Distribution of Recombination Hotspots in the Human Genome – A Comparison of Computer Simulations with Real Data

Recombination is the main cause of genetic diversity. Thus, errors in this process can lead to chromosomal abnormalities. Recombination events are confined to narrow chromosome regions called hotspots in which characteristic DNA motifs are found. Genomic analyses have shown that both recombination hotspots and DNA motifs are distributed unevenly along human chromosomes and are much more frequent in the subtelomeric regions of chromosomes than in their central parts. Clusters of motifs roughly follow the distribution of recombination hotspots whereas single motifs show a negative correlation with the hotspot distribution. To model the phenomena related to recombination, we carried out computer Monte Carlo simulations of genome evolution. Computer simulations generated uneven distribution of hotspots with their domination in the subtelomeric regions of chromosomes. They also revealed that purifying selection eliminating defective alleles is strong enough to cause such hotspot distribution. After sufficiently long time of simulations, the structure of chromosomes reached a dynamic equilibrium, in which number and global distribution of both hotspots and defective alleles remained statistically unchanged, while their precise positions were shifted. This resembles the dynamic structure of human and chimpanzee genomes, where hotspots change their exact locations but the global distributions of recombination events are very similar.     

FAS/FASL Expression Profile as a Prognostic Marker in Squamous Cell Carcinoma of the Oral Cavity

FAS/FASL altered expression may cause tumor protecting immunomodulation, with a direct impact on patient prognosis. FAS expression was studied in 60 squamous cell carcinomas of the oral cavity. FAS expression did not show a significant association with tumor histopathological characteristics, but was significantly associated with lymph node positivity. FAS expression was significantly associated with disease specific death and negative FAS expression was an independent risk factor, increasing risk 4 times when compared to positive expression. When FAS and FASL expression results were combined, we were able to define high, intermediate and low risk profiles. Disease-free and disease-specific survival were significantly correlated with FAS/FASL expression profiles. The high risk category was an independent marker for earlier disease relapse and disease-specific death, with approximately 4- and 6-fold increased risk, respectively, when compared to the low risk profile. Risk profiles based on FAS/FASL expression showed that high risk was significantly associated with increased disease relapse and death, as well as shorter disease-free or disease-specific survival. This categorization, added to patient clinical data, may facilitate the choice of therapy, minimizing treatment failure and increasing disease control.     

Industrial Scale Isolation,Structural and Spectroscopic Characterization of Epiisopiloturine from Pilocarpus microphyllus Stapf Leaves: A Promising Alkaloid against Schistosomiasis

This paper presents an industrial scale process for extraction, purification, and isolation of epiisopiloturine (EPI) (2(3H)-Furanone,dihydro-3-(hydroxyphenylmethyl)-4-[(1-methyl-1H-imidazol-4-yl)methyl]-, [3S-[3a(R*),4b]]), which is an alkaloid from jaborandi leaves (Pilocarpus microphyllus Stapf). Additionally for the first time a set of structural and spectroscopic techniques were used to characterize this alkaloid. EPI has shown schistomicidal activity against adults and young forms, as well as the reduction of the egg laying adult worms and low toxicity to mammalian cells (in vitro). At first, the extraction of EPI was done with toluene and methylene chloride to obtain a solution that was alkalinized with ammonium carbonate. The remaining solution was treated in sequence by acidification, filtration and alkalinization. These industrial procedures are necessary in order to remove impurities and subsequent application of the high performance liquid chromatography (HPLC). The HPLC was employed also to remove other alkaloids, to obtain EPI purity higher than 98%. The viability of the method was confirmed through HPLC and electrospray mass spectrometry, that yielded a pseudo molecular ion of m/z equal to 287.1 Da. EPI structure was characterized by single crystal X-ray diffraction (XRD), ¹H and ¹³C nuclear magnetic resonance (NMR) in deuterated methanol/chloroform solution, vibrational spectroscopy and mass coupled thermal analyses. EPI molecule presents a parallel alignment of the benzene and the methyl imidazol ring separated by an interplanar spacing of 3.758 Å indicating a π-π bond interaction. The imidazole alkaloid melts at 225°C and decomposes above 230°C under air. EPI structure was used in theoretical Density Functional Theory calculations, considering the single crystal XRD data in order to simulate the NMR, infrared and Raman spectra of the molecule, and performs the signals attribution.     

Leucine and HMB Differentially Modulate Proteasome System in Skeletal Muscle under Different Sarcopenic Conditions

In the present study we have compared the effects of leucine supplementation and its metabolite β-hydroxy-β-methyl butyrate (HMB) on the ubiquitin-proteasome system and the PI3K/Akt pathway during two distinct atrophic conditions, hindlimb immobilization and dexamethasone treatment. Leucine supplementation was able to minimize the reduction in rat soleus mass driven by immobilization. On the other hand, leucine supplementation was unable to provide protection against soleus mass loss in dexamethasone treated rats. Interestingly, HMB supplementation was unable to provide protection against mass loss in all treatments. While solely fiber type I cross sectional area (CSA) was protected in immobilized soleus of leucine-supplemented rats, none of the fiber types were protected by leucine supplementation in rats under dexamethasone treatment. In addition and in line with muscle mass results, HMB treatment did not attenuate CSA decrease in all fiber types against either immobilization or dexamethasone treatment. While leucine supplementation was able to minimize increased expression of both Mafbx/Atrogin and MuRF1 in immobilized rats, leucine was only able to minimize Mafbx/Atrogin in dexamethasone treated rats. In contrast, HMB was unable to restrain the increase in those atrogenes in immobilized rats, but in dexamethasone treated rats, HMB minimized increased expression of Mafbx/Atrogin. The amount of ubiquitinated proteins, as expected, was increased in immobilized and dexamethasone treated rats and only leucine was able to block this increase in immobilized rats but not in dexamethasone treated rats. Leucine supplementation maintained soleus tetanic peak force in immobilized rats at normal level. On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB.     

