71 research outputs found
Direct Measurements of the Convective Recycling of the Upper Troposphere
We present a statistical representation of the aggregate effects of deep convection on the chemistry and dynamics of the Upper Troposphere (UT) based on direct aircraft observations of the chemical composition of the UT over the Eastern United States and Canada during summer. These measurements provide new and unique observational constraints on the chemistry occurring downwind of convection and the rate at which air in the UT is recycled, previously only the province of model analyses. These results provide quantitative measures that can be used to evaluate global climate and chemistry models
ISSN exercise & sport nutrition review: research & recommendations
Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients
Climate Change, Coral Reef Ecosystems, and Management Options for Marine Protected Areas
Marine protected areas (MPAs) provide place-based management of marine ecosystems through various degrees and types of protective actions. Habitats such as coral reefs are especially susceptible to degradation resulting from climate change, as evidenced by mass bleaching events over the past two decades. Marine ecosystems are being altered by direct effects of climate change including ocean warming, ocean acidification, rising sea level, changing circulation patterns, increasing severity of storms, and changing freshwater influxes. As impacts of climate change strengthen they may exacerbate effects of existing stressors and require new or modified management approaches; MPA networks are generally accepted as an improvement over individual MPAs to address multiple threats to the marine environment. While MPA networks are considered a potentially effective management approach for conserving marine biodiversity, they should be established in conjunction with other management strategies, such as fisheries regulations and reductions of nutrients and other forms of land-based pollution. Information about interactions between climate change and more “traditional” stressors is limited. MPA managers are faced with high levels of uncertainty about likely outcomes of management actions because climate change impacts have strong interactions with existing stressors, such as land-based sources of pollution, overfishing and destructive fishing practices, invasive species, and diseases. Management options include ameliorating existing stressors, protecting potentially resilient areas, developing networks of MPAs, and integrating climate change into MPA planning, management, and evaluation
Synthetic RNA Recognition Motifs That Selectively Recognize HIV‑1 Trans-Activation Response Element Hairpin RNA
A multitude of RNA hairpins are directly
implicated in human disease.
Many of these RNAs are potentially valuable targets for drug discovery
and basic research. However, very little is known about the molecular
requirements for achieving sequence-selective recognition of a particular
RNA sequence and structure. Although a relatively modest number of
synthetic small to medium-sized RNA-binding molecules have been reported,
rapid identification of sequence-selective RNA-binding molecules remains
a daunting challenge. RNA recognition motif (RRM) domains may represent
unique privileged scaffolds for the generation of synthetic proteins
that selectively recognize structured disease-relevant RNAs, including
RNA hairpins. As a demonstration of this potential, we mutated putative
RNA-binding regions within the U1A RRM and a variant thereof and screened
these synthetic proteins for affinity to HIV-1 trans-activation response
(TAR) element hairpin RNA. Some of these U1A-derived proteins bind
TAR with single-digit micromolar dissociation constants, and they
do so preferentially over the native protein’s original target
RNA (U1hpII) and a DNA TAR variant. Binding affinity is not appreciably
diminished by addition of 10 molar equivalents of cellular tRNAs from Escherichia coli. Taken together, our findings represent
the first synthetic RRMs that selectively bind a disease-relevant
RNA hairpin and may represent a general approach for achieving sequence-selective
recognition of RNA hairpins, which are the focus of therapeutic discovery
and basic research
Resurfaced Shape Complementary Proteins That Selectively Bind the Oncoprotein Gankyrin
Increased cellular
levels of protein–protein interactions
involving the ankyrin repeat oncoprotein gankyrin are directly linked
to aberrant cellular events and numerous cancers. Inhibition of these
protein–protein interactions is thus an attractive therapeutic
strategy. However, the relatively featureless topology of gankyrin’s
putative binding face and large surface areas involved in gankyrin-dependent
protein–protein interactions present a dramatic challenge to
small molecule discovery. The size, high folding energies, and well-defined
surfaces present in many proteins overcome some of the challenges
faced by small molecule discovery. We used split-superpositive Green
Fluorescent Protein (split-spGFP) reassembly to screen a 5 ×
10<sup>9</sup> library of resurfaced proteins that are shape complementary
to the putative binding face of gankyrin and identified mutants that
potently and selectively bind this oncoprotein in vitro and in living
cells. Collectively, our findings represent the first synthetic proteins
that bind gankyrin and may represent a general strategy for developing
protein basic research tools and drug leads that bind disease-relevant
ankyrin repeats
Synthetic Proteins Potently and Selectively Bind the Oncoprotein Gankyrin, Modulate Its Interaction with S6 ATPase, and Suppress Gankyrin/MDM2-Dependent Ubiquitination of p53
Overexpression of the ankyrin repeat
oncoprotein gankyrin is directly
linked to the onset, proliferation, and/or metastasis of many cancers.
The role of gankyrin in multiple disease-relevant biochemical processes
is profound. In addition to other cellular processes, gankyrin overexpression
leads to decreased cellular levels of p53, through a complex that
involves MDM2. Thus, inhibition of this interaction is an attractive
strategy for modulating oncogenic phenotypes in gankyrin-overexpressing
cells. However, the lack of well-defined, hydrophobic, small-molecule
binding pockets on the putative ankyrin repeat binding face presents
a challenge to traditional small-molecule drug discovery. In contrast,
by virtue of their size and relatively high folding energies, synthetic
gankyrin-binding proteins could, in principle, compete with physiologically
relevant PPIs involving gankyrin. Previously, we showed that a shape-complementary
protein scaffold can be resurfaced to bind gankyrin with moderate
affinity (<i>K</i><sub>D</sub> ∼6 μM). Here,
we used yeast display high-throughput screening, error-prone PCR,
DNA shuffling, and protein engineering to optimize this complex. The
best of these proteins bind gankyrin with excellent affinity (<i>K</i><sub>D</sub> ∼21 nM), selectively co-purifies with
gankyrin from a complex cellular milieu, modulates an interaction
between gankyrin and a physiological binding partner (S6 ATPase),
and suppresses gankyrin/MDM2-dependent ubiquitination of p53
Engineered M13 Bacteriophage Nanocarriers for Intracellular Delivery of Exogenous Proteins to Human Prostate Cancer Cells
The
size, well-defined structure, and relatively high folding energies
of most proteins allow them to recognize disease-relevant receptors
that present a challenge to small molecule reagents. While multiple
challenges must be overcome in order to fully exploit the use of protein
reagents in basic research and medicine, perhaps the greatest challenge
is their intracellular delivery to a particular diseased cell. Here,
we describe the genetic and enzymatic manipulation of prostate cancer
cell-penetrating M13 bacteriophage to generate nanocarriers for the
intracellular delivery of functional exogenous proteins to a human
prostate cancer cell line
Effects of sodium phosphate and beetroot juice supplementation on repeated-sprint ability in females
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