Mesenchymal stromal cell‐derived factors promote the colonization of collagen 3D scaffolds with human skin cells

The development of stem cell technology in combination with advances in biomaterials has opened new ways of producing engineered tissue substitutes. In this study, we investigated whether the therapeutic potential of an acellular porous scaffold made of type I collagen can be improved by the addition of a powerful trophic agent in the form of mesenchymal stromal cells conditioned medium (MSC‐CM) in order to be used as an acellular scaffold for skin wound healing treatment. Our experiments showed that MSC‐CM sustained the adherence of keratinocytes and fibroblasts as well as the proliferation of keratinocytes. Moreover, MSC‐CM had chemoattractant properties for keratinocytes and endothelial cells, attributable to the content of trophic and pro‐angiogenic factors. Also, for the dermal fibroblasts cultured on collagen scaffold in the presence of MSC‐CM versus serum control, the ratio between collagen III and I mRNAs increased by 2‐fold. Furthermore, the gene expression for α‐smooth muscle actin, tissue inhibitor of metalloproteinase‐1 and 2 and matrix metalloproteinase‐14 was significantly increased by approximately 2‐fold. In conclusion, factors existing in MSC‐CM improve the colonization of collagen 3D scaffolds, by sustaining the adherence and proliferation of keratinocytes and by inducing a pro‐healing phenotype in fibroblasts.     

What is Killing Organic Photovoltaics: Light‐Induced Crosslinking as a General Degradation Pathway of Organic Conjugated Molecules

In view of a rapid development and increase in efficiency of organic solar cells, reaching their long‐term operational stability represents now one of the main challenges to be addressed on the way toward commercialization of this photovoltaic technology. However, intrinsic degradation pathways occurring in organic solar cells under realistic operational conditions remain poorly understood. The light‐induced dimerization of the fullerene‐based acceptor materials discovered recently is considered to be one of the main causes for burn‐in degradation of organic solar cells. In this work, it is shown that not only the fullerene derivatives but also different types of conjugated polymers and small molecules undergo similar light‐induced crosslinking regardless of their chemical composition and structure. In the case of conjugated polymers, crosslinking of macromolecules leads to a rapid increase in their molecular weight and consequent loss of solubility, which can be revealed in a straightforward way by gel permeation chromatography analysis via a reduction/loss of signal and/or smaller retention times. Results of this work, thus, shift the paradigm of research in the field toward designing a new generation of organic absorbers with enhanced intrinsic photochemical stability in order to reach practically useful operation lifetimes required for successful commercialization of organic photovoltaics.     

The effect of intrauterine inflammation on mTOR signaling in mouse fetal brain

Fetuses exposed to an inflammatory environment are predisposed to long‐term adverse neurological outcomes. However, the mechanism by which intrauterine inflammation (IUI) is responsible for abnormal fetal brain development is not fully understood. The mechanistic target of rapamycin (mTOR) signaling pathway is closely associated with fetal brain development. We hypothesized that mTOR signaling might be involved in fetal brain injury and malformation when fetuses are exposed to the IUI environment. A well‐established IUI model was utilized by intrauterine injection of lipopolysaccharide (LPS) to explore the effect of IUI on mTOR signaling in mouse fetal brains. We found that microglia activation in LPS fetal brains was increased, as demonstrated by elevated Iba‐1 protein level and immunofluorescence density. LPS fetal brains also showed reduced neuronal cell counts, decreased cell proliferation demonstrated by low Ki67‐positive density, and elevated neuron apoptosis evidenced by high expression of cleaved Caspase 3. Furthermore, we found that mTOR signaling in LPS fetal brains was elevated at 2 hr after LPS treatment, declined at 6 hr and showed overall inhibition at 24 hr. In summary, our study revealed that LPS‐induced IUI leads to increased activation of microglia cells, neuronal damage, and dynamic alterations in mTOR signaling in the mouse fetal brain. Our findings indicate that abnormal changes in mTOR signaling may underlie the development of future neurological complications in offspring exposed to prenatal IUI.     

RCSB Protein Data Bank: Enabling biomedical research and drug discovery

Analyses of publicly available structural data reveal interesting insights into the impact of the three‐dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G‐protein‐coupled receptors, voltage‐gated ion channels, ligand‐gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic‐level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open‐access, digital‐data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ～40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ～90% of the 210 new drugs approved by the US Food and Drug Administration 2010–2016. We review user‐driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure‐guided drug discovery for challenging targets (e.g., integral membrane proteins).     

In a comfort zone and beyond—Ecological plasticity of key marine mediators

Copepods of the genus Calanus are the key components of zooplankton. Understanding their response to a changing climate is crucial to predict the functioning of future warmer high‐latitude ecosystems. Although specific Calanus species are morphologically very similar, they have different life strategies and roles in ecosystems. In this study, C. finmarchicus and C. glacialis were thoroughly studied with regard to their plasticity in morphology and ecology both in their preferred original water mass (Atlantic vs. Arctic side of the Polar Front) and in suboptimal conditions (due to, e.g., temperature, turbidity, and competition in Hornsund fjord). Our observations show that “at the same place and time,” both species can reach different sizes, take on different pigmentation, be in different states of population development, utilize different reproductive versus lipid accumulation strategies, and thrive on different foods. Size was proven to be a very mutable morphological trait, especially with regard to reduced length of C. glacialis. Both species exhibited pronounced red pigmentation when inhabiting their preferred water mass. In other domains, C. finmarchicus individuals tended to be paler than C. glacialis individuals. Gonad maturation and population development indicated mixed reproductive strategies, although a surprisingly similar population age structure of the two co‐occurring species in the fjord was observed. Lipid accumulation was high and not species‐specific, and its variability was due to diet differences of the populations. According to the stable isotope composition, both species had a more herbivorous diatom‐based diet in their original water masses. While the diet of C. glacialis was rather consistent among the domains studied, C. finmarchicus exhibited much higher variability in its feeding history (based on lipid composition). Our results show that the plasticity of both Calanus species is indeed impressive and may be regulated differently, depending on whether they live in their “comfort zone” or beyond it.     

Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation

Exact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way.