Getting closer to a pre-vertebrate genome: the non-LTR retrotransposons of Branchiostoma floridae

Non-LTR retrotransposons are common in vertebrate genomes and although present in invertebrates they appear at a much lower frequency. The cephalochordate amphioxus is the closest living relative to vertebrates and has been considered a good model for comparative analyses of genome expansions during vertebrate evolution. With the aim to assess the involvement of transposable elements in these events, we have analysed the non-LTR retrotransposons of Branchiostoma floridae. In silico searches have allowed to reconstruct non-LTR elements of six different clades (CR1, I, L1, L2, NeSL and RTE) and assess their structural features. According to the estimated copy number of these elements they account for less than 1% of the haploid genome, which reminds of the low abundance also encountered in the urochordate Ciona intestinalis. Amphioxus (B. floridae) and Ciona share a pre-vertebrate-like organization for the non-LTR retrotransposons (<150 copies, < 1% of the genome) versus the complexity associated to higher vertebrates (Homo sapiens >1.3.10(6) copies, > 20% of the genome).     

Rehabilitation Profiles of Older Adult Stroke Survivors Admitted to Intermediate Care Units: A Multi-Centre Study

BackgroundStroke is a major cause of disability in older adults, but the evidence around post-acute treatment is limited and heterogeneous. We aimed to identify profiles of older adult stroke survivors admitted to intermediate care geriatric rehabilitation units.MethodsWe performed a cohort study, enrolling stroke survivors aged 65 years or older, admitted to 9 intermediate care units in Catalonia-Spain. To identify potential profiles, we included age, caregiver presence, comorbidity, pre-stroke and post-stroke disability, cognitive impairment and stroke severity in a cluster analysis. We also proposed a practical decision tree for patient’s classification in clinical practice. We analyzed differences between profiles in functional improvement (Barthel index), relative functional gain (Montebello index), length of hospital stay (LOS), rehabilitation efficiency (functional improvement by LOS), and new institutionalization using multivariable regression models (for continuous and dichotomous outcomes).ResultsAmong 384 patients (79.1±7.9 years, 50.8% women), we identified 3 complexity profiles: a) Lower Complexity with Caregiver (LCC), b) Moderate Complexity without Caregiver (MCN), and c) Higher Complexity with Caregiver (HCC). The decision tree showed high agreement with cluster analysis (96.6%). Using either linear (continuous outcomes) or logistic regression, both LCC and MCN, compared to HCC, showed statistically significant higher chances of functional improvement (OR = 4.68, 95%CI = 2.54–8.63 and OR = 3.0, 95%CI = 1.52–5.87, respectively, for Barthel index improvement ≥20), relative functional gain (OR = 4.41, 95%CI = 1.81–10.75 and OR = 3.45, 95%CI = 1.31–9.04, respectively, for top Vs lower tertiles), and rehabilitation efficiency (OR = 7.88, 95%CI = 3.65–17.03 and OR = 3.87, 95%CI = 1.69–8.89, respectively, for top Vs lower tertiles). In relation to LOS, MCN cluster had lower chance of shorter LOS than LCC (OR = 0.41, 95%CI = 0.23–0.75) and HCC (OR = 0.37, 95%CI = 0.19–0.73), for LOS lower Vs higher tertiles.ConclusionOur data suggest that post-stroke rehabilitation profiles could be identified using routine assessment tools and showed differential recovery. If confirmed, these findings might help to develop tailored interventions to optimize recovery of older stroke patients.     

Controlling chaos in ecology: From deterministic to individual-based models

The possibility of chaos control in biological systems has been stimulated by recent advances in the study of heart and brain tissue dynamics. More recently, some authors have conjectured that such a method might be applied to population dynamics and even play a nontrivial evolutionary role in ecology. In this paper we explore this idea by means of both mathematical and individual-based simulation models. Because of the intrinsic noise linked to individual behavior, controlling a noisy system becomes more difficult but, as shown here, it is a feasible task allowed to be experimentally tested.     

Coinfection and superinfection in RNA virus populations: a selection-mutation model

In this paper, we present a general selection-mutation model of evolution on a one-dimensional continuous fitness space. The formulation of our model includes both the classical diffusion approach to mutation process as well as an alternative approach based on an integral operator with a mutation kernel. We show that both approaches produce fundamentally equivalent results. To illustrate the suitability of our model, we focus its analytical study into its application to recent experimental studies of in vitro viral evolution. More specifically, these experiments were designed to test previous theoretical predictions regarding the effects of multiple infection dynamics (i.e., coinfection and superinfection) on the virulence of evolving viral populations. The results of these experiments, however, did not match with previous theory. By contrast, the model we present here helps to understand the underlying viral dynamics on these experiments and makes new testable predictions about the role of parameters such the time between successive infections and the growth rates of resident and invading populations.     

Adaptive walks in a gene network model of morphogenesis: insights into the Cambrian explosion

The emergence of complex patterns of organization close to the Cambrian boundary is known to have happened over a (geologically) short period of time. It involved the rapid diversification of body plans and stands as one of the major transitions in evolution. How it took place is a controversial issue. Here we explore this problem by considering a simple model of pattern formation in multicellular organisms. By modeling gene network-based morphogenesis and its evolution through adaptive walks, we explore the question of how combinatorial explosions might have been actually involved in the Cambrian event. Here we show that a small amount of genetic complexity including both gene regulation and cell-cell signaling allows one to generate an extraordinary repertoire of stable spatial patterns of gene expression compatible with observed anteroposterior patterns in early development of metazoans. The consequences for the understanding of the tempo and mode of the Cambrian event are outlined.     

