125 research outputs found
Pleiotropy of FRIGIDA enhances the potential for multivariate adaptation.
An evolutionary response to selection requires genetic variation; however, even if it exists, then the genetic details of the variation can constrain adaptation. In the simplest case, unlinked loci and uncorrelated phenotypes respond directly to multivariate selection and permit unrestricted paths to adaptive peaks. By contrast, 'antagonistic' pleiotropic loci may constrain adaptation by affecting variation of many traits and limiting the direction of trait correlations to vectors that are not favoured by selection. However, certain pleiotropic configurations may improve the conditions for adaptive evolution. Here, we present evidence that the Arabidopsis thaliana gene FRI (FRIGIDA) exhibits 'adaptive' pleiotropy, producing trait correlations along an axis that results in two adaptive strategies. Derived, low expression FRI alleles confer a 'drought escape' strategy owing to fast growth, low water use efficiency and early flowering. By contrast, a dehydration avoidance strategy is conferred by the ancestral phenotype of late flowering, slow growth and efficient water use during photosynthesis. The dehydration avoidant phenotype was recovered when genotypes with null FRI alleles were transformed with functional alleles. Our findings indicate that the well-documented effects of FRI on phenology result from differences in physiology, not only a simple developmental switch
National Landscape of Hospitalizations in Patients with Left Ventricular Assist Device. Insights from the National Readmission Database 2010-2015
The number of patients with left ventricular assist devices (LVAD) has increased over the years and it is important to identify the etiologies for hospital admission, as well as the costs, length of stay and in-hospital complications in this patient group. Using the National Readmission Database from 2010 to 2015, we identified patients with a history of LVAD placement using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code V43.21. We aimed to identify the etiologies for hospital admission, patient characteristics, and in-hospital outcomes. We identified a total of 15,996 patients with an LVAD, the mean age was 58 years and 76% were males. The most common cause of hospital readmission after LVAD was heart failure (HF, 13%), followed by gastrointestinal (GI) bleed (11.8%), device complication (11.5%), and ventricular tachycardia/fibrillation (4.2%). The median length of stay was 6 days (3-11 days) and the median hospital costs was $12,723 USD. The in-hospital mortality was 3.9%, blood transfusion was required in 26.8% of patients, 20.5% had acute kidney injury, 2.8% required hemodialysis, and 6.2% of patients underwent heart transplantation. Interestingly, the most common cause of readmission was the same as the diagnosis for the preceding admission. One in every four LVAD patients experiences a readmission within 30 days of a prior admission, most commonly due to HF and GI bleeding. Interventions to reduce HF readmissions, such as speed optimization, may be one means of improving LVAD outcomes and resource utilization
Recommended from our members
Direct Observation of Oligomerization by Single Molecule Fluorescence Reveals a Multistep Aggregation Mechanism for the Yeast Prion Protein Ure2
The self-assembly of polypeptides into amyloid structures is associated with a range of increasingly prevalent neurodegenerative diseases as well as with a select set of functional processes in biology. The phenomenon of self-assembly results in species with dramatically different sizes, from small oligomers to large fibrils; however, the kinetic relationship between these species is challenging to characterize. In the case of prion aggregates, these structures can self-replicate and act as infectious agents. Here we use single molecule spectroscopy to obtain quantitative information on the oligomer populations formed during aggregation of the yeast prion protein Ure2. Global analysis of the aggregation kinetics reveals the molecular mechanism underlying oligomer formation and depletion. Quantitative characterization indicates that the majority of Ure2 oligomers are relatively short-lived, and their rate of dissociation is much higher than their rate of conversion into growing fibrils. We identify an initial metastable oligomer, which can subsequently convert into a structurally distinct oligomer, which in turn converts into growing fibrils. We also show that fragmentation is responsible for the autocatalytic self-replication of Ure2 fibrils, but that preformed fibrils do not promote oligomer formation, indicating that secondary nucleation of the type observed for peptides and proteins associated with neurodegenerative disease does not occur at a significant rate for Ure2. These results establish a framework for elucidating the temporal and causal relationship between oligomers and larger fibrillar species in amyloid forming systems, and provide insights into why functional amyloid systems are not toxic to their host organisms
Recommended from our members
Deformable and Robust CoreâShell Protein Microcapsules Templated by LiquidâLiquid PhaseâSeparated Microdroplets
Abstract: Microcapsules are a key class of microscale materials with applications in areas ranging from personal care to biomedicine, and with increasing potential to act as extracellular matrix (ECM) models of hollow organs, tissues, or biomolecular condensates. Such capsules are conventionally generated from nonâECM materials including synthetic polymers. Here, robust microcapsules with controllable shell thickness from physicallyâ and enzymaticallyâcrosslinked gelatin are fabricated, and a coreâshell architecture is achieved by exploiting a liquidâliquid phaseâseparated aqueous system in a oneâstep microfluidic process. Microfluidic mechanical testing reveals that the mechanical robustness of thickerâshell capsules could be controlled through modulation of the shell thickness. Furthermore, the microcapsules demonstrate environmentallyâresponsive deformation, including buckling driven by osmosis and external mechanical forces. A sequential release of cargo species is obtained through the degradation of the capsules. Stability measurements show the capsules are stable at 37 °C for more than 2 weeks. Finally, through gelâsol transition, microgels function as precursors for the formation of allâaqueous liquidâliquid phaseâseparated systems that are twoâphase or multiphase. These smart capsules that can undergo phase transition are promising models of hollow biostructures, microscale drug carriers, and building blocks or compartments for active soft materials and robots
Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation.
