ND3, ND1 and 39 kDa subunits are more exposed in the de-active form of bovine mitochondrial complex I

An intriguing feature of mitochondrial complex I from several species is the so-called A/D transition, whereby the idle enzyme spontaneously converts from the active (A) form to the de-active (D) form. The A/D transition plays an important role in tissue response to the lack of oxygen and hypoxic deactivation of the enzyme is one of the key regulatory events that occur in mitochondria during ischaemia. We demonstrate for the first time that the A/D conformational change of complex I does not affect the macromolecular organisation of supercomplexes in vitro as revealed by two types of native electrophoresis. Cysteine 39 of the mitochondrially-encoded ND3 subunit is known to become exposed upon de-activation. Here we show that even if complex I is a constituent of the I + III + IV (S) supercomplex, cysteine 39 is accessible for chemical modification in only the D-form. Using lysine-specific fluorescent labelling and a DIGE-like approach we further identified two new subunits involved in structural rearrangements during the A/D transition: ND1 (MT-ND1) and 39 kDa (NDUFA9). These results clearly show that structural rearrangements during de-activation of complex I include several subunits located at the junction between hydrophilic and hydrophobic domains, in the region of the quinone binding site. De-activation of mitochondrial complex I results in concerted structural rearrangement of membrane subunits which leads to the disruption of the sealed quinone chamber required for catalytic turnover.

One-pot two-step mechanochemical synthesis: ligand and complex preparation without isolating intermediates

Although the use of ball milling to induce reactions between solids (mechanochemical synthesis) can provide lower-waste routes to chemical products by avoiding solvent during the reaction, there are further potential advantages in using one-pot multistep syntheses to avoid the use of bulk solvents for the purification of intermediates. We report here two-step syntheses involving formation of salen-type ligands from diamines and hydroxyaldehydes followed directly by reactions with metal salts to provide the corresponding metal complexes. Five salen-type ligands 2,2'-[1,2-ethanediylbis[(E)-nitrilomethylidyne]] bisphenol, ` salenH2', 1; 2,2'-[(+/-)-1,2-cyclohexanediylbis-[(E)-nitrilomethylidyne]] bis-phenol, 2; 2,2'-[1,2-phenylenebis( nitrilomethylidyne)]-bis-phenol, ` salphenH2' 3; 2-[[(2-aminophenyl) imino] methyl]-phenol, 4; 2,2'-[(+/-)-1,2-cyclohexanediylbis[(E)-nitrilomethylidyne]]-bis[4,6-bis(1,1-dimethylethyl)]-phenol, ` Jacobsen ligand', 5) were found to form readily in a shaker-type ball mill at 0.5 to 3 g scale from their corresponding diamine and aldehyde precursors. Although in some cases both starting materials were liquids, ball milling was still necessary to drive those reactions to completion because precipitation of the product and or intermediates rapidly gave in thick pastes which could not be stirred conventionally. The only ligand which required the addition of solvent was the Jacobsen ligand 5 which required 1.75 mol equivalents of methanol to go to completion. Ligands 1-5 were thus obtained directly in 30-60 minutes in their hydrated forms, due to the presence of water by-product, as free-flowing yellow powders which could be dried by heating to give analytically pure products. The one-armed salphen ligand 4 could also be obtained selectively by changing the reaction stoichiometry to 1 : 1. SalenH(2) 1 was explored for the onepot two-step synthesis of metal complexes. In particular, after in situ formation of the ligand by ball milling, metal salts (ZnO, Ni(OAc)2 center dot 4H(2)O or Cu(OAc)(2)center dot H2O) were added directly to the jar and milling continued for a further 30 minutes. Small amounts of methanol (0.4-1.1 mol equivalents) were needed for these reactions to run to completion. The corresponding metal complexes [M(salen)] (M = Zn, 6; Ni, 7; or Cu, 8) were thus obtained quantitatively after 30 minutes in hydrated form, and could be heated briefly to give analytically pure dehydrated products. The all-at-once ` tandem' synthesis of [Zn(salen)] 6 was also explored by milling ZnO, ethylene diamine and salicylaldehyde together in the appropriate mole ratio for 60 minutes. This approach also gave the target complex selectively with no solvent needing to be added. Overall, these syntheses were found to be highly efficient in terms of time and the in avoidance of bulk solvent both during the reaction and for the isolation of intermediates. The work demonstrates the applicability of mechanochemical synthesis to one-pot multi-step strategies.

