259 research outputs found

    Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms

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    In most sexually reproducing animals, replication and maintenance of telomeres occurs in the germ line and during early development in embryogenesis through the use of telomerase. Somatic cells generally do not maintain telomere sequences, and these cells become senescent in adults as telomeres shorten to a critical length. Some animals reproduce clonally and must therefore require adult somatic mechanisms for maintaining their chromosome ends. Here we study the telomere biology of planarian flatworms with apparently limitless regenerative capacity fueled by a population of highly proliferative adult stem cells. We show that somatic telomere maintenance is different in asexual and sexual animals. Asexual animals maintain telomere length somatically during reproduction by fission or when regeneration is induced by amputation, whereas sexual animals only achieve telomere elongation through sexual reproduction. We demonstrate that this difference is reflected in the expression and alternate splicing of the protein subunit of the telomerase enzyme. Asexual adult planarian stem cells appear to maintain telomere length over evolutionary timescales without passage through a germ-line stage. The adaptations we observe demonstrate indefinite somatic telomerase activity in proliferating stem cells during regeneration or reproduction by fission, and establish planarians as a pertinent model for studying telomere structure, function, and maintenance

    Fermi surface renormalization in Hubbard ladders

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    We derive the one-loop renormalization equations for the shift in the Fermi-wavevectors for one-dimensional interacting models with four Fermi-points (two left and two right movers) and two Fermi velocities v_1 and v_2. We find the shift to be proportional to (v_1-v_2)U^2, where U is the Hubbard-U. Our results apply to the Hubbard ladder and to the t_1-t_2 Hubbard model. The Fermi-sea with fewer particles tends to empty. The stability of a saddle point due to shifts of the Fermi-energy and the shift of the Fermi-wavevector at the Mott-Hubbard transition are discussed.Comment: 5 pages, 4 Postscript figure

    Indirect measurement of anterior-posterior ground reaction forces using a minimal set of wearable inertial sensors: from healthy to hemiparetic walking

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    BACKGROUND: The anterior-posterior ground reaction force (AP-GRF) and propulsion and braking point metrics derived from the AP-GRF time series are indicators of locomotor function across healthy and neurological diagnostic groups. In this paper, we describe the use of a minimal set of wearable inertial measurement units (IMUs) to indirectly measure the AP-GRFs generated during healthy and hemiparetic walking. METHODS: Ten healthy individuals and five individuals with chronic post-stroke hemiparesis completed a 6-minute walk test over a walking track instrumented with six forceplates while wearing three IMUs securely attached to the pelvis, thigh, and shank. Subject-specific models driven by IMU-measured thigh and shank angles and an estimate of body acceleration provided by the pelvis IMU were used to generate indirect estimates of the AP-GRF time series. Propulsion and braking point metrics (i.e., peaks, peak timings, and impulses) were extracted from the IMU-generated time series. Peaks and impulses were expressed as % bodyweight (%bw) and peak timing was expressed as % stance phase (%sp). A 75%-25% split of 6-minute walk test data was used to train and validate the models. Indirect estimates of the AP-GRF time series and point metrics were compared to direct measurements made by the forceplates. RESULTS: Indirect measurements of the AP-GRF time series approximated the direct measurements made by forceplates, with low error and high consistency in both the healthy (RMSE= 4.5%bw; R2= 0.93) and post-stroke (RMSE= 2.64%bw; R2= 0.90) cohorts. In the healthy cohort, the average errors between indirect and direct measurements of the peak propulsion magnitude, peak propulsion timing, and propulsion impulse point estimates were 2.37%bw, 0.67%sp, and 0.43%bw. In the post-stroke cohort, the average errors for these point estimates were 1.07%bw, 1.27%sp, and 0.31%bw. Average errors for the braking estimates were higher, but comparable. CONCLUSIONS: Accurate estimates of AP-GRF metrics can be generated using three strategically mounted IMUs and subject-specific calibrations. This study advances the development of point-of-care diagnostic systems that can catalyze the routine assessment and management of propulsion and braking locomotor deficits during rehabilitation.KL2 TR001411 - NCATS NIH HHSPublished versio

