An accurate density functional theory for the vapor-liquid interface of associating chain molecules based on the statistical associating fluid theory for potentials of variable range.

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Unrelated Helpers in a Primitively Eusocial Wasp: Is Helping Tailored Towards Direct Fitness?

The paper wasp Polistes dominulus is unique among the social insects in that nearly one-third of co-foundresses are completely unrelated to the dominant individual whose offspring they help to rear and yet reproductive skew is high. These unrelated subordinates stand to gain direct fitness through nest inheritance, raising the question of whether their behaviour is adaptively tailored towards maximizing inheritance prospects. Unusually, in this species, a wealth of theory and empirical data allows us to predict how unrelated subordinates should behave. Based on these predictions, here we compare helping in subordinates that are unrelated or related to the dominant wasp across an extensive range of field-based behavioural contexts. We find no differences in foraging effort, defense behaviour, aggression or inheritance rank between unrelated helpers and their related counterparts. Our study provides no evidence, across a number of behavioural scenarios, that the behaviour of unrelated subordinates is adaptively modified to promote direct fitness interests

Networks of High Mutual Information Define the Structural Proximity of Catalytic Sites: Implications for Catalytic Residue Identification

Identification of catalytic residues (CR) is essential for the characterization of enzyme function. CR are, in general, conserved and located in the functional site of a protein in order to attain their function. However, many non-catalytic residues are highly conserved and not all CR are conserved throughout a given protein family making identification of CR a challenging task. Here, we put forward the hypothesis that CR carry a particular signature defined by networks of close proximity residues with high mutual information (MI), and that this signature can be applied to distinguish functional from other non-functional conserved residues. Using a data set of 434 Pfam families included in the catalytic site atlas (CSA) database, we tested this hypothesis and demonstrated that MI can complement amino acid conservation scores to detect CR. The Kullback-Leibler (KL) conservation measurement was shown to significantly outperform both the Shannon entropy and maximal frequency measurements. Residues in the proximity of catalytic sites were shown to be rich in shared MI. A structural proximity MI average score (termed pMI) was demonstrated to be a strong predictor for CR, thus confirming the proposed hypothesis. A structural proximity conservation average score (termed pC) was also calculated and demonstrated to carry distinct information from pMI. A catalytic likeliness score (Cls), combining the KL, pC and pMI measures, was shown to lead to significantly improved prediction accuracy. At a specificity of 0.90, the Cls method was found to have a sensitivity of 0.816. In summary, we demonstrate that networks of residues with high MI provide a distinct signature on CR and propose that such a signature should be present in other classes of functional residues where the requirement to maintain a particular function places limitations on the diversification of the structural environment along the course of evolution

Quantitative EEG findings in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

<p>Abstract</p> <p>Background</p> <p>Patients with brief depressive episodes and concurrent rapidly fluctuating psychiatric symptoms do not fit current diagnostic criteria and they can be difficult to diagnose and treat in an acute psychiatric setting. We wanted to study whether these patients had signs of more epileptic or organic brain dysfunction than patients with depression without additional symptomatology.</p> <p>Methods</p> <p>Sixteen acutely admitted patients diagnosed with a brief depressive episode as well as another concurrent psychiatric diagnosis were included. Sixteen patients with major depression served as controls. Three electroencephalographic studies (EEG) were visually interpreted and the background activity was also analysed with quantitative electroencephalography (QEEG).</p> <p>Results</p> <p>The group with brief depression and concurrent symptoms had multiple abnormal features in their standard EEG compared to patients with major depression, but they did not show significantly more epileptiform activity. They also had significantly higher temporal QEEG delta amplitude and interhemispheric temporal delta asymmetry.</p> <p>Conclusion</p> <p>Organic brain dysfunction may be involved in the pathogenesis of patients with brief depressive episodes mixed with rapidly fluctuating psychiatric symptoms. This subgroup of depressed patients should be investigated further in order to clarify the pathophysiology and to establish the optimal evaluation scheme and treatment in an acute psychiatric setting.</p

A Combinatorial Approach to Detect Coevolved Amino Acid Networks in Protein Families of Variable Divergence

