18 research outputs found
Az SZR-104 neuroprotektĂv hatásának tesztelĂ©se akut neurodegeneráciĂł kĂsĂ©rletes egĂ©rmodelljĂ©ben : [absztrakt]
A Schwann sejtek kalcium homeosztázisának vizsgálata ülőideg axotómiát követő Waller-féle degenerációban : [absztrakt]
A Schwann sejtek kalcium homeosztázisának vizsgálata ülőideg axotómiát követő Waller-féle degenerációban
Passive Transfer of Blood Sera from ALS Patients with Identified Mutations Results in Elevated Motoneuronal Calcium Level and Loss of Motor Neurons in the Spinal Cord of Mice
Passive transfer of blood sera from ALS patients with identified mutations results in elevated motoneuronal calcium level and loss of motor neurons in the spinal cord of mice
Introduction: Previously, we demonstrated the degeneration of axon terminals in mice after repeated injections of blood sera from amyotrophic lateral sclerosis (ALS) patients with identified mutations. However, whether a similar treatment affects the cell body of motor neurons (MNs) remained unresolved. Methods: Sera from healthy individuals or ALS patients with a mutation in different ALS-related genes were intraperitoneally injected into ten-week-old male Balb/c mice (n = 3/serum) for two days. Afterward, the perikaryal calcium level was measured using electron microscopy. Furthermore, the optical disector method was used to evaluate the number of lumbar MNs. Results: The cytoplasmic calcium level of the lumbar MNs of the ALS-serum-treated mice, compared to untreated and healthy-serum-treated controls, was significantly elevated. While injections of the healthy serum did not reduce the number of MNs compared to the untreated control group, ALS sera induced a remarkable loss of MNs. Discussion: Similarly to the distant motor axon terminals, the injection of blood sera of ALS patients has a rapid degenerative effect on MNs. Analogously, the magnitude of the evoked changes was specific to the type of mutation; furthermore, the degeneration was most pronounced in the group treated with sera from ALS patients with a mutation in the chromosome 9 open reading frame 72 gene
Passive transfer of sera from als patients with identified mutations evokes an increased synaptic vesicle number and elevation of calcium levels in motor axon terminals, similar to sera from sporadic patients
Previously, we demonstrated increased calcium levels and synaptic vesicle densities in the motor axon terminals (MATs) of sporadic amyotrophic lateral sclerosis (ALS) patients. Such alterations could be conferred to mice with an intraperitoneal injection of sera from these patients or with purified immunoglobulin G. Later, we confirmed the presence of similar alterations in the superoxide dismutase 1 G93A transgenic mouse strain model of familial ALS. These consistent observations suggested that calcium plays a central role in the pathomechanism of ALS. This may be further reinforced by completing a similar analytical study of the MATs of ALS patients with identified mutations. However, due to the low yield of muscle biopsy samples containing MATs, and the low incidence of ALS patients with the identified mutations, these examinations are not technically feasible. Alternatively, a passive transfer of sera from ALS patients with known mutations was used, and the MATs of the inoculated mice were tested for alterations in their calcium homeostasis and synaptic activity. Patients with 11 different ALS-related mutations participated in the study. Intraperitoneal injection of sera from these patients on two consecutive days resulted in elevated intracellular calcium levels and increased vesicle densities in the MATs of mice, which is comparable to the effect of the passive transfer from sporadic patients. Our results support the idea that the pathomechanism underlying the identical manifestation of the disease with or without identified mutations is based on a common final pathway, in which increasing calcium levels play a central role
Molecular Characterization of Novel Mycoviruses in Seven Umbelopsis Strains
