Paracrine Effect of Mesenchymal Stem Cells Derived from Human Adipose Tissue in Bone Regeneration

Mesenchymal stem cell (MSC) transplantation has proved to be a promising strategy in cell therapy and regenerative medicine. Although their mechanism of action is not completely clear, it has been suggested that their therapeutic activity may be mediated by a paracrine effect. The main goal of this study was to evaluate by radiographic, morphometric and histological analysis the ability of mesenchymal stem cells derived from human adipose tissue (Ad-MSC) and their conditioned medium (CM), to repair surgical bone lesions using an in vivo model (rabbit mandibles). The results demonstrated that both, Ad-MSC and CM, induce bone regeneration in surgically created lesions in rabbit''s jaws, suggesting that Ad-MSC improve the process of bone regeneration mainly by releasing paracrine factors. The evidence of the paracrine effect of MSC on bone regeneration has a major impact on regenerative medicine, and the use of their CM can address some issues and difficulties related to cell transplants. In particular, CM can be easily stored and transported, and is easier to handle by medical personnel during clinical procedures.     

Determination of biological and physicochemical parameters of Artemia franciscana strains in hypersaline environments for aquaculture in the Colombian Caribbean

Background

Artemia (Crustacea, Anostraca), also known as brine shrimp, are typical inhabitants of extreme environments. These hypersaline environments vary considerably in their physicochemical composition, and even their climatic conditions and elevation. Several thalassohaline (marine) environments along the Colombian Caribbean coast were surveyed in order to contribute to the knowledge of brine shrimp biotopes in South America by determining some vital biological and physicochemical parameters for Artemia survival. Additionally, cyst quality tests, biometrical and essential fatty acids analysis were performed to evaluate the economic viability of some of these strains for the aquaculture industry.

Results

In addition to the three locations (Galerazamba, Manaure, and Pozos Colorados) reported in the literature three decades ago in the Colombian Caribbean, six new locations were registered (Salina Cero, Kangaru, Tayrona, Bahía Hondita, Warrego and Pusheo). All habitats sampled showed that chloride was the prevailing anion, as expected, because of their thalassohaline origin. There were significant differences in cyst diameter grouping strains in the following manner according to this parameter: 1) San Francisco Bay (SFB-Control, USA), 2) Galerazamba and Tayrona, 3) Kangarú, 4) Manaure, and 5) Salina Cero and Pozos Colorados. Chorion thickness values were smaller in Tayrona, followed by Salina Cero, Galerazamba, Manaure, SFB, Kangarú and Pozos Colorados. There were significant differences in naupliar size, grouping strains as follows (smallest to largest): 1) Galerazamba, 2) Manaure, 3) SFB, Kangarú, and Salina Cero, 4) Pozos Colorados, and 5) Tayrona. Overall, cyst quality analysis conducted on samples from Manaure, Galerazamba, and Salina Cero revealed that all sites exhibited a relatively high number of cysts.g^-1. Essential fatty acids (EFA) analysis performed on nauplii from cyst samples from Manaure, Galerazamba, Salina Cero and Tayrona revealed that cysts from all sites exhibited high arachidonic acid:20:4(n-6) (ArA) and eicosapentaenoic acid: 20:5(n-3) (EPA) levels comparable to the control sample (SFB). In contrast, most cysts collected (including SFB) at different locations, and during different months, presented low docosahexaenoic acid: 22:6(n-3) (DHA) levels (Manaure was the only exception with high DHA levels). Some variations in EPA and ArA levels were observed in all sites, contrasting with the much lower DHA levels which remained constant for all locations, except for Manaure which exhibited variable DHA levels. DHA/EPA ratio was overall very low for all sites compared to SFB cysts. All strains had a low DHA/ArA, but a high EPA/ArA ratio, including the control.

Conclusion

The Colombian A. franciscana habitats analyzed were determined to be thalassohaline, and suitable for A. franciscana development. EFA profiles demonstrated that Tayrona, Galerazamba, Manaure and Salina Cero strains are suitable food for marine fish and crustacean culture because of their high EPA/ArA ratio, but might have to be fortified with DHA rich emulsions depending on the nutritional requirements of the species to be cultured, because of their overall low DHA content. The relatively small nauplii are appropriate for marine larvaeculture. In contrast, the strains from Tayrona, Kangarú, Salina Cero, and Pozos Colorados may be of use but limited to Artemia small biomass production quantities, because of the small surface area of their respective locations; Artemia could be exploited at these locations for local aquaculture applications. In general, cyst quality evaluation for Manaure, Salina Cero and Galerazamba cysts revealed that cysts from these three locations could improve their quality by concentrating efforts on cyst processing techniques. Finally, most locations had great A. franciscana production potential and require different degrees of water quality and/or infrastructure management.     

