Fragile sites,chromosome evolution,and human neoplasia

Summary In a study of the possible relationship between human fragile sites, chromosomal rearrangements related to neoplasia, and chromosome regions involved in evolutionary changes, we have found that 17 fragile sites related to cancer, 15 fragile sites not related to cancer, and 17 non-fragile regions also related to human malignancy correspond or are close to bands involved in rearrangements that have taken place during chromosomal evolution in primates.     

Inhibition of cathepsin L-induced degradation of epidermal growth factor receptors by c-Ha-ras gene products

The inhibitory activities of c-Ha-ras gene products (p21s) toward several cysteine proteinases have been investigated. The activity of cathepsin L was inhibited by p21s most effectively while those of cathepsin B and papain were slightly inhibited by p21s. p21s did not show any inhibitory activity toward cathepsin H. In order to connect the protease-inhibitor activity of p21s with cell growth, the degradation of epidermal growth factor receptors (EGF-receptors) was investigated. EGF-receptors were preferentially cleaved by cathepsin L but not by cathepsin B or H. The cleavage of EGF-receptors by cathepsin L was inhibited by p21s dose-dependently. These results raise the possibility that p21s can suppress the degradation of growth-related proteins such as EGF-receptors and thereby affect cell growth.     

Different immunolocalizations of cathepsins B, H, and L in the liver

Different localizations of cathepsin B, H, and L in normal rat liver were revealed immunohistochemically with anticathepsin Fab'-horseradish peroxidase conjugates. Staining of cathepsin B was strong in the periportal sinusoids, possibly in Kupffer cells; and weaker in panlobular hepatocytes. Staining of cathepsin H was strong in panlobular hepatocytes, especially in the periphery of the cytoplasm, possibly representing the peribiliary dense bodies; and weaker in periportal sinusoidal cells, possibly Kupffer cells. Staining of cathepsin L was strongest in centrilobular hepatocytes and weaker in periportal sinusoidal cells, possibly Kupffer cells. These findings, revealed for the first time in the present study, show that the histologic and intracellular localizations of the three cathepsins are different, suggesting that they have different roles in degradation of exogenous and endogenous proteins.     

Photocontrol of somatic embryogenesis and polyamine content in Araujia sericifera petals

The effects of photoperiod and end-of-day phytochrome control on somatic embryogenesis and polyamine (PA) content in Araujia sericifera petals have been studied. Petals from immature flowers were cultured under 16- and 8-h photoperiods. Far red (FR), red (R) and FR followed by R light treatments were applied at the end of the photoperiods for three weeks. The number of somatic embryos, callus weight and the levels of free and bound PAs in the cultured petal explants were determined 40 days after the beginning of light treatments. Long day (LD) promoted somatic embryogenesis but did not have any significant effect on PA content. Short day (SD) reduced somatic embryogenesis and enhanced total PAs, mainly in the form of bound spermidine. End-of-day FR treatment increased PA content and inhibited somatic embryogensis under LD but had no significant effect under SD. This effect of FR on PA levels was cancelled by R and was independent of the presence of silver thiosulphate in the medium. End-of-day R treatment reduced the total PA content under SD. However, end-of-day R increased or reduced somatic embryogenesis under SD depending on the presence or absence of silver in the medium. The results suggest a photoperiodic control of somatic embryogenesis and PA content in A. sericifera. The effects of end-of-day R and FR treatments depend on the length of the photoperiod. This finding and the FR/R photoreversibility of end-of-day treatments indicate that phytochrome may be involved in both somatic embryogenesis and accumulation of PA.     

Effect of low-humidity treatment on growth of the lichenParmotrema tinctorum in a growth cabinet

Low-humidity treatment triggered an increase of the thallus area and the chlorophyll content in the following high-humidity condition. When low-humidity treatment for 4 days was intercalated in high-humidity conditions every 16 days, the thallus area increased 40% in 76 days.     

Mechanisms of generation of oxygen radicals and reductive mobilization of ferritin iron by lipoamide dehydrogenase.

The oxidase reaction of lipoamide dehydrogenase with NADH generates superoxide radicals and hydrogen peroxide under aerobic conditions. ESR spin trapping using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was applied to characterize the oxygen radical species generated by lipoamide dehydrogenase and the mechanism of their generation. During the oxidase reaction of lipoamide dehydrogenase, DMPO-OOH and DMPO-OH signals were observed. The DMPO-OOH signal disappeared on addition of superoxide dismutase. These results demonstrate that the DMPO-OOH adduct was produced from the superoxide radical generated by lipoamide dehydrogenase. In the presence of dimethyl sulfoxide, a DMPO-CH3 signal appeared at the expense of the DMPO-OH signal, indicating that the DMPO-OH adduct was produced directly from the hydroxyl radical rather than by decomposition of the DMPO-OOH adduct. The DMPO-OH signal decreased on addition of superoxide dismutase, catalase, or diethylenetriaminepentaacetic acid, indicating that the hydroxyl radical was generated via the metal-catalyzed Haber-Weiss reaction from the superoxide radical and hydrogen peroxide. Addition of ferritin to the NADH-lipoamide dehydrogenase system resulted in a decrease of the DMPO-OOH signal, indicating that the superoxide radical interacted with ferritin iron.     

