Suppression of cathepsins B and L causes a proliferation of lysosomes and the formation of meganeurites in hippocampus.

Cultured hippocampal slices exhibited prominent ultrastructural features of brain aging after exposure to an inhibitor of cathepsins B and L. Six days of treatment with N-CBZ-L-phenylalanyl-L-alanine-diazomethylketone (ZPAD) resulted in a dramatic increase in the number of lysosomes in the perikarya of neurons and glial cells throughout the slices. Furthermore, lysosomes in CA1 and CA3 pyramidal cells were not restricted to the soma but instead were located throughout dendritic processes. Clusters of lysosomes were commonly found within bulging segments of proximal dendrites that were notable for an absence of microtubules and neurofilaments. Although pyknotic nuclei were sometimes encountered, most of the cells in slices exposed to ZPAD for 6 d appeared relatively normal. Slices given 7 d of recovery contained several unique features, compared with those processed immediately after incubation with the inhibitor. Cell bodies of CA1 neurons were largely cleared of the excess lysosomes but had gained fusiform, somatic extensions that were filled with fused lysosomes and related complex, dense bodies. These appendages, similar in form and content to structures previously referred to as "meganeurites," were not observed in CA3 neurons or granule cells. Because meganeurites were often interposed between cell body and axon, they have the potential to interfere with processes requiring axonal transport. It is suggested that inactivation of cathepsins B and L results in a proliferation of lysosomes and that meganeurite generation provides a means of storing residual catabolic organelles. The accumulated material could be eliminated by pinching off the meganeurite but, at least in some cases, this action would result in axotomy. Reduced cathepsin L activity, increased numbers of lysosomes, and the formation of meganeurites are all reported to occur during brain aging; thus, it is possible that the infusion of ZPAD into cultured slices sets in motion a greatly accelerated gerontological sequence

Lysosomal dysfunction results in lamina-specific meganeurite formation but not apoptosis in frontal cortex.

An inhibitor of cathepsins B and L was used to test if lysosomal dysfunction in cultured slices of rat frontal cortex induces pathological features that develop in the human cortex during aging and Alzheimer's disease (AD). Incubation for 6 days with N-CBZ-L-phenylalanyl-L-alanine-diazomethylketone (ZPAD) resulted in a massive proliferation of endosomes-lysosomes in all cortical layers. Slices additionally exposed to a washout of 4 days had numerous meganeurites, blister-like structures in the region of the axon hillock, in layer III but not in other cortical laminae. Meganeurites are a characteristic feature of the human frontal cortex after age 50 and are largely restricted to layer III. Tests for apoptosis were carried out at two intervals following meganeurite formation. TUNEL-labeled neurons were confined to layers II/III on the surface of the slices but there was no evidence for a ZPAD effect. In all, 6 days of lysosomal dysfunction reproduces characteristic effects of normal aging in neocortex without generating some key features of AD

Therapists as Educators: the Importance of Client Education in Occupational Therapy

Client education is a major component of everyday health care practice. Entry-level occupational therapy (OT) accreditation standards require educators to teach students how to demonstrate the ability to educate clients, family, caregivers, and significant others to facilitate their skills related to personal occupations. Although these standards are a necessity, entry-level programs are not required to teach students the teaching methodologies that support human learning. However, the educational standards do require students to apply the principles of teaching and learning processes. This project explored the evidence in teaching and learning strategies and how these were introduced to OT students during their program. Faculty from the School of Occupational Therapy and School of Education developed a module for entry-level OT students. Data analysis found that students were able to benefit from the additional information on teaching and learning theory

Beam profile investigation of the new collimator system for the J-PET detector

Jagiellonian Positron Emission Tomograph (J-PET) is a multi-purpose detector which will be used for search for discrete symmetries violations in the decays of positronium atoms and for investigations with positronium atoms in life-sciences and medical diagnostics. In this article we present three methods for determination of the beam profile of collimated annihilation gamma quanta. Precise monitoring of this profile is essential for time and energy calibration of the J-PET detector and for the determination of the library of model signals used in the hit-time and hit-position reconstruction. We have we have shown that usage of two lead bricks with dimensions of 5x10x20 cm^3 enables to form a beam of annihilation quanta with Gaussian profile characterized by 1 mm FWHM. Determination of this characteristic is essential for designing and construction the collimator system for the 24-module J-PET prototype. Simulations of the beam profile for different collimator dimensions were performed. This allowed us to choose optimal collimation system in terms of the beam profile parameters, dimensions and weight of the collimator taking into account the design of the 24 module J-PET detector.Comment: 14 pages, 9 figure

Searches for discrete symmetries violation in ortho-positronium decay using the J-PET detector