The presence of viruses is less explored in Mucoromycota as compared to other fungal groups such as Ascomycota and Basidiomycota. Recently, more and more mycoviruses are identified from the early-diverging lineages of fungi. We have determined the genome of 11 novel dsRNA viruses in seven different Umbelopsis strains with next-generation sequencing (NGS). The identified viruses were named Umbelopsis ramanniana virus 5 (UrV5), 6a (UrV6a); 6b (UrV6b); 7 (UrV7); 8a (UrV8a); 8b (UrV8b); Umbelopsis gibberispora virus 1 (UgV1); 2 (UgV2) and Umbelopsis dimorpha virus 1a (UdV1a), 1b (UdV1b) and 2 (UdV2). All the newly identified viruses contain two open reading frames (ORFs), which putatively encode the coat protein (CP) and the RNA-dependent RNA polymerase (RdRp), respectively. Based on the phylogeny inferred from the RdRp sequences, eight viruses (UrV7, UrV8a, UrV8b, UgV1, UgV2, UdV1a, UdV1b and UdV2) belong to the genus Totivirus, while UrV5, UrV6a and UrV6b are placed into a yet unclassified but well-defined Totiviridae-related group. In UrV5, UgV1, UgV2, UrV8b, UdV1a, UdV2 and UdV1b, ORF2 is predicted to be translated as a fusion protein via a rare +1 (or-2) ribosomal frameshift, which is not characteristic to most members of the Totivirus genus. Virus particles 31 to 32 nm in diameter could be detected in the examined fungal strains by transmission electron microscopy. Through the identification and characterization of new viruses of Mucoromycota fungi, we can gain insight into the diversity of mycoviruses, as well as into their phylogeny and genome organization
VektorkonstrukciĂłk Candida albicans protein foszfatáz Z1 pontmutánsok előállĂtásához
Szakdolgozatom tĂ©mája a CaPPZ1 gĂ©n által kĂłdolt Candida albicans protein foszfatáz Z1 (CaPpz1). Ez az enzim gombaspecifikus foszfatáz, amely szabályozza a sejtfal integritását, a kation homeosztázist, a membránpotenciált, az oxidatĂv stressz választ Ă©s a virulenciát. A CaPPZ1 pontmutáciĂłjával olyan integráciĂłs Candida vektorokat hoztam lĂ©tre, melyek segĂtsĂ©gĂ©vel - a CaPPZ1 delĂ©ciĂłs Candida mutáns genomjába integrálva - a CaPpz1 enzim az R262L mutáciĂł következtĂ©ben inaktĂv formában, illetve a G2A mutáciĂł eredmĂ©nyekĂ©nt mirisztoiláciĂłs hely nĂ©lkĂĽl termelĹ‘dik. A lĂ©trejövĹ‘ mutánsok fenotĂpusábĂłl következtethetĂĽnk majd a mutáciĂłk fiziolĂłgiás szerepĂ©re.BSc/BABiolĂłgia BScD
Gray matter atrophy is primarily related to demyelination of lesions in multiple sclerosis: a diffusion tensor imaging MRI study
Objective: Cortical pathology, periventricular demyelination and lesion formation in
multiple sclerosis (MS) are related (hypothesis 1). Factors in the cerebrospinal fluid
close to these compartments could possibly drive the parallel processes. Alternatively,
the cortical atrophy could be caused by remote axonal transection (hypothesis 2). Since
MRI can differentiate between demyelination and axon loss, we used this imaging
modality to investigate the correlation between the pattern of diffusion parameter
changes in the periventricular- and deep white matter and the grey matter atrophy.
Methods: High-resolution T1-weighted, FLAIR and diffusion MRI images were acquired
in 52 RRMS patients and 50 healthy, age-matched controls. We used EDSS to estimate
the clinical disability. We used Tract Based Spatial Statistics to compare diffusion
parameters (fractional anisotropy, mean, axial and radial diffusivity) between groups. We
evaluated global brain, white and grey matter atrophy with SIENAX. Averaged, standard
diffusion parameters were calculated in four compartment: periventricular lesioned and
normal appearing white matter, non-periventricular lesioned and normal appearing white
matter. PLS regression was used to identify which diffusion parameter and in which
compartment best predicts the brain atrophy and clinical disability.
Results: In our diffusion tensor imaging study compared to controls we found extensive
alterations of fractional anisotropy, mean and radial diffusivity and smaller changes of
axial diffusivity (maximal p-value>0.0002) in patients that suggested demyelination in
the lesioned and in the normal appearing white matter. We found significant reduction in
total brain, total white and grey matter (patients: 718.764±14.968cm3,
323.237±7.246cm3, 395.527±8.050cm3, controls: 791.772±22.692cm3
355.350±10.929cm3, 436.422±12.011cm3 (mean±SE)), (p<0.015; p<0.0001; p<0.009;
respectively) of patients compared to controls.
The PLS analysis revealed a combination of demyelination-like diffusion parameters
(higher mean and radial diffusivity in patients) in the lesions and in the non-lesioned
periventricular white matter, which best predicted the grey matter atrophy (p<0.001).
Similarly, EDSS was best predicted by the radial diffusivity of the lesions and the non-
lesioned periventricular white matter, but axial diffusivity of the periventricular lesions
also contributed significantly (p<0.0001).
Interpretation: Our investigation showed that grey matter atrophy and white matter
demyelination are related in MS but white matter axonal loss does not significantly
contribute to the grey matter pathology