The interplay between local and landscape scales on the density of pond-dwelling anurans in subtropical grasslands

We investigated the role of local and landscape environmental variables on anurans density classified as habitat specialists and generalists in grassland landscapes, known as South Brazilian grasslands (SBG). In this region, we surveyed 187 ponds distributed over 40 landscape sampling units. For each pond, 31 local environmental variables were measured. Each landscape sampling unit was embedded within a larger regional sampling unit with different landscape properties. For each landscape and regional sampling units, 16 landscape metrics were extracted from a land cover and use map. We recorded 35 species, eleven of which are specialists in the SBG. The specialists were affected by 11 local and 2 landscape environmental variables, while generalists were affected by 14 local and one landscape environmental variable. Thus, specialists and generalists presented different relationships with local and landscape variables, but in general local variables had a greater influence on the density of anurans than the landscape variables. However, the landscape indirectly influenced local variables because higher quality ponds were in landscapes with higher percentages of natural habitat. In conclusion, reproductive sites with higher local quality and located within landscapes with higher percentages of natural grasslands are essential to conserve anurans in this habitat. Effective conservation of such sites would benefit from further studies that assess effects of land use and biotic integrity of ponds, which can help to determine (a) the relative effects of local habitat quality of ponds and (b) the effectiveness of protecting ponds and their local surroundings for anuran conservation in SBG. Abstract in Portuguese is available with online material.     

Independent evolution of song diversity and song motor performance in canaries,goldfinches and allies indicates clade-specific trade-offs in birdsong

The diversity and the motor performance of birdsongs can both be sexually selected. In wood warblers, most species with high motor performance sing a greater proportion of trills, presumably to advertise performance, and thus have lower syllable diversity. We tested if this trade-off between motor performance and syllable diversity extends to canaries, goldfinches and allies, a clade with much longer and more varied songs. We assembled a molecular phylogeny and inferred song motor performance based on the speed of frequency modulation either in trills or in within-song intervals. The two metrics of performance were positively, but only mildly, related across species. While performance evaluated in intervals had high phylogenetic signal, performance evaluated in trills changed independently of phylogeny and was constrained by body size. Species in densely vegetated habitats sang fewer trills, but did not differ in motor performance. Contrary to wood warblers, song motor performance did not predict the proportion of trilled syllables nor within-song syllable diversity, perhaps because large differences in the song duration of canaries, goldfinches and allies prevent trills from severely compromising syllable diversity. Opposed results in wood warblers and in these finches indicate the existence of clade-specific trade-offs in the evolution of birdsong.     

Species delimitation based on integrative approach suggests reallocation of genus in Hypostomini catfish (Siluriformes,Loricariidae)

Hydrobiologia - Integrative approaches are particularly useful to resolve taxonomic uncertainties in species-rich groups that have undergone explosive radiation, such as Hypostomini (suckermouth...     

Long-term temporal variation in the organization of an ant–plant network

Background and Aims

Functional groups of species interact and coevolve in space and time, forming complex networks of interacting species. A long-term study of temporal variation of an ant–plant network is presented with the aims of: (1) depicting its structural changes over a 20-year period; (2) detailing temporal variation in network topology, as revealed by nestedness and modularity analysis and other parameters (i.e. connectance, niche overlap); and (3) identifying long-term turnover in taxonomic structure (i.e. switches in ant resource use or plant visitor assemblages according to taxa).

Methods

Fieldwork was carried out at La Mancha, Mexico, and ant–plant interactions were observed between 1989 and 1991, between 1998 and 2000, and between May 2010 and 2011. Occurrences of ants on extrafloral nectaries (EFNs) were recorded. The resulting ant–plant networks were constructed from qualitative presence–absence data determined by a species–species matrix defined by the frequency of occurrence of each pairwise ant–plant interaction.

Key Results

Network variation across time was stable and a persistent nested structure may have contributed to the maintenance of resilient and species-rich communities. Modularity was lower than expected, especially in the most recent networks, indicating that the community exhibited high overlap among interacting species (e.g. few species were hubs in the more recent network, being partly responsible for the nested pattern). Structurally, the connections created among modules by super-generalists gave cohesion to subsets of species that otherwise would remain unconnected. This may have allowed an increasing cascade-effect of evolutionary events among modules. Mutualistic ant–plant interactions were structured 20 years ago mainly by the subdominant nectarivorous ant species Camponotus planatus and Crematogaster brevispinosa, which monopolized the best extrafloral nectar resources and out-competed other species with broader feeding habits. Through time, these ants, which are still present, lost their position as network hubs and diminished in their importance in structuring the network; simultaneously, plants gained in importance.

Conclusions

The long-term network analysis reveals a decrease in attended plant species richness, a notable increase in plant species participation from 1990 to 2010 (sustained by less plant taxonomic similarity in the older 1990 network), an increase in the number of ant species and a diminishing dominance of super-generalist ants. The structure of the community has remained highly nested and connected with low modularity, suggesting overall a more participative, homogeneous, cohesive interaction network. Although previous studies have suggested that interactions between ants and EFN-bearing plants are susceptible to seasonality, abiotic factors and perturbation, this cohesive structure appears to be the key for biodiversity and community maintenance.