Propranolol blocks ventricular refractory period changes with orthostatic stress in humans

The purpose of this study was to test the hypothesis that orthostatic stress shortens the right ventricular effective refractory period by reflex activation of beta-adrenergic receptors. Twelve patients undergoing electrophysiologic testing for standard clinical indications were studied. After a full electrophysiologic study, patients underwent graded lower body negative pressure before and after administration of either propranolol (0.2 mg/kg intravenously) in Group I or atropine (0.035 mg/kg intravenously) in Group II.Before the addition of drugs, lower body negative pressure produced decreases in systolic blood pressure and significant increases in sinus rate. The effective refractory period shortened from 214 ± 8 (mean ± SEM) to 206 ± 7 ms at −40 cm H2O and to 197 ± 4 ms at −60 cm H2O lower body negative pressure. After propranolol, Group I patients had no change in right ventricular effective refractory period despite similar changes in sinus rate and systolic blood pressure. In Group II patients, atropine did not alter effective refractory period responses to lower body negative pressure.Thus, reflex adjustments to orthostatic stress result in shortening of right ventricular effective refractory period mediated by way of beta-adrenergic mechanisms. These findings constitute the first evidence that sympathetic influences mobilized by the body can directly modulate ventricular electrophysiologic changes

Developmental Changes in the ECG of a Hamster Model of Muscular Dystrophy and Heart Failure

Aberrant autonomic signaling is being increasingly recognized as an important symptom in neuromuscular disorders. The δ-sarcoglycan-deficient BIO TO-2 hamster is recognized as a good model for studying mechanistic pathways and sequelae in muscular dystrophy and heart failure, including autonomic nervous system (ANS) dysfunction. Recent studies using the TO-2 hamster model have provided promising preclinical results demonstrating the efficacy of gene therapy to treat skeletal muscle weakness and heart failure. Methods to accelerate preclinical testing of gene therapy and new drugs for neuromuscular diseases are urgently needed. The purpose of this investigation was to demonstrate a rapid non-invasive screen for characterizing the ANS imbalance in dystrophic TO-2 hamsters. Electrocardiograms were recorded non-invasively in conscious ∼9-month old TO-2 hamsters (n = 10) and non-myopathic F1B control hamsters (n = 10). Heart rate was higher in TO-2 hamsters than controls (453 ± 12 bpm vs. 311 ± 25 bpm, P < 0.01). Time domain heart rate variability, an index of parasympathetic tone, was lower in TO-2 hamsters (12.2 ± 3.7 bpm vs. 38.2 ± 6.8, P < 0.05), as was the coefficient of variance of the RR interval (2.8 ± 0.9% vs. 16.2 ± 3.4%, P < 0.05) compared to control hamsters. Power spectral analysis demonstrated reduced high frequency and low frequency contributions, indicating autonomic imbalance with increased sympathetic tone and decreased parasympathetic tone in dystrophic TO-2 hamsters. Similar observations in newborn hamsters indicate autonomic nervous dysfunction may occur quite early in life in neuromuscular diseases. Our findings of autonomic abnormalities in newborn hamsters with a mutation in the δ-sarcoglycan gene suggest approaches to correct modulation of the heart rate as prevention or therapy for muscular dystrophies

The Lake Edgar Fault: an active fault in Southwestern Tasmania, Australia, with repeated displacement in the Quaternary

The Lake Edgar Fault in Western Tasmania, Australia is marked by a prominent fault scarp and is a recently reactivated fault initially of Cambrian age. The scarp has a northerly trend and passes through the western abutment of the Edgar Dam, a saddle dam on Lake Pedder. The active fault segment displaces geologically young river and glacial deposits. It is 29 ± 4 km long, and dips to the west. Movement on the fault has ruptured the ground surface at least twice within the Quaternary and possibly the last ca. 25 000 years; the most recent rupture has occurred since the last glaciation (within the last ca. 10000 years). This is the only known case of surface faulting in Australia with evidence for repeated ruptures in the Late Pleistocene. Along its central portion the two most recent surface-faulting earthquakes have resulted in about 2.5 m of vertical displacement each (western side up). The Lake Edgar Fault is considered capable of generating earthquakes in the order of magnitude 61/2-71/4. The Gell River Fault is another fault nearby that was apparently also active in the Late Pleistocene. It has yet to be studied in detail but the scarp appears to be more degraded and therefore older than the most recent movement on the Lake Edgar Fault

