Scn3b knockout mice exhibit abnormal sino-atrial and cardiac conduction properties.

AIM: In contrast to extensive reports on the roles of Na(v)1.5 alpha-subunits, there have been few studies associating the beta-subunits with cardiac arrhythmogenesis. We investigated the sino-atrial and conduction properties in the hearts of Scn3b(-/-) mice. METHODS: The following properties were compared in the hearts of wild-type (WT) and Scn3b(-/-) mice: (1) mRNA expression levels of Scn3b, Scn1b and Scn5a in atrial tissue. (2) Expression of the beta(3) protein in isolated cardiac myocytes. (3) Electrocardiographic recordings in intact anaesthetized preparations. (4) Bipolar electrogram recordings from the atria of spontaneously beating and electrically stimulated Langendorff-perfused hearts. RESULTS: Scn3b mRNA was expressed in the atria of WT but not Scn3b(-/-) hearts. This was in contrast to similar expression levels of Scn1b and Scn5a mRNA. Immunofluorescence experiments confirmed that the beta(3) protein was expressed in WT and absent in Scn3b(-/-) cardiac myocytes. Lead I electrocardiograms from Scn3b(-/-) mice showed slower heart rates, longer P wave durations and prolonged PR intervals than WT hearts. Spontaneously beating Langendorff-perfused Scn3b(-/-) hearts demonstrated both abnormal atrial electrophysiological properties and evidence of partial or complete dissociation of atrial and ventricular activity. Atrial burst pacing protocols induced atrial tachycardia and fibrillation in all Scn3b(-/-) but hardly any WT hearts. Scn3b(-/-) hearts also demonstrated significantly longer sinus node recovery times than WT hearts. CONCLUSION: These findings demonstrate, for the first time, that a deficiency in Scn3b results in significant atrial electrophysiological and intracardiac conduction abnormalities, complementing the changes in ventricular electrophysiology reported on an earlier occasion.

Properties of mitochondrial DNA polymerase in mitochondrial DNA synthesis in yeast.

Mitochondrial DNA polymerase from Saccharomyces cerevisiae, purified 3500 fold, was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into three polypeptides. The major 150 kDa polypeptide was probably the catalytic subunit of the mitochondrial (mt) DNA polymerase and the other two polypeptides could be either proteolytic cleavage products of the polymerase, other subunits of the enzyme or protein contaminants. The mtDNA polymerase preferred an A+T-rich DNA template and did not require any RNA primer for DNA synthesis, at least under in vitro reaction conditions. It showed higher processivity on a double-stranded linear DNA template than on a single-stranded circular DNA template, and was capable of synthesizing at least about 1200 nucleotide primer-extended products without any major pause on a double-stranded DNA template.

Nutrition and national development: the case of Chile.

This study is an historical analysis of food consumption and nutrition in Chile emphasizing the influence of political and economic factors on nutritional standards. It attempts to document and explain the persistence of malnutrition as a widespread social problem in Chile even as the country achieved a relatively advanced state of economic development and boasted an unusually progressive record of social legislation. The major findings of the study were: (a) Chile's pattern of development, social reform efforts notwithstanding, consistently discriminated against low-income groups, and (b) this discrimination perpetuated low standards of nutrition and low levels of food consumption among the country's poor and undermined the effectiveness of specific measures to alleviate malnutrition.

PIP: In the period from 1930 to 1970, Chile experienced economic growth as well as social and political changes. The per capita income more than doubled reaching upwards of $500/year by 1970. There was, however, consistent discrimination against low-income groups. As Chile became industrialized, there were no significant changes for the majority of the population who lost purchasing power by more than 1/3 from 1952 to 1970. Rural areas showed the most stratification of the economic classes with large landowners who comprised 2% of the rural population, controlling more than 65% of the land. 25% of the rural population, i.e., substance farmers, held approximately 1% of the cultivated land. The Chilean agricultural sector could not keep up with the population growth of the area, probably due to a combination of government discrimination and the social structure, during this 1930 to 1970 period. Government expenditures on health, education, and other social services increased from 28% of total government expenditures in 1940 to about 50% in 1970. The primary component was the social security system, but this only covered about 70% of the population and excluded many lower income strata workers, e.g., rural workers, recent migrants. Government services tended to reinforce the inequalities of the socioeconomic groups in Chile, rather than alleviate them. At least 21 surveys have been done on the nutritional status of children since 1940. 2 inferences can be drawn: 1) malnutrition was a long-time characteristic of a portion of Chile's population, and 2) the extent and seriousness of nutritional deprivations increased with declining income levels and their socioeconomic indicators. The data on food availability and consumption is not wholly reliable, although based on recent surveys it is likely that food consumption by low income groups probably did not increase by any significant amount between 1935 and 1970; nutritional deprivation affected 1/3 or more of the families. Infant mortality sharply decreased during the 1930 to 1970 period, although the drop occurred primarily in the higher income brackets. With the election of Salvador Allende in 1970, many changes were made in an attempt to move toward socialism. These changes included nationalizing foreign and domestically owned industry, bringing most mining and banking operations under state ownership, and redistribution of income, which resulted in a rise in the demand, particularly for food. When the military junta toppled Allende in September 1973, social changes and reforms were assigned a low priority. Also in 1973, the unemployment rate in both urban and rural areas rose reaching between 20% and 30% in 1976. The health and education sectors of the government have had the greatest influence of any programs aimed at eradicating malnutrition. 2 examples are the Milk Distribution program begun in 1937 and the School Feeding program begun in 1928. Another, the New Protein Foods programs were designed to develop protein concentrated formulae from nonconventional foods. The only lasting products of these attempts are 2 milk substitutes. In addition to these specific interventions, there have been several unsucessful attempts to develop government councils for Food and Nutrition. Malnutrition still remains a feature of Chile's social order, reinforced by the country's economic development strategies.