Photo‐biocatalytic Cascades:Combining Chemical and Enzymatic Transformations Fueled by Light

In the field of green chemistry, light – an attractive natural agent – has received particular attention for driving biocatalytic reactions. Moreover, the implementation of light to drive (chemo)enzymatic cascade reactions opens up a golden window of opportunities. However, there are limitations to many current examples, mostly associated with incompatibility between the enzyme and the photocatalyst. Additionally, the formation of reactive radicals upon illumination and the loss of catalytic activities in the presence of required additives are common observations. As outlined in this review, the main question is how to overcome current challenges to the exploitation of light to drive (chemo)enzymatic transformations. First, we highlight general concepts in photo-biocatalysis, then give various examples of photo-chemoenzymatic (PCE) cascades, further summarize current synthetic examples of PCE cascades and discuss strategies to address the limitations

Distribution of motor unit potential velocities in short static and prolonged dynamic contractions at low forces: use of the within-subject’s skewness and standard deviation variables

Behaviour of motor unit potential (MUP) velocities in relation to (low) force and duration was investigated in biceps brachii muscle using a surface electrode array. Short static tests of 3.8 s (41 subjects) and prolonged dynamic tests (prolonged tests) of 4 min (30 subjects) were performed as position tasks, applying forces up to 20% of maximal voluntary contraction (MVC). Four variables, derived from the inter-peak latency technique, were used to describe changes in the surface electromyography signal: the mean muscle fibre conduction velocity (CV), the proportion between slow and fast MUPs expressed as the within-subject skewness of MUP velocities, the within-subject standard deviation of MUP velocities [SD-peak velocity (PV)], and the amount of MUPs per second (peak frequency = PF). In short static tests and the initial phase of prolonged tests, larger forces induced an increase of the CV and PF, accompanied with the shift of MUP velocities towards higher values, whereas the SD-PV did not change. During the first 1.5–2 min of the prolonged lower force levels tests (unloaded, and loaded 5 and 10% MVC) the CV and SD-PV slightly decreased and the MUP velocities shifted towards lower values; then the three variables stabilized. The PF values did not change in these tests. However, during the prolonged higher force (20% MVC) test, the CV decreased and MUP velocities shifted towards lower values without stabilization, while the SD-PV broadened and the PF decreased progressively. It is argued that these combined results reflect changes in both neural regulatory strategies and muscle membrane state

Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis

Melanoma growth, angiogenesis and metastatic progression are strongly promoted by the inflammatory tumor microenvironment due to high levels of cytokine and chemokine secretion by the recruited inflammatory and stromal cells. In addition, platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis. In particular, thrombin, through the activity of its receptor protease-activated receptor-1 (PAR-1), regulates tumor cell adhesion to platelets and endothelial cells, stimulates tumor angiogenesis, and promotes tumor growth and metastasis. Notably, in many tumor types including melanoma, PAR-1 expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin-8, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor, platelet-derived growth factor, and integrins. Another proinflammatory receptor–ligand pair, platelet-activating factor (PAF) and its receptor (PAFR), have been shown to act as important modulators of tumor cell adhesion to endothelial cells, angiogenesis, tumor growth and metastasis. PAF is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid, and can be secreted by platelets, inflammatory cells, keratinocytes and endothelial cells. We have demonstrated that in metastatic melanoma cells, PAF stimulates the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and activating transcription factor 1 (ATF-1), which results in overexpression of MMP-2 and membrane type 1-MMP (membrane type 1-MMP). Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that metastatic melanoma cells are better equipped than their non-metastatic counterparts to respond to PAF within the tumor microenvironment. The evidence supporting the hypothesis that the two G-protein coupled receptors, PAR-1 and PAFR, contribute to the acquisition of the metastatic phenotype of melanoma is presented and discussed