Monoamine fluorescence in the median eminence of the Japanese quail,Coturnix coturnix japonica,following medial basal hypothalamic deafferentation

Summary Monoamine fluorescence was examined in the ventral hypothalamus of the Japanese quail, Coturnix coturnix japonica after medial basal hypothalamic deafferentation. In sham-operated control birds, numerous yellow-green fluorescent fibers were observed in the median eminence and the nucleus tuberis. In the area of the paraventricular organ, a number of fluorescent fibers and cell bodies were observed. In birds with deafferented hypothalami, fluorescence disappeared both in the median eminence and the nucleus tuberis. In the area of the paraventricular organ, which was within the area of deafferentation, fluorescence of neuronal perikarya did not change, but fluorescent fibers decreased markedly in number. Disappearance of monoamine fluorescence in the median eminence and the nucleus tuberis is discussed in relation to the tanycyte absorptive function and gonadal development.Supported by Grants from the Ministry of Education to Professors T. Bando and H. Kobayashi, and a Grant from the Ford Foundation to Prof. H. Kobayashi.     

Disparities in distribution of COVID-19 vaccines across US counties: A geographic information system–based cross-sectional study

BackgroundThe US Centers for Disease Control and Prevention has repeatedly called for Coronavirus Disease 2019 (COVID-19) vaccine equity. The objective our study was to measure equity in the early distribution of COVID-19 vaccines to healthcare facilities across the US. Specifically, we tested whether the likelihood of a healthcare facility administering COVID-19 vaccines in May 2021 differed by county-level racial composition and degree of urbanicity.Methods and findingsThe outcome was whether an eligible vaccination facility actually administered COVID-19 vaccines as of May 2021, and was defined by spatially matching locations of eligible and actual COVID-19 vaccine administration locations. The outcome was regressed against county-level measures for racial/ethnic composition, urbanicity, income, social vulnerability index, COVID-19 mortality, 2020 election results, and availability of nontraditional vaccination locations using generalized estimating equations.Across the US, 61.4% of eligible healthcare facilities and 76.0% of eligible pharmacies provided COVID-19 vaccinations as of May 2021. Facilities in counties with >42.2% non-Hispanic Black population (i.e., > 95th county percentile of Black race composition) were less likely to serve as COVID-19 vaccine administration locations compared to facilities in counties with <12.5% non-Hispanic Black population (i.e., lower than US average), with OR 0.83; 95% CI, 0.70 to 0.98, p = 0.030. Location of a facility in a rural county (OR 0.82; 95% CI, 0.75 to 0.90, p < 0.001, versus metropolitan county) or in a county in the top quintile of COVID-19 mortality (OR 0.83; 95% CI, 0.75 to 0.93, p = 0.001, versus bottom 4 quintiles) was associated with decreased odds of serving as a COVID-19 vaccine administration location.There was a significant interaction of urbanicity and racial/ethnic composition: In metropolitan counties, facilities in counties with >42.2% non-Hispanic Black population (i.e., >95th county percentile of Black race composition) had 32% (95% CI 14% to 47%, p = 0.001) lower odds of serving as COVID administration facility compared to facilities in counties with below US average Black population. This association between Black composition and odds of a facility serving as vaccine administration facility was not observed in rural or suburban counties. In rural counties, facilities in counties with above US average Hispanic population had 26% (95% CI 11% to 38%, p = 0.002) lower odds of serving as vaccine administration facility compared to facilities in counties with below US average Hispanic population. This association between Hispanic ethnicity and odds of a facility serving as vaccine administration facility was not observed in metropolitan or suburban counties.Our analyses did not include nontraditional vaccination sites and are based on data as of May 2021, thus they represent the early distribution of COVID-19 vaccines. Our results based on this cross-sectional analysis may not be generalizable to later phases of the COVID-19 vaccine distribution process.ConclusionsHealthcare facilities in counties with higher Black composition, in rural areas, and in hardest-hit communities were less likely to serve as COVID-19 vaccine administration locations in May 2021. The lower uptake of COVID-19 vaccinations among minority populations and rural areas has been attributed to vaccine hesitancy; however, decreased access to vaccination sites may be an additional overlooked barrier.

Inmaculada Hernandez and colleagues investigate the disparities in early-phase distribution of COVID-19 Vaccines across U.S. Counties.     

Increased bioethanol production from commercial tobacco cultivars overexpressing thioredoxin f grown under field conditions

Bioethanol is mainly produced from food crops such as sugar cane and maize, and this has been held partly responsible for the rise of food commodity prices. Tobacco, integrated in biorefinery facilities for the extraction of different compounds, could become an alternative feedstock for biofuel production. When grown for energy production, using high plant densities and several mowings during the growing season, tobacco can produce large amounts of inexpensive green biomass. We have bred two commercial tobacco cultivars (Virginia Gold and Havana 503B) to increase the carbohydrate content by the overexpression of thioredoxin f in the chloroplast. Marker-free transplastomic plants were recovered and their agronomic performance under field conditions was evaluated. These plants were phenotypically equivalent to their wild types yet showed increased starch (up to 280 %) and soluble sugar (up to 74 %) contents in leaves relative to their control plants. Fermentable sugars released from the stalk were also higher (up to 24 %) for transplastomic plants. After heat pretreatment, enzymatic hydrolysis and yeast fermentation of leaf and stalk hydrolysates, an average of 20–40 % more ethanol was obtained from transplastomic plants than their wild-type controls. We propose an integral exploitation of the entire tobacco plant managed as a forage crop (harvesting sugar and starch-rich leaves and lignocellulosic stalks) that could considerably cheapen the entire production process.