Protein self-modification by heme-generated reactive species

In the presence of H(2)O(2), heme proteins form active intermediates, which are able to oxidize exogenous molecules. Often these products are not stable compounds but reactive species on their own, such as organic radicals. They can both diffuse to the bulk of the solution or react with the protein that generated them. Here, we describe the self-modification underwent by heme proteins with globin-type fold, that is, myoglobin, hemoglobin, and neuroglobin when treated with NO(2) (-) or catechols in the presence of H(2)O(2). The reactive nitrogen species generated by NO(2) (-) give rise to nitration, oxidation, and/or crosslinking reactions between the proteins or their subunits. The quinones formed upon reaction with catechols easily modify Cys and His residues and eventually cause protein aggregation, which induces precipitation. The pattern of modifications undergone by the protein strongly depends on the nature of the protein and the reaction conditions.     

Summer and spring trophic niche of larval and juvenile <Emphasis Type="Italic">Pleuragramma antarcticum</Emphasis> in the Western Ross Sea,Antarctica

The aim of this paper is to contribute to the knowledge on the feeding habits of larvae and juvenile Pleuragramma antarcticum in the western Ross Sea. In summer, the diet of P. antarcticum postlarvae (8–17 mm) was dominated by calanoid eggs (35.5%), Limacina (32.1%) and tintinnids (17.6%), while the principal food of juveniles consisted mainly of copepods (98.2%), with Oncaea curvata being the most abundant (85.1%) and the most frequently consumed prey. The food composition of P. antarcticum postlarvae (24–29 mm), collected in spring, suggest that they fed actively under the sea ice. Stephos longipes, Harpacticus furcifer and Paralabidocera antarctica sea ice copepods represent, in all their different developmental stages, the most abundant biomass food in Terra Nova Bay in this period. Our results therefore suggest that the diet of younger Pleuragramma specimens shifted in prey composition from the first summer to the following spring. This study draws attention to the key role of the copepod, P. antarctica, in the food web of Terra Nova Bay. This article belongs to a special topic: Five articles coordinated by L. Guglielmo and V. Saggiomo appear in this issue of Polar Biology and are a result of a workshop on Sea-ice communities in Terra Nova Bay (Ross Sea) held in August 2007 in Capo Calavà, Messina, Italy.     

CSN complex controls the stability of selected synaptic proteins via a torsinA-dependent process

DYT1 dystonia is caused by an autosomal dominant mutation that leads to a glutamic acid deletion in torsinA (TA), a member of the AAA+ ATPase superfamily. In this study, we identified a novel-binding partner of TA, the subunit 4 (CSN4) of CSN signalosome. TA binds CSN4 and the synaptic regulator snapin in neuroblastoma cells and in brain synaptosomes. CSN4 and TA are required for the stability of both snapin and the synaptotagmin-specific endocytic adaptor stonin 2, as downregulation of CSN4 or TA reduces the levels of both proteins. Snapin is phosphorylated by the CSN-associated kinase protein kinase D (PKD) and its expression is decreased upon PKD inhibition. In contrast, the stability of stonin 2 is regulated by neddylation, another CSN-associated activity. Overexpression of the pathological TA mutant (ΔE-TA) reduces stonin 2 expression, causing the accumulation of the calcium sensor synaptotagmin 1 on the cell surface. Retrieval of surface-stranded synaptotagmin 1 is restored by overexpression of stonin 2 in ΔE-TA-expressing cells, suggesting that the DYT1 mutation compromises the role of TA in protein stabilisation and synaptic vesicle recycling.     

Hospital Admissions for Hypertensive Crisis in the Emergency Departments: A Large Multicenter Italian Study

Epidemiological data on the impact of hypertensive crises (emergencies and urgencies) on referral to the Emergency Departments (EDs) are lacking, in spite of the evidence that they may be life-threatening conditions. We performed a multicenter study to identify all patients aged 18 years and over who were admitted to 10 Italian EDs during 2009 for hypertensive crises (systolic blood pressure ≥220 mmHg and/or diastolic blood pressure ≥120 mmHg). We classified patients as affected by either hypertensive emergencies or hypertensive urgencies depending on the presence or the absence of progressive target organ damage, respectively. Logistic regression analysis was then performed to assess variables independently associated with hypertensive emergencies with respect to hypertensive urgencies. Of 333,407 patients admitted to the EDs over the one-year period, 1,546 had hypertensive crises (4.6/1,000, 95% CI 4.4–4.9), and 23% of them had unknown hypertension. Hypertensive emergencies (n = 391, 25.3% of hypertensive crises) were acute pulmonary edema (30.9%), stroke (22.0%,), myocardial infarction (17.9%), acute aortic dissection (7.9%), acute renal failure (5.9%) and hypertensive encephalopathy (4.9%). Men had higher frequency than women of unknown hypertension (27.9% vs 18.5%, p<0.001). Even among known hypertensive patients, a larger proportion of men than women reported not taking anti-hypertensive drug (12.6% among men and 9.4% among women (p<0.001). Compared to women of similar age, men had higher likelihood of having hypertensive emergencies than urgencies (OR = 1.34, 95% CI 1.06–1.70), independently of presenting symptoms, creatinine, smoking habit and known hypertension. This study shows that hypertensive crises involved almost 5 out of 1,000 patients-year admitted to EDs. Sex differences in frequencies of unknown hypertension, compliance to treatment and risk of hypertensive emergencies might have implications for public health programs.     