In this paper we present prospects for using the J-PET detector to search for discrete symmetries violations in a purely leptonic system of the positronium atom. We discuss tests of CP and CPT symmetries by means of ortho-positronium decays into three photons. No zero expectation values for chosen correlations between ortho-positronium spin and momentum vectors of photons would imply the existence of physics phenomena beyond the Standard Model. Previous measurements resulted in violation amplitude parameters for CP and CPT symmetries consistent with zero, with an uncertainty of about 10-3. The J-PET detector allows to determine those values with better precision thanks to a unique time and angular esolution combined with a high geometrical acceptance. Achieving the aforementioned is possible due to application of polymer scintillators instead of crystals as detectors of annihilation quanta.Comment: in Nukleonika 201

Potential of the J-PET detector for studies of discrete symmetries in decays of positronium atom - a purely leptonic system

The Jagiellonian Positron Emission Tomograph (J-PET) was constructed as a prototype of the cost-effective scanner for the simultaneous metabolic imaging of the whole human body. Being optimized for the detection of photons from the electron-positron annihilation with high time- and high angular-resolution, it constitutes a multi-purpose detector providing new opportunities for studying the decays of positronium atoms. Positronium is the lightest purely leptonic object decaying into photons. As an atom bound by a central potential it is a parity eigenstate, and as an atom built out of an electron and an anti-electron it is an eigenstate of the charge conjugation operator. Therefore, the positronium is a unique laboratory to study discrete symmetries whose precision is limited in principle by the effects due to the weak interactions expected at the level of (~10$^{-14}$) and photon-photon interactions expected at the level of (~10$^{-9}$). The J-PET detector enables to perform tests of discrete symmetries in the leptonic sector via the determination of the expectation values of the discrete-symmetries-odd operators, which may be constructed from the spin of ortho-positronium atom and the momenta and polarization vectors of photons originating from its annihilation. In this article we present the potential of the J-PET detector to test the C, CP, T and CPT symmetries in the decays of positronium atoms.Comment: 27 pages, 6 figure

Compressive Sensing of Signals Generated in Plastic Scintillators in a Novel J-PET Instrument

The J-PET scanner, which allows for single bed imaging of the whole human body, is currently under development at the Jagiellonian University. The dis- cussed detector offers improvement of the Time of Flight (TOF) resolution due to the use of fast plastic scintillators and dedicated electronics allowing for sam- pling in the voltage domain of signals with durations of few nanoseconds. In this paper we show that recovery of the whole signal, based on only a few samples, is possible. In order to do that, we incorporate the training signals into the Tikhonov regularization framework and we perform the Principal Component Analysis decomposition, which is well known for its compaction properties. The method yields a simple closed form analytical solution that does not require iter- ative processing. Moreover, from the Bayes theory the properties of regularized solution, especially its covariance matrix, may be easily derived. This is the key to introduce and prove the formula for calculations of the signal recovery error. In this paper we show that an average recovery error is approximately inversely proportional to the number of acquired samples

Application of the Compress Sensing Theory for Improvement of the TOF Resolution in a Novel J-PET Instrument

Nowadays, in Positron Emission Tomography (PET) systems, a Time of Flight information is used to improve the image reconstruction process. In Time of Flight PET (TOF-PET), fast detectors are able to measure the difference in the arrival time of the two gamma rays, with the precision enabling to shorten significantly a range along the line-of-response (LOR) where the annihilation occurred. In the new concept, called J-PET scanner, gamma rays are detected in plastic scintillators. In a single strip of J-PET system, time values are obtained by probing signals in the amplitude domain. Owing to Compress Sensing theory, information about the shape and amplitude of the signals is recovered. In this paper we demonstrate that based on the acquired signals parameters, a better signal normalization may be provided in order to improve the TOF resolution. The procedure was tested using large sample of data registered by a dedicated detection setup enabling sampling of signals with 50 ps intervals. Experimental setup provided irradiation of a chosen position in the plastic scintillator strip with annihilation gamma quanta

Studies of unicellular micro-organisms Saccharomyces cerevisiae by means of Positron Annihilation Lifetime Spectroscopy

Results of Positron Annihilation Lifetime Spectroscopy (PALS) and microscopic studies on simple microorganisms: brewing yeasts are presented. Lifetime of ortho - positronium (o-Ps) were found to change from 2.4 to 2.9 ns (longer lived component) for lyophilised and aqueous yeasts, respectively. Also hygroscopicity of yeasts in time was examined, allowing to check how water - the main component of the cell - affects PALS parameters, thus lifetime of o-Ps were found to change from 1.2 to 1.4 ns (shorter lived component) for the dried yeasts. The time sufficient to hydrate the cells was found below 10 hours. In the presence of liquid water an indication of reorganization of yeast in the molecular scale was observed. Microscopic images of the lyophilised, dried and wet yeasts with best possible resolution were obtained using Inverted Microscopy (IM) and Environmental Scanning Electron Microscopy (ESEM) methods. As a result visible changes to the surface of the cell membrane were observed in ESEM images.Comment: Nukleonika (2015