteogenic lineages. We found no substantial differences between cells from the adult and elderly cohorts. As positive controls, we studied the impact of in vitro aging and inflammatory cytokine stimulation. Both conditions clearly affected the cellular properties, independent of donor age. We conclude that in vitro aging rather than in vivo donor aging influences BMSC characteristics

Low catalytic activity is insufficient to induce disease pathology in triosephosphate isomerase deficiency

Triosephosphate isomerase (TPI) deficiency is a fatal genetic disorder characterized by hemolytic anemia and neurological dysfunction. Although the enzyme defect in TPI was discovered in the 1960s, the exact etiology of the disease is still debated. Some aspects indicate the disease could be caused by insufficient enzyme activity, whereas other observations indicate it could be a protein misfolding disease with tissue-specific differences in TPI activity. We generated a mouse model in which exchange of a conserved catalytic amino acid residue (isoleucine to valine, Ile170Val) reduces TPI specific activity without affecting the stability of the protein dimer. TPIIle170Val/Ile170Val mice exhibit an approximately 85% reduction in TPI activity consistently across all examined tissues, which is a stronger average, but more consistent, activity decline than observed in patients or symptomatic mouse models that carry structural defect mutant alleles. While monitoring protein expression levels revealed no evidence for protein instability, metabolite quantification indicated that glycolysis is affected by the active site mutation. TPIIle170Val/Ile170Val mice develop normally and show none of the disease symptoms associated with TPI deficiency. Therefore, without the stability defect that affects TPI activity in a tissue-specific manner, a strong decline in TPI catalytic activity is not sufficient to explain the pathological onset of TPI deficiency

Sumoylation inhibits α-synuclein aggregation and toxicity

Sumoylation of α-synuclein decreases its rate of aggregation and its deleterious effects in vitro and in vivo

Data from: Island bat diets: does it matter more who you are or where you live?

Differences in body size, echolocation call frequency, and location may result in diet partitioning among bat species. Comparisons among island populations are one way to evaluate these competing hypotheses. We conducted a species-level diet analysis of three Rhinolophus and one Hipposideros species on the Philippine islands of Cebu, Bohol, and Siquijor. We identified 655 prey (MOTUs) in the guano from 77 individual bats. There was a high degree of overlap among species’ diets despite differences in body size and call frequency. For example, the diet of the 3 g-Hipposideros pygmaeus (mean CF = 102 kHz) exhibited a diet overlap higher than expected by chance with all three Rhinolophus species, even the 13 g-Rhinolophus inops (mean CF = 54 kHz). We observed more convergence in diet between Rhinolophus species and H. pygmaeus than between Rhinolophus species themselves, which may be explained by the broad diet of H. pygmaeus. There was less dietary overlap between Rhinolophus virgo from two islands than between R. virgo and congeners from Cebu. These data suggest that location causes convergence in diet, but specific species characteristics may drive niche specialization. The complex interplay between location and the perceptual ability of each species leads to a situation where simple explanations, for example, body size, do not translate into predictable prey partitioning. In particular, our observations raise interesting questions about the foraging strategy and adaptability of the tiny H. pygmaeus

Key To FIles Used For Analysis

Key to sequence title

Unique Haplotypes wtih bat ID

Unique Haplotypes wtih bat I

R_inops_BLAST

R_inops_BLAS

R_arcuatus_BLAST

Please see the read me file for details

H_pygmaeus_BLAST

Please see read me file for instructions