15 research outputs found
Molecular elements of ion permeation and selectivity within calcium channels
Voltage-dependent calcium channels are located in the plasma membrane and form a highly selective conduit by which Ca2+ ions enter all excitable cells and some nonexcitable cells. Extensive characterization studies have revealed the existence of one low (T) and five high-voltage-activated calcium channel types (L, N, P, Q, and R). The high voltage-activated calcium channels have been found to exist as heteromultimers, consisting of an alpha(1), beta, alpha(2)/delta, and gamma subunit. Molecular cloning has revealed the existence of 10 channel transcripts, and expression of these cloned calcium channel genes has shown that basic voltage-activated calcium channel function is strictly carried by the corresponding a, subunits. In turn, the auxiliary subunits serve to modulate calcium channel function by altering the voltage dependence of channel gating, kinetics, and current amplitude, thereby creating a likelihood for calcium channels with multiple properties. Although for calcium channels to be effective, Ca2+ ions must enter selectively through the pore of the alpha(1)-subunit, bypassing competition with other extracellular ions. The structural determinants of this highly selective Ca2+ filter reside within the four glutamic acid residues located at homologous positions within each of the four pore-forming segments. Together, these residues form a single or multiple Ca2+ affinity site(s) that entrap calcium ions, which are then electrostatically repulsed through the intracellular opening of the pore. This mechanism of high-selectivity calcium filtration, the spatial arrangement of pore glutamic acid residues; and the coordination chemistry of calcium binding are discussed in this review
Functional Characterization of Ion Permeation Pathway in the N-Type Ca<sup>2+</sup>Channel
Wakamori, Minoru, Mark Strobeck, Tetsuhiro Niidome, Tetsuyuki Teramoto, Keiji Imoto, and Yasuo Mori. Functional characterization of ion permeation pathway in the N-type Ca2+channel. J. Neurophysiol. 79: 622–634, 1998. Multiple types of high-voltage-activated Ca2+channels, including L-, N-, P-, Q- and R-types have been distinguished from each other mainly employing pharmacological agents that selectively block particular types of Ca2+channels. Except for the dihydropyridine-sensitive L-type Ca2+channels, electrophysiological characterization has yet to be conducted thoroughly enough to biophysically distinguish the remaining Ca2+channel types. In particular, the ion permeation properties of N-type Ca2+channels have not been clarified, although the kinetic properties of both the L- and N-type Ca2+channels are relatively well described. To establish ion conducting properties of the N-type Ca2+channel, we examined a homogeneous population of recombinant N-type Ca2+channels expressed in baby hamster kidney cells, using a conventional whole cell patch-clamp technique. The recombinant N-type Ca2+channel, composed of the α1B, α2a, and β1asubunits, displayed high-voltage-activated Ba2+currents elicited by a test pulse more positive than −30 mV, and were strongly blocked by the N-type channel blocker ω-conotoxin-GVIA. In the presence of 110 mM Ba2+, the unitary current showed a slope conductance of 18.2 pS, characteristic of N-type channels. Ca2+and Sr2+resulted in smaller ion fluxes than Ba2+, with the ratio 1.0:0.72:0.75 of maximum conductance in current-voltage relationships of Ba2+, Ca2+, and Sr2+currents, respectively. In mixtures of Ba2+and Ca2+, where the Ca2+concentration was steadily increased in place of Ba2+, with the total concentration of Ba2+and Ca2+held constant at 3 mM, the current amplitude went through a clear minimum when 20% of the external Ba2+was replaced by Ca+2. This anomalous mole fraction effect suggests an ion-binding site where two or more permeant ions can sit simultaneously. By using an external solution containing 110 mM Na+without polyvalent cations, inward Na+currents were evoked by test potentials more positive than −50 mV. These currents were activated and inactivated in a kinetic manner similar to that of Ba2+currents. Application of inorganic Ca2+antagonists blocked Ba2+currents through N-type channels in a concentration-dependent manner. The rank order of inhibition was La3+≥ Cd2+≫ Zn2+> Ni2+≥ Co2+. When a short strong depolarization was applied before test pulses of moderate depolarizing potentials, relief from channel blockade by La3+and Cd2+and subsequent channel reblocking was observed. The measured rate (2 × 108M−1s−1) of reblocking approached the diffusion-controlled limit. These results suggest that N-type Ca2+channels share general features of a high affinity ion-binding site with the L-type Ca2+channel, and that this site is easily accessible from the outside of the channel pore.</jats:p
Figure 1 in Craniodental characters and the relationships of Procyonidae (Mammalia: Carnivora)
