A spectroscopic investigation of the metal binding site of bleomycin A2. The Cu(II) and Zn(II) derivatives.

Using a combination of ultraviolet-visible absorption, 1H NMR and ESR techniques we have established that N(1) of the imidazole and N(1) of the pyrimidine residues of bleomycin A2 bind to Cu(II) and Zn(II). The observations coupled with the earlier results that the alpha-amino group of the alpha-amino carboxamide function and the carbamoyl moiety are also Cu(II)-ligating groups makes it possible to reconstruct the detailed geometry and stereochemistry of the metal binding site of bleomycin A2.     

Immunologic and hematologic effects of neuroendocrine hormones. Studies on DW/J dwarf mice.

DW/J dwarf mice lack acidophilic anterior pituitary cells and are deficient in growth hormone and other neuroendocrine mediators. These mice were examined to determine the effects of these deficiencies on hematopoietic and immune system development. Previous studies have suggested that these mice had immunologic defects primarily involving T cell development. However, we have found that these mice exhibit decreased peripheral blood cell counts affecting all lineages (erythrocytic, leukocytic, and platelets). Examination of lymphoid tissues of dwarf mice indicated that their spleens were hypoplastic. Treatment of these mice with recombinant human growth hormone resulted in a significant improvement of peripheral blood counts and spleen cell number. Analysis of the bone marrow indicated a profound deficiency of B cell progenitors in the dwarf mice. However, in untreated dwarf mice, mature B cells and T cells were observed in the spleens. Although treatment with recombinant human growth hormone could correct the hematopoietic deficiencies in these mice, it did not restore the B cell progenitor populations, suggesting that an absence of growth hormone is not solely responsible for this deficiency. Thus, these mice display significant myeloid and lymphoid deficiencies that have been previously undetected.     

Induction of mitochondrial manganese superoxide dismutase by interleukin 1

Interleukin 1 (IL 1) inhibits the growth of human melanoma A375 cells. To identify the subcellular events preceding inhibition of growth by IL 1, we have examined the effect of IL 1 on protein synthesis caused by A375 cells. IL 1 selectively and predominantly induced a 25-kDa polypeptide (p25) in A375 cells after 12 h. On subcellular fractionation, p25 was exclusively located in the 10,000 x g-pelleted (mitochondria-enriched) fraction. To identify the p25 moiety, it was purified to homogeneity by sequential chromatography on DEAE-Sephacel and reverse-phase, high-pressure liquid chromatography and its amino-terminal amino acid sequence was determined. The sequence of the 35 amino-terminal amino acids of the p25 moiety was identical to that of human manganese superoxide dismutase (Mn SOD). The enzymatic activities of SOD were induced only in the mitochondria-enriched fraction of IL 1-treated A375 cells. However, IL 1 also induced Mn SOD in normal human skin fibroblasts and peripheral blood mononuclear cells, whose growth was stimulated by IL 1. The results show that induction of Mn SOD by IL 1 is a common biochemical event in IL 1-responsive cells.     

The Circadian System of Ruin Lizards: A Seasonally Changing Neuroendocrine Loop?

Previous studies have shown that the amplitude of daily melatonin production in cultured ruin lizard pineal organs explanted in the summer is significantly higher than that from organs explanted in the winter. To test whether seasonal photoperiodic changes are decoded autonomously by the pineal gland, pineals explanted in summer were cultured in vitro and exposed to changes between winter and summer photoperiods. The changes in photoperiod duration did not affect the daily profiles of in vitro melatonin production. The discrepancy between the present in vitro results and those from lizards exposed to winter or summer photoperiods before pineal explantation supports the view that circadian information entering the pineal gland via its innervation is involved in determining seasonal changes of melatonin production in ruin lizards. We further examined whether a central component of the circadian system of ruin lizards, specifically the retinae of the lateral eyes, expresses similar seasonal changes in function as does the pineal gland. We did not find any difference between summer and autumn‐winter in the effectiveness of either bilateral retinalectomy or optic nerve lesion—at the level of the optic chiasm—in altering circadian locomotor behavior in constant conditions. Both surgical procedures mostly induced a shortening of the free‐running period of the locomotor rhythm of similar magnitude in all seasons. Thus, the retinae do not appear to participate in the seasonal reorganization of the circadian system in ruin lizards.     

CO Rebinding Kinetics and Molecular Dynamics Simulations Highlight Dynamic Regulation of Internal Cavities in Human Cytoglobin

Cytoglobin (Cygb) was recently discovered in the human genome and localized in different tissues. It was suggested to play tissue-specific protective roles, spanning from scavenging of reactive oxygen species in neurons to supplying oxygen to enzymes in fibroblasts. To shed light on the functioning of such versatile machinery, we have studied the processes supporting transport of gaseous heme ligands in Cygb. Carbon monoxide rebinding shows a complex kinetic pattern with several distinct reaction intermediates, reflecting rebinding from temporary docking sites, second order recombination, and formation (and dissociation) of a bis-histidyl heme hexacoordinated reaction intermediate. Ligand exit to the solvent occurs through distinct pathways, some of which exploit temporary docking sites. The remarkable change in energetic barriers, linked to heme bis-histidyl hexacoordination by HisE7, may be responsible for active regulation of the flux of reactants and products to and from the reaction site on the distal side of the heme. A substantial change in both protein dynamics and inner cavities is observed upon transition from the CO-liganded to the pentacoordinated and bis-histidyl hexacoordinated species, which could be exploited as a signalling state. These findings are consistent with the expected versatility of the molecular activity of this protein.     

