Dopamine Regulates Mobilization of Mesenchymal Stem Cells during Wound Angiogenesis

Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by sympathetic nerves which secrete dopamine (DA) and we have recently shown that concentration of DA present in synaptic cleft can significantly inhibit wound tissue neovascularization. As recent reports indicate that MSCs by mobilizing into wound bed play an important role in promoting wound angiogenesis, we therefore investigated the effect of DA on the migration of MSCs in wound tissues. DA acted through its D2 receptors present in the MSCs to inhibit their mobilization to the wound beds by suppressing Akt phosphorylation and actin polymerization. In contrast, this inhibitory effect of DA was reversed after treatment with specific DA D2 receptor antagonist. Increased mobilization of MSCs was demonstrated in the wound site following blockade of DA D2 receptor mediated actions, and this in turn was associated with significantly more angiogenesis in wound tissues. This study is of translational value and indicates use of DA D2 receptor antagonists to stimulate mobilization of these stem cells for faster regeneration of damaged tissues

Light regulation of metabolic pathways in fungi

Light represents a major carrier of information in nature. The molecular machineries translating its electromagnetic energy (photons) into the chemical language of cells transmit vital signals for adjustment of virtually every living organism to its habitat. Fungi react to illumination in various ways, and we found that they initiate considerable adaptations in their metabolic pathways upon growth in light or after perception of a light pulse. Alterations in response to light have predominantly been observed in carotenoid metabolism, polysaccharide and carbohydrate metabolism, fatty acid metabolism, nucleotide and nucleoside metabolism, and in regulation of production of secondary metabolites. Transcription of genes is initiated within minutes, abundance and activity of metabolic enzymes are adjusted, and subsequently, levels of metabolites are altered to cope with the harmful effects of light or to prepare for reproduction, which is dependent on light in many cases. This review aims to give an overview on metabolic pathways impacted by light and to illustrate the physiological significance of light for fungi. We provide a basis for assessment whether a given metabolic pathway might be subject to regulation by light and how these properties can be exploited for improvement of biotechnological processes

Prior Repeated Stress Attenuates Cold-Induced Immunomodulation Associated with “Browning” in Mesenteric Fat of Rats

Continuous exposure to cold leads to activation of adaptive thermogenesis in brown adipose tissue but also to induction of brown/beige cell phenotype in white adipose tissue. The aim of this work was to investigate whether prior exposure to immobilization (IMO) stress may affect immune response associated with adipocyte browning in mesenteric adipose tissue (mWAT). In the first experiment, Sprague-Dawley rats were exposed to acute (3 h) or prolonged (7 days) cold exposure (4 +/- 1 degrees C). 7-day cold stimulated gene expression of uncoupling protein 1 and other browning -associated factors. In the second experiment, rats were immobilized for 7 days (2 h daily) followed by exposure to continuous cold for 1 or 7 days. Prior IMO exaggerated cold-induced sympathetic response manifested by elevated tyrosine hydroxylase (TH) protein and norepinephrine in mWAT. Induction of non-sympathetic catecholamine production demonstrated by elevated TH and PNMT (phenylethanolamine N-methyltransferase) mRNAs was observed after 7-day cold; however, prior IMO attenuated this response. 7-day cold-induced gene expression of anti-inflammatory mediators (IL-4, IL-13, IL-10, adiponectin), markers of M2 macrophages (Arg1, Retnlalpha), and eosinophil-associated molecules (eotaxin, IL-5), while inhibited expression of pro-inflammatory cytokines (IFNgamma, IL-1b, IL-6, IL-17) and monocytes (MCP-1, Ly6C). This immune response was accompanied by elevated expression of uncoupling protein-1 and other thermogenic factors. Rats exposed to prior IMO exhibited inhibition of cold-induced immune and browning -related expression pattern. Overall, we demonstrated that 7-day cold-induced browning -associated changes in rat mWAT, while prior history of repeated stress prevented this response

Remodelling the genetic evaluation of NFI in beef cattle - Part 1: Developing an equivalent genetic model

Net feed intake (NFI) is the residual portion of daily feed intake (DFI) not explained by growth or maintenance requirements. The NFI phenotype (NFIp) is based on a 70-day test period where DFI and fortnightly weights (to calculate average daily gain (ADG) and maintenance as metabolic mid-weight (MMWT)) are measured. Recording NFIp is costly, and shortening the test length would be advantageous. However, research has shown that ADG cannot be accurately measured from a shortened test. Genetic NFI EBVs (NFIg) were calculated using DFI EBV adjusted for ADG and MMWT EBV and were shown to have a Pearson correlation of 0.99 with the NFIp EBV from 3,088 Angus steers. The regression slope between NFIg and NFIp EBVs was 1.14. Alternative NFIg models where growth and maintenance requirements were obtained from BREEDPLAN live weight traits instead of live weights recorded in the test period, demonstrated high Pearson correlations (r=0.87 to 0.93) and regression slopes between 0.63 and 0.97 with NFIp EBVs. Results suggest that genetic NFI EBVs can be obtained, with growth and maintenance requirements being determined from BREEDPLAN live weight traits. This provides the opportunity to determine if the length of the test to measure DFI can be shortened, reducing the cost of recording NFI per animal

Remodelling the genetic evaluation of NFI in beef cattle - Part 2: Shortening the length of the feed intake test

BREEDPLAN net feed intake (NFI) EBV is derived from a phenotypic regression based on a 70-day feed intake test. Genetic NFI (NFIg) EBVs have been proposed as an alternative EBV and this recent development may also allow for a shortened feed intake test period. This study used feed intake records of 3,088 Angus steers from the full 70-day test and compared them to daily feed intake (DFI) from shortened test periods. Results showed DFI from shortened test periods had similar means but increased phenotypic variation. Phenotypic correlation with DFI from the full test period decreased as the test period decreased in weekly intervals and ranged between 0.75 and 0.99. NFIg EBVs were predicted using DFI from different length tests. The mean of all NFIg EBVs was close to zero, but the EBV standard deviation increased as the test period decreased. Pearson correlations between NFIg EBVs from a full test period and reduced test periods ranged between 0.73 and 0.99, the regression slope of NFIg from reduced test periods on NFIg from the full test period ranged between 0.73 and 0.95, and the bias ranged between 0.00 and 0.02. These results indicate that as the test period decreases, the spread of EBVs increases, resulting in extreme animals having overestimated NFIg EBVs. A shortened DFI test period could be used to estimate NFIg EBVs