Principles of entrainment: diagnostic utility for supraventricular tachycardia

Entrainment is an important pacing maneuver that can be used to identify reentry as a tachycardia mechanism and define components of the circuit. This review examines how principles of entrainment can be used to arrive at a firm supraventricular tachycardia diagnosis using a simple algorithm and builds a foundation for the application of entrainment to more complex or unknown circuits.     

CED-10/Rac1 mediates axon guidance by regulating the asymmetric distribution of MIG-10/lamellipodin

Axon migrations are guided by extracellular cues that induce asymmetric outgrowth activity in the growth cone. Several intracellular signaling proteins have been implicated in the guidance response. However, how these proteins interact to generate asymmetric outgrowth activity is unknown. Here, we present evidence that in C. elegans, the CED-10/Rac1 GTPase binds to and causes asymmetric localization of MIG-10/lamellipodin, a protein that regulates actin polymerization and has outgrowth-promoting activity in neurons. Genetic analysis indicates that mig-10 and ced-10 function together to orient axon outgrowth. The RAPH domain of MIG-10 binds to activated CED-10/Rac1, and ced-10 function is required for the asymmetric MIG-10 localization that occurs in response to the UNC-6/netrin guidance cue. We also show that asymmetric localization of MIG-10 in growth cones is associated with asymmetric concentrations of f-actin and microtubules. These results suggest that CED-10/Rac1 is asymmetrically activated in response to the UNC-6/netrin signal and thereby causes asymmetric recruitment of MIG-10/lamellipodin. We propose that the interaction between activated CED-10/Rac1 and MIG-10/lamellipodin triggers local cytoskeletal assembly and polarizes outgrowth activity in response to UNC-6/netrin.     

Axon guidance: asymmetric signaling orients polarized outgrowth

A network of connections is established as neural circuits form between neurons. To make these connections, neurons initiate asymmetric axon outgrowth in response to extracellular guidance cues. Within the specialized growth cones of migrating axons, F-actin and microtubules asymmetrically accumulate where an axon projects forward. Although many guidance cues, receptors and intracellular signaling components that are required for axon guidance have been identified, the means by which the asymmetry is established and maintained is unclear. Here, we discuss recent studies in invertebrate and vertebrate organisms that define a signaling module comprising UNC-6 (the Caenorhabditis elegans ortholog of netrin), UNC-40 (the C. elegans ortholog of DCC), PI3K, Rac and MIG-10 (the C. elegans ortholog of lamellipodin) and we consider how this module could establish polarized outgrowth in response to guidance cues.     

Selenium hyperaccumulation reduces plant arthropod loads in the field

The elemental defense hypothesis proposes that some plants hyperaccumulate toxic elements as a defense mechanism. In this study the effectiveness of selenium (Se) as an arthropod deterrent was investigated under field conditions. Arthropod loads were measured over two growing seasons in Se hyperaccumulator habitats in Colorado, USA, comparing Se hyperaccumulator species (Astragalus bisulcatus and Stanleya pinnata) with nonhyperaccumulators (Camelina microcarpa, Astragalus americanus, Descurainia pinnata, Medicago sativa, and Helianthus pumilus). The Se hyperaccumulating plant species, which contained 1000-14 000 microg Se g(-1) DW, harbored significantly fewer arthropods (c. twofold) and fewer arthropod species (c. 1.5-fold) compared with nonhyperaccumulator species that contained < 30 microg Se g(-1) DW. Arthropods collected on Se-hyperaccumulating plants contained three- to 10-fold higher Se concentrations than those found on nonhyperaccumulating species, but > 10-fold lower Se concentrations than their hyperaccumulator hosts. Several arthropod species contained > 100 microg Se g(-1) DW, indicating Se tolerance and perhaps feeding specialization. These results support the elemental defense hypothesis and suggest that invertebrate herbivory may have contributed to the evolution of Se hyperaccumulation.     

