Studies on the metabolism of rat liver copper-metallothionein.

The degradation of purified 35S-labelled rat liver isometallothioneins (MT) by lysosomal extracts was studied. Zn-MT-I was more readily hydrolysed than Zn-MT-II, but no significant degradation of the Cu-containing metallothioneins could be detected, even after 24 h incubation. The susceptibility of MT to degradation in vitro may be related to the strength of the metal-thiolate bonds. However, the turnover rates of cytosolic MT in vivo, as established by pulse-labelling techniques, are apparently subject to different controls. The half-lives of MT-I and -II in the liver cytosol of Cu2+-injected rats were only 15.4 +/- 1.5 and 18.2 +/- 1.1 h respectively. Approx. 25% of the total liver MT was present in particulate fractions (probably in lysosomes) of the liver and had a half-life of 25.1 +/- 4.1 h.     

Fingernails as biological indices of metal exposure

Metal determination in human tissues is the most common application of biological monitoring for screening, diagnosis and assessment of metal exposures and their risks. Various biopsy-materials may be used. This paper deals with the quantitative determination of Cd, Pb, Cr, Mn, Fe, Ni, Cu, and Zn concentrations in nails of male subjects exposed to these metals alongwith their respective controls, while working in locomotive, carriage and roadways workshops, and lead battery factories. The levels of Cd, Pb, Cr, Mn, Fe, Ni, Cu and Zn in fingernails, assayed by atomic absorption spectrophotometry, were compared with their respective controls by student ‘t’ test. All the obtained values were correlated to the personal and medical history of the subjects under study. Significantly high levels of Cd, Pb, Cr, Fe, Ni, Cu and Zn were present in smokers, compared to nonsmokers. The concentrations of Cd, Pb, Cr, Mn and Fe were not significantly high in vegetarian subjects. It was also observed that there is no contribution of liquor towards nail-metal concentration. Significant correlations were observed between skin disease and Cr, Mn, Fe, Cu; hypertension and Cd, Mn, Cu; mental stress and Cd, Pb, Mn, Ni, Cu, Zn; diabetes and Cr, Mn, Ni; chest pain and Pb; respiratory trouble and Cr, Mn, Fe, Ni, Zn; tuberculosis and Zn; acidity and Cd; and ophthalmic problems and Mn, Fe, Ni, and Zn     

The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to activate multiple TGFbeta family signaling pathways

Wishful thinking (Wit) is a Drosophila transforming growth factor-beta (TGFbeta) superfamily type II receptor most related to the mammalian bone morphogenetic protein (BMP) type II receptor, BMPRII. To better understand its function, we undertook a biochemical approach to establish the ligand binding repertoire and downstream signaling pathway. We observed that BMP4 and BMP7, bound to receptor complexes comprised of Wit and the type I receptor thickveins and saxophone to activate a BMP-like signaling pathway. Further we demonstrated that both myoglianin and its most closely related mammalian ligand, myostatin, interacted with a Wit and Baboon (Babo) type II-type I receptor complex to activate TGFbeta/activin-like signaling pathways. These results thereby demonstrate that Wit binds multiple ligands to activate both BMP and TGFbeta-like signaling pathways. Given that myoglianin is expressed in muscle and glial-derived cells, these results also suggest that Wit may mediate myoglianin-dependent signals in the nervous system.     

The von Hippel-Lindau tumor suppressor protein influences microtubule dynamics at the cell periphery

The von Hippel-Lindau (VHL) protein protects microtubules (MTs) from destabilization by nocodazole treatment. Based on this fixed-cell assay with static end points, VHL has been reported to directly stabilize the MT cytoskeleton. To investigate the dynamic changes in MTs induced by VHL in living cells, we measured the influence of VHL on tubulin turnover using fluorescence recovery after photobleaching (FRAP). To this end, we engineered VHL-deficient renal cell carcinoma cells to constitutively incorporate fluorescently labeled tubulin and to inducibly express VHL. Induction of VHL in these cells resulted in a decrease of tubulin turnover as measured by FRAP at the cell periphery, while minimally influencing MT dynamics around the centrosome. Our data indicates that VHL changes the behavior of MTs dependent on their subcellular localization implying a role for VHL in cellular processes such as migration, polarization, and cell-cell interactions. Here we propose a complementary method to directly measure VHL-induced subcellular changes in microtubule dynamics, which may serve as a tool to study the effect of MT binding proteins such as VHL.     

