The diet of juvenile and adult female California sea lions (
Zalophus californianus
(Lesson, 1828)) at San Miguel Island, California, was estimated and compared using fecal and stable isotope ...analyses to determine dietary differences by age. Fecal samples were collected during 2002-2006 and prey remains were identified. Stable carbon ( δ
13
C) and stable nitrogen ( δ
15
N) isotope values were determined from plasma and fur obtained from yearlings, 2- to 3-year-old juveniles, and adult females during 2005 and 2006. Juveniles ate more than 15 prey taxa, whereas adult females consumed more than 33 taxa. Relative importance of prey was determined using percent frequency of occurrence (%FO).
Engraulis mordax
Girard, 1854,
Sardinops sagax
(Jenyns, 1842),
Merluccius productus
(Ayres, 1855), genus
Sebastes
Cuvier, 1829, and
Loligo opalescens
Berry, 1911 were the most frequently occurring (%FO > 10%) prey in the feces of both juvenile and adult female sea lions, although their importance varied between age groups. Only yearlings had significantly different isotopic values than older conspecifics, indicating that older juveniles were feeding at a similar trophic level and in similar habitats as adult females. Whereas each method had biases, combining the two provided a better understanding of the diet of California sea lions and intraspecific differences.
The peritoneal cavity (PNC) and intestine of northern fur seal (
Callorhinus ursinus
) pups and California sea lion (
Zalophus californianus)
pups that died in late July and early August, 2003, on ...San Miguel Island, California, were examined for hookworms. Prevalence and morphometric studies were done with the hookworms in addition to molecular characterization. Based on this and previous molecular studies, hookworms from fur seals are designated as
Uncinaria lucasi
and the species from sea lions as
Uncinaria
species A. Adult hookworms were found in the PNC of 35 of 57 (61.4%) fur seal pups and of 13 of 104 (12.5%) sea lion pups. The number of hookworms located in the PNC ranged from 1 to 33 (median = 3) for the infected fur seal pups and 1 to 16 (median = 2) for the infected sea lion pups. In addition to the PNC, intestines of 43 fur seal and 32 sea lion pups were examined. All of these pups were positive for adult hookworms. The worms were counted from all but one of the sea lion pups. Numbers of these parasites in the intestine varied from 3 to 2,344 (median = 931) for the fur seal pups and 39 to 2,766 (median = 643) for the sea lion pups. Sea lion pups with peritoneal infections had higher intensity infections in the intestines than did pups without peritoneal infections, lending some support for the hypothesis that peritoneal infections result from high-intensity infections of adult worms. There was no difference in intestinal infection intensities between fur seal pups with and without peritoneal infections. Female adult hookworms in the intestines of both host species were significantly larger than males, and sea lion hookworms were larger than those in fur seals. Worms in the intestine also were larger than worms found in the PNC. Gene sequencing and (RFLP) analysis of (PCR) amplified (ITS) ribosomal DNA were used to diagnose the species of 172 hookworms recovered from the PNC and intestine of 18
C. ursinus
and seven
Z. californianus
hosts. These molecular data revealed that
U. lucasi
(hookworm of
C. ursinus
) and
Uncinaria
species A (of
Z. californianus
) infrequently mature in the intestine of the opposite host species in California rookeries. However, there is no support from molecular data for the hypothesis that cross-infection with “the wrong”
Uncinaria
species is a contributing factor in these cases of host peritonitis. The major significance of this research is the unusual finding of adult hookworms in the PNC of so many dead pups. No obvious explanation for this occurrence could be determined. Further research, like in the present study, should help understand and monitor the apparent ever changing role of hookworm disease in the health of northern fur seal and California sea lion pups on SMI.
The basal ganglia are currently viewed as components of segregated corticosubcortical reentrant circuits. One of these circuits, the "motor" circuit, is critically involved in the development of ...parkinsonian motor signs. Current pathophysiologic models postulate that parkinsonism is associated with increased activity in the basal ganglia output nuclei. The neuronal activity in the motor portion of one of these output nuclei, the internal segment of the globus pallidus (GPi), has been characterized in detail in intact and parkinsonian animals, but the neuronal activity in the second major basal ganglia output nucleus, the substantia nigra pars reticulata (SNr), has received far less attention. This study in primates represents a comparison of the effects of parkinsonism, induced by injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on the neuronal discharge in the GPi and SNr. These electrophysiologic recording experiments were carried out in three African green and two rhesus monkeys. One hundred and twenty-four neurons were recorded in the GPi before treatment with MPTP, and 93 neurons thereafter. In the SNr, 55 cells were recorded before treatment with MPTP, and 41 cells thereafter. MPTP induced a non-significant increase in the average discharge rate and a significant decrease in the median interspike interval length (ISI) in the GPi (by 13%), whereas no changes were detected in either parameter in the SNr. The average ISI distributions were markedly asymmetric in both structures, and could be modeled by a logarithmic normal distribution. With the MPTP treatment, the mode of the ISI distribution fell by 24% in the GPi (P< or =0.01), whereas it did not change significantly in the SNr. An algorithm that detects burst discharges in the raw ISI data (based on the method by Legendy and Salcman) detected a significant increase in the proportion of action potentials that participated in bursts of discharge in both structures (increase by 257% in the GPi, and by 67% in the SNr). Power spectral and autocorrelation analysis revealed that treatment with MPTP increased the proportion of cells with oscillatory burst patterns at 3-8 Hz in both structures (from 0.8% to 27% of all neurons in the GPi, and from none to 10% in the SNr). The results show that neuronal discharge in the SNr is affected in parkinsonism, but that the changes in the SNr are less pronounced then those seen in the GPi.