Polymorphisms of the apolipoprotein B and E genes and their relationship to plasma lipid variables in healthy Chinese men

In this study we have analysed the apolipoprotein (Apo) E polymorphism and polymorphisms of the ApoB gene, including the ApoB/Xba I and ApoB/4311 diallelic polymorphisms and a hypervariable region (HVR) situated in the 3 region of the gene (ApoB/3HVR), in a sample of healthy male subjects from Taiyuan (northern People's Republic of China). In comparison to Caucasian populations, in the Chinese sample, the Xba I2 allele (presence of cutting site; frequency 6.1%; and 95% confidence interval, 3.3–8.9) and the long HVR alleles (9.4%; 6.0–12.8) were rare, whereas the ApoB/4311 (Ser) allele (70.8%; 65.4–76.2) and the 34-repeat allele of the HVR (HVR34; 62.4%; 56.8–68.0) were frequent. In subjects having none, one, or two HVR34 alleles, the mean levels of plasma triglycerides were 2.32±1.44 (SD), 1.45+0.74, and 1.75±1.07 g/l, respectively (P < 0.007). Similar trends were observed for very low density lipoprotein (VLDL) cholesterol, LpE:B, and LpCIII:B. The frequencies of the ApoE alleles were similar to those reported in other populations of Asian origin; E2 (7.4%; 4.2–10.6), E3 (84.4%; 80.2–88.6), and E4 (8.2%; 5.0–11.4). Individuals carrying the E2 allele had a lower mean level of ApoB than E33 individuals: 0.87±0.16 and 1.00±0.22 g/l, respectively (P < 0.007). Individuals carrying the E4 allele had higher levels of ApoE than E33 individuals: 0.140±0.084 and 0.094±0.052 g/l, respectively (P < 0.004); similar trends were observed for VLDL cholesterol, triglycerides, LpE:B, and LpCIII:B. The ApoB/ HVR34 and ApoE/E4 polymorphisms accounted for 10% to 15% of the variability of the plasma levels of VLDL cholesterol, ApoE, triglycerides, LpE:B, and LpCIII:B. Several lipid variables appeared to be favourably affected by specific forms of ApoB and ApoE that are particularly frequent in this Chinese population.     

Thermodynamics of information transfer between subunits in oligomeric enzymes and kinetic cooperativity. 2. Thermodynamics of kinetic cooperativity

The principles of structural kinetics allow one to define the thermodynamic conditions that are sufficient to generate a certain type of kinetic behavior. If subunits are loosely coupled, that is if no quaternary constraint exists between them, the kinetic behavior of the polymeric enzyme is qualitatively defined by the behavior of an ideal dimer. The nature and the extent of the kinetic cooperativity are defined by the energy of interaction, delta G rho, between two subunits. This energy of interaction is that of an ideal dimer relative to that of the A2 and B2 states. This thermodynamic formulation of a given type of cooperativity holds whatever the degree of polymerization of the enzyme. Under these conditions of loose coupling between subunits, positive kinetic cooperativity cannot be associated with any sigmoidicity of the rate curve. The range of energy coupling where positive kinetic cooperativity must, of necessity, be observed becomes more and more narrow as the number of subunit interactions is increased. This range, however, is independent of the number of subunits. The same situation is not observed for negative cooperativity which appears to be independent of both the number of subunits and the number of subunit interactions. If the subunits are tightly coupled, that is if quaternary constraints exist between them, three thermodynamic parameters, delta G' rho, delta G lambda, delta G mu, are required to define the nature of kinetic cooperativity. delta G' rho is the free energy of an ideal strained dimer relative to that of strained A2 and B2 states. delta G lambda and delta G mu represent the difference of strain energies between conformations A and B and B and B relative to that existing between conformations A and A. One may determine in the parametric space (delta G' rho, delta G lambda, delta G mu) the boundaries between the sufficient conditions that generate a certain type of cooperativity and the lack of these conditions. The kinetic parameters of the rate equation are not all independent. A number of constraint conditions exist between them which depend upon the subunit design of the polymeric enzyme. The existence of these constraint conditions may be diagnostic of a certain type of subunit interactions.     

Microbial hydroxylation of natural drimenic lactones.

Incubation of confertifolin and isodrimenin with Mucor plumbeus, Aspergillus niger or Rhizopus arrhizus gave in good yields the corresponding 3 beta-hydroxy derivatives. From isodrimenin, the known natural 7 alpha-hydroxy derivative (futronolide) was also obtained and its structure was definitely established by X-ray crystallographic study of its acetate derivative.     

Protocell self-reproduction in a spatially extended metabolism-vesicle system

Cellular life requires the presence of a set of biochemical mechanisms in order to maintain a predictable process of growth and division. Several attempts have been made towards the building of minimal protocells from a top-down approach, i.e. by using available biomolecules. This type of synthetic approach has so far been only partially successful, and appropriate models of the synthetic protocell cycle might be needed to guide future experiments. In this paper, we present a simple biochemically and physically feasible model of cell replication involving a discrete semi-permeable vesicle with an internal minimal metabolism involving two reactive centers. It is shown that such a system can effectively undergo a whole cell replication cycle. The model can be used as a basic framework to model whole protocell dynamics including more complex sets of reactions. The possible implementation of our design in future synthetic protocells is outlined.