Tactical Voting in Plurality Elections

How often will elections end in landslides? What is the probability for a head-to-head race? Analyzing ballot results from several large countries rather anomalous and yet unexplained distributions have been observed. We identify tactical voting as the driving ingredient for the anomalies and introduce a model to study its effect on plurality elections, characterized by the relative strength of the feedback from polls and the pairwise interaction between individuals in the society. With this model it becomes possible to explain the polarization of votes between two candidates, understand the small margin of victories frequently observed for different elections, and analyze the polls'' impact in American, Canadian, and Brazilian ballots. Moreover, the model reproduces, quantitatively, the distribution of votes obtained in the Brazilian mayor elections with two, three, and four candidates.     

Ecosystem-level effects of re-oligotrophication and N:P imbalances in rivers and estuaries on a global scale

Trends and ecological consequences of phosphorus (P) decline and increasing nitrogen (N) to phosphorus (N:P) ratios in rivers and estuaries are reviewed and discussed. Results suggest that re-oligotrophication is a dominant trend in rivers and estuaries of high-income countries in the last two–three decades, while in low-income countries widespread eutrophication occurs. The decline in P is well documented in hundreds of rivers of United States and the European Union, but the biotic response of rivers and estuaries besides phytoplankton decline such as trends in phytoplankton composition, changes in primary production, ecosystem shifts, cascading effects, changes in ecosystem metabolism, etc., have not been sufficiently monitored and investigated, neither the effects of N:P imbalance. N:P imbalance has significant ecological effects that need to be further investigated. There is a growing number of cases in which phytoplankton biomass have been shown to decrease due to re-oligotrophication, but the potential regime shift from phytoplankton to macrophyte dominance described in shallow lakes has been documented only in a few rivers and estuaries yet. The main reasons why regime shifts are rarely described in rivers and estuaries are, from one hand the scarcity of data on macrophyte cover trends, and from the other hand physical factors such as peak flows or high turbidity that could prevent a general spread of submerged macrophytes as observed in shallow lakes. Moreover, re-oligotrophication effects on rivers may be different compared to lakes (e.g., lower dominance of macrophytes) or estuaries (e.g., limitation of primary production by N instead of P) or may be dependent on river/estuary type. We conclude that river and estuary re-oligotrophication effects are complex, diverse and still little known, and in some cases are equivalent to those described in shallow lakes, but the regime shift is more likely to occur in mid to high-order rivers and shallow estuaries.     

The detection and attribution of extreme reductions in vegetation growth across the global land surface

Negative extreme anomalies in vegetation growth (NEGs) usually indicate severely impaired ecosystem services. These NEGs can result from diverse natural and anthropogenic causes, especially climate extremes (CEs). However, the relationship between NEGs and many types of CEs remains largely unknown at regional and global scales. Here, with satellite-derived vegetation index data and supporting tree-ring chronologies, we identify periods of NEGs from 1981 to 2015 across the global land surface. We find 70% of these NEGs are attributable to five types of CEs and their combinations, with compound CEs generally more detrimental than individual ones. More importantly, we find that dominant CEs for NEGs vary by biome and region. Specifically, cold and/or wet extremes dominate NEGs in temperate mountains and high latitudes, whereas soil drought and related compound extremes are primarily responsible for NEGs in wet tropical, arid and semi-arid regions. Key characteristics (e.g., the frequency, intensity and duration of CEs, and the vulnerability of vegetation) that determine the dominance of CEs are also region- and biome-dependent. For example, in the wet tropics, dominant individual CEs have both higher intensity and longer duration than non-dominant ones. However, in the dry tropics and some temperate regions, a longer CE duration is more important than higher intensity. Our work provides the first global accounting of the attribution of NEGs to diverse climatic extremes. Our analysis has important implications for developing climate-specific disaster prevention and mitigation plans among different regions of the globe in a changing climate.     

Neurotrophic Requirements of Human Motor Neurons Defined Using Amplified and Purified Stem Cell-Derived Cultures

Human motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK) inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC₅₀ 1–2 pM). The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening.     

Effect of poly(ADP-ribosyl)ation inhibitors on the genotoxic effects of the boron neutron capture reaction

The boron neutron capture (BNC) reaction results from the interaction of 10B with low-energy thermal neutrons and gives rise to highly damaging lithium and alpha-particles. In this work the genotoxicity caused by the BNC reaction in V79 Chinese hamster cells was evaluated in the presence of poly(ADP-ribosyl)ation inhibitors. Poly(ADP-ribose) polymerase-1 (PARP-1), the most important member of the PARP enzyme family, is considered to be a constitutive factor of the DNA damage surveillance network present in eukaryotic cells, acting through a DNA break sensor function. Inhibition of poly(ADP-ribosyl)ation was achieved with the classical compound 3-aminobenzamide (3-AB), and with two novel and very potent inhibitors, 5-aminoisoquinolinone (5-AIQ) and PJ-34. Dose-response increases in the frequencies of aberrant cells excluding gaps (%ACEG) and chromosomal aberrations excluding gaps per cell (CAEG/cell) were observed for increasing exposures to the BNC reaction. The presence of 3-AB did not increase the %ACEG or CAEG/cell, nor did it change the pattern of the induced chromosomal aberrations. Results with 5-AIQ and PJ-34 were in agreement with the results obtained with 3-AB. We further studied the combined effect of a PARP inhibitor and a DNA-dependent protein kinase (DNA-PK) inhibitors (3-AB and wortmannin, respectively) on the genotoxicity of the BNC reaction, by use of the cytokinesis-block micronucleus assay. DNA-PK is also activated by DNA breaks and binds DNA ends, playing a role of utmost importance in the repair of double-strand breaks. Our results show that the inhibition of poly(ADP-ribosyl)ation does not particularly modify the genotoxicity of the BNC reaction, and that PARP inhibition together with a concomitant inhibition of DNA-PK revealed barely the same sensitizing effect as DNA-PK inhibition per se.     

