Impact of the Southern Ecuadorian Andes on Oxygen and Hydrogen Isotopes in Precipitation

Determining how the elevation of the Northern Andes has evolved over time is of paramount importance for understanding the response of the Northern Andes to deformational and geodynamic processes and its role as an orographic barrier for atmospheric vapor transport over geologic time. However, a fundamental requirement when using stable isotope data for paleoaltimetry reconstructions is knowledge about the present-day changes of δ18O and δD with elevation (isotopic lapse rate). This study defines the present-day river isotopic lapse rate near the Equator (∼3°S) based on analysis of δ18O and δD of surface waters collected from streams across the Western Cordillera and the Inter-Andean depression in Southern Ecuador. The results for the two domains show a decrease of δ18O with elevation which fits a linear regression with a slope of −0.18‰/100 m (R2 = 0.73, n = 83). However, we establish a present-day lapse rate of −0.15‰/100 m for δ18O (R2 = 0.88, n = 19) and -1.4‰/100 m for δD (R2 = 0.93, n = 19) from water samples collected along the west facing slopes of the Western Ecuadorian Cordillera which is mainly subject to moisture transport from the Pacific. We argue that this empirical relationship, consistent with those obtained in different tropical areas of the world, can inform stable isotope paleoaltimetry reconstructions in tropical latitudes.</jats:p

The effects of demineralisation and sampling point variability on the measurement of glutamine deamidation in type I collagen extracted from bone

The level of glutamine (Gln) deamidation in bone collagen provides information on the diagenetic history of bone but, in order to accurately assess the extent of Gln deamidation, it is important to minimise the conditions that may induce deamidation during the sample preparation. Here we report the results of a preliminary investigation of the variability in glutamine deamidation levels in an archaeological bone due to: a) sampling location within a bone; b) localised diagenesis; and c) sample preparation methods. We then investigate the effects of pre-treatment on three bone samples: one modern, one Medieval and one Pleistocene. The treatment of bone with acidic solutions was found to both induce deamidation and break down the collagen fibril structure. This is particularly evident in the Pleistocene material (∼80,000 years BP) considered in this study. We show that ethylenediaminetetraacetic acid (EDTA), when used as an alternative to hydrochloric acid (HCl) demineralisation, induces minimal levels of deamidation and maintains the collagen fibril structure. Areas of bone exhibiting localised degradation are shown to be correlated with an increase in the levels of Gln deamidation. This indicates that the extent of Gln deamidation could provide a marker for diagenesis but that sampling is important, and that, whenever possible, subsamples should be taken from areas of the bone that are visually representative of the bone as a whole. Although validation of our observations will require analysis of a larger sample set, deamidation measurements could be a valuable screening tool to evaluate the suitability of bone for further destructive collagen analyses such as isotopic or DNA analysis, as well as assessing the overall preservation of bone material at a site. The measure of bone preservation may be useful to help conservators identify bones that may require special long-term storage conditions

Can work ability explain the social gradient in sickness absence: a study of a general population in Sweden

<p>Abstract</p> <p>Background</p> <p>Understanding the reasons for the social gradient in sickness absence might provide an opportunity to reduce the general rates of sickness absence. The complete explanation for this social gradient still remains unclear and there is a need for studies using randomized working population samples. The main aim of the present study was to investigate if self-reported work ability could explain the association between low socioeconomic position and belonging to a sample of new cases of sick-listed employees.</p> <p>Methods</p> <p>The two study samples consisted of a randomized working population (n = 2,763) and a sample of new cases of sick-listed employees (n = 3,044), 19-64 years old. Both samples were drawn from the same randomized general population. Socioeconomic status was measured with occupational position and physical and mental work ability was measured with two items extracted from the work ability index.</p> <p>Results</p> <p>There was an association between lower socioeconomic status and belonging to the sick-listed sample among both women and men. In men the crude Odds ratios increased for each downwards step in socioeconomic status, OR 1.32 (95% CI 0.98-1.78), OR 1.53 (1.05-2.24), OR 2.80 (2.11-3.72), and OR 2.98 (2.27-3.90). Among women this gradient was not as pronounced. Physical work ability constituted the strongest explanatory factor explaining the total association between socioeconomic status and being sick-listed in women. However, among men, the association between skilled non-manual, OR 2.07 (1.54-2.78), and non-skilled manual, OR 2.03 (1.53-2.71) positions in relation to being sick-listed remained. The explanatory effect of mental work ability was small. Surprisingly, even in the sick-listed sample most respondents had high mental and physical work ability.</p> <p>Conclusions</p> <p>These results suggest that physical work ability may be an important key in explaining the social gradient in sickness absence, particularly in women. Hence, it is possible that the factors associated with the social gradient in sickness absence may differ, to some extent, between women and men.</p

Probing the Flexibility of Large Conformational Changes in Protein Structures through Local Perturbations