Biological monitoring of lead and cadmium in human hair and nail and their correlations with biopsy materials, age and exposure

Hair and fingernails of exposed and unexposed subjects were analyzed for their lead (Pb) and cadmium (Cd) contents by atomic absorption spectrophotometer with graphite furnace and air-acetylene flame. Hair and nail Pb concentrations in occupationally exposed subjects ranged between 1.020-409.726 and 8.130-765.306 microg/g and in environmentally unexposed subjects 0.123-25.160 and 1.076-65.613 microg/g, respectively. Similarly, hair and nail Cd concentrations in occupationally exposed subjects ranged between 0.014-22.086 and 0.214-35.714 microg/g and in environmentally unexposed subjects 0.113-1.627 and 0.028-8.108 microg/g, respectively. A significant correlation was observed between Pb hair and nail concentrations in exposed subjects at P < 0.05, as compared to unexposed subjects and Cd hair and nail in exposed, as well as unexposed subjects. With respect to exposure, levels of Pb in hair and nails were found to be significant in exposed subjects, compared to unexposed ones and levels of Cd were significant only in nails of exposed ones. With respect to age, no significant correlation was found between hair and nail Pb and Cd concentrations in both exposed and unexposed subjects.     

Comparative study of 222Rn/220Rn progeny concentration and estimation of age-dependent dose due to inhalation of radon progeny for different body organs

In the present study, the age-dependent doses due to inhalation of short lived decay progeny of radon, i.e., ²¹⁴Po to different body organs have been calculated for the inhabitants of the Jammu district, Jammu &; Kashmir, India. The estimated age-dependent doses for different body organs due to inhalation of radon progeny through air for all age groups varied between 0.002E-06 and 0.10 n Svy^?1 which were found to be well within the recommended limit of 1000 µ Svy^?1 (ICRP). The progeny concentration of radon and thoron was calculated and compared by two different techniques. The attached and un-attached progeny concentration of radon and thoron was calculated by using a passive time integrating, deposition-based technique. The measured attached and un-attached radon and thoron progeny concentrations have been cross-checked by on-line active technique, i.e., Flow-mode Integrated Sampler. A weak positive correlation has been observed between the two devices. The median value of un-attached fraction was found to be 0.15 and 0.12 for thoron and radon progeny, respectively and found to have a log-normal distribution. A good positive correlation has been observed between radon and thoron progeny concentrations.     

Study of radon/thoron exhalation rate,soil-gas radon concentration,and assessment of indoor radon/thoron concentration in Siwalik Himalayas of Jammu & Kashmir

In the present study, the soil-gas radon concentration was assessed at different depth intervals, i.e., 15 cm, 30 cm, 60 cm, and 100 cm from the 30 villages of Jammu &; Kashmir, India using RAD7, an electrostatic solid state alpha detector. The radon mass exhalation and thoron surface exhalation rate has also been measured in the selected 18 soil samples out of 30 of different grain sizes (i.e., 1 mm, 300 µm, 150 µm). The active radon and thoron concentrations were also assessed in the 20 villages. Both the exhalation rates and active radon/thoron concentration were measured using SMART Rn Duo, a portable radon monitor. The average values of soil-gas radon concentration were 210 ± 84 Bq m^?3, 1261 ± 963 Bq m^?3, 4210 ± 1994 Bq m^?3, and 671 ± 305 Bq m^?3 at the depth intervals of 15 cm, 30 cm, 60 cm, and 100 cm, respectively. The exhalation rate of radon and thoron from soil was found to decrease with the increase of grain size, as smaller soil particles make relatively more contribution to radon and thoron exhalations from the ground surface than larger soil particles. The measured Pearson's correlation coefficient was obtained as statistically significant between different quantities under two-tailed test.     

