Ribosomal localization of translation initiation factor IF2

Bacterial translation initiation factor IF2 is a GTP-binding protein that catalyzes binding of initiator fMet-tRNA in the ribosomal P site. The topographical localization of IF2 on the ribosomal subunits, a prerequisite for understanding the mechanism of initiation complex formation, has remained elusive. Here, we present a model for the positioning of IF2 in the 70S initiation complex as determined by cleavage of rRNA by the chemical nucleases Cu(II):1,10-orthophenanthroline and Fe(II):EDTA tethered to cysteine residues introduced into IF2. Two specific amino acids in the GII domain of IF2 are in proximity to helices H3, H4, H17, and H18 of 16S rRNA. Furthermore, the junction of the C-1 and C-2 domains is in proximity to H89 and the thiostrepton region of 23S rRNA. The docking is further constrained by the requisite proximity of the C-2 domain with P-site-bound tRNA and by the conserved GI domain of the IF2 with the large subunit's factor-binding center. Comparison of our present findings with previous data further suggests that the IF2 orientation on the 30S subunit changes during the transition from the 30S to 70S initiation complex.     

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.     

Different sensitivity to apoptosis in cells of monocytic or lymphocytic origin chronically infected with human immunodeficiency virus type-1

Apoptotic death of CD4+ T lymphocytes is a major cause of the immunodeficiency caused by human immunodeficiency virus (HIV), but it is still unclear how this process precisely occurs. To characterize a potentially useful cellular model, we have analyzed the tendency of chronically HIV-infected CD4+ human cell lines of different origin to undergo apoptosis. We studied ACH-2 and U1 lines, derived from the CD4+ T-cell A301 and the promonocytic U937 cell lines, respectively, and induced apoptosis via several stimuli that trigger different pathways. Their capacity to regulate plasma membrane CD95 expression and to produce soluble CD95 was also analyzed. Using staurosporine, TNF-alpha plus cycloheximide, and gamma-radiations, we observed that ACH-2 were more sensitive to programmed cell death than A301, while U1 were less sensitive than U937. Both infected cell types had a lower sensitivity to CD95-induced apoptosis; the analysis of changes in mitochondrial membrane potential corroborated these observations. Plasma membrane CD95 was similarly regulated in all cell types, which, however, presented a different capacity to produce soluble CD95 molecules. Our in vitro results may offer a new perspective for developing further studies on the pathogenesis of HIV infection. A chronically infected cell line of lymphocytic origin is more susceptible to apoptosis than its parental cell type, while infected monocytic cells are less sensitive than their uninfected counterpart. Thus, it is possible to hypothesize that one of the reasons by which circulating monocytes survive and represent a viral reservoir is the capacity of HIV to decrease the sensitivity to apoptosis of this cell type. However, further studies on ex-vivo collected fresh cells, as well as on other cell lines, are urgently needed to confirm such hypothesis.     

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.