Influence of pretreatment on surface interaction between Cu and anatase-TiO2 in the simultaneous photoremediation of nitrate and oxalic acid

This research work was partly supported by the Petroleum Technology Development Fund (PTDF) of Nigeria. We are grateful to Abubakar Tafawa Balewa University, Bauchi-Nigeria for the award of fellowship to Haruna Adamu.Peer reviewedPostprin

Gait dynamics in mouse models of Parkinson's disease and Huntington's disease

BACKGROUND: Gait is impaired in patients with Parkinson's disease (PD) and Huntington's disease (HD), but gait dynamics in mouse models of PD and HD have not been described. Here we quantified temporal and spatial indices of gait dynamics in a mouse model of PD and a mouse model of HD. METHODS: Gait indices were obtained in C57BL/6J mice treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day for 3 days) for PD, the mitochondrial toxin 3-nitropropionic acid (3NP, 75 mg/kg cumulative dose) for HD, or saline. We applied ventral plane videography to generate digital paw prints from which indices of gait and gait variability were determined. Mice walked on a transparent treadmill belt at a speed of 34 cm/s after treatments. RESULTS: Stride length was significantly shorter in MPTP-treated mice (6.6 ± 0.1 cm vs. 7.1 ± 0.1 cm, P < 0.05) and stride frequency was significantly increased (5.4 ± 0.1 Hz vs. 5.0 ± 0.1 Hz, P < 0.05) after 3 administrations of MPTP, compared to saline-treated mice. The inability of some mice treated with 3NP to exhibit coordinated gait was due to hind limb failure while forelimb gait dynamics remained intact. Stride-to-stride variability was significantly increased in MPTP-treated and 3NP-treated mice compared to saline-treated mice. To determine if gait disturbances due to MPTP and 3NP, drugs affecting the basal ganglia, were comparable to gait disturbances associated with motor neuron diseases, we also studied gait dynamics in a mouse model of amyotrophic lateral sclerosis (ALS). Gait variability was not increased in the SOD1 G93A transgenic model of ALS compared to wild-type control mice. CONCLUSION: The distinct characteristics of gait and gait variability in the MPTP model of Parkinson's disease and the 3NP model of Huntington's disease may reflect impairment of specific neural pathways involved

Imaging spontaneous MMTVneu transgenic murine mammary tumors: targeting metabolic activity versus genetic products.

INTRODUCTION: Despite the great strides made in imaging breast cancer (BC) in humans, the current imaging modalities miss up to 30% of BC, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. Annually in the United States, approximately 5.6 million biopsies find benign lesions. More than 50% of human BCs overexpress cyclin D1, and all BCs exhibit VPAC1 oncogene products. Together, these gene products may provide an excellent biomarker for the early and accurate detection of BC. We have evaluated 4 biologically active peptide analogs that have high affinity for VPAC1. The transgenic MMTVneu mice spontaneously develop BC and metastatic lesions that overexpress cyclin D1 and VPAC1 biomarkers. The MMTVneu mouse, therefore, provides an excellent animal model that mimics the pathogenesis of human BC. The objective of this investigation was to determine the ability of 1 of the peptide analogs, (64)Cu-TP3805, to detect BC in MMTVneu mice using (18)F-FDG as a gold standard. METHODS: The transgenic MMTVneu mouse colony was maintained. Offspring were screened for transgenic status by reverse transcriptase polymerase chain reaction (RT-PCR). Nine mice with visible, palpable, or unknown metastatic lesions were entered into the protocol. (18)F-FDG (6,475 +/- 1,628 kBq [175 +/- 44 microCi]) PET served as a control, followed by a CT scan and 24-48 h later by PET with (64)Cu-TP3805 (4,588 +/- 962 kBq [124 +/- 26 microCi]). RT-PCR on excised tumors determined VPAC1 expression, and histology ascertained the pathology. RESULTS: Ten tumors were detected by PET. Four tumors were detected both by (18)F-FDG and by (64)Cu-TP3805. Additionally, 4 tumors were imaged with (64)Cu-TP3805 only. These 8 tumors overexpressed VPAC1 receptors and were malignant by histology. The 2 remaining tumors were visualized with (18)F-FDG only. These tumors did not express the VPAC1 oncogene product and had benign histology. The standard uptake value ranged from 3.1 to 18.3 for (64)Cu-TP3805 and 0.9 to 1.4 for (18)F-FDG. CONCLUSION: (64)Cu-TP3805 identified all malignant lesions unequivocally that overexpressed the VPAC1 oncogene surface product. The 2 benign tumors that did not express the VPAC1 receptor were not imaged. (64)Cu-TP3805 promises to have the potential for the early and accurate imaging of primary and metastatic BC