We compared the nonbreeding-season foraging behavior of lactating California sea lions (
Zalophus californianus californianus
(Lesson, 1828)) at San Miguel Island, California, during El Niño ...conditions in 1993 and non-El Niño conditions in 1996. Lactating females were instrumented with satellite-linked time-depth recorders between January and March in 1993 (n = 6) and 1996 (n = 10) and data were collected through May in each year. Females foraged northwest of the colony, up to 367 km from it and 230 km from the California coast. Mean dive depths ranged from 19.5 to 279.3 m, but most females achieved dives deeper than 400 m. Most females fed exclusively in the offshore habitat, traveled farther from the colony, spent more time traveling, made deeper and longer dives, and terminated lactation earlier during the 1993 El Niño. The results suggest that prey were concentrated in the offshore habitat and located farther from the colony and deeper in the water column during El Niño. Females did not change their foraging direction, foraging-trip duration, foraging effort, or prey species consumed.
We have fabricated a hepatic tissue construct using a multilayer photopatterning platform for embedding cells in hydrogels of complex architecture. We first explored the potential of established ...hepatocyte culture models to stabilize isolated hepatocytes for photoencapsulation (e.g., double gel, Matrigel, cocultivation with nonparenchymal cells). Using photopolymerizable PEG hydrogels, we then tailored both the chemistry and architecture of the hydrogels to further support hepatocyte survival and liver-specific function. Specifically, we incorporated adhesive peptides to ligate key integrins on these adhesion-dependent cells. To identify the appropriate peptides for incorporation, the integrin expression of cultured hepatocytes was monitored by flow cytometry and their functional role in cell adhesion was assessed on full-length extracellular matrix (ECM) molecules and their adhesive peptide domains. In addition, we modified the hydrogel architecture to minimize barriers to nutrient transport for these highly metabolic cells. Viability of encapsulated cells was improved in photopatterned hydrogels with structural features of 500 μm in width over unpatterned, bulk hydrogels. Based on these findings, we fabricated a multilayer photopatterned PEG hydrogel structure containing the adhesive RGD peptide sequence to ligate the α₅β₁ integrin of cocultured hepatocytes. Three-dimensional photopatterned constructs were visualized by digital volumetric imaging and cultured in a continuous flow bioreactor for 12 d where they performed favorably in comparison to unpatterned, unperfused constructs. These studies will have impact in the field of liver biology as well as provide enabling tools for tissue engineering of other organs.--Liu Tsang, V., Chen, A. A., Cho, L. M., Jadin, K. D., Sah, R. L., DeLong, S., West, J. L., Bhatia, S. N. Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels.
Carcasses of northern fur seal pups,
Callorhinus ursinus
, collected from the rookeries of Bering Island (
n
= 133), were examined for hookworms
Uncinaria
spp. The parasite was found in 90% of the ...pups from the Severo-Zapadnoe rookery and in 45% of the pups from the Severnoe rookery. This difference in prevalence of nematode infection between the rookeries is associated with the type of substrate, as well as with the pattern of distribution of the seal reproductive groups on each of the rookeries.
Necropsy and extensive parasitological examination of dead northern elephant seal (NES) pups was done on San Miguel Island, California, in February, 2015. The main interest in the current study was ...to determine if hookworms were present in NESs on San Miguel Island where two hookworm species of the genus Uncinaria are known to be present - Uncinaria lyonsi in California sea lions and Uncinaria lucasi in northern fur seals. Hookworms were not detected in any of the NESs examined: stomachs or intestines of 16 pups, blubber of 13 pups and blubber of one bull. The results obtained in the present study of NESs on San Miguel Island plus similar finding on Año Nuevo State Reserve and The Marine Mammal Center provide strong indication that NES are not appropriate hosts for Uncinaria spp. Hookworm free-living third stage larvae, developed from eggs of California sea lions and northern fur seals, were recovered from sand. It seems that at this time, further search for hookworms in NESs would be nonproductive.
