13/14 translocation in a man with reproductive failure

Summary An inherited (maternal origin) 13/14 translocation with the nucleolus organizer regions eliminated and one centromere was found in an oligospermic man whose wife had had two spontaneous abortions. Meiotic studies revealed all stages of spermatogenesis with a trivalent configuration in diakinesis. Possible reasons for his subfertility and his mother's normal fertility are discussed.     

The Novel 6–(N-Pyrrolyl)purine Acyclic Nucleosides: 1H and 13C NMR and X-ray Structural Study†

Abstract

Synthesis of the novel nucleoside analogues containing exocyclic pyrrolo moiety and acyclic side chains attached to the purine ring at N-9 and N-7 is described. The site of alkylation was determined by ¹H and ¹³C NMR on the basis of chemical shifts, C-H coupling constants and connectivity in NOESY and HETCOR spectra. The N-9 substitution of 7 was proved by its X-ray crystallographic analysis.

     

Amyloid Assemblies of Influenza A Virus PB1-F2 Protein Damage Membrane and Induce Cytotoxicity

PB1-F2 is a small accessory protein encoded by an alternative open reading frame in PB1 segments of most influenza A virus. PB1-F2 is involved in virulence by inducing mitochondria-mediated immune cells apoptosis, increasing inflammation, and enhancing predisposition to secondary bacterial infections. Using biophysical approaches we characterized membrane disruptive activity of the full-length PB1-F2 (90 amino acids), its N-terminal domain (52 amino acids), expressed by currently circulating H1N1 viruses, and its C-terminal domain (38 amino acids). Both full-length and N-terminal domain of PB1-F2 are soluble at pH values ≤6, whereas the C-terminal fragment was found soluble only at pH ≤ 3. All three peptides are intrinsically disordered. At pH ≥ 7, the C-terminal part of PB1-F2 spontaneously switches to amyloid oligomers, whereas full-length and the N-terminal domain of PB1-F2 aggregate to amorphous structures. When incubated with anionic liposomes at pH 5, full-length and the C-terminal part of PB1-F2 assemble into amyloid structures and disrupt membrane at nanomolar concentrations. PB1-F2 and its C-terminal exhibit no significant antimicrobial activity. When added in the culture medium of mammalian cells, PB1-F2 amorphous aggregates show no cytotoxicity, whereas PB1-F2 pre-assembled into amyloid oligomers or fragmented nanoscaled fibrils was highly cytotoxic. Furthermore, the formation of PB1-F2 amyloid oligomers in infected cells was directly reflected by membrane disruption and cell death as observed in U937 and A549 cells. Altogether our results demonstrate that membrane-lytic activity of PB1-F2 is closely linked to supramolecular organization of the protein.     

Different outcomes of a cardiac rehabilitation programme in functional parameters among myocardial infarction survivors according to ejection fraction

Introduction

Exercise-based cardiac rehabilitation (EBCR) is part of the management of patients who have suffered an acute myocardial infarction (AMI). Patients with a reduced ejection fraction (EF) comprise a higher-risk subgroup and are referred less often for these programmes. This study aimed at assessing the impact of the baseline EF on the functional benefits, as assessed by peak oxygen uptake (pVO₂) and exercise duration, of an EBCR programme in AMI survivors.

Methods

Observational, retrospective cohort study including all patients admitted to a tertiary centre due to an AMI who completed a phase II EBCR programme after discharge, between November 2012 and April 2017. Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test.

Results

A total of 379 patients were included [40.9% with reduced EF (<50%) at discharge]. After the programme, pVO₂ and exercise duration increased significantly (p < 0.001). Patients with a reduced EF had a lower pVO₂ and completed a shorter duration of exercise at the beginning and end of the programme. This group presented a higher increase in pVO₂ (p = 0.001) and exercise duration (p = 0.007). This was maintained after adjusting for age, gender, history of coronary artery disease, number of sessions, Killip classification, arterial hypertension, dyslipidaemia, diabetes mellitus, smoking status and baseline pVO₂.

Conclusion

A phase II EBCR programme was associated with significant improvements in pVO₂ and exercise duration among AMI survivors, irrespective of baseline EF classification. Those with a reduced baseline EF derived an even greater improvement, highlighting the importance of EBCR in this subgroup of patients.

     

Tuning of the FMN binding and oxido-reduction properties by neighboring side chains in Anabaena flavodoxin

Contribution of three regions (phosphate-binding, 50’s and 90’s loops) of Anabaena apoflavodoxin to FMN binding and reduction potential was studied. Thr12 and Glu16 did not influence FMN redox properties, but Thr12 played a role in FMN binding. Replacement of Trp57 with Glu, Lys or Arg moderately shifted E_ox/sq and E_sq/hq and altered the energetic of the FMN redox states binding profile. Our data indicate that the side chain of position 57 does not modulate E_ox/sq by aromatic stacking or solvent exclusion, but rather by influencing the relative strength of the H-bond between the N(5) of the flavin and the Asn58-Ile59 bond. A correlation was observed between the isoalloxazine increase in solvent accessibility and less negative E_sq/hq. Moreover, E_sq/hq became less negative as positively charged residues were added near to the isoalloxazine. Ile59 and Ile92 were simultaneously mutated to Ala or Glu. These mutations impaired FMN binding, while shifting E_sq/hq to less negative values and E_ox/sq to more negative. These effects are discussed on the bases of the X-ray structures of some of the Fld mutants, suggesting that in Anabaena Fld the structural control of both electron transfer steps is much more subtle than in other Flds.     