The expression of native and oxidized LDL receptors in brain microvessels is specifically enhanced by astrocytes-derived soluble factor(s)

Based on the functional characterization of sucrose biosynthesis related protiens[SBP: sucrose-phosphate synthase (SPS), sucrose-phosphate phosphatase (SPP), and sucrose synthase (SuS)] in Anabaena sp. PCC7120 and sequence analysis, we have shown that SBP are restricted to cyanobacterium species and plants, and that they are multidomain proteins with modular architecture. Anabaena SPS, a minimal catalytic SPS unit, defines a glucosyltransferase domain present in all SPSs and SuSs. Similarly, Anabaena SPP defines a phosphohydrolase domain characteristic of all SPPs and some SPSs. Phylogenetic analysis points towards the evolution of modern cyanobacterial and plant SBP from a bidomainal common ancestral SPS-like gene.     

Hsp90‐mediated regulation of DYRK3 couples stress granule disassembly and growth via mTORC1 signaling

Stress granules (SGs) are dynamic condensates associated with protein misfolding diseases. They sequester stalled mRNAs and signaling factors, such as the mTORC1 subunit raptor, suggesting that SGs coordinate cell growth during and after stress. However, the molecular mechanisms linking SG dynamics and signaling remain undefined. We report that the chaperone Hsp90 is required for SG dissolution. Hsp90 binds and stabilizes the dual‐specificity tyrosine‐phosphorylation‐regulated kinase 3 (DYRK3) in the cytosol. Upon Hsp90 inhibition, DYRK3 dissociates from Hsp90 and becomes inactive. Inactive DYRK3 is subjected to two different fates: it either partitions into SGs, where it is protected from irreversible aggregation, or it is degraded. In the presence of Hsp90, DYRK3 is active and promotes SG disassembly, restoring mTORC1 signaling and translation. Thus, Hsp90 links stress adaptation and cell growth by regulating the activity of a key kinase involved in condensate disassembly and translation restoration.     

Hydroxyamino compounds produced by the oxidation of diamines with diamine oxidase in the presence of alcohol dehydrogenase.

When the diamines putrescine, cadaverine, cystamine and lanthionamine are oxidized by purified pig kidney diamine oxidase in the presence of NADH and either liver or yeast crystalline alcohol dehydrogenase, NADH is oxidized. Chromatographic evidence obtained in the case of putrescine and cystamine indicates the production of the respective hydroxy-amino compound. In the case of cystamine, the product of the reaction is mercapto-ethanol-cysteamine mixed disulfide which may represent a biological source for the production of mercaptoethanol used for other reactions.     

Resistance training of long duration modulates force and unloaded shortening velocity of single muscle fibres of young women

The aim of the present study was to clarify the impact of long term (1 year) resistance training (RT) on structure and function of single muscle fibres of vastus lateralis in young female subjects. Five young women (age: 25.4 ± 6.2 year) performed exercise sessions at 60% of single subject own repetition maximum (1 RM) 1 h twice a week. Maximum voluntary force was determined pre- and post-RT and was found to significantly increase post-RT ensuring a successful impact of RT on muscle performance in vivo. Needle muscle biopsy samples were obtained both pre- and post-RT and the following determinations were performed: myosin heavy chain isoform (MHC) distribution of the whole muscle samples by SDS–PAGE; cross sectional area (CSA), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n = 358) of single skinned muscle fibres classified on the basis of MHC isoform composition by SDS–PAGE. The results suggest that the long duration of RT can determine a significant increase in specific force (Po/CSA) and unloaded shortening velocity (Vo) of single muscle fibres in female subjects, whereas no muscle fibre hypertrophy and no shift in MHC isoform content was observed.