Cu(I) binding to the Schizosaccharomyces pombe gamma-glutamyl peptides varying in chain lengths

The metal-gamma-glutamyl peptide complex of Schizosaccharomyces pombe is an oligomer of peptides of the general structure (gamma-Glu-Cys)n-Gly with n defining the number of dipeptide repeats. The complexes induced with either cadmium or copper salts are heterogeneous with respect to the number of repeat units or n. Peptides isolated from two preparations of the Cd-gamma-Glu complex by reverse-phase HPLC at low pH were of an n range of 2 to 6 with n3 and n4 peptides being predominant. In addition to peptides of the mentioned structure, peptides of n3 and n4 without the terminal Gly were isolated. These n3 and n4 desGly peptides were present in an abundance of about 10-20% of the concentration of the parent peptide. Peptides of unique n were studied in Cu(I) reconstitution experiments in an attempt to understand the significance of the peptide length heterogeneity in the oligomeric metal-thiolate cluster. Cu-gamma-Glu complexes were formed with each peptide as determined by the characteristic 260-nm shoulder in the ultraviolet absorption spectrum and luminescence indicative of Cu(I)-thiolate coordination in a solvent-inaccessible environment. Cluster formation also occurs with desGly peptides, so the carboxyl-terminal Gly is not critical for cluster formation. Maximal Cu binding stoichiometry with n3 and n4 peptides was markedly less than the maximal Cu(I) stoichiometry of a peptide mixture or the native complex. Cu ions in complexes formed with unique n peptides were more reactive with bathocuproine than Cu ions in complexes with a peptide n mixture. The results suggest that metal-peptide complexes consisting of peptides differing in n probably exist and not all metal-peptide complexes have the same n peptide constituents.     

Early newborn ritual foods correlate with delayed breastfeeding initiation in rural Bangladesh

Background

Early and exclusive breastfeeding may improve neonatal survival in low resource settings, but suboptimal breastfeeding still exists in areas with high infant mortality. Prelacteal feeding, the practice of giving a non-breastmilk food as a neonate’s first food, has been associated with suboptimal breastfeeding practices. We examined the association of feeding a non-breastmilk food in the first three days of life (early neonatal food, or ENF) with time from birth to initiation of breastfeeding among 25,286 Bangladeshi mother-neonate pairs, in a secondary analysis of a randomized controlled trial in northwestern rural Bangladesh conducted from 2001–2007.

Methods

Trained interviewers assessed the demographic characteristics during pregnancy. At three months postpartum, the interviewers visited participants again and retrospectively assessed demographic and breastfeeding characteristics surrounding the birth. We assessed the relationship between ENF and time to initiation of breastfeeding in hours in both unadjusted and adjusted linear regression analyses. We also calculated reverse cumulative distribution curves for time to initiation of breastfeeding and analyses were stratified by an infant’s ability to breastfeed normally at birth.

Results

The mean?±?SD time from birth to initiation of breastfeeding was 30.6?±?27.9 hours. Only 2,535 (10.0%) of women reported initiating breastfeeding in the first hour after birth and 10,207 (40.4%) reported initiating breastfeeding in the first 12 hours after birth. In adjusted linear regression analyses, feeding ENF was associated with a significant increase in time, in hours, to breastfeeding initiation both among children not able to breastfeed at birth (37.4; 95% CI 33.3, 41.5) and among children able to breastfeed at birth (13.3; 95% CI 12.7, 14.0).

Conclusions

Feeding ENF was strongly associated with delayed initiation of breastfeeding, even after adjusting for other related factors and stratifying on the neonate’s ability to suckle normally after birth. More research is needed to understand the impact of these findings on optimal breastfeeding in this setting. It is possible that ENF feeding and the ability to breastfeed immediately after birth are interrelated in their respective associations to suboptimal breastfeeding initiation. This study in a large population representative of other populations in rural South Asia, demonstrates significantly longer times to breastfeeding initiation than previously appreciated, with a possible important role of ENF feeding.

Trial registration

The randomized controlled trial on which this analysis is based, “Impact of Maternal Vitamin A or Beta-Carotene Supplementation on Maternal and Infant Mortality in Bangladesh”, was registered with ClinicalTrials.gov as trial number ID GHS-A-00-03-00019-00 and identifier NCT00198822. The identifier was first received September 12, 2005 (retrospectively registered). The first participant was enrolled in August 2001.