Nonlinearity of Mechanochemical Motions in Motor Proteins

The assumption of linear response of protein molecules to thermal noise or structural perturbations, such as ligand binding or detachment, is broadly used in the studies of protein dynamics. Conformational motions in proteins are traditionally analyzed in terms of normal modes and experimental data on thermal fluctuations in such macromolecules is also usually interpreted in terms of the excitation of normal modes. We have chosen two important protein motors - myosin V and kinesin KIF1A - and performed numerical investigations of their conformational relaxation properties within the coarse-grained elastic network approximation. We have found that the linearity assumption is deficient for ligand-induced conformational motions and can even be violated for characteristic thermal fluctuations. The deficiency is particularly pronounced in KIF1A where the normal mode description fails completely in describing functional mechanochemical motions. These results indicate that important assumptions of the theory of protein dynamics may need to be reconsidered. Neither a single normal mode, nor a superposition of such modes yield an approximation of strongly nonlinear dynamics.Comment: 10 pages, 6 figure

Speciation of phosphorus in a fertilized, reduced-till soil system: in-field treatment incubation study

Citation: Khatiwada, Raju, Ganga M. Hettiarachchi, David B. Mengel, and Mingwei Fei. “Speciation of Phosphorus in a Fertilized, Reduced-Till Soil System: In-Field Treatment Incubation Study.” Soil Science Society of America Journal 76, no. 6 (2012): 2006–18. https://doi.org/10.2136/sssaj2011.0299.Phosphorus management in reduced-tillage systems is a great concern for farmers. Conclusive positive results of deep-banding P fertilizers compared with broadcast application and the chemistry of reduced-tillage systems remain unclear. Knowledge of the dominant solid P species present in soil following application of P fertilizers and the resulting potential P availability would help us understand and efficiently manage P in reduced-tillage systems. The objective of this research was to study the influence of placement (broadcast vs. deep-band P), fertilizer source (granular vs. liquid P), and time on the reaction products of P under field conditions. Changes in soil pH, resin-extractable P, total P, and speciation of P were determined at different distances from the point of fertilizer application at 5 wk and 6 mo after P application at a rate of 75 kg ha−1 to a soil system that was under long-term reduced tillage. Resin-extractable P was lower for broadcast treatments compared with deep-band treatments for both time periods. Resin-extractable P was greater in the liquid P-treated soils than in the granular P-treated soils. Speciation results showed that granular P fertilizers tended to form Fe–P-like forms, whereas liquid forms remained in adsorbed P-like forms in the soil 5 wk after application; moreover, speciation results showed granular P fertilizers precipitated less when deep-banded. During the 6-mo period following application, reaction products of broadcast granular, broadcast liquid, and deep-band granular fertilizers transformed to Ca-phosphate or mixtures of Ca-, Fe- and adsorbed-phosphate-like forms, whereas deep-band liquid P remained as mainly adsorbed P-like forms. Deep-banding of P would most likely provide a solution that is both agronomically and environmentally efficient for reduced-till farmers

The function of the alula in avian flight

The alula is a small structure located at the joint between the hand-wing and arm-wing of birds and is known to be used in slow flight with high angles of attack such as landing. It is assumed to function similarly to a leading-edge slat that increases lift and delays stall. However, in spite of its universal presence in flying birds and the wide acceptance of stall delay as its main function, how the alula delays the stall and aids the flight of birds remains unclear. Here, we investigated the function of alula on the aerodynamic performance of avian wings based on data from flight tasks and wind-tunnel experiments. With the alula, the birds performed steeper descending flights with greater changes in body orientation. Force measurements revealed that the alula increases the lift and often delays the stall. Digital particle image velocimetry showed that these effects are caused by the streamwise vortex, formed at the tip of the alula, that induces strong downwash and suppresses the flow separation over the wing surface. This is the first experimental evidence that the alula functions as a vortex generator that increases the lift force and enhances manoeuvrability in flights at high angles of attack.open1

Rapid Initial Morphospace Expansion and Delayed Morphological Disparity Peak in the First 100 Million Years of the Archosauromorph Evolutionary Radiation

