Role of reflex gain and reflex delay in spinal stability--a dynamic simulation

The goal of this study was to investigate the role of reflex and reflex time delay in muscle recruitment and spinal stability. A dynamic biomechanical model of the musculoskeletal spine with reflex response was implemented to investigate the relationship between reflex gain, co-contraction, and stability in the spine. The first aim of the study was to investigate how reflex gain affected co-contraction predicted in the model. It was found that reflexes allowed the model to stabilize with less antagonistic co-contraction and hence lower metabolic power than when limited to intrinsic stiffness alone. In fact, without reflexes there was no feasible recruitment pattern that could maintain spinal stability when the torso was loaded with 200N external load. Reflex delay is manifest in the paraspinal muscles and represents the time from a perturbation to the onset of reflex activation. The second aim of the study was to investigate the relationship between reflex delay and the maximum tolerable reflex gain. The maximum acceptable upper bound on reflex gain decreased logarithmically with reflex delay. Thus, increased reflex delay and reduced reflex gain requires greater antagonistic co-contraction to maintain spinal stability. Results of this study may help understanding of how patients with retarded reflex delay utilize reflex for stability, and may explain why some patients preferentially recruit more intrinsic stiffness than healthy subjects.     

Plasma membrane domain organization regulates EGFR signaling in tumor cells

Macromolecular complexes exhibit reduced diffusion in biological membranes; however, the physiological consequences of this characteristic of plasma membrane domain organization remain elusive. We report that competition between the galectin lattice and oligomerized caveolin-1 microdomains for epidermal growth factor (EGF) receptor (EGFR) recruitment regulates EGFR signaling in tumor cells. In mammary tumor cells deficient for Golgi beta1,6N-acetylglucosaminyltransferase V (Mgat5), a reduction in EGFR binding to the galectin lattice allows an increased association with stable caveolin-1 cell surface microdomains that suppresses EGFR signaling. Depletion of caveolin-1 enhances EGFR diffusion, responsiveness to EGF, and relieves Mgat5 deficiency-imposed restrictions on tumor cell growth. In Mgat5(+/+) tumor cells, EGFR association with the galectin lattice reduces first-order EGFR diffusion rates and promotes receptor interaction with the actin cytoskeleton. Importantly, EGFR association with the lattice opposes sequestration by caveolin-1, overriding its negative regulation of EGFR diffusion and signaling. Therefore, caveolin-1 is a conditional tumor suppressor whose loss is advantageous when beta1,6GlcNAc-branched N-glycans are below a threshold for optimal galectin lattice formation.     

Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphisms

To date, only the H1 MAPT haplotype has been consistently associated with risk of developing the neurodegenerative disease progressive supranuclear palsy (PSP). We hypothesized that additional genetic loci may be involved in conferring risk of PSP that could be identified through a pooling-based genomewide association study of >500,000 SNPs. Candidate SNPs with large differences in allelic frequency were identified by ranking all SNPs by their probe-intensity difference between cohorts. The MAPT H1 haplotype was strongly detected by this methodology, as was a second major locus on chromosome 11p12-p11 that showed evidence of association at allelic (P<.001), genotypic (P<.001), and haplotypic (P<.001) levels and was narrowed to a single haplotype block containing the DNA damage-binding protein 2 (DDB2) and lysosomal acid phosphatase 2 (ACP2) genes. Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, both genes are viable candidates for conferring risk of disease.     

An amphibious bryozoan from living mangrove leaves - Amphibiobeania new genus (Beaniidae)

Amphibiobeania epiphylla is a new, monotypic taxon of Beaniidae (Cheilostomata) from Darwin, Northern Territory. It is unique among the 6,000 living species of Bryozoa in that it encrusts mainly living tree leaves (chiefly the mangrove Rhizophora stylosa). The consequence of living in such a specialized habitat is that colonies are emergent (subaerial) for a significant part of the tidal cycle-around 12 of every 24 hours during spring tides and for several days during neap tides. Desiccation is prevented or minimized by the high humidity of the habitat and a cohesive coating of silt covering the colony. Zooids are weakly calcified and lie alternately on their left and right sides in a lineal series, with opercula displaced to the outer corner of the distal zooidal rim. Organisms associated with A. epiphylla include a colony-damaging ceratopogonid (Diptera) larva and a tarsonemid mite that may use dead zooidal interiors, beneath the silt crust, for shelter.     

Substratum and morphometric relationships in the bryozoan genus Odontoporella, with a description of a new paguridean-symbiont species from New Zealand

Members of the bryozoan family Hippoporidridae have frequently been found encrusting gastropod shells inhabited by hermit crabs, with which they appear to enter into a symbiotic relationship-shells occupied by hermits may in some species have a tubular extension of the encrusting bryozoan from the shell opening, induced by the presence of the crab. Such colony growth is characteristic of some species of Hippoporidra Canu and Bassler and Odontoporella Héjjas. The type species of Odontoporella, O. adpressa (Busk), has been attributed a nominal distribution from Chiloe Island, Chile (the type locality), to the Falkland Islands, New Zealand, and New Caledonia. In New Zealand, colonies are relatively easily obtainable from some localities, so a study was undertaken to ascertain substratum and morphometric relationships across the range of distribution of the species, using museum specimens and, where possible, fresh material. It became clear that the New Zealand population constitutes a separate species, here named O. bishopi n. sp., in which the orifice is proportionately larger than in O. adpressa. In contrast to O. adpressa, which settles on a range of substrata, O. bishopi preferentially settles on gastropod shells occupied by hermit crabs (mostly Paguristes setosus (H. Milne Edwards)) and shows sexual dimorphism at the level of the polypide. Male polypides not only have modified lophophores but also reduced guts.     

Blastomycosis in indoor cats: Suburban Chicago, Illinois, USA

Blastomyces dermatitidis, the etiologic agent of blastomycosis, a potentially life-threatening systemic mycosis of humans and animals, is acquired from a yet incompletely defined environmental niche. There is controversy regarding the potential for contact with the fungus in or near one’s home, particularly in urban areas. We investigated an outbreak of blastomycosis among five urban, indoor cats diagnosed at three veterinary clinics March 3–July 13, 2005, in suburban Chicago, Illinois, by owner interviews, site visits, environmental cultures for B. dermatitidis, GIS analysis, and analysis of local weather data. There were no environmental exposures common to the five cats that lived a median of 300 m from nearest body of water, in homes on a loam soil. Closest and farthest case home sites were 3.4 and 26.1 km, respectively. All cats were confined indoors except one cat that averaged 15 min/week in his backyard and was exposed to excavation. B. dermatitidis was not isolated from any of 60 environmental samples. The annualized incidence rate March through July 2005 among 6,761 cats in these practices was 178/100,000, compared to none in the previous 4 years, and 0.14/100,000 cat visits from a nationwide animal hospital registry. Precipitation January through June 2005 was 9.30 versus period mean of 14.05 ± 1.69 inches the previous 4 years (P = 0.01). Circumstantial evidence suggests acquisition of B. dermatitidis from the home site environment in five cats. Relative drought may have contributed to an apparent outbreak of blastomycosis in this urban locale.     

Pressure dissociation of integration host factor-DNA complexes reveals flexibility-dependent structural variation at the protein-DNA interface

E. coli Integration host factor (IHF) condenses the bacterial nucleoid by wrapping DNA. Previously, we showed that DNA flexibility compensates for structural characteristics of the four consensus recognition elements associated with specific binding (Aeling et al., J. Biol. Chem. 281, 39236–39248, 2006). If elements are missing, high-affinity binding occurs only if DNA deformation energy is low. In contrast, if all elements are present, net binding energy is unaffected by deformation energy. We tested two hypotheses for this observation: in complexes containing all elements, (1) stiff DNA sequences are less bent upon binding IHF than flexible ones; or (2) DNA sequences with differing flexibility have interactions with IHF that compensate for unfavorable deformation energy. Time-resolved Förster resonance energy transfer (FRET) shows that global topologies are indistinguishable for three complexes with oligonucleotides of different flexibility. However, pressure perturbation shows that the volume change upon binding is smaller with increasing flexibility. We interpret these results in the context of Record and coworker's model for IHF binding (J. Mol. Biol. 310, 379–401, 2001). We propose that the volume changes reflect differences in hydration that arise from structural variation at IHF–DNA interfaces while the resulting energetic compensation maintains the same net binding energy.     

Small multicopy, non-integrative shuttle vectors based on the plasmid pRN1 for Sulfolobus acidocaldarius and Sulfolobus solfataricus, model organisms of the (cren-)archaea

The extreme thermoacidophiles of the genus Sulfolobus are among the best-studied archaea but have lacked small, reliable plasmid vectors, which have proven extremely useful for manipulating and analyzing genes in other microorganisms. Here we report the successful construction of a series of Sulfolobus–Escherichia coli shuttle vectors based on the small multicopy plasmid pRN1 from Sulfolobus islandicus. Selection in suitable uracil auxotrophs is provided through inclusion of pyrEF genes in the plasmid. The shuttle vectors do not integrate into the genome and do not rearrange. The plasmids allow functional overexpression of genes, as could be demonstrated for the β-glycosidase (lacS) gene of S. solfataricus. In addition, we demonstrate that this β-glycosidase gene could function as selectable marker in S. solfataricus. The shuttle plasmids differ in their interruption sites within pRN1 and allowed us to delineate functionally important regions of pRN1. The orf56/orf904 operon appears to be essential for pRN1 replication, in contrast interruption of the highly conserved orf80/plrA gene is tolerated. The new vector system promises to facilitate genetic studies of Sulfolobus and to have biotechnological uses, such as the overexpression or optimization of thermophilic enzymes that are not readily performed in mesophilic hosts.     

The LOC387715 gene, smoking, body mass index, environmental associations with advanced age-related macular degeneration

BACKGROUND AND AIMS: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. It is now evident that both genetic and environmental factors contribute to disease susceptibility. We tested the hypotheses that (a) a common coding SNP in the LOC387715 gene is associated with advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that modifiable environmental exposures alter AMD susceptibility associated with this SNP. METHODS: A case-control association analysis was performed on participants (530 advanced AMD cases and 280 controls) ascertained as part of the multi-center Age-Related Eye Disease Study. AMD status was determined by the reading center from fundus photographs using the AREDS AMD grading categorization. Environmental risk factor exposure data was collected from participants whose DNA was also genotyped for the LOC387715 gene SNP rs10490924. Multivariate logistic regression analyses were performed. RESULTS AND CONCLUSIONS: The number of risk alleles at the LOC387715 SNP was associated with advanced AMD, with odds ratios (OR) = 3.0 (95% confidence interval (CI) 2.1-4.3) for the GT heterozygous genotype and OR = 12.1 (5.6-26.5) for the homozygous TT risk genotype, after controlling for demographic and behavioral risk factors. The LOC387715 SNP was associated with both forms of advanced AMD. Current cigarette smoking and body mass index were independently related to AMD, controlling for genotype. However, there was no statistical interaction between LOC387715 genotype and smoking with regard to advanced AMD development.