Fate mapping analysis reveals that adult microglia derive from primitive macrophages

Microglia are the resident macrophages of the central nervous system and are associated with the pathogenesis of many neurodegenerative and brain inflammatory diseases; however, the origin of adult microglia remains controversial. We show that postnatal hematopoietic progenitors do not significantly contribute to microglia homeostasis in the adult brain. In contrast to many macrophage populations, we show that microglia develop in mice that lack colony stimulating factor-1 (CSF-1) but are absent in CSF-1 receptor-deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors that arise before embryonic day 8. These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.     

Quantitation of 13 heterocyclic aromatic amines in cooked beef, pork, and chicken by liquid chromatography-electrospray ionization/tandem mass spectrometry

The concentrations of heterocyclic aromatic amines (HAAs) were determined, by liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI-MS/MS), in 26 samples of beef, pork, and chicken cooked to various levels of doneness. The HAAs identified were 2-amino-3-methylimidazo[4,5- f]quinoline, 2-amino-1-methylimidazo[4,5- b]quinoline, 2-amino-1-methylimidazo[4,5- g]quinoxaline (I gQx), 2-amino-3-methylimidazo[4,5- f]quinoxaline, 2-amino-1,7-dimethylimidazo[4,5- g]quinoxaline (7-MeI gQx), 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline, 2-amino-1,6-dimethyl-furo[3,2- e]imidazo[4,5- b]pyridine, 2-amino-1,6,7-trimethylimidazo[4,5- g]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5- f]quinoxaline, 2-amino-1,7,9-trimethylimidazo[4,5- g]quinoxaline, 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP), 2-amino-9 H-pyrido[2,3- b]indole, and 2-amino-3-methyl-9 H-pyrido[2,3- b]indole. The concentrations of these compounds ranged from <0.03 to 305 parts per billion (micrograms per kilogram). PhIP was the most abundant HAA formed in very well done barbecued chicken (up to 305 microg/kg), broiled bacon (16 microg/kg), and pan-fried bacon (4.9 microg/kg). 7-MeI gQx was the most abundant HAA formed in very well done pan-fried beef and steak, and in beef gravy, at concentrations up to 30 microg/kg. Several other linear tricyclic ring HAAs containing the I gQx skeleton are formed at concentrations in cooked meats that are relatively high in comparison to the concentrations of their angular tricyclic ring isomers, the latter of which are known experimental animal carcinogens and potential human carcinogens. The toxicological properties of these recently discovered I gQx derivatives warrant further investigation and assessment.     

Endothelial cell activation and neovascularization are prominent in dermatomyositis

Background

While vascular and immune abnormalities are common in juvenile and adult dermatomyositis (DM), the molecular changes that contribute to these abnormalities are not clear. Therefore, we investigated pathways that facilitate new blood vessel formation and dendritic cell migration in dermatomyositis.

Methods

Muscle biopsies from subjects with DM (9 children and 6 adults) and non-myositis controls (6 children and 7 adults) were investigated by immunohistochemistry using antibodies that recognize existing (anti-CD146) and newly formed blood vessels (anti-αVβ3) and mature dendritic cells (anti-DC-LAMP). Blood vessel quantification was performed by digitalized image analysis. Additional muscle biopsies from subjects with adult DM and non-myositis controls were used for global gene expression profiling experiments.

Results

A significant increase in neovascularization was found in muscle biopsies of DM patients; neovascularization (αVβ3 positive capillaries and vessels per muscle fiber) was much higher in juvenile than in adult DM patients (control vs juvenile DM: Mean ± SE: 0.06 ± 0.01 vs 0.6 ± 0.05; p < 0.0001 and control vs adult DM: Mean ± SE: 0.60 ± 0.1 vs 0.75 ± 0.1; p = 0.051). Gene expression analysis demonstrated that genes that participate not only in angiogenesis but also in leukocyte trafficking and the complement cascade were highly up regulated in DM muscle in comparison to age matched controls. DC-LAMP positive dendritic cells were highly enriched at perivascular inflammatory sites in juvenile and adult DM patients along with molecules that facilitate dendritic cell transmigration and reverse transmigration (CD142 and CD31).

Conclusion

These results suggest active neovascularization and endothelial cell activation in both juvenile and adult DM. It is likely that close association of monocytes with endothelial cells initiate rapid dendritic cell maturation and an autoimmune response in DM.

     

A LAT mutation that inhibits T cell development yet induces lymphoproliferation

Mice homozygous for a single tyrosine mutation in LAT (linker for activation of T cells) exhibited an early block in T cell maturation but later developed a polyclonal lymphoproliferative disorder and signs of autoimmune disease. T cell antigen receptor (TCR)-induced activation of phospholipase C-gamma1 (PLC-gamma1) and of nuclear factor of activated T cells, calcium influx, interleukin-2 production, and cell death were reduced or abrogated in T cells from LAT mutant mice. In contrast, TCR-induced Erk activation was intact. These results identify a critical role for integrated PLC-gamma1 and Ras-Erk signaling through LAT in T cell development and homeostasis.     

First report of dry rot of potato caused by Fusarium proliferatum in India

Journal of Plant Diseases and Protection - Potato stands first as a non-cereal food crop for global consumption purposes. During the year 2019–20, dry rot disease symptoms were observed on...