Comparison of plasma viremia and antibody responses in macaques inoculated with envelope variants of single-cycle simian immunodeficiency virus differing in infectivity and cellular tropism

Molecular differences in the envelope glycoproteins of human immunodeficiency virus type 1 and simian immunodeficiency virus (SIV) determine virus infectivity and cellular tropism. To examine how these properties contribute to productive infection in vivo, rhesus macaques were inoculated with strains of single-cycle SIV (scSIV) engineered to express three different envelope glycoproteins with full-length (TM_open) or truncated (TM_stop) cytoplasmic tails. The 239 envelope uses CCR5 for infection of memory CD4⁺ T cells, the 316 envelope also uses CCR5 but has enhanced infectivity for primary macrophages, and the 155T3 envelope uses CXCR4 for infection of both naive and memory CD4⁺ T cells. Separate groups of six rhesus macaques were inoculated intravenously with mixtures of TM_open and TM_stop scSIV_mac239, scSIV_mac316, and scSIV_mac155T3. A multiplex real-time PCR assay specific for unique sequence tags engineered into each virus was then used to measure viral loads for each strain independently. Viral loads in plasma peaked on day 4 for each strain and were resolved below the threshold of detection within 4 to 10 weeks. Truncation of the envelope cytoplasmic tail significantly increased the peak of viremia for all three envelope variants and the titer of SIV-specific antibody responses. Although peak viremias were similar for both R5- and X4-tropic viruses, clearance of scSIV_mac155T3 TM_stop was significantly delayed relative to the other strains, possibly reflecting the infection of a CXCR4⁺ cell population that is less susceptible to the cytopathic effects of virus infection. These studies reveal differences in the peaks and durations of a single round of productive infection that reflect envelope-specific differences in infectivity, chemokine receptor specificity, and cellular tropism.     

The effect of feeding propylene glycol to dairy cows during the early postpartum period on follicular dynamics and on metabolic parameters related to fertility

Postpartum dairy cows (n=35) were used to determine the effects of feeding propylene glycol (PG) on metabolic variables related to ovarian function and on oocyte developmental competence. Starting on Day 7 postpartum, each animal received an oral dose (500 ml) of either PG or water once daily. Blood samples were collected on Days 5, 15, 25 and 35 pp to measure insulin, non-esterified fatty acids (NEFAs), beta-hydroxybutyrate (BHB) and glucose concentrations. Oocytes were recovered by ultrasound guided follicular aspiration starting on approximately Day 30 postpartum and submitted to in vitro fertilization. Ovarian follicular activity was examined daily by ultrasonography from Day 7 until ovulation or Days 35-40 postpartum. Animals receiving PG had elevated insulin concentrations over the subsequent 90 min following dosing (P<0.05) compared to control animals. Glucose concentrations followed a similar pattern. Irrespective of treatment, concentrations of NEFA declined significantly from Days 15 to 35 postpartum. Administration of PG resulted in a decrease in NEFA (P<0.001) and BHB (P<0.001) over the subsequent 90 min compared to control animals. Treatment with PG had no effect on follicular dynamics, mean days to emergence of the first cohort of follicles postpartum, or days to dominance and duration of dominance for any follicular wave recorded postpartum. There was also no difference in mean days to first ovulation or in size of the preovulatory follicle between treatments. Oocyte quality as measured by blastocyst development after IVF was not affected by treatment. These results suggest that administration of PG has the ability to positively alter the systemic concentrations of a number of metabolic variables which have been related to fertility. However, we did not observe an effect of PG treatment on follicular dynamics or the length of the postpartum interval. An effect on oocyte developmental competence remains to be proven.     

Static compression of articular cartilage can reduce solute diffusivity and partitioning: implications for the chondrocyte biological response.

Chondrocytes depend upon solute transport within the avascular extracellular matrix of adult articular cartilage for many of their biological activities. Alterations to bioactive solute transport may, therefore, represent a mechanism by which cartilage compression is transduced into cellular metabolic responses. We investigated the effects of cartilage static compression on diffusivity and partitioning of a range of model solutes including dextrans of molecular weights 3 and 40 kDa, and tetramethylrhodamine (a 430 Da fluorophore). New fluorescence methods were developed for real-time visualization and measurement of transport within compressed cartilage explants. Experimental design allowed for multiple measurements on individual explants at different compression levels in order to minimize confounding influences of compositional variations. Results demonstrate that physiological levels of static compression may significantly decrease solute diffusivity and partitioning in cartilage. Effects of compression were most dramatic for the relatively high molecular weight solutes. For 40 kDa dextran, diffusivity decreased significantly (p<0.01) between 8% and 23% compression, while partitioning of 3 and 40 kDa dextran decreased significantly (p<0.01) between free-swelling conditions and 8% compression. Since diffusivity and partitioning can influence pericellular concentrations of bioactive solutes, these observations support a role for perturbations to solute transport in mediating the cartilage biological response to compression.     

