Metabolomics meets lipidomics: Assessing the small molecule component of metabolism

Metabolomics, including lipidomics, is emerging as a quantitative biology approach for the assessment of energy flow through metabolism and information flow through metabolic signaling; thus, providing novel insights into metabolism and its regulation, in health, healthy ageing and disease. In this forward-looking review we provide an overview on the origins of metabolomics, on its role in this postgenomic era of biochemistry and its application to investigate metabolite role and (bio)activity, from model systems to human population studies. We present the challenges inherent to this analytical science, and approaches and modes of analysis that are used to resolve, characterize and measure the infinite chemical diversity contained in the metabolome (including lipidome) of complex biological matrices. In the current outbreak of metabolic diseases such as cardiometabolic disorders, cancer and neurodegenerative diseases, metabolomics appears to be ideally situated for the investigation of disease pathophysiology from a metabolite perspective.     

Predicting the accuracy of multiple sequence alignment algorithms by using computational intelligent techniques

Multiple sequence alignments (MSAs) have become one of the most studied approaches in bioinformatics to perform other outstanding tasks such as structure prediction, biological function analysis or next-generation sequencing. However, current MSA algorithms do not always provide consistent solutions, since alignments become increasingly difficult when dealing with low similarity sequences. As widely known, these algorithms directly depend on specific features of the sequences, causing relevant influence on the alignment accuracy. Many MSA tools have been recently designed but it is not possible to know in advance which one is the most suitable for a particular set of sequences. In this work, we analyze some of the most used algorithms presented in the bibliography and their dependences on several features. A novel intelligent algorithm based on least square support vector machine is then developed to predict how accurate each alignment could be, depending on its analyzed features. This algorithm is performed with a dataset of 2180 MSAs. The proposed system first estimates the accuracy of possible alignments. The most promising methodologies are then selected in order to align each set of sequences. Since only one selected algorithm is run, the computational time is not excessively increased.     

Characterizing Ipomopsis rubra (Polemoniaceae) germination under various thermal scenarios with non-parametric and semi-parametric statistical methods

Time-to-event analysis represents a collection of relatively new, flexible, and robust statistical techniques for investigating the incidence and timing of transitions from one discrete condition to another. Plant biology is replete with examples of such transitions occurring from the cellular to population levels. However, application of these statistical methods has been rare in botanical research. Here, we demonstrate the use of non- and semi-parametric time-to-event and categorical data analyses to address questions regarding seed to seedling transitions of Ipomopsis rubra propagules exposed to various doses of constant or simulated seasonal diel temperatures. Seeds were capable of germinating rapidly to >90 % at 15–25 or 22/11–29/19 °C. Optimum temperatures for germination occurred at 25 or 29/19 °C. Germination was inhibited and seed viability decreased at temperatures ≥30 or 33/24 °C. Kaplan–Meier estimates of survivor functions indicated highly significant differences in temporal germination patterns for seeds exposed to fluctuating or constant temperatures. Extended Cox regression models specified an inverse relationship between temperature and the hazard of germination. Moreover, temperature and the temperature × day interaction had significant effects on germination response. Comparisons to reference temperatures and linear contrasts suggest that summer temperatures (33/24 °C) play a significant role in differential germination responses. Similarly, simple and complex comparisons revealed that the effects of elevated temperatures predominate in terms of components of seed viability. In summary, the application of non- and semi-parametric analyses provides appropriate, powerful data analysis procedures to address various topics in seed biology and more widespread use is encouraged.     

Conflict and contestation in the cross-border community: hometown associations reassessed

Drawing on a broad variety of field research projects among Salvadoran immigrant hometown associations in Los Angeles, conducted over a ten-year period, this paper seeks to contribute to the emerging literature on hometown associations by shifting the focus to the political processes underlying associational politics and the characteristics of the organizational field that structures their activities. We argue that conflict, both among migrants in the ‘hostland’ and between migrants in the hostland and stay-behinds in the ‘homeland’, is an inherent aspect of hometown association activities and their efforts to create sociability ‘here’ and development ‘there’. We demonstrate that the hometowners abroad have difficulty deciding what they share in common; those who do engage in organized efforts to span here and there represent a select few. Moreover, the issue of how the migrants and their associations relate to the people and institutions left behind is often a dilemma, resolved in any number of ways, not all of which render satisfaction at either ends of the chain.     

Individual N-Glycans Added at Intervals along the Stalk of the Nipah Virus G Protein Prevent Fusion but Do Not Block the Interaction with the Homologous F Protein

The promotion of membrane fusion by most paramyxoviruses requires an interaction between the viral attachment and fusion (F) proteins to enable receptor binding by the former to trigger the activation of the latter for fusion. Numerous studies demonstrate that the F-interactive sites on the Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) and measles virus (MV) hemagglutinin (H) proteins reside entirely within the stalk regions of those proteins. Indeed, stalk residues of NDV HN and MV H that likely mediate the F interaction have been identified. However, despite extensive efforts, the F-interactive site(s) on the Nipah virus (NiV) G attachment glycoprotein has not been identified. In this study, we have introduced individual N-linked glycosylation sites at several positions spaced at intervals along the stalk of the NiV G protein. Five of the seven introduced sites are utilized as established by a retardation of electrophoretic mobility. Despite surface expression, ephrinB2 binding, and oligomerization comparable to those of the wild-type protein, four of the five added N-glycans completely eliminate the ability of the G protein to complement the homologous F protein in the promotion of fusion. The most membrane-proximal added N-glycan reduces fusion by 80%. However, unlike similar NDV HN and MV H mutants, the NiV G glycosylation stalk mutants retain the ability to bind F, indicating that the fusion deficiency of these mutants is not due to prevention of the G-F interaction. These findings suggest that the G-F interaction is not mediated entirely by the stalk domain of G and may be more complex than that of HN/H-F.     