Figure 1. Phylogenetic hypotheses based on morphology recovered by: A, Decker & Wozencraft (1991) and B, Baskin (2004). Phylogenetic hypotheses based on molecular data recovered by: C, Koepfli et al. (2007) and D, Fulton & Strobeck (2007). Asterisk denotes Procyonidae, as defined by the author. Extinct taxa denoted by a dagger (†).Published as part of Ahrens, Heather E., 2012, Craniodental characters and the relationships of Procyonidae (Mammalia: Carnivora), pp. 669-713 in Zoological Journal of the Linnean Society 164 (3) on page 671, DOI: 10.1111/j.1096-3642.2011.00778.x, http://zenodo.org/record/540682
Lower body symmetry and running performance in elite Jamaican track and field athletes
In a study of degree of lower body symmetry in 73 elite Jamaican track and field athletes we show that both their knees and ankles (but not their feet) are-on average-significantly more symmetrical than those of 116 similarly aged controls from the rural Jamaican countryside. Within the elite athletes, events ranged from the 100 to the 800 m, and knee and ankle asymmetry was lower for those running the 100 m dashes than those running the longer events with turns. Nevertheless, across all events those with more symmetrical knees and ankles (but not feet) had better results compared to international standards. Regression models considering lower body symmetry combined with gender, age and weight explain 27 to 28% of the variation in performance among athletes, with symmetry related to about 5% of this variation. Within 100 m sprinters, the results suggest that those with more symmetrical knees and ankles ran faster. Altogether, our work confirms earlier findings that knee and probably ankle symmetry are positively associated with sprinting performance, while extending these findings to elite athletes
Genetic tagging of free-ranging black and brown bears
Identification of individuals in a free-ranging animal population is potentially hampered by a lack of distinguishing features (e.g., scars, unique color patterns), poor visibility (e.g., densely forested environments), cost and invasiveness of physical capture, and mark loss. Advances in DNA-analysis technology offer alternative methods of individual identification that may overcome several of these problems. We investigated the genetic variability of American black bears (Ursus americanus) and brown (grizzly) bears (Ursus arctos) in the Columbia River basin of British Columbia, Canada, and developed a method to obtain genetic samples from free-ranging bears. We established the background genetic variability using microsatellite genotyping at 9 loci using tissue and blood samples from captured bears. In 3 field trials, we tested methods to obtain hair from free-ranging bears. Although all methods collected hair suitable for DNA analysis, the barbed-wire enclosure hair-trap was superior. We extracted DNA from hair roots and identified sample species with a species-specific mitochondrial DNA (mtDNA) test and sample sex from a Y-chromosome test. Using 6 microsatellite loci from nuclear DNA (nDNA), we screened all hair samples for individual identity and developed match probability functions based on scenarios of random sampling (P(random)), the likely presence of parent-offspring groupings in the samples (P(par-offs)), and the likely presence of siblings in the samples (P(sib)). We applied the P(sib) to each hair sample (match criteria at P(sib
What is a Company Really Worth? Intangible Capital and the "Market to Book Value" Puzzle
"What is a company really worth?" is a question asked repeatedly during the recent financial crisis. Attention has been focused on short-term valuation issues, like the "mark-to-market" controversy. Sorting out these issues is complicated by the fact that the market puts a value on shareholder equity that is consistently more than twice the reported book value of a company. Numerous observers have pointed to the absence of most intangible assets from financial statements as an important source of this puzzle. We use Compustat financial data for 617 R&D intensive firms to test this possibility. We find that conventional book value alone explains only 31 percent of the market capitalization of these firms in 2006, and that this increases to 75 percent when our estimates of intangible capital are included. The debt-equity ratio also falls from 1.46 to 0.61. These findings suggest that financial reports tend to substantially understate the long-run intrinsic value of corporate America.
The biology of South African Bryde's whales
The biology of South African Bryde’s whales (Balaenoptera brydei/edeni), with a focus on the inshore form, was investigated through estimates of abundance and survival rate, seasonality of occurrence and variation in mitochondrial and nuclear DNA. Photographs, sightings data and biopsy samples were collected in Plettenberg Bay, on the south-east coast of South Africa. Additional genetic material was obtained from the Iziko South African Museum, Marine and Coastal Management, and the Port Elizabeth Museum.
Mark-recapture methods applied to photo-identification data were used to estimate abundance and survival rate. Estimates of abundance ranged from 130 to 250 (CV = 0.07 - 0.38) and the estimated annual survival rate was 0.93 (CV = 0.047, 95% CI = 0.852 - 1.0). Seasonal increases in the encounter rate and number of individual whales were observed during summer and autumn, with a peak in April, which corresponded to increased feeding activity and larger average aggregation sizes. Chlorophyll-a, sea surface temperature and wind speed were all significant factors in explaining the variability in the occurrence of whales. No seasonality in the occurrence of calves was detected.
Mitochondrial DNA control region sequences (685bp) were compared to published sequences. This confirmed the offshore form as Balaenoptera brydei and the inshore form as closely related to B.brydei, possibly at the sub-specific level, but excluded it as B.edeni. Phylogenetic analyses support complete separation between the two forms. The use of 10 polymorphic microsatellite loci revealed no population structure among the inshore samples (FST = 0.006). Pairwise estimates of relatedness found most individuals to be unrelated, with only a few distant relatives detected
First direct evidence for natal wintering ground fidelity and estimate of juvenile survival in the New Zealand Southern right whale Eubalaena australis
E. Carroll was supported by a Tertiary Education Commission Top Achiever Scholarship, an OMV New Zealand Ltd Scholarship and the School of Biological Sciences, University of Auckland.Juvenile survival and recruitment can be more sensitive to environmental, ecological and anthropogenic factors than adult survival, influencing population-level processes like recruitment and growth rate in long-lived, iteroparous species such as southern right whales. Conventionally, Southern right whales are individually identified using callosity patterns, which do not stabilise until 6–12 months, by which time the whale has left its natal wintering grounds. Here we use DNA profiling of skin biopsy samples to identify individual Southern right whales from year of birth and document their return to the species’ primary wintering ground in New Zealand waters, the Subantarctic Auckland Islands. We find evidence of natal fidelity to the New Zealand wintering ground by the recapture of 15 of 57 whales, first sampled in year of birth and available for subsequent recapture, during winter surveys to the Auckland Islands in 1995–1998 and 2006–2009. Four individuals were recaptured at the ages of 9 to 11, including two females first sampled as calves in 1998 and subsequently resampled as cows with calves in 2007. Using these capture-recapture records of known-age individuals, we estimate changes in survival with age using Cormack-Jolly-Sebermodels. Survival is modelled using discrete age classes and as a continuous function of age. Using a bootstrap method to account for uncertainty in model selection and fitting, we provide the first direct estimate of juvenile survival for this population. Our analyses indicate a high annual apparent survival for juveniles at between 0.87 (standard error (SE) 0.17, to age 1) and 0.95 (SE 0.05: ages 2–8). Individual identification by DNA profiling is an effective method for long-term demographic and genetic monitoring, particularly in animals that change identifiable features as they develop or experience tag loss over time.Peer reviewe
Spatially structured genetic variation in a broadcast spawning bivalve: quantitative vs. molecular traits
Understanding the origin, maintenance and significance of phenotypic variation is one of the central issues in evolutionary biology. An ongoing discussion focuses on the relative roles of isolation and selection as being at the heart of genetically based spatial variation. We address this issue in a representative of a taxon group in which isolation is unlikely: a marine broadcast spawning invertebrate. During the free-swimming larval phase, dispersal is potentially very large. For such taxa, small-scale population genetic structuring in neutral molecular markers tends to be limited, conform expectations. Small-scale differentiation of selective traits is expected to be hindered by the putatively high gene flow. We determined the geographical distribution of molecular markers and of variation in a shell shape measure, globosity, for the bivalve Macoma balthica (L.) in the western Dutch Wadden Sea and adjacent North Sea in three subsequent years, and found that shells of this clam are more globose in the Wadden Sea. By rearing clams in a common garden in the laboratory starting from the gamete phase, we show that the ecotypes are genetically different; heritability is estimated at 23%. The proportion of total genetic variation that is between sites is much larger for the morphological additive genetic variation (QST = 0.416) than for allozyme (FST = 0.000–0.022) and mitochondrial DNA cytochrome-c-oxidase-1 sequence variation (ΦST = 0.017). Divergent selection must be involved and intraspecific spatial genetic differentiation in marine broadcast spawners is apparently not constrained by low levels of isolation.
