Production via good manufacturing practice of exofucosylated human mesenchymal stromal cells for clinical applications

Background

The regenerative and immunomodulatory properties of human mesenchymal stromal cells (hMSCs) have raised great hope for their use in cell therapy. However, when intravenously infused, hMSCs fail to reach sites of tissue injury. Fucose addition in α(1,3)-linkage to terminal sialyllactosamines on CD44 creates the molecule known as hematopoietic cell E-/L-selectin ligand (HCELL), programming hMSC binding to E-selectin that is expressed on microvascular endothelial cells of bone marrow (BM), skin and at all sites of inflammation. Here we describe how this modification on BM-derived hMSCs (BM-hMSCs) can be adapted to good manufacturing practice (GMP) standards.

Andrenocorticotropin and β-lipotropin in the hypothalamus

Adrenocorticotropin and β-lipotropin (β-LPH) have been localized by immunoperoxidase methods in nerve cells and fibers of the hypothalamus and brain stem of the ewe. 6-μm sections were immunostained first for either ACTH or β-LPH. The reaction products and the antibody complexes were then eluted completely from the tissue, and the same section was immunostained for the second peptide. Absorption of the primary antisera with a variety of peptide fragments of ACTH and β-LPH demonstrated, immunocytochemically as well as by radioimmunoassay, that the ACTH and β-LPH antisera were directed to the COOH- and NH(2)-termini of the peptides, respectively. Neither antiserum recognized any portion of the heterologous peptide. In the sequential staining procedure on the same tissue section, preincubation of the antisera with the homologous peptide abolished the staining, whereas preincubation with the heterologous peptide did not affect it, regardless of the order followed. Every nerve cell in the arcuate nucleus that contained ACTH also contained β-LPH, but β-LPH cells appeared, probably falsely, to be twice as numerous as ACTH cells. β-LPH-positive fibers in and beyond the hypothalamus were also more numerous and stained more intensively than ACTH fibers. The salient exception was fibers in the infundibular zona externa, where the opposite was true. Our observations establish that ACTH and β-LPH are contained in the same nerve cells They stongly favor biosynthesis in brain, probably from a common precursor molecule, as has been demonstrated in the pituitary gland. The complexity of the cytologic distribution pattern described suggests that the two peptides are not processed in the same manner by the nerve cell.     

Evolutionary Implications of Persistence Hunting: An Examination of Energy Return on Investment for !Kung Hunting

Hominins are smaller, slower, and weaker than most large mammals, yet they have been eating meat from freshly killed large mammals since before the invention of sophisticated weaponry. It is thought that they could have achieved this seemingly impossible feat through persistence hunting, a practice powered by endurance running. Essentially, one or more hunters pursue a prey animal in the heat of the day until it reaches the point of hyperthermia. This allows a hunter to safely kill the weakened animal at close range using methods such as beating, strangling, or spearing. The energy balance of this approach to getting food is controversial and has not been calculated previously. We examined the energy costs and gains of persistence hunting through several energy returned on investment (EROI) calculations based on synthesizing available field and laboratory data on the energy used by the hunters and the energy returned from the greater kudu (Tragelaphus strepsiceros). We estimate that the EROI of these hunter-gatherers hunting a kudu ranged from 26:1 to 69:1. The net energy gained from such an effort would sustain an average sized !Kung family for 6.7 to 11.2 days. The “profit” energy within these ranges would have supported the early human societies that practiced persistence hunting, contributing to the often-noted “leisure” characterizing many foraging societies (Sahlins 1974).     

Vertical transmission in feather mites: insights into its adaptive value

1. The consequences of symbiont transmission strategies are better understood than their adaptive causes. 2. Feather mites are permanent ectosymbionts of birds assumed to be transmitted mainly vertically from parents to offspring. The transmission of Proctophyllodes doleophyes Gaud (Astigmata, Proctophyllodidae) was studied in two European populations of pied flycatchers, Ficedula hypoleuca Pallas (Passeriformes, Muscicapidae). 3. The vertical transmission of this mite species is demonstrated here with an acaricide experiment. This study also compared (for two distant populations during 4 years) patterns in reductions in mite intensity in adult birds, from egg incubation to chick‐rearing periods, with the predictions of three hypotheses on how host survival prospects and mite intraspecific competition might drive feather mites' transmission strategy. 4. The results are in agreement with previous studies and show that feather mites transmit massively from parents to chicks. 5. The magnitude of the transmission was closer to that predicted by the hypothesis based on intraspecific competition, while a bet‐hedging strategy is also partially supported.     

Escape from natural enemies during climate-driven range expansion: a case study

Abstract.  1. A major, and largely unexplored, uncertainty in projecting the impact of climate change on biodiversity is the consequence of altered interspecific interactions, for example between parasitoids and their hosts. The present study investigated parasitism in the Brown Argus butterfly, Aricia agestis ; a species that has expanded northward in Britain during the last 30  years in association with climate warming.
2.  Aricia agestis larvae suffered lower mortality from parasitoids in newly colonised areas compared with long-established populations. This result was consistent over four consecutive generations (2 years) when comparing one population of each type, and also when several populations within the historical and recently colonised range of the species were compared within a single year. Thus, A. agestis appears to be partially escaping from parasitism as it expands northwards.
3. Reduced parasitism occurred despite the fact that several of the parasitoid species associated with A. agestis were already present in the newly colonised areas, supported predominantly by an alternative host species, the Common Blue butterfly, Polyommatus icarus .
4. As the species expand their distributions into areas of increased climatic suitability, invasion fronts may escape from natural enemies, enhancing rates of range expansion. The results suggest that the decoupling of interspecific interactions may allow some species to exploit a wider range of environments and to do so more rapidly than previously thought possible.     

Genetic relationships among populations of Aedes aegypti from Uruguay and northeastern Argentina inferred from ISSR‐PCR data

Aedes aegypti (L.) (Diptera: Culicidae), the main vector of yellow fever and dengue viruses, was eradicated from Argentina between 1955 and 1963, but reinvaded the country in 1986. In Uruguay, the species was reintroduced in 1997. In this study we used highly polymorphic inter‐simple sequence repeats (ISSR) markers to analyse the genetic structure of Ae. aegypti populations from Uruguay and northeastern Argentina to identify possible colonization patterns of the vector. Overall genetic differentiation among populations was high (F_ST = 0.106) and showed no correlation with geographic distance, which is consistent with the short time since the reintroduction of the species in the area. Differentiation between pairs of Argentine populations (F_ST 0.072 to 0.221) was on average higher than between Uruguayan populations (F_ST?0.044 to 0.116). Bayesian estimation of population structure defined four genetic clusters and most populations were admixtures of two of them: Mercedes and Treinta y Tres (Uruguay) were mixtures of clusters 1 and 3; Salto (Uruguay) and Paraná (Argentina) of clusters 1 and 4; Fray Bentos (Uruguay) of clusters 2 and 3, and Gualeguaychú (Argentina) of clusters 2 and 3. Posadas and Buenos Aires in Argentina were fairly genetically homogeneous. Our results suggest that Ae. aegypti recolonized Uruguay from bordering cities in Argentina via bridges over the Uruguay River and also from Brazil.