Adaptive radiations have played a major role in generating modern and deep-time biodiversity. The Triassic radiation of the Archosauromorpha was one of the most spectacular vertebrate radiations, giving rise to many highly ecomorphologically varied lineages—including the dinosaurs, pterosaurs, and stem-crocodylians—that dominated the larger-bodied land fauna for the following 150 Ma, and ultimately gave rise to today’s > 10,000 species of birds and crocodylians. This radiation provides an outstanding testbed for hypotheses relating to adaptive radiations more broadly. Recent studies have started to characterize the tempo and mode of the archosauromorph early adaptive radiation, indicating very high initial rates of evolution, non-competitive niche-filling processes, and previously unrecognized morphological disparity even among non-crown taxa. However, these analyses rested primarily either on discrete characters or on geometric morphometrics of the cranium only, or even failed to fully include phylogenetic information. Here we expand previous 2D geometric morphometric cranial datasets to include new taxa and reconstructions, and create an analogous dataset of the pelvis, thereby allowing comparison of anatomical regions and the transition from “sprawling” to “upright” posture to be examined. We estimated morphological disparity and evolutionary rates through time. All sampled clades showed a delayed disparity peak for sum of variances and average nearest neighbor distances in both the cranium and pelvis, with disparity likely not saturated by the end of the studied time span (Late Jurassic); this contrasts with smaller radiations, but lends weight to similar results for large, ecomorphologically-varied groups. We find lower variations in pelvic than cranial disparity among Triassic-Jurassic archosaurs, which may be related to greater morphofunctional constraints on the pelvis. Contrasting with some previous work, but also confirming some previous findings during adaptive radiations, we find relatively widespread evidence of correlation between sampled diversity and disparity, especially at the largest phylogenetic scales and using average displacement rather than sum of variances as disparity metric; this also demonstrates the importance of comparing disparity metrics, and the importance of phylogenetic scale. Stem and crown archosauromorphs show a morphological diversification of both the cranium and pelvis with higher initial rates (Permian–Middle Triassic and at the base of major clades) followed by lower rates once diversification into niches has occurred (Late Triassic–Jurassic), indicating an “early burst” pattern sensu lato. Our results provide a more detailed and comprehensive picture of the early archosauromorph radiation and have significant bearing on the understanding of deep-time adaptive radiations more broadly, indicating widespread patterns of delayed disparity peaks, initial correlation of diversity and disparity, and evolutionary early bursts.Fil: Foth, Christian. University of Fribourg; Alemania. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Sookias, Roland B.. Université de Liège; Bélgica. University of Oxford; Reino Unido. Staatliches Museum fur Naturkunde Stuttgart; AlemaniaFil: Ezcurra, Martin Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin

Optimal estimation of water vapour profiles using a combination of Raman lidar and microwave radiometer

In this work, a two-step algorithm to obtain water vapour profiles from a combination of Raman lidar and microwave radiometer is presented. Both instruments were applied during an intensive 2-month measurement campaign (HOPE) close to Jülich, western Germany, during spring 2013. To retrieve reliable water vapour information from inside or above the cloud a two-step algorithm is applied. The first step is a Kalman filter that extends the profiles, truncated at cloud base, to the full height range (up to 10 km) by combining previous information and current measurement. Then the complete water vapour profile serves as input to the one-dimensional variational (1D-VAR) method, also known as optimal estimation. A forward model simulates the brightness temperatures which would be observed by the microwave radiometer for the given atmospheric state. The profile is iteratively modified according to its error bars until the modelled and the actually measured brightness temperatures sufficiently agree. The functionality of the retrieval is presented in detail by means of case studies under different conditions. A statistical analysis shows that the availability of Raman lidar data (night) improves the accuracy of the profiles even under cloudy conditions. During the day, the absence of lidar data results in larger differences in comparison to reference radiosondes. The data availability of the full-height water vapour lidar profiles of 17 % during the 2-month campaign is significantly enhanced to 60 % by applying the retrieval. The bias with respect to radiosonde and the retrieved a posteriori uncertainty of the retrieved profiles clearly show that the application of the Kalman filter considerably improves the accuracy and quality of the retrieved mixing ratio profiles

Utilizing Multimedia Case Studies to Teach the Professional Side of Project Management

