Segmental Duplications: a Possible Mechanism of Hominid Uplift Through MicroRNA Diversification

MicroRNAs (miRNA) are ~21 nucleotide-long gene silencers. Segmental duplications (SD) are among the driving forces in acquiring new genes. Both miRNA and SD are believed to have played a significant role in evolution, particularly in the divergence of humans (Homo sapiens) from the chimpanzee (Pan troglodytes). This study determines the distribution of miRNAs in humans and in chimpanzees, and presents a hypothesis on its significance in the occurrence of segmental duplications. MiRNA sequences from miRBASE were subjected to BLAT and BLAST to determine if miRNAs are located in SD regions or not. Homology between miRNAs was determined with ClustalW. BLAST was then used to determine whether the non-homologous human miRNA are homologous to any other part of the chimpanzee genome. We found that all 695 human miRNAs are found exclusively in SD regions, and that 67 are de novo miRNAs. Thirteen are homologues of chimpanzee miRNA, and 11 were possibly derived from non-miRNA regions in chimp. Of these, 6 were located in SD regions of the chimpanzee genome. Results indicate that miRNA evolution occurs within regions of segmental duplication and suggest that the presence of miRNA duplicates allows more exposure to mutations that could necessitate diversification, and possibly evolution, through sub- and neofunctionalization

A novel method to accurately locate and count large numbers of steps by photobleaching

Photobleaching event counting is a single-molecule fluorescence technique that is increasingly being used to determine the stoichiometry of protein and RNA complexes composed of many subunits in vivo as well as in vitro. By tagging protein or RNA subunits with fluorophores, activating them, and subsequently observing as the fluorophores photobleach, one obtains information on the number of subunits in a complex. The noise properties in a photobleaching time trace depend on the number of active fluorescent subunits. Thus, as fluorophores stochastically photobleach, noise properties of the time trace change stochastically, and these varying noise properties have created a challenge in identifying photobleaching steps in a time trace. Although photobleaching steps are often detected by eye, this method only works for high individual fluorophore emission signal-to-noise ratios and small numbers of fluorophores. With filtering methods or currently available algorithms, it is possible to reliably identify photobleaching steps for up to 20-30 fluorophores and signal-to-noise ratios down to ∼1. Here we present a new Bayesian method of counting steps in photobleaching time traces that takes into account stochastic noise variation in addition to complications such as overlapping photobleaching events that may arise from fluorophore interactions, as well as on-off blinking. Our method is capable of detecting ≥50 photobleaching steps even for signal-to-noise ratios as low as 0.1, can find up to ≥500 steps for more favorable noise profiles, and is computationally inexpensive

Potential Anti-cancer and Anti-bacterial Activities of Philippine Echinoderm Extracts

In high-throughput search for bioactive compounds under resource-limited settings from Philippine echinoderms, the aqueous, methanol, chloroform and hexane extracts of seven Philippine echinoderms namely Holothuria nobilis (sea cucumber), Bohadscia marmorata (sea cucumber), Stichopus chloronatus (sea cucumber), Holothuria axiologa (sea cucumber), Linckia laevigata (starfish), Oreaster nodusus (starfish) and Ophiocoma ochoenleinii (brittle star) were screened for antitumor and antibacterial activity. Antitumor activity was determined using brine shrimp lethality assay while antibacterial assay was performed using turbidimetric method. Both assays utilized 96-well microtiter plates to facilitate speed and ease in screening. The chloroform extract of H. nobilis gave a positive result on antitumor activity while almost all sample extracts showed antibacterial activity against E. coli

Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone

Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD) is a dominantly inherited degenerative disorder caused by mutations in the valosin-containing protein (VCP) gene. VCP (p97 in mouse, TER94 in Drosophila melanogaster and CDC48 in Saccharomyces cerevisiae) is a highly conserved AAA+-ATPase that regulates a wide array of cellular processes. The mechanism of IBMPFD pathogenesis is unknown. Towards elucidating the pathogenic mechanism we have developed and characterized transgenic mice with ubiquitous expression of wild-type and disease-causing versions of human VCP/p97. Here, we report that mice expressing VCP/p97 harboring the mutations R155H or A232E develop pathology that is limited to muscle, brain and bone, recapitulating the spectrum of disease in humans with IBMPFD. The mice exhibit progressive muscle weakness and pathological examination of muscle shows classic characteristics of inclusion body myopathy including rimmed vacuoles and TDP-43 pathology. The mice exhibit abnormalities in behavioral testing and pathological examination of the brain shows widespread TDP-43 pathology. Furthermore, radiological examination of the skeleton reveals that mutant mice develop severe osteopenia accompanied by focal lytic and sclerotic lesions in vertebrae and femur. In vitro studies indicate that mutant VCP causes inappropriate activation of the NF-κB signaling cascade, which could contribute to the mechanism of pathogenesis in multiple tissues including muscle, bone and brai