    Failure of diplodiatoxin to induce diplodiosis in juvenile goats

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    Diplodiosis is an important neuromycotoxicosis of ruminants in South Africa when grazing on harvested maize fields in winter. It is believed to be caused by mycotoxin(s) synthesised by Stenocarpella (Diplodia) maydis. Although several metabolites have been isolated from S. maydis culture material, none of these have been administered to ruminants to reproduce the disease. The objectives of this study were to isolate diplodiatoxin and to administer it to juvenile goats. Diplodiatoxin, considered as a major metabolite, was purified from S. maydis-infected maize cultures (Coligny 2007 isolate). Following intravenous administration of 2 mg and 4 mg diplodiatoxin/kg body weight for five consecutive days to two juvenile goats, no clinical signs reminiscent of diplodiosis were observed. Based on previous experimental results and if diplodiatoxin was the causative compound, the dosage regimen employed was seemingly appropriate to induce diplodiosis. In addition, intraruminal administration of 2 mg/kg diplodiatoxin to one goat for three consecutive days also did not induce clinical signs. It appears as if diplodiatoxin alone is not the causative compound. Other metabolites and/or mixtures of diplodiatoxin and other mycotoxins, when available in sufficient quantities, should also be evaluated.The Maize Trust of South Africahttp://www.ojvr.orgam2021Paraclinical SciencesProduction Animal Studie

    A first-principles approach to electrical transport in atomic-scale nanostructures

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    We present a first-principles numerical implementation of Landauer formalism for electrical transport in nanostructures characterized down to the atomic level. The novelty and interest of our method lies essentially on two facts. First of all, it makes use of the versatile Gaussian98 code, which is widely used within the quantum chemistry community. Secondly, it incorporates the semi-infinite electrodes in a very generic and efficient way by means of Bethe lattices. We name this method the Gaussian Embedded Cluster Method (GECM). In order to make contact with other proposed implementations, we illustrate our technique by calculating the conductance in some well-studied systems such as metallic (Al and Au) nanocontacts and C-atom chains connected to metallic (Al and Au) electrodes. In the case of Al nanocontacts the conductance turns out to be quite dependent on the detailed atomic arrangement. On the contrary, the conductance in Au nanocontacts presents quite universal features. In the case of C chains, where the self-consistency guarantees the local charge transfer and the correct alignment of the molecular and electrode levels, we find that the conductance oscillates with the number of atoms in the chain regardless of the type of electrode. However, for short chains and Al electrodes the even-odd periodicity is reversed at equilibrium bond distances.Comment: 14 pages, two-column format, submitted to PR

    Non-monotonic variation with salt concentration of the second virial coefficient in protein solutions

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    The osmotic virial coefficient B2B_2 of globular protein solutions is calculated as a function of added salt concentration at fixed pH by computer simulations of the ``primitive model''. The salt and counter-ions as well as a discrete charge pattern on the protein surface are explicitly incorporated. For parameters roughly corresponding to lysozyme, we find that B2B_2 first decreases with added salt concentration up to a threshold concentration, then increases to a maximum, and then decreases again upon further raising the ionic strength. Our studies demonstrate that the existence of a discrete charge pattern on the protein surface profoundly influences the effective interactions and that non-linear Poisson Boltzmann and Derjaguin-Landau-Verwey-Overbeek (DLVO) theory fail for large ionic strength. The observed non-monotonicity of B2B_2 is compared to experiments. Implications for protein crystallization are discussed.Comment: 43 pages, including 17 figure

    Healthcare costs related to respiratory syncytial virus in paediatric intensive care units in the Netherlands:a nationwide prospective observational study (the BRICK study)

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    Background: The implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands. Methods: A nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity.Findings: A total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25–89). The median length of PICU admission was 5 days (IQR 3–8). The total RSV-related PICU costs are € 3,826,386 in 2021–2022, and € 3,183,888 in 2022–2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection. Interpretation: RSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs. </p

    Sesquiterpene lactones from Geigeria aspera Harv. and their cytotoxicity

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    Geigeria poisoning, referred to as ‘vermeersiekte’ is an important plant poisoning in southern Africa. Three sesquiterpene lactones, isogeigerin acetate (1) ivalin (2) and geigerin (3) were isolated and purified from Geigeria aspera Harv. (Asteraceae). Structures were deduced using 1 and 2D NMR spectroscopy and mass spectrometry, while the absolute configurations of compounds 1 and 3 were determined for the first time by X-ray crystal diffraction analyses. Cytotoxicity of isogeigerin acetate, ivalin and geigerin were compared by exposing a murine skeletal myoblast (C2C12) cell line to varying concentrations of the three sesquiterpene lactones isolated. Cell viability was assessed using the methyl-thiazolyl-tetrazolium (MTT) assay. The EC50s were 3.746, 0.0029 and 3.792 mM for isogeigerin acetate (1), ivalin (2) and geigerin (3), respectively. The results indicate that ivalin is much more toxic, approximately 1000 times, in vitro compared to isogeigerin acetate and geigerin.http://www.tandfonline.com/loi/gnpl202020-10-16hj2020ChemistryParaclinical Science
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