Clinical trials have shown that beta-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients ...with advanced disease have not been evaluated.
We enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.16 +/- 0.01 and a mean maximal oxygen consumption of 13.6 +/- 0.6 mL.kg-1.min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n = 33) or matching placebo (n = 16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P = .005) and stroke volume index (P = .010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P = .003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P = .002), functional class (P = .013), and submaximal exercise tolerance (P = .006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P = .028), but carvedilol-treated patients had more dizziness and advanced heart block.
Carvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors.
Survival after coronary artery bypass graft surgery (CABG) and medical therapy in patients with coronary artery disease (CAD) has been studied in both randomized trials and observational treatment ...comparisons. Over the past decade, the use of coronary angioplasty (PTCA) has increased dramatically, without guidance from either randomized trials or prospective observational comparisons. The purpose of this study was to describe the survival experience of a large prospective cohort of CAD patients treated with medicine, PTCA, or CABG.
The study was designed as a prospective nonrandomized treatment comparison in the setting of an academic medical center (tertiary care). Subjects were 9263 patients with symptomatic CAD referred for cardiac catheterization (1984 through 1990). Patients with prior PTCA or CABG, valvular or congenital disease, nonischemic cardiomyopathy, or significant (> or = 75%) left main disease were excluded. Baseline clinical, laboratory, and catheterization data were collected prospectively in the Duke Cardiovascular Disease Databank. All patients were contacted at 6 months, 1 year, and annually thereafter (follow-up 97% complete). Cardiovascular death was the primary end point. Of this cohort, 2788 patients were treated with PTCA (2626 within 60 days) and 3422 with CABG (3080 within 60 days). Repeat or crossover revascularization procedures were counted as part of the initial treatment strategy. Kaplan-Meier survival curves (both unadjusted and adjusted for all known imbalances in baseline prognostic factors) were used to examine absolute survival differences, and treatment pair hazard ratios from the Cox model were used to summarize average relative survival benefits. For the latter, a 13-level CAD prognostic index was used to examine the relation between survival and revascularization as a function of CAD severity. The effects of revascularization on survival depended on the extent of CAD. For the least severe forms of CAD (ie, one-vessel disease), there were no survival advantages out to 5 years for revascularization over medical therapy. For intermediate levels of CAD (ie, two-vessel disease), revascularization was associated with higher survival rates than medical therapy. For less severe forms of two-vessel disease, PTCA had a small advantage over CABG, whereas for the most severe form of two-vessel disease (with a critical lesion of the proximal left anterior descending artery), CABG was superior. For the most severe forms of CAD (ie, three-vessel disease), CABG provided a consistent survival advantage over medicine. PTCA appeared prognostically equivalent to medicine in these patients, but the number of PTCA patients in this subgroup was low.
In this first large-scale, prospective observational treatment comparison of PTCA, CABG, and medicine, we confirmed the previously reported survival advantages for CABG over medical therapy for three-vessel disease and severe two-vessel disease. For less severe CAD, the primary treatment choices are between medicine and PTCA. In these patients, there is a trend for a relative survival advantage with PTCA, although absolute survival differences were modest. In this setting, treatment decisions should be based not only on survival differences but also on symptom relief, quality of life outcomes, and patient preferences.
PAMAM G5 dendrimer (P) was conjugated to Tat peptide (T), a cell penetrating peptide, in search of an efficient cellular delivery vehicle for antisense and siRNA oligonucleotides.
PAMAM G5 dendrimer ...was reacted with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionic acid, sulfosuccinimidyl ester, sodium salt (BODIPY) for visualization to yield the conjugate BP. Bifunctional sulfosuccinimidyl 6-alpha-methyl-alpha-(2-pyridyldithio)toluamidohexanoate (sulfo-LC-SMPT) was then used to conjugate primary amino groups of BP to cysteine derivatized Tat peptide to give the designed conjugate, BPT. This conjugate was complexed with antisense and siRNA oligonucleotides designed to inhibit MDR1 gene expression. NIH 3T3 MDR cells were used for the evaluation of biological activity of the conjugate.
Both antisense and siRNA readily formed complexes with the synthesized BPT, introduced into NIH 3T3 MDR cells, and primarily accumulated in intracellular vesicles. MDR1 gene expression was partially inhibited by the antisense-BPT complex and weakly inhibited by the siRNA-BPT complex when both were tested at nontoxic levels of dendrimer. Conjugation with Tat peptide did not improve the delivery efficiency of the dendrimer.
Dendrimer-oligonucleotide complexes were moderately effective for delivery of antisense and only poorly effective for delivery of siRNA. Conjugation of the dendrimer with the Tat cell penetrating peptide failed to further enhance the effectiveness of the dendrimer.
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