32 research outputs found
Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity
Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects thus all lead to glucose intolerance. As our findings reveal that chronic rapamycin treatment could be diabetogenic, monitoring glucose homeostasis is crucial when using rapamycin as a therapeutic as well as experimental reagent
Normalization of Voltage-Sensitive Dye Signal with Functional Activity Measures
In general, signal amplitude in optical imaging is normalized using the
well-established ΔF/F method, where functional activity is divided by
the total fluorescent light flux. This measure is used both directly, as a
measure of population activity, and indirectly, to quantify spatial and
spatiotemporal activity patterns. Despite its ubiquitous use, the stability and
accuracy of this measure has not been validated for voltage-sensitive dye
imaging of mammalian neocortex in vivo. In this report, we find
that this normalization can introduce dynamic biases. In particular, the
ΔF/F is influenced by dye staining quality, and the ratio is also
unstable over the course of experiments. As methods to record and analyze
optical imaging signals become more precise, such biases can have an
increasingly pernicious impact on the accuracy of findings, especially in the
comparison of cytoarchitechtonic areas, in area-of-activation measurements, and
in plasticity or developmental experiments. These dynamic biases of the
ΔF/F method may, to an extent, be mitigated by a novel method of
normalization, ΔF/ΔFepileptiform. This normalization
uses as a reference the measured activity of epileptiform spikes elicited by
global disinhibition with bicuculline methiodide. Since this normalization is
based on a functional measure, i.e. the signal amplitude of
“hypersynchronized” bursts of activity in the cortical
network, it is less influenced by staining of non-functional elements. We
demonstrate that such a functional measure can better represent the amplitude of
population mass action, and discuss alternative functional normalizations based
on the amplitude of synchronized spontaneous sleep-like activity. These findings
demonstrate that the traditional ΔF/F normalization of voltage-sensitive
dye signals can introduce pernicious inaccuracies in the quantification of
neural population activity. They further suggest that normalization-independent
metrics such as waveform propagation patterns, oscillations in single detectors,
and phase relationships between detector pairs may better capture the biological
information which is obtained by high-sensitivity imaging
Measurement of the W mass in collisions at 183 GeV
The mass of the W boson is obtained from reconstructed invariant mass distributions in W-pair events. The sample of W pairs is selected from 57 pb collected with the ALEPH detector in 1997 at a centre-of-mass energy of 183 GeV. The invariant mass distributions of reweighted Monte Carlo events are fitted separately to the experimental distributions in the and all l\nuqqbar channels to give the following W masses: , where the theory error represents the possible effects of final state interactions. The combination of these two measurements, including the LEP energy calibration uncertainty, gives $m_{W} = 80.393 \pm 0.128(stat.)\pm 0.041(syst.) \pm 0.028(theory)\pm 0.021(LEP) GeV/c^2