A methodological review of the Short Form Health Survey 36 (SF-36) and its derivatives among breast cancer survivors

Purpose: A systematic review of the validity, reliability and sensitivity of the Short Form (SF) health survey measures among breast cancer survivors.
Methods: We searched a number of databases for peer-reviewed papers. The methodological quality of the papers was assessed using the COnsenus-based Standards for the selection of health Measurement INstruments (COSMIN).
Results: The review identified seven papers that assessed the psychometric properties of the SF-36 (n = 5), partial SF-36 (n = 1) and SF-12 (n = 1) among breast cancer survivors. Internal consistency scores for the SF measures ranged from acceptable to good across a range of language and ethnic sub-groups. The SF-36 demonstrated good convergent validity with respective subscales of the Functional Assessment of Cancer Treatment—General scale and two lymphedema-specific measures. Divergent validity between the SF-36 and Lymph-ICF was modest. The SF-36 demonstrated good factor structure in the total breast cancer survivor study samples. However, the factor structure appeared to differ between specific language and ethnic sub-groups. The SF-36 discriminated between survivors who reported or did not report symptoms on the Breast Cancer Prevention Trial Symptom Checklist and SF-36 physical sub-scales, but not mental sub-scales, discriminated between survivors with or without lymphedema. Methodological quality scores varied between and within papers.
Conclusion: Short Form measures appear to provide a reliable and valid indication of general health status among breast cancer survivors though the limited data suggests that particular caution is required when interpreting scores provided by non-English language groups. Further research is required to test the sensitivity or responsiveness of the measure.

The solution structure of 1:2 phenol/N-methylpyridinium bis{(trifluoromethyl)sulfonyl}imide liquid mixtures

Neutron diffraction has been used to investigate the liquid structure of a 1:2 solution of phenol in the ionic liquid N-methylpyridinium bis{(trifluoromethyl)sulfonyl}imide at 60 ◦C, using the empirical potential structure refinement (EPSR) process to model the data obtained from the SANDALS diffractometer at ISIS. Addition of phenol results in suppression of the melting point of the pyridinium salt and formation of a room temperature solution with aromatic phenol–cation and phenol-OH to anion hydrogen-bonding interactions.

(Dis‑)Harmony in movement: effects of musical dissonance on movement timing and form

While the origins of consonance and dissonance in terms of acoustics, psychoacoustics and physiology have been debated for centuries, their plausible effects on movement synchronization have largely been ignored. The present study aims to address this by investigating whether, and if so how, consonant/dissonant pitch intervals affect the spatiotemporal properties of regular reciprocal aiming movements. We compared movements synchronized either to consonant or to dissonant sounds, and showed that they were differently influenced by the degree of consonance of the sound presented. Interestingly, the difference was present after the sound stimulus was removed. In this case, the performance measured after consonant sound exposure was found to be more stable and accurate, with a higher percentage of information/movement coupling (tau-coupling) and a higher degree of movement circularity when compared to performance measured after the exposure to dissonant sounds. We infer that the neural resonance representing consonant tones leads to finer perception/action coupling which in turn may help explain the prevailing preference for these types of tones.

Authenticity, Identity and Sustainability in Post-war Iraq: Reshaping the Urban Form of Erbil City

Issues of authenticity and identity are particularly significant in cities where social and cultural change is shaping active transformation of its urban fabric and structure in the post-war condition. In search of sustainable future, Iraqi cities are stretched between the two ends of the spectrum, authentic quarters with its traditional fabric and modern districts with their global sense of living. This paper interrogates the reciprocal influences, distinct qualities and sustainable performance of both authentic and modern quarters of Erbil, the
capital of the Iraqi province of Kurdistan, as factors in shaping sustainable urban forms for Iraqi cities. In doing so, the paper, firstly, seeks to highlight the urban identity as an effective factor in relation to sustainable urban form. Secondly, the city of Erbil in Iraq has been chosen as a field study, due to its regional, social, political and historical role in the region. Thirdly, the study emphasises the dynamic activities and performance of residential projects according to rational sustainable criteria. The research concludes that urban identity and the sense of place in traditional and historical places should inform design strategies in order to achieve a more sustainable urban context.

A Revised Disrupted Langmuir-Adsorption Model of Photocatalysis

The increasingly popular disrupted Langmuir–adsorption (DLA) kinetic model of photocatalysis does not contain an explicit function for the dependence of rate on the irradiance, ρ, but instead has a term αρθ, where, α is a constant of the system, and θ is also a constant equal to 1 or 0.5 at low or high ρ values, respectively. Several groups have recently replaced the latter term with an explicit function of the form χ1(−1 + (1 + χ2ρ)1/2), where χ1 and χ2, are constants that can be related to a proposed reaction scheme. Here the latter schemes are investigated, and revised to create a more credible form by assuming an additional hole trapping step. The latter may be the oxidation of water or a surface saturated with O2–. Importantly, this revision suggests that it is only applicable for low quantum yield/efficiency processes. The revised disrupted Langmuir–adsorption model is used to provide good fits to the kinetic data reported for a number of different systems including the photocatalytic oxidation of nitric oxide (NO), phenol (PhOH), and formic acid (FA).