Direct simulation of ion beam induced stressing and amorphization of silicon

Using molecular dynamics (MD) simulation, we investigate the mechanical response of silicon to high dose ion-irradiation. We employ a realistic and efficient model to directly simulate ion beam induced amorphization. Structural properties of the amorphized sample are compared with experimental data and results of other simulation studies. We find the behavior of the irradiated material is related to the rate at which it can relax. Depending upon the ability to deform, we observe either the generation of a high compressive stress and subsequent expansion of the material, or generation of tensile stress and densification. We note that statistical material properties, such as radial distribution functions are not sufficient to differentiate between different densities of amorphous samples. For any reasonable deformation rate, we observe an expansion of the target upon amorphization in agreement with experimental observations. This is in contrast to simulations of quenching which usually result in denser structures relative to crystalline Si. We conclude that although there is substantial agreement between experimental measurements and most simulation results, the amorphous structures being investigated may have fundamental differences; the difference in density can be attributed to local defects within the amorphous network. Finally we show that annealing simulations of our amorphized samples can lead to a reduction of high energy local defects without a large scale rearrangement of the amorphous network. This supports the proposal that defects in amorphous silicon are analogous to those in crystalline silicon.Comment: 13 pages, 12 figure

HOX Gene Promoter Prediction and Inter-genomic Comparison: an Evo-Devo Study

Homeobox genes direct the anterior-posterior axis of the body plan in eukaryotic organisms. Promoter regions upstream of the Hox genes jumpstart the transcription process. CpG islands found within the promoter regions can cause silencing of these promoters. The locations of the promoter regions and the CpG islands of Homeo sapiens sapiens (human), Pan troglodytes (chimpanzee), Mus musculus (mouse), and Rattus norvegicus (brown rat) are compared and related to the possible influence on the specification of the mammalian body plan. The sequence of each gene in Hox clusters A-D of the mammals considered were retrieved from Ensembl and locations of promoter regions and CpG islands predicted using Exon Finder. The predicted promoter sequences were confirmed via BLAST and verified against the Eukaryotic Promoter Database. The significance of the locations was determined using the Kruskal-Wallis test. Among the four clusters, only promoter locations in cluster B showed significant difference. HOX B genes have been linked with the control of genes that direct the development of axial morphology, particularly of the vertebral column bones. The magnitude of variation among the body plans of closely-related species can thus be partially attributed to the promoter kind, location and number, and gene inactivation via CpG methylation

Priority sites for wildfowl conservation in Mexico

A set of priority sites for wildfowl conservation in Mexico was determined using contemporary count data (1991–2000) from the U.S. Fish & Wildlife Service mid-winter surveys. We used a complementarity approach implemented through linear integer programming that addresses particular conservation concerns for every species included in the analysis and large fluctuations in numbers through time. A set of 31 priority sites was identified, which held more than 69% of the mid-winter count total in Mexico during all surveyed years. Six sites were in the northern highlands, 12 in the central highlands, six on the Gulf of Mexico coast and seven on the upper Pacific coast. Twenty-two sites from the priority set have previously been identified as qualifying for designation as wetlands of international importance under the Ramsar Convention and 20 sites are classified as Important Areas for Bird Conservation in Mexico. The information presented here provides an accountable, spatially-explicit, numerical basis for ongoing conservation planning efforts in Mexico, which can be used to improve existing wildfowl conservation networks in the country and can also be useful for conservation planning exercises elsewhere

New Constraints on Terrestrial and Oceanic Sources of Atmospheric Methanol

We use a global 3-D chemical transport model (GEOS-Chem) to interpret new aircraft, surface, and oceanic observations of methanol in terms of the constraints that they place on the atmospheric methanol budget. Recent measurements of methanol concentrations in the ocean mixed layer (OML) imply that in situ biological production must be the main methanol source in the OML, dominating over uptake from the atmosphere. It follows that oceanic emission and uptake must be viewed as independent terms in the atmospheric methanol budget. We deduce that the marine biosphere is a large primary source (85 Tg a−1) of methanol to the atmosphere and is also a large sink (101 Tg a−1), comparable in magnitude to atmospheric oxidation by OH (88 Tg a−1). The resulting atmospheric lifetime of methanol in the model is 4.7 days. Aircraft measurements in the North American boundary layer imply that terrestrial plants are a much weaker source than presently thought, likely reflecting an overestimate of broadleaf tree emissions, and this is also generally consistent with surface measurements. We deduce a terrestrial plant source of 80 Tg a−1, comparable in magnitude to the ocean source. The aircraft measurements show a strong correlation with CO (R2=0.51−0.61) over North America during summer. We reproduce this correlation and slope in the model with the reduced plant source, which also confirms that the anthropogenic source of methanol must be small. Our reduced plant source also provides a better simulation of methanol observations over tropical South America.Earth and Planetary SciencesEngineering and Applied Science