Inferring protein interactions from phylogenetic distance matrices

Finding the interacting pairs of proteins between two different protein families whose members are known to interact is an important problem in molecular biology. We developed and tested an algorithm that finds optimal matches between two families of proteins by comparing their distance matrices. A distance matrix provides a measure of the sequence similarity of proteins within a family. Since the protein sets of interest may have dozens of proteins each, the use of an efficient approximate solution is necessary. Therefore the approach we have developed consists of a Metropolis Monte Carlo optimization algorithm which explores the search space of possible matches between two distance matrices. We demonstrate that by using this algorithm we are able to accurately match chemokines and chemokine-receptors as well as the tgfbeta family of ligands and their receptors.     

Peak-to-peak dynamics in food chain models

We show in this paper that the chaotic regimes of many food chain models often enjoy a very peculiar property, known as peak-to-peak dynamics. This means that the maximum (peak) density of the populations of any trophic level can be easily forecasted provided the last two peaks of the same population are known. Moreover, extensive simulation shows that only the last peak is needed if the forecast concerns the population at the top of the food chain and that peaks variability often increases from bottom to top. All these findings bring naturally to the conclusion that top populations should be sampled in order to have higher chances to detect peak-to-peak dynamics. The analysis is carried out by studying ditrophic food chain models with seasonally varying parameters, tritrophic food chain models with constant parameters, and more complex food chain and food web models.     

Metal chelates of 2-hydroxy-4-methylthiobutanoic acid in animal feeding: preliminary investigations on stability and bioavailability

The alpha-hydroxyacid 2-hydroxy-4-methylthiobutanoic acid (the so-called methionine hydroxy-analogue, MHA), largely used in animal nutrition as a source of methionine, forms stable metal chelates with divalent metals of formula [[CH(3)SCH(2)CH(2)CH(OH)COO](2)M].ZnH(2)O. Protonation and zinc(II) complex formation constants have been determined by pH-metry at 25 degrees C; the ternary system Zn(2+)/MHA/glycine was also studied by pH-metry and the formation constant of the species [ZnLA] was determined [log beta=6.57(11)]. Experiments in vitro with human intestinal CACO-2 cells indicated that the MHA/Fe chelate was taken up by the cells without any apparent toxic effect.     

Protease inhibitors: synthesis of bacterial collagenase and matrix metalloproteinase inhibitors incorporating succinyl hydroxamate and iminodiacetic acid hydroxamate moieties

A series of succinyl hydroxamates/bishydroxamates as well as a new structural type of matrix metalloproteinase (MMP)/bacterial protease (BP) inhibitors, incorporating iminodiacetic (IDA) hydroxamate/bishydroxamate moieties, has been synthesized and tested for interaction with four vertebrate proteases, MMP-1, MMP-2, MMP-8 and MMP-9, and a BP, the collagenase isolated from Clostridium histolyticum (ChC). The new derivatives generally showed inhibition constants in the range of 8-62 nM against the five proteases mentioned above.     

Estimating the cumulative incidence of COVID-19 in the United States using influenza surveillance,virologic testing,and mortality data: Four complementary approaches

Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the prevalence of COVID-19 across the United States (US). Equipment shortages and varying testing capabilities have however hindered the usefulness of the official reported positive COVID-19 case counts. We introduce four complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 in each state in the US as well as Puerto Rico and the District of Columbia, using a combination of excess influenza-like illness reports, COVID-19 test statistics, COVID-19 mortality reports, and a spatially structured epidemic model. Instead of relying on the estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our four approaches emerges the consistent conclusion that on April 4, 2020, the estimated case count was 5 to 50 times higher than the official positive test counts across the different states. Nationally, our estimates of COVID-19 symptomatic cases as of April 4 have a likely range of 2.3 to 4.8 million, with possibly as many as 7.6 million cases, up to 25 times greater than the cumulative confirmed cases of about 311,000. Extending our methods to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 4.9 to 10.1 million, as opposed to 1.5 million positive test counts. The proposed combination of approaches may prove useful in assessing the burden of COVID-19 during resurgences in the US and other countries with comparable surveillance systems.     