Consumption choice by bears feeding on salmon

Consumption choice by brown (Ursus arctos) and black bears (U. americanus) feeding on salmon was recorded for over 20,000 bear-killed fish from 1994 to 1999 in Bristol Bay (sockeye salmon, Oncorhynchus nerka) and southeastern Alaska (pink, O. gorbuscha and chum salmon O. keta). These data revealed striking patterns of partial and selective consumption that varied with relative availability and attributes of the fish. As the availability of salmon decreased, bears consumed a larger proportion of each fish among both years and habitats. When availability was high (absolute number and density of salmon), bears consumed less biomass per captured fish, targeting energy-rich fish (those that had not spawned) or energy-rich body parts (eggs in females; brain in males). In contrast, individual fish were consumed to a much greater extent, regardless of sex or spawning status, in habitats or years of low salmon availability. The proportion of biomass consumed per fish was similar for males and females, when spawning status was statistically controlled, but bears targeted different body parts: the body flesh, brain and dorsal hump in males and the roe in females. Bears thus appeared to maximize energy intake by modifying the amount and body parts consumed, based on availability and attributes of spawning salmon.     

Fetal lung growth after short-term tracheal occlusion is linearly related to intratracheal pressure.

Prenatal tracheal occlusion (TO) has been shown to accelerate fetal lung growth, yet the mechanism is poorly understood. The goal of this study was to determine the relationship between fetal intratracheal pressure (Pitr) and fetal lung growth after TO. Fetal lambs underwent placement of an intratracheal catheter and a reference catheter at 115--120 days gestation (term, 145 days). Fetal Pitr was continuously controlled at three levels (high, 8 mmHg; moderate, 4 mmHg; low, 1 mmHg) by a servo-regulated pump. The animals were killed after 4 days, and the parameters of lung growth were compared. Lung volume (136.0 +/- 16.7, 94.9 +/- 9.7, 55.5 +/- 12.4 ml/kg), lung-to-body weight ratio (6.31 +/- 0.70, 4.89 +/- 0.38, 3.39 +/- 0.22%), whole right lung dry weight (3.01 +/- 0.29, 2.53 +/- 0.15, 2.07 +/- 0.24 g/kg), right lung DNA (130.0 +/- 11.3, 116.7 +/- 8.6, 97.5 +/- 10.9 mg/kg), and protein contents (1,865.5 +/- 92.5, 1,657.6 +/- 106.8, 1,312.0 +/- 142.5 mg/kg) in high, moderate, and low groups, respectively, all increased in the moderate compared with the low group and increased further in the high compared with the moderate group. Morphometry confirmed a stepwise increase in the volume of respiratory region and alveolar surface area. We conclude that lung growth in the first 4 days after TO is closely correlated with fetal Pitr, offering additional evidence that an increase in lung expansion is one of the major factors responsible for TO-induced lung growth.     

Kinship analysis of Pacific salmon: insights into mating, homing, and timing of reproduction

Multilocus microsatellite genotypes were used to infer kinship and relatedness in two species of Pacific salmon from three populations in Washington State. Even in the absence of direct genetic data from parents, clustering of individuals according to allele sharing and reconstruction of parental genotypes allowed resolution of full- and half-sib relationships among 135 chinook salmon (Oncorhynchus tshawytscha) sampled as preemergent juveniles from 14 redds in the Dungeness River. Inferred reproductive behaviors included single-pair matings, polyandry in which females mated with two to three males at a single redd, polygyny in which males mated with two females at different redds, use of two redds by a single female, and use of one redd site by two females. Greater average relatedness (rxy) in the upper reach of the Dungeness River implied within-reach homing of returning adults. In steelhead trout (O. mykiss), the frequency of related pairs (dyads) of mature individuals that migrated up Snow Creek less than a week apart was greater than expected for randomly chosen dyads, as was the frequency of steelhead dyads that were spawned on the same day in the Forks Creek hatchery. These results imply a heritable basis for upstream migration date and maturation date in steelhead trout.