A novel polarisation modulation scheme for polarimeters based on Fabry–Perot cavities is presented. The application to the measurement of the magnetic birefringence of vacuum with the HERA ...superconducting magnets in the ALPS-II configuration is discussed.
Disarrangement in functions and quality control of mitochondria at synapses are early events in Alzheimer's disease (AD) pathobiology. We reported that a 20-22 kDa NH2-tau fragment mapping between 26 ...and 230 amino acids of the longest human tau isoform (aka NH2htau): (i) is detectable in cellular and animal AD models, as well in synaptic mitochondria and cerebrospinal fluids (CSF) from human AD subjects; (ii) is neurotoxic in primary hippocampal neurons; (iii) compromises the mitochondrial biology both directly, by inhibiting the ANT-1-dependent ADP/ATP exchange, and indirectly, by impairing their selective autophagic clearance (mitophagy). Here, we show that the extensive Parkin-dependent turnover of mitochondria occurring in NH2htau-expressing post-mitotic neurons plays a pro-death role and that UCHL-1, the cytosolic Ubiquitin-C-terminal hydrolase L1 which directs the physiological remodeling of synapses by controlling ubiquitin homeostasis, critically contributes to mitochondrial and synaptic failure in this in vitro AD model. Pharmacological or genetic suppression of improper mitophagy, either by inhibition of mitochondrial targeting to autophagosomes or by shRNA-mediated silencing of Parkin or UCHL-1 gene expression, restores synaptic and mitochondrial content providing partial but significant protection against the NH2htau-induced neuronal death. Moreover, in mitochondria from human AD synapses, the endogenous NH2htau is stably associated with Parkin and with UCHL-1. Taken together, our studies show a causative link between the excessive mitochondrial turnover and the NH2htau-induced in vitro neuronal death, suggesting that pathogenetic tau truncation may contribute to synaptic deterioration in AD by aberrant recruitment of Parkin and UCHL-1 to mitochondria making them more prone to detrimental autophagic clearance.
Although experimental efforts have been active for about 30 years, a direct laboratory observation of vacuum magnetic birefringence, due to vacuum fluctuations, still needs confirmation: the ...predicted birefringence of vacuum is
Δ
n
=
4.0
×
10
-
24
@ 1 T. Key ingredients of a polarimeter for detecting such a small birefringence are a long optical path within the magnetic field and a time dependent effect. To lengthen the optical path a Fabry–Perot is generally used with a finesse ranging from
F
≈
10
4
to
F
≈
7
×
10
5
. Interestingly, there is a difficulty in reaching the predicted shot noise limit of such polarimeters. We have measured the ellipticity and rotation noises along with Cotton-Mouton and Faraday effects as a function of the finesse of the cavity of the PVLAS polarimeter. The observations are consistent with the idea that the cavity mirrors generate a birefringence-dominated noise whose ellipticity is amplified by the cavity itself. The optical path difference sensitivity at
10
Hz
is
S
Δ
D
=
6
×
10
-
19
m
/
Hz
, a value which we believe is consistent with an intrinsic thermal noise in the mirror coatings. Our findings prove that the continuous efforts to increase the finesse of the cavity to improve the sensitivity has reached a limit.
Optical Fabry–Perot cavities always show a non-degeneracy of two orthogonal polarisation states. This is due to the unavoidable birefringence of dielectric mirrors whose effects are extremely ...important in Fabry–Perot-based high-accuracy polarimeters: in birefringent cavities, ellipticities and rotations mix. We have developed and present here a theory of the polarisation state dynamics in a birefringent Fabry–Perot resonator, and we validate it through measurements performed with the polarimeter of the PVLAS experiment. The measurements are performed while a laser is frequency-locked to the cavity, and provide values for the phase difference between the two orthogonal polarisation components introduced by the combination of the two cavity mirrors (equivalent wave-plate) and for the finesse of the cavity. The theoretical formulas and the experimental data agree well showing that the consequences of the mirror birefringence must be taken into account in this and in any other similar experiment.
This paper describes the 25 year effort to measure vacuum magnetic birefringence and dichroism with the PVLAS experiment. The experiment went through two main phases: the first using a rotating ...superconducting magnet and the second using two rotating permanent magnets. The experiment was not able to reach the predicted value from QED. Nonetheless the experiment has set the current best limits on vacuum magnetic birefringence and dichroism for a field of Bext=2.5 T, namely, Δn(PVLAS)=(12±17)×10−23 and |Δκ|(PVLAS)=(10±28)×10−23. The uncertainty on Δn(PVLAS) is about a factor 7 above the predicted value of Δn(QED)=2.5×10−23 @ 2.5 T.
The PVLAS collaboration is presently assembling a new apparatus (at the INFN section of Ferrara, Italy) to detect vacuum magnetic birefringence (VMB). VMB is related to the structure of the quantum ...electrodynamics (QED) vacuum and is predicted by the Euler-Heisenberg-Weisskopf effective Lagrangian. It can be detected by measuring the ellipticity acquired by a linearly polarized light beam propagating through a strong magnetic field. Using the very same optical technique it is also possible to search for hypothetical low-mass particles interacting with two photons, such as axion-like (ALP) or millicharged particles. Here we report the results of a scaled-down test setup and describe the new PVLAS apparatus. This latter is in construction and is based on a high-sensitivity ellipsometer with a high-finesse Fabry-Perot cavity (>4 × 105) and two 0.8 m long 2.5 T rotating permanent dipole magnets. Measurements with the test setup have improved, by a factor 2, the previous upper bound on the parameter Ae, which determines the strength of the nonlinear terms in the QED Lagrangian: A(PVLAS)e < 3.3 × 10−21 T−2 at 95% c.l. Furthermore, new laboratory limits have been put on the inverse coupling constant of ALPs to two photons and confirmation of previous limits on the fractional charge of millicharged particles is given.
The NH
2
tau 26–44 aa (i.e., NH
2
htau) is the minimal biologically active moiety of longer 20–22-kDa NH
2
-truncated form of human tau—a neurotoxic fragment mapping between 26 and 230 amino acids of ...full-length protein (htau40)—which is detectable in presynaptic terminals and peripheral CSF from patients suffering from AD and other non-AD neurodegenerative diseases. Nevertheless, whether its exogenous administration in healthy nontransgenic mice is able to elicit a neuropathological phenotype resembling human tauopathies has not been yet investigated. We explored the in vivo effects evoked by subchronic intracerebroventricular (i.c.v.) infusion of NH
2
htau or its reverse counterpart into two lines of young (2-month-old) wild-type mice (C57BL/6 and B6SJL). Six days after its accumulation into hippocampal parenchyma, significant impairment in memory/learning performance was detected in NH
2
htau-treated group in association with reduced synaptic connectivity and neuroinflammatory response. Compromised short-term plasticity in paired-pulse facilitation paradigm (PPF) was detected in the CA3/CA1 synapses from NH
2
htau-impaired animals along with downregulation in calcineurin (CaN)-stimulated pCREB/c-Fos pathway(s). Importantly, these behavioral, synaptotoxic, and neuropathological effects were independent from the genetic background, occurred prior to frank neuronal loss, and were specific because no alterations were detected in the control group infused with its reverse counterpart. Finally, a 2.0-kDa peptide which biochemically and immunologically resembles the injected NH
2
htau was endogenously detected in vivo, being present in hippocampal synaptosomal preparations from AD subjects. Given that the identification of the neurotoxic tau species is mandatory to develop a more effective tau-based immunological approach, our evidence can have important translational implications for cure of human tauopathies.
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