Inter-comparison of models to estimate radionuclide activity concentrations in non-human biota

A number of models have recently been, or are currently being, developed to enable the assessment of radiation doses from ionising radiation to non-human species. A key component of these models is the ability to predict whole-organism activity concentrations in a wide range of wildlife. In this paper, we compare the whole-organism activity concentrations predicted by eight models participating within the IAEA Environmental Modelling for Radiation Safety programme for a range of radionuclides to terrestrial and freshwater organisms. In many instances, there was considerable variation, ranging over orders of magnitude, between the predictions of the different models. Reasons for this variability (including methodology, data source and data availability) are identified and discussed. The active participation of groups responsible for the development of key models within this exercise is a useful step forward in providing the transparency in methodology and data provenance required for models which are either currently being used for regulatory purposes or which may be used in the future. The work reported in this paper, and supported by other findings, demonstrates that the largest contribution to variability between model predictions is the parameterisation of their transfer components. There is a clear need to focus efforts and provide authoritative compilations of those data which are available.     

Synthesis, crystal structure, magnetic and redox properties of copper(II) complexes of N-alkyl(aryl) tBu-salicylaldimines

A series of novel copper(II) complexes, L₂Cu with newly synthesized 3,5--salicylaldimine (or 5--salicylaldimine) ligands derived from 2,4-di-tert-butyl phenol (or 4-tert-butyl phenol) and alkyl (aryl) amines have been prepared and their spectroscopic (IR, UV-Vis, ESI-MS), X-ray, magnetic and redox properties have been investigated. The X-ray crystallography analysis shows that all complexes are monomeric and their copper(II) centers are surrounded by phenolate oxygens and imine nitrogen atoms. Therefore, the coordination sphere around the copper atoms is N₂O₂ as seen in galactose oxidase active site. In addition, the geometric configurations of all complexes are square planar or slightly distorted square planar. The crystal system for all complexes is monoclinic, except for which is orthorhombic. The temperature dependence of magnetic susceptibility of complexes confirms the mononuclear structure of complexes. Oxidation of the Cu(II) complexes yielded the corresponding Cu(II)-phenoxyl radical species during the cyclic voltammetry experiments.     

RecF recombination pathway in Escherichia coli cells lacking RecQ, UvrD and HelD helicases

In recBCD sbcB sbcC(D) mutants of Escherichia coli homologous recombination proceeds via RecF pathway, which is thought to require RecQ, UvrD and HelD helicases at its initial stage. It was previously suggested that depletion of all three helicases totally abolishes the RecF pathway. The present study (re)examines the roles of these helicases in transductional recombination, and in recombinational repair of UV-induced DNA damage in the RecF pathway. The study has employed the ΔrecBCD ΔsbcB sbcC201 and ΔrecBCD sbcB15 sbcC201 strains, carrying combinations of mutations in recQ, uvrD, and helD genes. We show that in ΔrecBCD ΔsbcB sbcC201 strains, recombination requires exclusively the RecQ helicase. In ΔrecBCD sbcB15 sbcC201 strains, RecQ may be partially substituted by UvrD helicase. The HelD helicase is dispensable for recombination in both backgrounds. Our results also suggest that significant portion of recombination events in the RecF pathway is independent of RecQ, UvrD and HelD. These events are initiated either by RecJ nuclease alone or by RecJ nuclease associated with an unknown helicase. Inactivation of exonuclease VII by a xseA mutation further decreases the requirement for helicase activity in the RecF pathway. We suggest that elimination of nucleases acting on 3' single-strand DNA ends reduces the necessity for helicases in initiation of recombination.     

Aminoacid composition and hydrophobicity index of mitochondrial polypeptides

The aminoacid composition of protein stained bands in polyacrylamide gels, after electrophoresis of proteins from inner mitochondrial membranes, was investigated hydrolyzing directly the gel slices. The Hydrophobicity Index of 18 prominent polypeptide bands was calculated after their aminoacid analysis. The polypeptides less related to the membrane have low hydrophobicity as inferred from their Hydrophobicity Indexes.     

Fatty acid composition and antioxidant activity of Antarctic marine sponges of the genus <Emphasis Type="Italic">Latrunculia</Emphasis>

The fatty acid composition of marine cold-water sponges of genus Latrunculia, namely Latrunculia bocagei Ridley and Dendy, 1886, and Latrunculia biformis Kirkpatrick, 1907, for which no fatty acid data had been previously reported, has been examined. High levels of long-chain fatty acids (C_24–30) with high unsaturation levels (mainly polyunsaturation), and high incidence of branched- and odd-chain fatty acids in sponges are suggested to be partially connected with their specific cell membrane requirements to surmount the negative effects of low temperatures and to enable growth in extreme environments. Furthermore, variations in the fatty acid profile at the species level may reflect variations in compositions or quantities of symbiotic microorganisms that commonly represent up to 60 % of the sponge wet weight. The fatty acid compositions of lipid-rich sponge extracts from five Latrunculia specimens dredged from the Bransfield Strait near the Antarctic Peninsula, were obtained using supercritical carbon dioxide and analyzed using gas chromatography–mass spectrometry–flame ionization detection. Furthermore, the antioxidant activities of these extracts were determined using the photochemiluminescent method. Along with common fatty acids, the chemical analyses revealed very long-chain fatty acids (C22, C24). Differences were seen for the fatty acid levels between both species and different specimens of the same species. The observed differences do not seem connected to the habitat depth of the specimen, but rather indicate the variations within the associated microbiome. Furthermore, these sponge extracts showed antioxidant activities, confirming that they contain lipidic compounds that strongly scavenge free radicals.