Ramin Zand

Abstract Introduction of an amino and a carboxyl group onto carbon 2 of the bicycloheptane ring of norcamphor, by way of the corresponding spirohydantoin, produced a model substrate in which rigidly specified positions are taken by carbon atoms corresponding to those of the ordinary branched chain amino acids. This substance is transported by the system serving for amino acids with apolar (usually, branched) side chains in all cells and tissues tested. No measurable transport of it by any other system has yet been observed, the Na+-dependent systems of various erythrocytes and the Ehrlich cell having been specifically excluded. No unsuspected heterogeneity was detected in the Na+-independent transport of amino acids with apolar side chains by its use. We have used another new synthetic amino acid to illustrate how this substance can be used in conjunction with α-(methylamino)-isobutyric acid for determining by what routes a given amino acid is transported. When the bicyclic amino acid was prepared instead by way of the aminonitrile, the product contained only 31% (rather than the 92% obtained by way of the hydantoin) of the generally effective component, as separated by chromatography on sulfonated polystyrene resin. These two components are presumed to be the endo and exo isomers, although conformations have not yet been assigned. Of the two forms, only the one migrating more slowly on resin columns was taken up by Escherichia coli and that by the system serving for branched chain amino acids. The same product was taken up 2.5 times as fast by the human red blood cell, 3.7 times as fast by the pigeon red blood cell, and 5 times as fast in the Ehrlich cell, as the a isomer. The binding of b-2-aminobicyclo[2,2,1]heptane-2-carboxylic acid to the leucine-binding protein of E. coli and its inhibition of the binding of leucine were far weaker than predicted from its Km and Ki values for transport and inhibition of leucine transport. The bicyclic amino acid has permitted new discriminations of transport agencies and interactions, and may be expected to assist in the further discrimination of transport systems and other biological receptor systems. Determination of the absolute configuration and conformation of the active isomer should assist in the description of specific transport receptor sites, both that which accepts it and those that exclude it.

BACKGROUND: There is preliminary evidence of racial and social-economic disparities in the population infected by and dying from COVID-19. The goal of this study is to report the associations of COVID-19 with respect to race, health and economic inequality in the United States. METHODS: We performed a cross-sectional study of the associations between infection and mortality rate of COVID-19 and demographic, socioeconomic and mobility variables from 369 counties (total population: 102,178,117 [median: 73,447, IQR: 30,761-256,098]) from the seven most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts). FINDINGS: The risk factors for infection and mortality are different. Our analysis shows that counties with more diverse demographics, higher population, education, income levels, and lower disability rates were at a higher risk of COVID-19 infection. However, counties with higher disability and poverty rates had a higher death rate. African Americans were more vulnerable to COVID-19 than other ethnic groups (1,981 African American infected cases versus 658 Whites per million). Data on mobility changes corroborate the impact of social distancing. INTERPRETATION: The observed inequality might be due to the workforce of essential services, poverty, and access to care. Counties in more urban areas are probably better equipped at providing care. The lower rate of infection, but a higher death rate in counties with higher poverty and disability could be due to lower levels of mobility, but a higher rate of comorbidities and health care access.

Myelin basic protein (MBP) represents a candidate autoantigen in multiple sclerosis (MS). We isolated MBP from normal and MS human white matter and purified six components (charge isomers) to compare the post-translational modifications on each. The sites and extent of methylation, deimination, and phosphorylation were documented for all tryptic peptides by mass spectrometry. We found that mono and dimethylated arginine 107 was increased in MS samples; deimination of arginine occurred at a number of sites and was elevated in MS; phosphorylation was observed in 10 peptides in normal samples but was greatly reduced or absent in most peptides from MS samples. Data obtained with MBP isolated from fresh brain obtained from a spontaneously demyelinating mouse model supported the view that the changes observed in human brain were probably related to pathogenesis of demyelination, i.e. we found decreased phosphorylation and decreased amounts of glycogen synthesis kinase in brain homogenates using specific antibodies. This study represents the first to define post-translational modifications in demyelinating disease and suggest an important role in pathogenesis.