Highlights ► Substantial progress has been made in the development of CBP. ► Production of ethanol at high yield and titer using ‘native strategy’. ► Production of CBHI and CBHII in yeast at levels ...sufficient for industrial process. ► Economic benefits of CBP result from more-effective biomass solubilization.
Mosses are a highly diverse lineage of land plants, whose diversification, spanning at least 400 million years, remains phylogenetically ambiguous due to the lack of fossils, massive early ...extinctions, late radiations, limited morphological variation, and conflicting signal among previously used markers. Here, we present phylogenetic reconstructions based on complete organellar exomes and a comparable set of nuclear genes for this major lineage of land plants. Our analysis of 142 species representing 29 of the 30 moss orders reveals that relative average rates of non-synonymous substitutions in nuclear versus plastid genes are much higher in mosses than in seed plants, consistent with the emerging concept of evolutionary dynamism in mosses. Our results highlight the evolutionary significance of taxa with reduced morphologies, shed light on the relative tempo and mechanisms underlying major cladogenic events, and suggest hypotheses for the relationships and delineation of moss orders.
In 2007, a chromosomal rearrangement resulting in a gene fusion leading to expression of a constitutively active anaplastic lymphoma kinase (ALK) fusion protein was identified as an oncogenic driver ...in non-small-cell lung cancer (NSCLC). ALK rearrangements are detected in 3%-7% of patients with NSCLC and are particularly enriched in younger patients with adenocarcinoma and a never or light smoking history. Fortuitously, crizotinib, a small molecule tyrosine kinase inhibitor initially developed to target cMET, was able to be repurposed for ALK-rearranged (ALK+) NSCLC. Despite dramatic and durable initial responses to crizotinib; however, the vast majority of patients will develop resistance within a few years. Diverse molecular mechanisms underlie resistance to crizotinib. This review will describe the clinical activity of crizotinib, review identified mechanisms of crizotinib resistance, and end with a survey of emerging therapeutic strategies aimed at overcoming crizotinib resistance.
The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in ~3–5% of non–small cell lung cancer (NSCLC) tissues and the demonstration that the ...first‐in‐class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. Single‐arm studies demonstrating rapid and durable responses in the majority of ALK‐positive NSCLC patients treated with crizotinib have been followed by a randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK‐positive NSCLC patients. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK‐positive NSCLC are currently under evaluation in clinical trials, including second‐generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802802), and AP26113, and heat shock protein 90 inhibitors.
Clinical Pharmacology & Therapeutics (2013); 95 1, 15–23 advance online publication 13 November 2013. doi:10.1038/clpt.2013.200
We have examined the neurotoxicity of aluminum in humans and animals under various conditions, following different routes of administration, and provide an overview of the various associated disease ...states. The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. In adults, aluminum exposure can lead to apparently age-related neurological deficits resembling Alzheimer’s and has been linked to this disease and to the Guamanian variant, ALS–PDC. Similar outcomes have been found in animal models. In addition, injection of aluminum adjuvants in an attempt to model Gulf War syndrome and associated neurological deficits leads to an ALS phenotype in young male mice. In young children, a highly significant correlation exists between the number of pediatric aluminum-adjuvanted vaccines administered and the rate of autism spectrum disorders. Many of the features of aluminum-induced neurotoxicity may arise, in part, from autoimmune reactions, as part of the ASIA syndrome.
The "bryophytes" comprise three phyla of plants united by a similar haploid-dominant life cycle and unbranched sporophytes bearing one sporangium: the liverworts (Marchantiophyta), mosses ...(Bryophyta), and hornworts (Anthocerophyta). Combined, these groups include some 20000 species. As descendents of embryophytes that diverged before tracheophytes appeared, bryophytes offer unique windows into the early evolution of land plants. We review insights into the evolution of plant life cycles, in particular the elaboration of the sporophyte generation, the major lineages within bryophyte phyla, and reproductive processes that shape patterns of bryophyte evolution. Recent transcriptomic work suggests extensive overlap in gene expression in bryophyte sporophytes vs. gametophytes, but also novel patterns in the sporophyte, supporting Bower's antithetic hypothesis for origin of alternation of generations. Major lineages of liverworts, mosses, and hornworts have been resolved and general patterns of morphological evolution can now be inferred. The life cycles of bryophytes, arguably more similar to those of early embryophytes than are those in any other living plant group, provide unique insights into gametophyte mating patterns, sexual conflicts, and the efficacy and effects of spore dispersal during early land plant evolution.
Turbulence is ubiquitous in atmospheric clouds, which have enormous
turbulence Reynolds numbers owing to the large range of spatial scales present.
Indeed, the ratio of energy-containing and ...dissipative length scales is on the
order of 10
5
for a typical convective cloud, with a corresponding
large-eddy Reynolds number on the order of 10
6
to 10
7
. A
characteristic trait of high-Reynolds-number turbulence is strong intermittency
in energy dissipation, Lagrangian acceleration, and scalar gradients at small
scales. Microscale properties of clouds are determined to a great extent by
thermodynamic and fluid-mechanical interactions between droplets and the
surrounding air, all of which take place at small spatial scales. Furthermore,
these microscale properties of clouds affect the efficiency with which clouds
produce rain as well as the nature of their interaction with atmospheric
radiation and chemical species. It is expected, therefore, that fine-scale
turbulence is of direct importance to the evolution of, for example, the
droplet size distribution in a cloud. In general, there are two levels of
interaction that are considered in this review: (
a
) the growth of cloud
droplets by condensation and (
b
) the growth of large drops through the
collision and coalescence of cloud droplets. Recent research suggests that the
influence of fine-scale turbulence on the condensation process may be limited,
although several possible mechanisms have not been studied in detail in the
laboratory or the field. There is a growing consensus, however, that the
collision rate and collision efficiency of cloud droplets can be increased by
turbulence-particle interactions. Adding strength to this notion is the growing
experimental evidence for droplet clustering at centimeter scales and below,
most likely due to strong fluid accelerations in turbulent clouds. Both types
of interaction, condensation and collision-coalescence, remain open areas of
research with many possible implications for the physics of atmospheric
clouds.
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