No Arabic abstract
The technological and economic benefits of engineered nanomaterials may be offset by their adverse effects on living organisms. One of the highly produced nanomaterials under such scrutiny is amorphous silica nanoparticles, which are known to have an appreciable, although reversible, inflammatory potential. This is due to their selective toxicity toward macrophages, and it is thus important to study the cellular responses of this cell type to silica nanoparticles to better understand the direct or indirect adverse effects of nanosilica. We have here studied the responses of the RAW264.7 murine macrophage cells and of the control MPC11 plasma cells to subtoxic concentrations of nanosilica, using a combination of pro-teomic and targeted approaches. This allowed us to document alterations in the cellular cytoskeleton, in the phagocytic capacity of the cells as well as their ability to respond to bacterial stimuli. More surprisingly, silica nanoparticles also induce a greater sensitivity of macrophages to DNA alkylating agents, such as styrene oxide, even at doses which do not induce any appreciable cell death.
the MIAPE Gel Electrophoresis (MIAPE-GE) guidelines specify the minimum information that should be provided when reporting the use of n-dimensional gel electrophoresis in a proteomics experiment. Developed through a joint effort between the gel-based analysis working group of the Human Proteome Organisations Proteomics Standards Initiative (HUPO-PSI; http://www.psidev.info/) and the wider proteomics community, they constitute one part of the overall Minimum Information about a Proteomics Experiment (MIAPE) documentation system published last August in Nature Biotechnology
The genetic structure of human populations is extraordinarily complex and of fundamental importance to studies of anthropology, evolution, and medicine. As increasingly many individuals are of mixed origin, there is an unmet need for tools that can infer multiple origins. Misclassification of such individuals can lead to incorrect and costly misinterpretations of genomic data, primarily in disease studies and drug trials. We present an advanced tool to infer ancestry that can identify the biogeographic origins of highly mixed individuals. reAdmix is an online tool available at http://chcb.saban-chla.usc.edu/reAdmix/.
We present two algorithms designed to learn a pattern of correspondence between two data sets in situations where it is desirable to match elements that exhibit an affine relationship. In the motivating case study, the challenge is to better understand micro-RNA (miRNA) regulation in the striatum of Huntingtons disease (HD) model mice. The two data sets contain miRNA and messenger-RNA (mRNA) data, respectively, each data point consisting in a multi-dimensional profile. The biological hypothesis is that if a miRNA induces the degradation of a target mRNA or blocks its translation into proteins, or both, then the profile of the former should be similar to minus the profile of the latter (a particular form of affine relationship). The algorithms unfold in two stages. During the first stage, an optimal transport plan P and an optimal affine transformation are learned, using the Sinkhorn-Knopp algorithm and a mini-batch gradient descent. During the second stage, P is exploited to derive either several co-clusters or several sets of matched elements. A simulation study illustrates how the algorithms work and perform. A brief summary of the real data application in the motivating case-study further illustrates the applicability and interest of the algorithms.
To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we analyzed novel high-quality genome sequences of three gray wolves, one from each of three putative centers of dog domestication, two ancient dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. We find dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow, which confounds previous inferences of dog origins. In dogs, the domestication bottleneck was severe involving a 17 to 49-fold reduction in population size, a much stronger bottleneck than estimated previously from less intensive sequencing efforts. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was far larger than represented by modern wolf populations. Conditional on mutation rate, we narrow the plausible range for the date of initial dog domestication to an interval from 11 to 16 thousand years ago. This period predates the rise of agriculture, implying that the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that surprisingly, none of the extant wolf lineages from putative domestication centers are more closely related to dogs, and the sampled wolves instead form a sister monophyletic clade. This result, in combination with our finding of dog-wolf admixture during the process of domestication, suggests a re-evaluation of past hypotheses of dog origin is necessary. Finally, we also detect signatures of selection, including evidence for selection on genes implicated in morphology, metabolism, and neural development. Uniquely, we find support for selective sweeps at regulatory sites suggesting gene regulatory changes played a critical role in dog domestication.
Identifying which taxa in our microbiota are associated with traits of interest is important for advancing science and health. However, the identification is challenging because the measured vector of taxa counts (by amplicon sequencing) is compositi