Is Preening Behaviour Sexually Selected? An Experimental Approach

Elaborate or colourful feathers are important traits in female mate choice in birds but little attention has been given to potential costs of maintaining these traits in good condition with preening behaviour. Recent studies indicate that the time and energy required to maintain ornamental plumage in good condition reinforces the honesty of plumage trait. It has been proposed that some behaviours, whose primary function is not to transfer information, can also evolve as signalling components. Here we investigate whether the preening behaviour intensity has a signalling component: we hypothesized that if only high quality males can invest a lot of time in preening, this behaviour may be used by females as a quality signal (attractive preening hypothesis). We tested this hypothesis by using female budgerigars in mate‐choice tests in captivity. We tried to experimentally manipulate the preening behaviour of two groups of budgerigar males (treatment and control group). The proportion of time in which treated males preened in front of females was statistically higher than for control males, however, females spent similar amounts of time with treated males and control males. Moreover, males did not show significant quantitative changes in preening (for both groups) when females were present, suggesting that male budgerigars did not use this behaviour to convey information. These results are inconsistent with the ‘attractive preening’ hypothesis which predicts that preening behaviour itself provides information on condition and is used in female choice.     

Dual Utility of a Melanin‐Based Ornament in Bearded Tits

A general mechanism to account for the maintenance of sexually selected traits is the armament–ornament model, which predicts that females exploit signals used in male–male aggressive contests. Melanin‐based ornaments are good candidates to be dual utility traits because they are usually involved in male–male competition and function as signals of male dominance or fighting ability. Despite this, very few studies have investigated the dual utility of melanin‐based plumage traits and results remain generally ambiguous. In this study, we investigated the dual function of a melanin‐based trait (the black beard) in the male bearded tit, Panurus biarmicus. In a controlled aviary experiment, beard length was the best predictor of dominance in male–male competition. In a choice experiment, females showed a proximity preference for males whose beard length was experimentally elongated. Our results indicate that beard length plays an important role in both male–male competition and female choice in bearded tits, as proposed by the dual utility model.     

Single step determination of PCB 126 and 153 in rat tissues by using solid phase microextraction/gas chromatography–mass spectrometry: Comparison with solid phase extraction and liquid/liquid extraction

A simple and reliable solid phase microextraction/gas chromatography–mass spectrometry (SPME/GC–MS) method was developed for the single-step determination of PCBs 126 and 153 in rat brain and serum, using liquid/liquid and solid phase extraction (SPE) as reference techniques. The multi-factor categorical experimental design used to study simultaneously the main parameters and their interactions affecting the efficiency of the method, showed that the use of an 85 μm PA exposed at 100 °C for 40 min was the optimum sampling condition for both PCBs. SPME was then validated by studying its linear dynamic (over two orders of magnitude), limits of detection (brain: 2 ng/g, serum: 0.2 ng/g) and analytical precision that was within 9% for SPME in both brain and serum. Finally, the method was used to determine the brain and blood target dose in mothers and pups after oral exposure of the mothers.     

Interaction between Calpain-1 and HSP90: New Insights into the Regulation of Localization and Activity of the Protease

Here we demonstrate that heat shock protein 90 (HSP90) interacts with calpain-1, but not with calpain-2, and forms a discrete complex in which the protease maintains its catalytic activity, although with a lower affinity for Ca²⁺. Equilibrium gel distribution experiments show that this complex is composed by an equal number of molecules of each protein partner. Moreover, in resting cells, cytosolic calpain-1 is completely associated with HSP90. Since calpain-1, in association with HSP90, retains its proteolytic activity, and the chaperone is displaced by calpastatin also in the absence of Ca²⁺, the catalytic cleft of the protease is not involved in this association. Thus, calpain-1 can form two distinct complexes depending on the availability of calpastatin in the cytosol. The occurrence of a complex between HSP90 and calpain-1, in which the protease is still activable, can prevent the complete inhibition of the protease even in the presence of high calpastatin levels. We also demonstrate that in basal cell conditions HSP90 and calpain-1, but not calpain-2, are inserted in the multi-protein N-Methyl-D-Aspartate receptor (NMDAR) complex. The amount of calpain-1 at the NMDAR cluster is not modified in conditions of increased [Ca²⁺]_i, and this resident protease is involved in the processing of NMDAR components. Finally, the amount of calpain-1 associated with NMDAR cluster is independent from Ca²⁺-mediated translocation. Our findings show that HSP90 plays an important role in maintaining a given and proper amount of calpain-1 at the functional sites.     

Monosodium Urate Crystals Promote Innate Anti-Mycobacterial Immunity and Improve BCG Efficacy as a Vaccine against Tuberculosis

A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination.