Elastin-like polypeptide (ELP) containing materials have spurred significant research interest for biomedical applications exploiting their biocompatible, biodegradable and nonimmunogenic nature ...while maintaining precise control over their chemical structure and functionality through genetic engineering. Physical, mechanical and biological properties of ELPs could be further manipulated using genetic engineering or through conjugation with a variety of chemical moieties. These chemical and physical modifications also achieve interesting micro- and nanostructured ELP-based materials. Here, we review the recent developments during the past decade in the methods to engineer elastin-like materials, available genetic and chemical modification methods and applications of ELP micro and nanostructures in tissue engineering and drug delivery.
In a personal series, 22 patients (11 men, 11 women) of median age 60 (range 25-81) years with primary duodenal adenocarcinoma underwent operation between 1979 and 1993. Tumours arising from bile ...duct, ampullary or pancreatic tissue were excluded. Principal presenting symptoms were jaundice (12 patients), pain (seven), anaemia (six) and vomiting (six). A pre-existing villous adenoma was seen in 11 patients and adjacent duodenal dysplasia in 13. Sites of origin were mostly the second part of the duodenum (18 patients) but also the third and fourth parts (two each). Seventeen patients underwent 'curative' resection with one hospital death at 25 days; the 5-year survival rate thereafter was 40 per cent. Five patients who received palliative surgery survived for a median of 7 months. Primary duodenal carcinoma is a distinct entity with a better prognosis than pancreatic cancer after radical resection. It favours the descending duodenum and is closely linked with villous adenoma and epithelial dysplasia.
The second Gravitational-Wave Transient Catalog, GWTC-2, reported on 39 compact binary coalescences observed by the Advanced LIGO and Advanced Virgo detectors between 1 April 2019 15∶00 UTC and 1 ...October 2019 15∶00 UTC. Here, we present GWTC-2.1, which reports on a deeper list of candidate events observed over the same period. We analyze the final version of the strain data over this period with improved calibration and better subtraction of excess noise, which has been publicly released. We employ three matched-filter search pipelines for candidate identification, and estimate the probability of astrophysical origin for each candidate event. While GWTC-2 used a false alarm rate threshold of 2 per year, we include in GWTC-2.1, 1201 candidates that pass a false alarm rate threshold of 2 per day. We calculate the source properties of a subset of 44 high-significance candidates that have a probability of astrophysical origin greater than 0.5. Of these candidates, 36 have been reported in GWTC-2. We also calculate updated source properties for all binary black hole events previously reported in GWTC-1. If the eight additional high-significance candidates presented here are astrophysical, the mass range of events that are unambiguously identified as binary black holes (both objects ≥3M⊙) is increased compared to GWTC-2, with total masses from ∼14M⊙ for GW190924_021846 to ∼182M⊙ for GW190426_190642. Source properties calculated using our default prior suggest that the primary components of two new candidate events (GW190403_051519 and GW190426_190642) fall in the mass gap predicted by pair-instability supernova theory. We also expand the population of binaries with significantly asymmetric mass ratios reported in GWTC-2 by an additional two events (the mass ratio is less than 0.65 and 0.44 at 90% probability for GW190403_051519 and GW190917_114630 respectively), and find that two of the eight new events have effective inspiral spins χeff>0 (at 90% credibility), while no binary is consistent with χeff<0 at the same significance. We provide updated estimates for rates of binary black hole and binary neutron star coalescence in the local Universe.
The production of isotopically labeled RNA remains critical to current NMR structural studies. One approach to obtain simple NMR spectra is to label with a nucleus that is not naturally occurring in ...RNA. Fluorine-19 can serve as a sensitive site-specific probe upon incorporation into RNA. Here we report the efficient in vitro enzymatic synthesis of 2-fluoroadenosine-5‘-triphosphate and its incorporation into the HIV-2 transactivation region (TAR) of RNA by DNA template-directed transcription using phage T7 RNA polymerase. We provide unequivocal evidence for this 19F-substituted base analogue capability to selectively interact with uracil, forming 2F-A−U base pairs in RNA. The introduction of a 2-fluoroadenyl substitution is relatively nonperturbing and provides us with uniquely positioned, sensitive NMR reporter groups to monitor structural changes in the local RNA environment.
Tertiary interactions are critical for proper RNA folding and ribozyme catalysis. RNA tertiary structure is often condensed through long-range helical packing interactions mediated by loop-receptor ...motifs. RNA structures displaying helical packing by loop-receptor interactions have been solved by X-ray crystallography, but not by NMR. Here, we report the NMR structure of a 30kDa GAAA tetraloop-receptor RNA complex. In order to stabilize the complex, we used a modular design in which the RNA was engineered to form a homodimer, with each subunit containing a GAAA tetraloop phased one helical turn apart from its cognate 11-nucleotide receptor domain. The structure determination utilized specific isotopic labeling patterns ( super(2)H, super(1) super(3)C and super(1) super(5)N) and refinement against residual dipolar couplings. We observe a unique and highly unusual chemical shift pattern for an adenosine platform interaction that reveals a spectroscopic fingerprint for this motif. The structure of the GAAA tetraloop-receptor interaction is well defined solely from experimental NMR data, shows minor deviations from previously solved crystal structures, and verifies the previously inferred hydrogen bonding patterns within this motif. This work demonstrates the feasibility of using engineered homodimers as modular systems for the determination of RNA tertiary interactions by NMR.
Cryptococcosis is a potentially lethal disease of humans/animals caused by
and
. Distinction between the two species is based on phenotypic and genotypic characteristics. Recently, it was proposed ...that
be divided into two species and
into five species based on a phylogenetic analysis of 115 isolates. While this proposal adds to the knowledge about the genetic diversity and population structure of cryptococcosis agents, the published genotypes of 2,606 strains have already revealed more genetic diversity than is encompassed by seven species. Naming every clade as a separate species at this juncture will lead to continuing nomenclatural instability. In the absence of biological differences between clades and no consensus about how DNA sequence alone can delineate a species, we recommend using "
species complex" and "
species complex" as a practical intermediate step, rather than creating more species. This strategy recognizes genetic diversity without creating confusion.
Assessment of habitat suitability provides natural resource managers with insights on the quality and spatial distribution of habitat for wildlife species. However, habitat suitability models only ...provide information on current habitat parameters, and do not consider changes in habitat due to forest succession and disturbances. Habitat potential models have been developed by identifying habitat types and their successional trajectories to provide insights on how landscapes change with time. We developed habitat suitability index (HSI) models and habitat potential models for elk (Cervus elaphus nelsoni) on public and private lands within theMichigan elk range (1,220 km²) in northeastern lower Michigan, USA. Our objective was to demonstrate how integration of habitat suitability and habitat potential models can provide spatio-temporal insights on wildlife habitat. When constructing public-lands models, we used state forest compartment-inventory data to identify cover types important to elk, and assigned suitability values (0 = low, 1 = high) to each cover type for elk life requisites (i.e., spring food, winter food, winter thermal cover). Additionally, we modified suitability values based on stand conditions acquired from state forest inventory records (e.g., stand size, percent canopy closure, age of aspen Populus spp.). For our private-lands models, we used satellite imagery to classify cover types and assigned suitability values to cover types for each elk life requisite, and modified values based on percent canopy closure for winter thermal cover. Elk habitat potential was modeled by delineating habitat types by overlaying digital spatial data layers (soils, land-type associations, vegetation) and identifying successional trajectories using habitat classification guides and literature. We assigned suitability values to each habitat type for life requisites at early to late successional stages. The highest suitability value of each habitat type’s successional stage determined the habitat potential for each habitat type. Our winter thermal cover HSI model indicated several large areas (5–13 km²) of high suitability (i.e., lowland conifers) in the southern third of our study area. Our winter food HSI model indicated a heterogeneous arrangement of high suitability areas (hardwoods, upland conifers, aspen) throughout our study area. Our spring food HSI model indicated few areas of high suitability (openings) primarily on private lands. Our habitat potential models indicated high potential for each elk life requisite across the elk range. Comparisons between current elk habitat suitability and habitat potential identify key areas where managers can maximize management efforts for elk in Michigan. Areas determined to have high habitat potential (e.g., mature aspen stands) may become focus areas if they currently have low habitat suitability. Conversely, managers can avoid committing resources to areas with low habitat potential. Integrating habitat suitability and potential models provides insights on how wildlife habitats may respond to forest succession, land management practices, and disturbances, and ultimately help natural resource professionals prioritize and meet a diversity of wildlife management goals.
Simulation and experiment have been used to establish that significant artifacts can be generated in X-pulse CPMG relaxation dispersion experiments recorded on heteronuclear ABX spin-systems, such as ...¹³C i -¹³C j -¹H, where ¹³C i and ¹³C j are strongly coupled. A qualitative explanation of the origin of these artifacts is presented along with a simple method to significantly reduce them. An application to the measurement of ¹H CPMG relaxation dispersion profiles in an HIV-2 TAR RNA molecule where all ribose sugars are protonated at the 2' position, deuterated at all other sugar positions and ¹³C labeled at all sugar carbons is presented to illustrate the problems that strong ¹³C-¹³C coupling introduces and a simple solution is proposed.
Paradoxically, both anticancer immunosurveillance and tumor progression have been associated with intact autophagy, which is regulated by the target of rapamycin (Tor1). Here, we describe the ...potential impact on the design of cancer therapeutics of a newly described highly conserved post-transcriptional mechanism whereby Tor regulates autophagy.
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