Preliminary Testing of a Pressurized Space Suit and Candidate Fabrics Under Simulated Mars Dust Storm and Dust Devil Conditions

In August 2009 YAP Films (Toronto) received permission from all entities involved to create a documentary film illustrating what it might be like to be on the surface of Mars in a space suit during a dust storm or in a dust devil. The science consultants on this project utilized this opportunity to collect data which could be helpful to assess the durability of current space suit construction to the Martian environment. The NDX?1 prototype planetary space suit developed at the University of North Dakota was used in this study. The suit features a hard upper torso garment, and a soft lower torso and boots assembly. On top of that, a nylon-cotton outer layer is used to protect the suit from dust. Unmanned tests were carried out in the Martian Surface Wind Tunnel (MARSWIT) at the NASA Ames Research Center, with the suit pressurized to 10 kPa gauge. These tests blasted the space suit upper torso and helmet, and a collection of nine candidate outer layer fabrics, with wind-borne simulant for five different 10 minute tests under both terrestrial and Martian surface pressures. The infiltration of the dust through the outer fabric of the space suit was photographically documented. The nine fabric samples were analyzed under light and electron microscopes for abrasion damage. Manned tests were carried out at Showbiz Studios (Van Nuys, CA) with the pressure maintained at 20?2 kPa gauge. A large fan-created vortex lifted Martian dust simulant (Fullers Earth or JSC Mars?1) off of the floor, and one of the authors (Lee) wearing the NDX?1 space suit walked through it to judge both subjectively and objectively how the suit performed under these conditions. Both the procedures to scale the tests to Martian conditions and the results of the infiltration and abrasion studies will be discussed

A cyclin D1/microRNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation

Decreased expression of specific microRNAs (miRNAs) occurs in human tumors, which suggests a function for miRNAs in tumor suppression. Herein, levels of the miR-17-5p/miR-20a miRNA cluster were inversely correlated to cyclin D1 abundance in human breast tumors and cell lines. MiR-17/20 suppressed breast cancer cell proliferation and tumor colony formation by negatively regulating cyclin D1 translation via a conserved 3′ untranslated region miRNA-binding site, thereby inhibiting serum-induced S phase entry. The cell cycle effect of miR-17/20 was abrogated by cyclin D1 siRNA and in cyclin D1–deficient breast cancer cells. Mammary epithelial cell–targeted cyclin D1 expression induced miR-17-5p and miR-20a expression in vivo, and cyclin D1 bound the miR-17/20 cluster promoter regulatory region. In summary, these studies identify a novel cyclin D1/miR-17/20 regulatory feedback loop through which cyclin D1 induces miR-17-5p/miR-20a. In turn, miR-17/20 limits the proliferative function of cyclin D1, thus linking expression of a specific miRNA cluster to the regulation of oncogenesis

Satellite tracking of leatherback and loggerhead sea turtles on the Southeast African coastline

The waters of southeast Africa contain important habitats for several sea turtle species, including the leatherback Dermochelys coriacea, loggerhead Caretta caretta, hawksbill Eretmochelys imbricata, green Chelonia mydas, and olive ridley turtle Lepidochelys olivacea. Many of these species are of conservation concern (Rakotoniria & Cooke, 1994; Thorson et al., 2012; Nel et al., 2013) and vulnerable to regional threats such as fisheries by-catch or boat-strikes (Bourjea et al., 2008; Grantham et al., 2008; Pusineri & Quillard, 2008). To help in the development of effective conservation plans for these species, many conservation or research organisations have used satellite transmitters to help identify critical habitats for sea turtles (Harris et al., 2015; Robinson et al., 2016). Here, we review the movement patterns of sea turtles that have been tracked through satellite telemetry from their nesting beaches on the east coast of South Africa