This research was conducted to evaluate the effectiveness of using a LITEE multimedia case study to teaching concepts in engineering courses. The LITEE Superstar case study was implemented in an engineering Project Management course. Numerous surveys regarding student expectations, outcomes, and attitudes were collected and results are presented herein. Overall, the study provided evidence that the students felt that the LITEE case study added value to the course via the different methods of teaching material, aided in the understanding of the project selection process, and ultimately helped them be successful in their course project which was conducted for a real rural Missouri city. The data was unable to be tracked on a per student basis; this yields areas for future research to track individual student improvement and attitudes. This research provides evidence that using multimedia case studies, such as the case studies published by LITEE, are effective and well received by engineering students in their coursework

An overview of the first decade of PollyNET : an emerging network of automated Raman-polarization lidars for continuous aerosol profiling

© Author(s) 2016. This work is distributed under the Creative Commons Attribution 3.0 LicenseA global vertically resolved aerosol data set covering more than 10 years of observations at more than 20 measurement sites distributed from 63° N to 52° S and 72° W to 124° E has been achieved within the Raman and polarization lidar network PollyNET. This network consists of portable, remote-controlled multiwavelength-polarization-Raman lidars (Polly) for automated and continuous 24/7 observations of clouds and aerosols. PollyNET is an independent, voluntary, and scientific network. All Polly lidars feature a standardized instrument design with different capabilities ranging from single wavelength to multiwavelength systems, and now apply unified calibration, quality control, and data analysis. The observations are processed in near-real time without manual intervention, and are presented online at http://polly.tropos.de/. The paper gives an overview of the observations on four continents and two research vessels obtained with eight Polly systems. The specific aerosol types at these locations (mineral dust, smoke, dust-smoke and other dusty mixtures, urban haze, and volcanic ash) are identified by their Ångström exponent, lidar ratio, and depolarization ratio. The vertical aerosol distribution at the PollyNET locations is discussed on the basis of more than 55 000 automatically retrieved 30 min particle backscatter coefficient profiles at 532 nm as this operating wavelength is available for all Polly lidar systems. A seasonal analysis of measurements at selected sites revealed typical and extraordinary aerosol conditions as well as seasonal differences. These studies show the potential of PollyNET to support the establishment of a global aerosol climatology that covers the entire troposphere.Peer reviewe

Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of cells incubated with sub-lethal concentrations of an oxaborole identified a subtle but significant accumulation of G2 and >G2 cells. Given the possibility of compromised DNA fidelity, we investigated long-term exposure of T. brucei to oxaboroles by generating resistant cell lines in vitro. Resistance proved more difficult to generate than for drugs currently used in the field, and in one of our three cell lines was unstable. Whole-genome sequencing of the resistant cell lines revealed single nucleotide polymorphisms in 66 genes and several large-scale genomic aberrations. The absence of a simple consistent mechanism among resistant cell lines and the diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field. The combined genetic and chemical biology approaches have provided lists of candidates to be investigated for more detailed information on the mode of action of this promising new drug clas

Comparative genomics of the major parasitic worms

Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms

Expression of a malarial Hsp70 improves defects in chaperone-dependent activities in ssa1 mutant yeast

Plasmodium falciparum causes the most virulent form of malaria and encodes a large number of molecular chaperones. Because the parasite encounters radically different environments during its lifecycle, many members of this chaperone ensemble may be essential for P. falciparum survival. Therefore, Plasmodium chaperones represent novel therapeutic targets, but to establish the mechanism of action of any developed therapeutics, it is critical to ascertain the functions of these chaperones. To this end, we report the development of a yeast expression system for PfHsp70-1, a P. falciparum cytoplasmic chaperone. We found that PfHsp70-1 repairs mutant growth phenotypes in yeast strains lacking the two primary cytosolic Hsp70s, SSA1 and SSA2, and in strains harboring a temperature sensitive SSA1 allele. PfHsp70-1 also supported chaperone-dependent processes such as protein translocation and ER associated degradation, and ameliorated the toxic effects of oxidative stress. By introducing engineered forms of PfHsp70-1 into the mutant strains, we discovered that rescue requires PfHsp70-1 ATPase activity. Together, we conclude that yeast can be co-opted to rapidly uncover specific cellular activities mediated by malarial chaperones. © 2011 Bell et al