Deep Autoencoders for Additional Insight into Protein Dynamics

The study of protein dynamics through analysis of conformational transitions represents a significant stage in understanding protein function. Using molecular simulations, large samples of protein transitions can be recorded. However,extractingfunctionalmotionsfromthesesamplesisstillnotautomated andextremelytime-consuming.Inthispaperweinvestigatetheusefulnessofunsupervised machine learning methods for uncovering relevant information about protein functional dynamics. Autoencoders are being explored in order to highlight their ability to learn relevant biological patterns, such as structural characteristics. This study is aimed to provide a better comprehension of how protein conformational transitions are evolving in time, within the larger framework of automatically detecting functional motions

Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways

Migration and proliferation of smooth muscle cells are key to a number of physiological and pathological processes, including wound healing and the narrowing of the vessel wall.Previous work has shown links between inflammatory stimuli and vascular smooth muscle cell proliferation and migration through mitogen activated protein kinase (MAPK) activation, though the molecular mechanisms of this process are poorly understood. Here we report that tribbles-1, a recently described modulator of MAPK activation controls vascular smooth muscle cell proliferation and chemotaxis via the Jun Kinase pathway. Our findings demonstrate that this regulation takes place via direct interactions between tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is dependent on tribbles-1 levels, whilst the activation and the expression of MKK4/SEK1 is not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries compared to non-atherosclerotic controls, suggesting that this protein may pay a role in disease in vivo. In summary, the data presented here suggest an important regulatory role for trb-1 in vascular smooth muscle cell biology

Adaptive dynamics in a two-patch environment: A simple model for allopatric and parapatric speciation

Adaptation to an environment consisting of two patches (each with different optimal strategy) is investigated. The patches have independent density regulation ('soft selection'). If the patches are similar enough and migration between them is strong, then evolution ends up with a generalist ESS. If either the difference between the patches increases or migration weakens, then the generalist strategy represents a branching singularity: The initially monomorphic population first evolves towards the generalist strategy, there it undergoes branching, and finally two specialist strategies form an evolutionarily stable coalition. Further increasing the between-patch difference or decreasing migration causes the generalist to lose its convergence stability as well, and an initially monomorphic population evolves towards one of the specialists optimally adapted to one of the two patches. Bifurcation pattern of the singularities is presented as a function of patch difference and migration rate. Connection to speciation theory is discussed. The transition from the generalist ESS to the coexisting pair of specialist strategies is regarded as a clonal prototype of parapatric (if the between-patch difference increases) or allopatric (if the migration decreases) speciation. We conclude that the geographic and the competitive speciation modes are not distinct classes

Adaptive Dynamics in a 2-patch Environment: a Simple Model for Allopatric and Parapatric Speciation.

Adaptation to an environment consisting of two patches (each with different optimal strategy) is investigated. The patches have independent density regulation ('soft selection'). If the patches are similar enough and migration between them is strong, then evolution ends up with a generalist ESS. If either the difference between the patches increases or migration weakens, then the generalist strategy represent a branching singularity: The initially monomorphic population first evolves towards the generalist strategy, there it undergoes branching, and finally two specialist strategies form an evolutionarily stable coalition. Further increasing the between-patch difference or decreasing migration causes the generalist to lose its convergence stability as well, and an initially monomorphic population evolves towards one of the specialists optimally adapted to one of the two patches. Bifurcation pattern of the singularities is presented as a function of patch difference and migration rate. Connection to speciation theory is discussed. The transition from the generalist ESS to the coexisting pair of specialist strategies is regarded as a clonal prototype of parapatric (if the between-patch difference increases) or allopatric (if the migration decreases) speciation. We conclude that the geographic and the competitive speciation modes are not distinct classes.

Characterization and therapeutic application of canine adipose mesenchymal stem cells to treat elbow osteoarthritis

Visceral adipose tissue (AT) obtained from surgical waste during routine ovariectomies was used as a source for isolating canine mesenchymal stem cells (MSCs). As determined by cytofluorimetry, passage 2 cells expressed MSC markers CD44 and CD90 and were negative for lineage-specific markers CD34 and CD45. The cells differentiated toward osteogenic, adipogenic, and chondrogenic directions. With therapeutic aims, 30 dogs (39 joints) suffering from elbow dysplasia (ED) and osteoarthritis (OA) were intra-articularly transplanted with allogeneic MSCs suspended in 0.5% hyaluronic acid (HA). A highly significant improvement was achieved without any medication as demonstrated by the degree of lameness during the follow-up period of 1 y. Control arthroscopy of 1 transplanted dog indicated that the cartilage had regenerated. Histological analysis of the cartilage biopsy confirmed that the regenerated cartilage was of hyaline type. These results demonstrate that transplantation of allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSCs) is a novel, noninvasive, and highly effective therapeutic tool in treating canine elbow dysplasia