Protein conformational changes and dynamic behavior are fundamental for such processes as catalysis, regulation, and substrate recognition. Although protein dynamics have been successfully explored in computer simulation, there is an intermediate-scale of motions that has proven difficult to simulate—the motion of individual segments or domains that move independently of the body the protein. Here, we introduce a molecular-dynamics perturbation method, the Rotamerically Induced Perturbation (RIP), which can generate large, coherent motions of structural elements in picoseconds by applying large torsional perturbations to individual sidechains. Despite the large-scale motions, secondary structure elements remain intact without the need for applying backbone positional restraints. Owing to its computational efficiency, RIP can be applied to every residue in a protein, producing a global map of deformability. This map is remarkably sparse, with the dominant sites of deformation generally found on the protein surface. The global map can be used to identify loops and helices that are less tightly bound to the protein and thus are likely sites of dynamic modulation that may have important functional consequences. Additionally, they identify individual residues that have the potential to drive large-scale coherent conformational change. Applying RIP to two well-studied proteins, Dihdydrofolate Reductase and Triosephosphate Isomerase, which possess functionally-relevant mobile loops that fluctuate on the microsecond/millisecond timescale, the RIP deformation map identifies and recapitulates the flexibility of these elements. In contrast, the RIP deformation map of α-lytic protease, a kinetically stable protein, results in a map with no significant deformations. In the N-terminal domain of HSP90, the RIP deformation map clearly identifies the ligand-binding lid as a highly flexible region capable of large conformational changes. In the Estrogen Receptor ligand-binding domain, the RIP deformation map is quite sparse except for one large conformational change involving Helix-12, which is the structural element that allosterically links ligand binding to receptor activation. RIP analysis has the potential to discover sites of functional conformational changes and the linchpin residues critical in determining these conformational states

Cooperative Transition between Open and Closed Conformations in Potassium Channels

Potassium (K+) ion channels switch between open and closed conformations. The nature of this important transition was revealed by comparing the X-ray crystal structures of the MthK channel from Methanobacterium thermoautotrophicum, obtained in its open conformation, and the KcsA channel from Streptomyces lividans, obtained in its closed conformation. We analyzed the dynamic characteristics and energetics of these homotetrameric structures in order to study the role of the intersubunit cooperativity in this transition. For this, elastic models and in silico alanine-scanning mutagenesis were used, respectively. Reassuringly, the calculations manifested motion from the open (closed) towards the closed (open) conformation. The calculations also revealed a network of dynamically and energetically coupled residues. Interestingly, the network suggests coupling between the selectivity filter and the gate, which are located at the two ends of the channel pore. Coupling between these two regions was not observed in calculations that were conducted with the monomer, which emphasizes the importance of the intersubunit interactions within the tetrameric structure for the cooperative gating behavior of the channel

Organizational configuration of hospitals succeeding in attracting and retaining nurses

Organizational configuration of hospitals succeeding in attracting and retaining nurses. This paper contrasts structural and managerial characteristics of low- and high-turnover hospitals, and describes the organizational configuration of attractive hospitals. In countries facing nurse shortages and turnover, some hospitals succeed in recruiting and retaining nurses. In Magnet Hospitals, managerial practices and environmental characteristics increase nurses\u2019 job satisfaction and their commitment to the organization, which in turn decreases nurse turnover. Such an approach suggests that organizations are best understood as clusters of interconnected structures and practices, i.e. organizational configurations rather than entities whose components can be understood in isolation. From a sample of 12 hospitals whose nurse turnover was studied for 1 year, structural and organizational features of hospitals in the first and fourth quartiles, i.e. attractive (turnover11\uc68%) were contrasted. A questionnaire, including perceptions of health-related factors, job demands, stressors, work schedules, organizational climate, and work adjustments antecedent to turnover, was received from 401 nurses working in attractive hospitals (response rate - 53\uc68%) and 774 nurses in conventional hospitals (response rate \ubc 54\uc65%). Structural characteristics did not differentiate attractive and conventional hospitals, but employee perceptions towards the organization differed strikingly. Differences were observed for risk exposure, emotional demands, role ambiguity and conflicts, work-family conflicts, effort-reward imbalance and the meaning of work, all in favour of attractive hospitals (P < 0.01). Relationships with nursing management, work ability and satisfaction with working time, handover shifts and schedules were also better in attractive hospitals (P < 0.001). Job satisfaction and commitment were higher in attractive hospitals, whereas burnout and intention to leave were lower (P < 0.001). Organizational characteristics are key factors in nurse attraction and retention. Nurses face difficulties in their work situations, but some hospitals are perceived as healthy organizations. The concept of attractive institutions could serve as a catalyst for improvement in nurses\u2019 work environments in Europe

Evolutionarily Conserved Linkage between Enzyme Fold, Flexibility, and Catalysis

Proteins are intrinsically flexible molecules. The role of internal motions in a protein's designated function is widely debated. The role of protein structure in enzyme catalysis is well established, and conservation of structural features provides vital clues to their role in function. Recently, it has been proposed that the protein function may involve multiple conformations: the observed deviations are not random thermodynamic fluctuations; rather, flexibility may be closely linked to protein function, including enzyme catalysis. We hypothesize that the argument of conservation of important structural features can also be extended to identification of protein flexibility in interconnection with enzyme function. Three classes of enzymes (prolyl-peptidyl isomerase, oxidoreductase, and nuclease) that catalyze diverse chemical reactions have been examined using detailed computational modeling. For each class, the identification and characterization of the internal protein motions coupled to the chemical step in enzyme mechanisms in multiple species show identical enzyme conformational fluctuations. In addition to the active-site residues, motions of protein surface loop regions (>10 Å away) are observed to be identical across species, and networks of conserved interactions/residues connect these highly flexible surface regions to the active-site residues that make direct contact with substrates. More interestingly, examination of reaction-coupled motions in non-homologous enzyme systems (with no structural or sequence similarity) that catalyze the same biochemical reaction shows motions that induce remarkably similar changes in the enzyme–substrate interactions during catalysis. The results indicate that the reaction-coupled flexibility is a conserved aspect of the enzyme molecular architecture. Protein motions in distal areas of homologous and non-homologous enzyme systems mediate similar changes in the active-site enzyme–substrate interactions, thereby impacting the mechanism of catalyzed chemistry. These results have implications for understanding the mechanism of allostery, and for protein engineering and drug design