Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.

The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information

A Factorization Algorithm for G-Algebras and Applications

It has been recently discovered by Bell, Heinle and Levandovskyy that a large class of algebras, including the ubiquitous $G$-algebras, are finite factorization domains (FFD for short). Utilizing this result, we contribute an algorithm to find all distinct factorizations of a given element $f \in \mathcal{G}$, where $\mathcal{G}$ is any $G$-algebra, with minor assumptions on the underlying field. Moreover, the property of being an FFD, in combination with the factorization algorithm, enables us to propose an analogous description of the factorized Gr\"obner basis algorithm for $G$-algebras. This algorithm is useful for various applications, e.g. in analysis of solution spaces of systems of linear partial functional equations with polynomial coefficients, coming from $\mathcal{G}$. Additionally, it is possible to include inequality constraints for ideals in the input

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

Symbiosis is a dominant form of life that has been observed numerous times in marine ecosystems. For example, macroalgae coexist with bacteria that produce factors that promote algal growth and morphogenesis. The green macroalga Ulva mutabilis (Chlorophyta) develops into a callus-like phenotype in the absence of its essential bacterial symbionts Roseovarius sp. MS2 and Maribacter sp. MS6. Spatially resolved studies are required to understand symbiont interactions at the microscale level. Therefore, we used mass spectrometry profiling and imaging techniques with high spatial resolution and sensitivity to gain a new perspective on the mutualistic interactions between bacteria and macroalgae. Using atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionisation high-resolution mass spectrometry (AP-SMALDI-HRMS), low-molecular-weight polar compounds were identified by comparative metabolomics in the chemosphere of Ulva. Choline (2-hydroxy-N,N,N-trimethylethan-1-aminium) was only determined in the alga grown under axenic conditions, whereas ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) was found in bacterial presence. Ectoine was used as a metabolic marker for localisation studies of Roseovarius sp. within the tripartite community because it was produced exclusively by these bacteria. By combining confocal laser scanning microscopy (cLSM) and AP-SMALDI-HRMS, we proved that Roseovarius sp. MS2 settled mainly in the rhizoidal zone (holdfast) of U. mutabilis. Our findings provide the fundament to decipher bacterial symbioses with multicellular hosts in aquatic ecosystems in an ecologically relevant context. As a versatile tool for microbiome research, the combined AP-SMALDI and cLSM imaging analysis with a resolution to level of a single bacterial cell can be easily applied to other microbial consortia and their hosts. The novelty of this contribution is the use of an in situ setup designed to avoid all types of external contamination and interferences while resolving spatial distributions of metabolites and identifying specific symbiotic bacteria

Speech rhythm: a metaphor?

Is speech rhythmic? In the absence of evidence for a traditional view that languages strive to coordinate either syllables or stress-feet with regular time intervals, we consider the alternative that languages exhibit contrastive rhythm subsisting merely in the alternation of stronger and weaker elements. This is initially plausible, particularly for languages with a steep ‘prominence gradient’, i.e. a large disparity between stronger and weaker elements; but we point out that alternation is poorly achieved even by a ‘stress-timed’ language such as English, and, historically, languages have conspicuously failed to adopt simple phonological remedies that would ensure alternation. Languages seem more concerned to allow ‘syntagmatic contrast’ between successive units and to use durational effects to support linguistic functions than to facilitate rhythm. Furthermore, some languages (e.g. Tamil, Korean) lack the lexical prominence which would most straightforwardly underpin prominence alternation. We conclude that speech is not incontestibly rhythmic, and may even be antirhythmic. However, its linguistic structure and patterning allow the metaphorical extension of rhythm in varying degrees and in different ways depending on the language, and that it is this analogical process which allows speech to be matched to external rhythms

Antimicrobial resistance in urosepsis: outcomes from the multinational, multicenter global prevalence of infections in urology (GPIU) study 2003–2013

Primary objective was to identify the (1) relationship of clinical severity of urosepsis with the pathogen spectrum and resistance and (2) appropriateness of using the pathogen spectrum and resistance rates of health-care-associated urinary tract infections (HAUTI) as representative of urosepsis. The secondary objective was to provide an overview of the pathogens and their resistance profile in patients with urosepsis. POPULATION AND METHODS: A point prevalence study carried out in 70 countries (2003-2013). Population studied included; 408 individuals with microbiologically proven urosepsis, 1606 individuals with microbiological proof of HAUTI and 27,542 individuals hospitalised in urology wards. Main outcomes are pathogens and resistance identified in HAUTIs and urosepsis including its clinical severity. A statistical model that included demographic factors (study year, geographical location, hospital setting) was used for analysis. RESULTS: Amongst urology practices, the prevalence of microbiologically proven HAUTI and urosepsis was 5.8 and 1.5 %, respectively. Frequent pathogens in urosepsis were E. coli (43 %), Enterococcus spp. (11 %), P. aeruginosa (10 %) and Klebsiella spp. (10 %). Resistance to commonly prescribed antibiotics was high and rates ranged from 8 % (imipenem) to 62 % (aminopenicillin/β lactamase inhibitors); 45 % of Enterobacteriaceae and 21 % of P. aeruginosa were multidrug-resistant. Resistance rates in urosepsis were higher than in other clinical diagnosis of HAUTI (Likelihood ratio <0.05). CONCLUSIONS: It is not appropriate to use the pathogen spectrum and resistance rates of other HAUTIs as representative of urosepsis to decide on empirical treatment of urosepsis. Resistance rates in urosepsis are high, and precautions should be made to avoid further increas