Communication between distant sites often defines the biological role of a protein: amino acid long-range interactions are as important in binding specificity, allosteric regulation and conformational change as residues directly contacting the substrate. The maintaining of functional and structural coupling of long-range interacting residues requires coevolution of these residues. Networks of interaction between coevolved residues can be reconstructed, and from the networks, one can possibly derive insights into functional mechanisms for the protein family. We propose a combinatorial method for mapping conserved networks of amino acid interactions in a protein which is based on the analysis of a set of aligned sequences, the associated distance tree and the combinatorics of its subtrees. The degree of coevolution of all pairs of coevolved residues is identified numerically, and networks are reconstructed with a dedicated clustering algorithm. The method drops the constraints on high sequence divergence limiting the range of applicability of the statistical approaches previously proposed. We apply the method to four protein families where we show an accurate detection of functional networks and the possibility to treat sets of protein sequences of variable divergence

Patients' functioning as predictor of nursing workload in acute hospital units providing rehabilitation care: a multi-centre cohort study

<p>Abstract</p> <p>Background</p> <p>Management decisions regarding quality and quantity of nurse staffing have important consequences for hospital budgets. Furthermore, these management decisions must address the nursing care requirements of the particular patients within an organizational unit. In order to determine optimal nurse staffing needs, the extent of nursing workload must first be known. Nursing workload is largely a function of the composite of the patients' individual health status, particularly with respect to functioning status, individual need for nursing care, and severity of symptoms. The International Classification of Functioning, Disability and Health (ICF) and the derived subsets, the so-called ICF Core Sets, are a standardized approach to describe patients' functioning status. The objectives of this study were to (1) examine the association between patients' functioning, as encoded by categories of the Acute ICF Core Sets, and nursing workload in patients in the acute care situation, (2) compare the variance in nursing workload explained by the ICF Core Set categories and with the Barthel Index, and (3) validate the Acute ICF Core Sets by their ability to predict nursing workload.</p> <p>Methods</p> <p>Patients' functioning at admission was assessed using the respective Acute ICF Core Set and the Barthel Index, whereas nursing workload data was collected using an established instrument. Associations between dependent and independent variables were modelled using linear regression. Variable selection was carried out using penalized regression.</p> <p>Results</p> <p>In patients with neurological and cardiopulmonary conditions, selected ICF categories and the Barthel Index Score explained the same variance in nursing workload (44% in neurological conditions, 35% in cardiopulmonary conditions), whereas ICF was slightly superior to Barthel Index Score for musculoskeletal conditions (20% versus 16%).</p> <p>Conclusions</p> <p>A substantial fraction of the variance in nursing workload in patients with rehabilitation needs in the acute hospital could be predicted by selected categories of the Acute ICF Core Sets, or by the Barthel Index score. Incorporating ICF Core Set-based data in nursing management decisions, particularly staffing decisions, may be beneficial.</p

EMIRGE: reconstruction of full-length ribosomal genes from microbial community short read sequencing data

Recovery of ribosomal small subunit genes by assembly of short read community DNA sequence data generally fails, making taxonomic characterization difficult. Here, we solve this problem with a novel iterative method, based on the expectation maximization algorithm, that reconstructs full-length small subunit gene sequences and provides estimates of relative taxon abundances. We apply the method to natural and simulated microbial communities, and correctly recover community structure from known and previously unreported rRNA gene sequences. An implementation of the method is freely available at https://github.com/csmiller/EMIRGE

γCOP Is Required for Apical Protein Secretion and Epithelial Morphogenesis in Drosophila melanogaster

Background: There is increasing evidence that tissue-specific modifications of basic cellular functions play an important role in development and disease. To identify the functions of COPI coatomer-mediated membrane trafficking in Drosophila development, we were aiming to create loss-of-function mutations in the γCOP gene, which encodes a subunit of the COPI coatomer complex. Principal Findings: We found that γCOP is essential for the viability of the Drosophila embryo. In the absence of zygotic γCOP activity, embryos die late in embryogenesis and display pronounced defects in morphogenesis of the embryonic epidermis and of tracheal tubes. The coordinated cell rearrangements and cell shape changes during tracheal tube morphogenesis critically depend on apical secretion of certain proteins. Investigation of tracheal morphogenesis in γCOP loss-of-function mutants revealed that several key proteins required for tracheal morphogenesis are not properly secreted into the apical lumen. As a consequence, γCOP mutants show defects in cell rearrangements during branch elongation, in tube dilation, as well as in tube fusion. We present genetic evidence that a specific subset of the tracheal defects in γCOP mutants is due to the reduced secretion of the Zona Pellucida protein Piopio. Thus, we identified a critical target protein of COPI-dependent secretion in epithelial tube morphogenesis. Conclusions/Significance: These studies highlight the role of COPI coatomer-mediated vesicle trafficking in both general and tissue-specific secretion in a multicellular organism. Although COPI coatomer is generally required for protein secretion, we show that the phenotypic effect of γCOP mutations is surprisingly specific. Importantly, we attribute a distinct aspect of the γCOP phenotype to the effect on a specific key target protein