The spectral networks paradigm in high throughput mass spectrometry

High-throughput proteomics is made possible by a combination of modern mass spectrometry instruments capable of generating many millions of tandem mass (MS(2)) spectra on a daily basis and the increasingly sophisticated associated software for their automated identification. Despite the growing accumulation of collections of identified spectra and the regular generation of MS(2) data from related peptides, the mainstream approach for peptide identification is still the nearly two decades old approach of matching one MS(2) spectrum at a time against a database of protein sequences. Moreover, database search tools overwhelmingly continue to require that users guess in advance a small set of 4-6 post-translational modifications that may be present in their data in order to avoid incurring substantial false positive and negative rates. The spectral networks paradigm for analysis of MS(2) spectra differs from the mainstream database search paradigm in three fundamental ways. First, spectral networks are based on matching spectra against other spectra instead of against protein sequences. Second, spectral networks find spectra from related peptides even before considering their possible identifications. Third, spectral networks determine consensus identifications from sets of spectra from related peptides instead of separately attempting to identify one spectrum at a time. Even though spectral networks algorithms are still in their infancy, they have already delivered the longest and most accurate de novo sequences to date, revealed a new route for the discovery of unexpected post-translational modifications and highly-modified peptides, enabled automated sequencing of cyclic non-ribosomal peptides with unknown amino acids and are now defining a novel approach for mapping the entire molecular output of biological systems that is suitable for analysis with tandem mass spectrometry. Here we review the current state of spectral networks algorithms and discuss possible future directions for automated interpretation of spectra from any class of molecules.     

Selective antibacterial activity of the cationic peptide PaDBS1R6 against Gram-negative bacteria

Infections caused by Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa foremost among them, constitute a major worldwide health problem. Bioinformatics methodologies are being used to rationally design new antimicrobial peptides, a potential alternative for treating these infections. One of the algorithms used to develop antimicrobial peptides is the Joker, which was used to design the peptide PaDBS1R6. This study evaluates the antibacterial activities of PaDBS1R6 in vitro and in vivo, characterizes the peptide interaction to target membranes, and investigates the PaDBS1R6 structure in contact with mimetic vesicles. Moreover, we demonstrate that PaDBS1R6 exhibits selective antimicrobial activity against Gram-negative bacteria. In the presence of negatively charged and zwitterionic lipids the structural arrangement of PaDBS1R6 transits from random coil to α-helix, as characterized by circular dichroism. The tertiary structure of PaDBS1R6 was determined by NMR in zwitterionic dodecylphosphocholine (DPC) micelles. In conclusion, PaDBS1R6 is a candidate for the treatment of nosocomial infections caused by Gram-negative bacteria, as template for producing other antimicrobial agents.     

How weekly monitoring variables influence players’ and teams’ match performance in elite futsal players

This study aimed to investigate how weekly training load constrains the performance of players and teams in official futsal competitions. Data from a professional male team were collected during two seasons (46 weeks). The applied monitoring system analysed the training load (as measured by session perceived exertion, sRPE), the total recovery status (TQR), the well-being score (WBs) and the variability of neuromuscular performance during each week (CMJ-cv). In addition, the performance was assessed for all the matches. A path analysis model was performed to test the associations across variables. Results from the path analysis model revealed that it explains 31% of the teams’ performance. In general, the results show that previous team performance has no significant effects on the training week. A significant negative relationship was found between CMJ-cv and match performance (β = -.34; CI95% -.359 to -.070), as well as a significant negative relationship between players’ match performance and the team’s match performance (β = -.55; CI95% -.292 to .740). Regarding indirect effects, only a negative association between CMJ-cv and team match performance via players’ match performance (β = -.19; CI95% -.342 to -.049) was identified. The small variation of the weekly CMJ (CMJ-cv) seems to be a key variable to monitor and explain both player and team performance. Based on this model, and only looking at the physical variables, it was possible to explain 31% of the team’s performance. Longitudinal and multi-team studies should be conducted to integrate other technical, tactical and psychological variables that allow the level of understanding of players’ and teams’ performance to be improved.     

Role of AIP56 disulphide bond and its reduction by cytosolic redox systems for efficient intoxication

Apoptosis‐inducing protein of 56 kDa (AIP56) is a major virulence factor of Photobacterium damselae subsp. piscicida, a gram‐negative pathogen that infects warm water fish species worldwide and causes serious economic losses in aquacultures. AIP56 is a single‐chain AB toxin composed by two domains connected by an unstructured linker peptide flanked by two cysteine residues that form a disulphide bond. The A domain comprises a zinc‐metalloprotease moiety that cleaves the NF‐kB p65, and the B domain is involved in binding and internalisation of the toxin into susceptible cells. Previous experiments suggested that disruption of AIP56 disulphide bond partially compromised toxicity, but conclusive evidences supporting the importance of that bond in intoxication were lacking. Here, we show that although the disulphide bond of AIP56 is dispensable for receptor recognition, endocytosis, and membrane interaction, it needs to be intact for efficient translocation of the toxin into the cytosol. We also show that the host cell thioredoxin reductase‐thioredoxin system is involved in AIP56 intoxication by reducing the disulphide bond of the toxin at the cytosol. The present study contributes to a better understanding of the molecular mechanisms operating during AIP56 intoxication and reveals common features shared with other AB toxins.