Participation of eIF4F complex in Junin virus infection: blockage of eIF4E does not impair virus replication

Translation efficiency of viral mRNAs is a key factor defining both cytopathogenicity and virulence of viruses, which are entirely dependent on the cellular translation machinery to synthesize their proteins. This dependence has led them to develop different translational reprogramming strategies to ensure viral mRNAs can effectively compete with cellular mRNAs. Junin virus (JUNV) is a member of the family Arenaviridae, whose mRNAs are capped but not polyadenylated. In this work we evaluated the relevance to JUNV replication of the main components of the eIF4F complex: eIF4A, eIF4GI and eIF4E. We found the viral nucleoprotein (N) of JUNV colocalized with eIF4A and eIF4GI but not with eIF4E. Moreover, N could be immunoprecipitated in association with eIF4A and eIF4GI but not with eIF4E. Accordingly, functional impairment of eIF4A as well as eIF4GI reduced JUNV multiplication. By contrast, inhibition of eIF4E did not show a significant effect on JUNV protein synthesis. A similar situation was observed for another two members of arenaviruses: Tacaribe (TCRV) and Pichinde (PICV) viruses. Finally, the nucleoproteins of JUNV, TCRV and PICV were able to interact with 7 methyl‐guanosine (cap), suggesting that the independence of JUNV multiplication on eIF4E, the cap‐binding protein, may be due to the replacement of this factor by N protein.     

Comparative analysis of numerical integration schemes of density equation for a computational model of bone remodelling

In this study, a computational model of bone remodelling problem as proposed by Weinans et al. (1992) is described and solved by other temporal integration techniques different from the Euler scheme. This model considers three types of numerical integration schemes of the evolution of the material density during the remodelling: Euler, Heun and Runge-Kutta methods. Also the strain and the density field are obtained inside each element, at Gauss points or at the nodes of the mesh. A square plate with 1.00?m of side subjected to non-uniform pressure is simulated with two meshes of quadrilateral element with size [Formula: see text] and [Formula: see text]?m. Two increments time size: [Formula: see text] and [Formula: see text] days are used. The results show that Euler, Heun and Runge-Kutta's methods correctly approached the problem of bone remodelling and that there were no appreciable differences in the patterns obtained by the mesh and time step used. In contrast, using an element-based approach and node-based approach, substantial differences were produced in bone remodelling density pattern. 'Chess board' type discontinuities were found in the element approach near the applied pressure area, as were well-defined columns away from this. The node-based approach showed continuity in density distribution. These patterns were well represented by the methods for resolving the density equation. This study concluded that any method of time integration could be used for these meshes and time steps size.     

<Emphasis Type="Italic">In vitro</Emphasis> isolation of variants of herpes simplex virus attenuated with altered thymidine kinase and DNA polymerase genes using carrageenans as selection agents

Natural polysaccharides known as carrageenans are potent and selective inhibitors of herpes simplex virus through blocking the interaction of the virus with the cellular receptor. Passaging the virus in vitro in the presence of carrageenans types k and ι enabled us to generate variants of herpes simplex type 2. At passage 22, four clones were selected for further characterization: ι22-9, ι22-12, k22-12 and k22-13. Variants showed a syncytial phenotype, grew at similar titers when compared to parental virus and exhibited moderate resistance to carrageenans. These were found to have a mutation in the thymidine kinase gene in the case of k22-13 (aa 149 Val to Ala) and in the DNA pol gene in the case of ι22-12 (aa 789 Met to Thr). In variant k22-12, three substitutions in the DNA pol gene were identified. Variants were less virulent than parental strain when tested intravaginally or intranasally in mice. Attenuation correlated with higher levels of IL-6 and TNF-α in animals inoculated with the variants. Selective pressure on the external glycoproteins of the virus may generate viruses with alterations in genes unrelated to the target of action of the selection agent. Study of this type of variation might help us to understand the basis of persistent viral strategies, which in turn may play a role in the development of virus-host symbioses.     

Semiparametric mixed-scale models using shared Bayesian forests

This paper demonstrates the advantages of sharing information about unknown features of covariates across multiple model components in various nonparametric regression problems including multivariate, heteroscedastic, and semicontinuous responses. In this paper, we present a methodology which allows for information to be shared nonparametrically across various model components using Bayesian sum-of-tree models. Our simulation results demonstrate that sharing of information across related model components is often very beneficial, particularly in sparse high-dimensional problems in which variable selection must be conducted. We illustrate our methodology by analyzing medical expenditure data from the Medical Expenditure Panel Survey (MEPS). To facilitate the Bayesian nonparametric regression analysis, we develop two novel models for analyzing the MEPS data using Bayesian additive regression trees—a heteroskedastic log-normal hurdle model with a “shrink-toward-homoskedasticity” prior and a gamma hurdle model.