Quantitative Analysis of Pedogenic Thresholds and Domains in Volcanic Soils

Ecosystems - Pedogenic thresholds describe where soil properties or processes change in an abrupt/nonlinear fashion in response to small changes in environmental forcing. Contrastingly, soil...     

Selection for genetics‐based architecture traits in a native cottonwood negatively affects invasive tamarisk in a restoration field trial

Climate change and competition from invasive species remain two important challenges in restoration. We examined the hypothesis that non‐native tamarisk (Tamarix spp.) reestablishment after aboveground removal is affected by genetics‐based architecture of native Fremont cottonwood (Populus fremontii) used in restoration. As cottonwood architecture (height, canopy width, number of stems, and trunk diameter) is, in part, determined by genetics, we predicted that trees from different provenances would exhibit different architecture, and mean annual maximum temperature transfer distance from the provenances would interact with the architecture to affect tamarisk. In a common garden in Chevelon, AZ, U.S.A. (elevation 1,496 m), with cottonwoods from provenances spanning its elevation distribution, we measured the performance of both cottonwoods and tamarisk. Several key findings emerged. On average, cottonwoods from higher elevations were (1) two times taller and wider, covered approximately 3.5 times more basal area, and were less shrubby in appearance, by exhibiting four times fewer number of stems than cottonwoods from lower elevations; (2) had 50% fewer tamarisk growing underneath, which were two times shorter and covered 6.5 times less basal area than tamarisk growing underneath cottonwoods of smaller stature; and (3) the number of cottonwood stems did not affect tamarisk growth, possibly because the negative relationship between cottonwood stems and basal area. In combination, these findings argue that cottonwood architecture is affected by local conditions that interact with genetics‐based architecture. These interactions can negatively affect the growth of reinvading tamarisk and enhance restoration success. Our study emphasizes the importance of incorporating genetic and environmental interactions of plants used in restoration.     

Current perspectives on biosimilars

In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10–20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.

     

Thermodynamics of neutral protein evolution

Naturally evolving proteins gradually accumulate mutations while continuing to fold to stable structures. This process of neutral evolution is an important mode of genetic change and forms the basis for the molecular clock. We present a mathematical theory that predicts the number of accumulated mutations, the index of dispersion, and the distribution of stabilities in an evolving protein population from knowledge of the stability effects (delta deltaG values) for single mutations. Our theory quantitatively describes how neutral evolution leads to marginally stable proteins and provides formulas for calculating how fluctuations in stability can overdisperse the molecular clock. It also shows that the structural influences on the rate of sequence evolution observed in earlier simulations can be calculated using just the single-mutation delta deltaG values. We consider both the case when the product of the population size and mutation rate is small and the case when this product is large, and show that in the latter case the proteins evolve excess mutational robustness that is manifested by extra stability and an increase in the rate of sequence evolution. All our theoretical predictions are confirmed by simulations with lattice proteins. Our work provides a mathematical foundation for understanding how protein biophysics shapes the process of evolution.     

Angiotensin type 1 receptor antagonist losartan, reduces MPTP-induced degeneration of dopaminergic neurons in substantia nigra

Background

Recent attention has focused on understanding the role of the brain-renin-angiotensin-system (RAS) in stroke and neurodegenerative diseases. Direct evidence of a role for the brain-RAS in Parkinson's disease (PD) comes from studies demonstrating the neuroprotective effect of RAS inhibitors in several neurotoxin based PD models. In this study, we show that an antagonist of the angiotensin II (Ang II) type 1 (AT₁) receptor, losartan, protects dopaminergic (DA) neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity both in primary ventral mesencephalic (VM) cultures as well as in the substantia nigra pars compacta (SNpc) of C57BL/6 mice (Fig. 1).

Results

In the presence of exogenous Ang II, losartan reduced MPP⁺ (5 μM) induced DA neuronal loss by 72% in vitro. Mice challenged with MPTP showed a 62% reduction in the number of DA neurons in the SNpc and a 71% decrease in tyrosine hydroxylase (TH) immunostaining of the striatum, whereas daily treatment with losartan lessened MPTP-induced loss of DA neurons to 25% and reduced the decrease in striatal TH⁺ immunostaining to 34% of control.

Conclusion

Our study demonstrates that the brain-RAS plays an important neuroprotective role in the MPTP model of PD and points to AT₁ receptor as a potential novel target for neuroprotection.     

Good enhancer hunting

By combining activity-based proteomics and metabolomics, researchers have developed a new systems biology strategy for characterizing enzymes in the context of metabolic networks.     

Semi-supervised learning for peptide identification from shotgun proteomics datasets

Shotgun proteomics uses liquid chromatography-tandem mass spectrometry to identify proteins in complex biological samples. We describe an algorithm, called Percolator, for improving the rate of confident peptide identifications from a collection of tandem mass spectra. Percolator uses semi-supervised machine learning to discriminate between correct and decoy spectrum identifications, correctly assigning peptides to 17% more spectra from a tryptic Saccharomyces cerevisiae dataset, and up to 77% more spectra from non-tryptic digests, relative to a fully supervised approach.     

Tinkering with the fly genome

A new strategy provides a leap forward in making transgenic flies.     

Telomere protection by mammalian Pot1 requires interaction with Tpp1

The shelterin complex at mammalian telomeres contains the single-stranded DNA-binding protein Pot1, which regulates telomere length and protects chromosome ends. Pot1 binds Tpp1, the shelterin component that connects Pot1 to the duplex telomeric DNA-binding proteins Trf1 and Trf2. Control of telomere length requires that Pot1 binds Tpp1 as well as the single-stranded telomeric DNA, but it is not known whether the protective function of Pot1 depends on Tpp1. Alternatively, Pot1 might function similarly to the Pot1-like proteins of budding and fission yeast, which have no known Tpp1-like connection to the duplex telomeric DNA. Using mutant mouse cells with diminished Tpp1 levels, RNA interference directed to mouse Tpp1 and Pot1, and complementation of mouse Pot1 knockout cells with human and mouse Pot1 variants, we show here that Tpp1 is required for the protective function of mammalian Pot1 proteins.