Free Testosterone Drives Cancer Aggressiveness: Evidence from US Population Studies

Cancer incidence and mortality are higher in males than in females, suggesting that some gender-related factors are behind such a difference. To analyze this phenomenon the most recent Surveillance, Epidemiology and End Results (SEER) database served to access cancer survival data for the US population. Patients with gender-specific cancer and with limited information were excluded and this fact limited the sample size to 1,194,490 patients. NHANES III provided the distribution of physiologic variables in US population (n = 29,314). Cox model and Kaplan-Meier method were used to test the impact of gender on survival across age, and to calculate the gender-specific hazard ratio of dying from cancer five years following diagnosis. The distribution of the hazard ratio across age was then compared with the distribution of 65 physiological variables assessed in NHANES III. Spearman and Kolmogorov-Smirnov test assessed the homology. Cancer survival was lower in males than in females in the age range 17 to 61 years. The risk of death from cancer in males was about 30% higher than that of females of the same age. This effect was present only in sarcomas and epithelial solid tumors with distant disease and the effect was more prominent in African-Americans than Caucasians. When compared to the variables assessed in the NHANES III study, the hazard ratio almost exactly matched the distribution of free testosterone in males; none of the other analyzed variables exhibited a similar homology. Our findings suggest that male sex hormones give rise to cancer aggressiveness in patients younger than 61 years.     

Cytogenetic and Molecular Analyses Reveal a Divergence between Acromyrmex striatus (Roger, 1863) and Other Congeneric Species: Taxonomic Implications

The leafcutter ants, which consist of Acromyrmex and Atta genera, are restricted to the New World and they are considered the main herbivores in the neotropics. Cytogenetic studies of leafcutter ants are available for five species of Atta and 14 species of Acromyrmex, both including subspecies. These two ant genera have a constant karyotype with a diploid number of 22 and 38 chromosomes, respectively. The most distinct Acromyrmex species from Brazil is A. striatus, which is restricted to the southern states of Santa Catarina and Rio Grande do Sul. Several cytogenetic and phylogenetic studies have been conducted with ants, but the karyotypic characterization and phylogenetic position of this species relative to leafcutter ants remains unknown. In this study, we report a diploid number of 22 chromosomes for A. striatus. The phylogenetic relationship between A. striatus and other leafcutter ants was estimated based on the four nuclear genes. A. striatus shared the same chromosome number as Atta species and the majority of metacentric chromosomes. Nuclear data generated a phylogenetic tree with a well-supported cluster, where A. striatus formed a different clade from other Acromyrmex spp. This combination of cytogenetic and molecular approaches provided interesting insights into the phylogenetic position of A. striatus among the leafcutter ants and the tribe Attini.     

Infield greenhouse gas emissions from sugarcane soils in Brazil: effects from synthetic and organic fertilizer application and crop trash accumulation

Bioethanol from sugarcane is becoming an increasingly important alternative energy source worldwide as it is considered to be both economically and environmentally sustainable. Besides being produced from a tropical perennial grass with high photosynthetic efficiency, sugarcane ethanol is commonly associated with low N fertilizer use because sugarcane from Brazil, the world's largest sugarcane producer, has a low N demand. In recent years, several models have predicted that the use of sugarcane ethanol in replacement to fossil fuel could lead to high greenhouse gas (GHG) emission savings. However, empirical data that can be used to validate model predictions and estimates from indirect methodologies are scarce, especially with regard to emissions associated with different fertilization methods and agricultural management practices commonly used in sugarcane agriculture in Brazil. In this study, we provide in situ data on emissions of three GHG (CO₂, N₂O, and CH₄) from sugarcane soils in Brazil and assess how they vary with fertilization methods and management practices. We measured emissions during the two main phases of the sugarcane crop cycle (plant and ratoon cane), which include different fertilization methods and field conditions. Our results show that N₂O and CO₂ emissions in plant cane varied significantly depending on the fertilization method and that waste products from ethanol production used as organic fertilizers with mineral fertilizer, as it is the common practice in Brazil, increase emission rates significantly. Cumulatively, the highest emissions were observed for ratoon cane treated with vinasse (liquid waste from ethanol production) especially as the amount of crop trash on the soil surface increased. Emissions of CO₂ and N₂O were 6.9 kg ha^?1 yr^?1 and 7.5 kg ha^?1 yr^?1, respectively, totaling about 3000 kg in CO₂ equivalent ha^?1 yr^?1.     

Sulle cause determinanti la formazione di tumori in ibridi di Nicotiana. Prime ricerche sierologiche

Abstract

PRELIMINARY SEROLOGICAL RESEARCHES ON MECHANISM OF TUMOR INDUCTION IN NICOTIANA HYBRIDS. According to GOODSPEED'S phyletic scheme, based on a cytogenetic evidence, both Nicotiana rustica and N. paniculata should be assigned to the sub-genus Rustica, while N. langsdorffiii and N. sanderae fit with the sub-genus Petunioides. Indeed the fact that genetical tumors are produced by the hybrids of these species only when the parents belong to different sub-genera, seems to support GOODSPEED'S views, just as KOSTOFF'S hypothesis of tumor production as a consequence of uncongeniality and incompatibility of parent's protein set, receives by this scheme a valid support.

Immunological research work has been carried out to test the possible affinities of the protein sets of the four Nicotiana species. It was observed that the protein set of N. paniculata is more similar to the protein set of N. langsdorffiii — a species included in a different sub-genus and whose hybrids with. N. paniculata bear tumors — than to the one of N. rustica, a species included in the same sub-genus and whose hybrids with N. paniculata never bear tumors. These studies are still in progress.