Identification of Bacterial Infection in Neotropical Primates

Emerging infectious diseases usually arise from wild animal populations. In the present work, we performed a screening for bacterial infection in natural populations of New World primates. The blood cell bulk DNAs from 181 individuals of four Platyrrhini genera were PCR screened for eubacterial 16S rRNA genes. Bacteria were detected and identified in 13 distinct individuals of Alouatta belzebul, Alouatta caraya, and Cebus apella monkeys from geographically distant regions in the states of Mato Grosso and Pará, Brazil. Sequence analyses showed that these Platyrrhini bacteria are closely related not only to human pathogens Pseudomonas spp. but also to Pseudomonas simiae and sheep-Acari infecting Pseudomonas spp. The identified Pseudomonas possibly represents a group of bacteria circulating in natural monkey populations.     

A mutational analysis of active site residues in trans-3-chloroacrylic acid dehalogenase

trans-3-Chloroacrylic acid dehalogenase (CaaD) catalyzes the hydrolytic dehalogenation of trans-3-haloacrylates to yield malonate semialdehyde by a mechanism utilizing βPro-1, αArg-8, αArg-11, and αGlu-52. These residues are implicated in a promiscuous hydratase activity where 2-oxo-3-pentynoate is processed to acetopyruvate. The roles of three nearby residues (βAsn-39, αPhe-39, and αPhe-50) are unexplored. Mutants were constructed at these positions (βN39A, αF39A, αF39T, αF50A and αF50Y) and kinetic parameters determined along with those of the αR8K and αR11K mutants. Analysis indicates that αArg-8, αArg-11, and βAsn-39 are critical for dehalogenase activity whereas αArg-11 and αPhe-50 are critical for hydratase activity. Docking studies suggest structural bases for these observations.     

Functional properties of a manganese-activated exo-polygalacturonase produced by a thermotolerant fungus Aspergillus niveus

A thermotolerant fungus identified as Aspergillus niveus was isolated from decomposing materials and it has produced excellent levels of hydrolytic enzymes that degrade plant cell walls. A. niveus germinated faster at 40 °C, presenting protein levels almost twofold higher than at 25 °C. The crude extract of the A. niveus culture was purified by diethylaminoethyl (DEAE)-cellulose, followed by Biogel P-100 column. Polygalacturonase (PG) is a glycoprotein with 37.7 % carbohydrate, molecular mass of 102.6 kDa, and isoelectric point of 5.4. The optimum temperature and pH were 50 °C and 4.0–6.5, respectively. The enzyme was stable at pH 3.0 to 9.0 for 24 h. The DEAE-cellulose derivative was about sixfold more stable at 60 °C than the free enzyme. Moreover, the monoaminoethyl-N-aminoethyl-agarose derivative was tenfold more stable than the free enzyme. PG was 232 % activated by Mn²⁺. The hydrolysis product of sodium polypectate corresponded at monogalacturonic acid, which classifies the enzyme as an exo-PG. The K _m, V _max, K _cat, and K _cat/K _m values were 6.7 mg/ml, 230 U/mg, 393.3/s, and 58.7 mg/ml/s, respectively. The N-terminal amino acid sequence presented 80 % identity with PglB1, PglA2, and PglA3 putative exo-PG of Aspergillus fumigatus and an exo-PG Neosartorya fischeri.     

A dynamic metabolic flux balance based model of fed‐batch fermentation of bordetella pertussis

A mathematical model based on a dynamic metabolic flux balance (DMFB) is developed for a process of fed‐batch fermentation of Bordetella pertussis. The model is based on the maximization of growth rate at each time interval subject to stoichiometric constraints. The model is calibrated and verified with experimental data obtained in two different bioreactor experimental systems. It was found that the model calibration was mostly sensitive to the consumption or production rates of tyrosine and, for high supplementation rates, to the consumption rate of glutamate. Following this calibration the model correctly predicts biomass and by‐products concentrations for different supplementation rates. Comparisons of model predictions to oxygen uptake and carbon emission rates measurements indicate that the TCA cycle is fully functional. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 520–531, 2013     

Punish and Voice: Punishment Enhances Cooperation when Combined with Norm-Signalling

Material punishment has been suggested to play a key role in sustaining human cooperation. Experimental findings, however, show that inflicting mere material costs does not always increase cooperation and may even have detrimental effects. Indeed, ethnographic evidence suggests that the most typical punishing strategies in human ecologies (e.g., gossip, derision, blame and criticism) naturally combine normative information with material punishment. Using laboratory experiments with humans, we show that the interaction of norm communication and material punishment leads to higher and more stable cooperation at a lower cost for the group than when used separately. In this work, we argue and provide experimental evidence that successful human cooperation is the outcome of the interaction between instrumental decision-making and the norm psychology humans are provided with. Norm psychology is a cognitive machinery to detect and reason upon norms that is characterized by a salience mechanism devoted to track how much a norm is prominent within a group. We test our hypothesis both in the laboratory and with an agent-based model. The agent-based model incorporates fundamental aspects of norm psychology absent from previous work. The combination of these methods allows us to provide an explanation for the proximate mechanisms behind the observed cooperative behaviour. The consistency between the two sources of data supports our hypothesis that cooperation is a product of norm psychology solicited by norm-signalling and coercive devices.