The Contribution of Coevolving Residues to the Stability of KDO8P Synthase

The evolutionary tree of 3-deoxy-D-manno-octulosonate 8-phosphate (KDO8P) synthase (KDO8PS), a bacterial enzyme that catalyzes a key step in the biosynthesis of bacterial endotoxin, is evenly divided between metal and non-metal forms, both having similar structures, but diverging in various degrees in amino acid sequence. Mutagenesis, crystallographic and computational studies have established that only a few residues determine whether or not KDO8PS requires a metal for function. The remaining divergence in the amino acid sequence of KDO8PSs is apparently unrelated to the underlying catalytic mechanism.The multiple alignment of all known KDO8PS sequences reveals that several residue pairs coevolved, an indication of their possible linkage to a structural constraint. In this study we investigated by computational means the contribution of coevolving residues to the stability of KDO8PS. We found that about 1/4 of all strongly coevolving pairs probably originated from cycles of mutation (decreasing stability) and suppression (restoring it), while the remaining pairs are best explained by a succession of neutral or nearly neutral covarions.Both sequence conservation and coevolution are involved in the preservation of the core structure of KDO8PS, but the contribution of coevolving residues is, in proportion, smaller. This is because small stability gains or losses associated with selection of certain residues in some regions of the stability landscape of KDO8PS are easily offset by a large number of possible changes in other regions. While this effect increases the tolerance of KDO8PS to deleterious mutations, it also decreases the probability that specific pairs of residues could have a strong contribution to the thermodynamic stability of the protein

Gender differences in patients with dizziness and unsteadiness regarding self-perceived disability, anxiety, depression, and its associations

BACKGROUND: It is known that anxiety and depression influence the level of disability experienced by persons with vertigo, dizziness or unsteadiness. Because higher prevalence rates of disabling dizziness have been found in women and some studies reported a higher level of psychiatric distress in female patients our primary aim was to explore whether women and men with vertigo, dizziness or unsteadiness differ regarding self-perceived disability, anxiety and depression. Secondly we planned to investigate the associations between disabling dizziness and anxiety and depression. METHOD: Patients were recruited from a tertiary centre for vertigo and balance disorders. Participants rated their global disability as mild, moderate or severe. They filled out the Dizziness Handicap Inventory and the two subscales of the Hospital Anxiety Depression Scale (HADS). The HADS was analysed 1) by calculating the median values, 2) by estimating the prevalence rates of abnormal anxiety/depression based on recommended cut-off criteria. Mann-Whitney U-tests, Chi-square statistics and odds ratios (OR) were calculated to compare the observations in both genders. Significance values were adjusted with respect to multiple comparisons. RESULTS: Two-hundred and two patients (124 women) mean age (standard deviation) of 49.7 (13.5) years participated. Both genders did not differ significantly in the mean level of self-perceived disability, anxiety, depression and symptom severity. There was a tendency of a higher prevalence of abnormal anxiety and depression in men (23.7%; 28.9%) compared to women (14.5%; 15.3%). Patients with abnormal depression felt themselves 2.75 (95% CI: 1.31-5.78) times more severely disabled by dizziness and unsteadiness than patients without depression. In men the OR was 8.2 (2.35-28.4). In women chi-square statistic was not significant. The ORs (95% CI) of abnormal anxiety and severe disability were 4.2 (1.9-8.9) in the whole sample, 8.7 (2.5-30.3) in men, and not significant in women. CONCLUSIONS: In men with vertigo, dizziness or unsteadiness emotional distress and its association with self-perceived disability should not be underestimated. Longitudinal surveys with specific pre-defined co-variables of self-perceived disability, anxiety and depression are needed to clarify the influence of gender on disability, anxiety and depression in patients with vertigo, dizziness or unsteadiness