561 research outputs found
Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels
Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD
Calcium-insensitive splice variants of mammalian E1 subunit of 2-oxoglutarate dehydrogenase complex with tissue-specific patterns of expression
Non-response bias in physical activity trend estimates
© 2009 Craig et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
A multidimensional view of racial differences in access to prostate cancer care
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139082/1/cncr30894.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139082/2/cncr30894_am.pd
Constructing a man-made c-type cytochrome maquette in vivo:electron transfer, oxygen transport and conversion to a photoactive light harvesting maquette
The successful use of man-made proteins to advance synthetic biology requires both the fabrication of functional artificial proteins in a living environment, and the ability of these proteins to interact productively with other proteins and substrates in that environment. Proteins made by the maquette method integrate sophisticated oxidoreductase function into evolutionarily naive, non-computationally designed protein constructs with sequences that are entirely unrelated to any natural protein. Nevertheless, we show here that we can efficiently interface with the natural cellular machinery that covalently incorporates heme into natural cytochromes c to produce in vivo an artificial c-type cytochrome maquette. Furthermore, this c-type cytochrome maquette is designed with a displaceable histidine heme ligand that opens to allow functional oxygen binding, the primary event in more sophisticated functions ranging from oxygen storage and transport to catalytic hydroxylation. To exploit the range of functions that comes from the freedom to bind a variety of redox cofactors within a single maquette framework, this c-type cytochrome maquette is designed with a second, non-heme C, tetrapyrrole binding site, enabling the construction of an elementary electron transport chain, and when the heme C iron is replaced with zinc to create a Zn porphyrin, a light-activatable artificial redox protein. The work we describe here represents a major advance in de novo protein design, offering a robust platform for new c-type heme based oxidoreductase designs and an equally important proof-of-principle that cofactor-equipped man-made proteins can be expressed in living cells, paving the way for constructing functionally useful man-made proteins in vivo
Gravitational Waves from Mesoscopic Dynamics of the Extra Dimensions
Recent models which describe our world as a brane embedded in a higher
dimensional space introduce new geometrical degrees of freedom: the shape
and/or size of the extra dimensions, and the position of the brane. These modes
can be coherently excited by symmetry breaking in the early universe even on
``mesoscopic'' scales as large as 1 mm, leading to detectable gravitational
radiation. Two sources are described: relativistic turbulence caused by a
first-order transition of a radion potential, and Kibble excitation of
Nambu-Goldstone modes of brane displacement. Characteristic scales and spectral
properties are estimated and the prospects for observation by LISA are
discussed. Extra dimensions with scale between 10 \AA and 1 mm, which enter the
3+1-D era at cosmic temperatures between 1 and 1000 TeV, produce backgrounds
with energy peaked at observed frequencies in the LISA band, between
and Hz. The background is detectable above instrument and
astrophysical foregrounds if initial metric perturbations are excited to a
fractional amplitude of or more, a likely outcome for the
Nambu-Goldstone excitations.Comment: Latex, 5 pages, plus one figure, final version to appear in Phys.
Rev. Let
Group interventions to improve health outcomes : a framework for their design and delivery
Peer reviewedPublisher PD
Chromosome and DNA methylation dynamics during meiosis in autotetraploid Arabidopsis arenosa
Variation in chromosome number due to
polyploidy can seriously compromise meiotic stability. In
autopolyploids, the presence of more than two homologous
chromosomes may result in complex pairing patterns
and subsequent anomalous chromosome
segregation. In this context, chromocenter, centromeric,
telomeric and ribosomal DNA locus topology and DNA
methylation patterns were investigated in the natural
autotetraploid, Arabidopsis arenosa. The data show that
homologous chromosome recognition and association
initiates at telomeric domains in premeiotic interphase,
followed by quadrivalent pairing of ribosomal 45S RNA
gene loci (known as NORs) at leptotene. On the other hand, centromeric regions at early leptotene show pairwise
associations rather than associations in fours. These
pairwise associations are maintained throughout prophase
I, and therefore likely to be related to the diploid-like
behavior of A. arenosa chromosomes at metaphase I,
where only bivalents are observed. In anthers, both cells
at somatic interphase as well as at premeiotic interphase
show 5-methylcytosine (5-mC) dispersed throughout the
nucleus, contrasting with a preferential co-localization
with chromocenters observed in vegetative nuclei. These
results show for the first time that nuclear distribution
patterns of 5-mC are simultaneously reshuffled in meiocytes
and anther somatic cells. During prophase I, 5-mC
is detected in extended chromatin fibers and chromocenters
but interestingly is excluded from the NORs what
correlates with the pairing patter
Dose Precision Using a Pretransplant Test PK of Intravenous Busulfan Prior to BuCyVP-16 Preparative Regimen in Lymphoma
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