α-Synuclein (α-syn) is a 140-residue intrinsically disordered protein that is involved in neuronal and synaptic vesicle plasticity, but its aggregation to form amyloid fibrils is the hallmark of Parkinson's disease (PD). The interaction between α-syn and lipid surfaces is believed to be a key feature for mediation of its normal function, but under other circumstances it is able to modulate amyloid fibril formation. Using a combination of experimental and theoretical approaches, we identify the mechanism through which facile aggregation of α-syn is induced under conditions where it binds a lipid bilayer, and we show that the rate of primary nucleation can be enhanced by three orders of magnitude or more under such conditions. These results reveal the key role that membrane interactions can have in triggering conversion of α-syn from its soluble state to the aggregated state that is associated with neurodegeneration and to its associated disease states.This work was supported by the UK BBSRC and the Wellcome Trust (CMD, TPJK, MV), the
Frances and Augustus Newman Foundation (TPJK), Magdalene College, Cambridge (AKB) , St Johnâs College,
Cambridge (TCTM), the Cambridge Home and EU Scholarship Scheme (GM), Elan Pharmaceuticals
(CMD, TPJK, MV, CG) and the Leverhulme Trust (AKB).This is the accepted manuscript. The final version is available from NPG at http://www.nature.com/nchembio/journal/v11/n3/abs/nchembio.1750.htm
Outlook for inverse design in nanophotonics
Recent advancements in computational inverse design have begun to reshape the
landscape of structures and techniques available to nanophotonics. Here, we
outline a cross section of key developments at the intersection of these two
fields: moving from a recap of foundational results to motivation of emerging
applications in nonlinear, topological, near-field and on-chip optics.Comment: 13 pages, 6 figure
Traffic and Related Self-Driven Many-Particle Systems
Since the subject of traffic dynamics has captured the interest of
physicists, many astonishing effects have been revealed and explained. Some of
the questions now understood are the following: Why are vehicles sometimes
stopped by so-called ``phantom traffic jams'', although they all like to drive
fast? What are the mechanisms behind stop-and-go traffic? Why are there several
different kinds of congestion, and how are they related? Why do most traffic
jams occur considerably before the road capacity is reached? Can a temporary
reduction of the traffic volume cause a lasting traffic jam? Under which
conditions can speed limits speed up traffic? Why do pedestrians moving in
opposite directions normally organize in lanes, while similar systems are
``freezing by heating''? Why do self-organizing systems tend to reach an
optimal state? Why do panicking pedestrians produce dangerous deadlocks? All
these questions have been answered by applying and extending methods from
statistical physics and non-linear dynamics to self-driven many-particle
systems. This review article on traffic introduces (i) empirically data, facts,
and observations, (ii) the main approaches to pedestrian, highway, and city
traffic, (iii) microscopic (particle-based), mesoscopic (gas-kinetic), and
macroscopic (fluid-dynamic) models. Attention is also paid to the formulation
of a micro-macro link, to aspects of universality, and to other unifying
concepts like a general modelling framework for self-driven many-particle
systems, including spin systems. Subjects such as the optimization of traffic
flows and relations to biological or socio-economic systems such as bacterial
colonies, flocks of birds, panics, and stock market dynamics are discussed as
well.Comment: A shortened version of this article will appear in Reviews of Modern
Physics, an extended one as a book. The 63 figures were omitted because of
storage capacity. For related work see http://www.helbing.org
- âŠ