Biotehnoloogilisi lähenemisi neurodegeneratiivsete haiguste raviks

Vananemine, vigastused ja neurodegeneratiivsed haigused põhjustavad närvirakkude kängumist ja surma. Parkinsoni tõve haigetel juhtub see eelkõige keskaju mustaine dopamiini tootvates närvirakkudes. Parkinsoni tõve raviks kasutatavad ravimid leevendavad haiguse sümptomeid, kuid ei kõrvalda haiguse põhjuseid ega pidurda närvirakkude surma. Närvikasvufaktorid GDNF ja NRTN suudavad Parkinsoni tõve näriliste ja primaatide loommudelites dopamiini närvirakkude surma pidurdada ning isegi känguvaid närvirakke taastada. Paraku on kliinilised katsetused nende faktoritega seni andnud tagasihoidlikke tulemusi. Närvikasvufaktorid on rakkude poolt eritatavad väikesed valgud, mis seondudes närvirakkude pinnal paiknevate retseptoritega, kaitsevad neuroneid vigastuste eest ning hoiavad neid elus. Hiljuti avastatud CDNF on loomkatsetes tõhusamate raviomadustega kui GDNF või NRTN. Kuna CDNFil ja tema sugulasfaktor MANFil on muude närvikasvufaktoritega võrreldes hulk uusi omadusi, siis loodetakse neist läbimurret Parkinsoni tõve ravis. Eesti Arst 2010; 89(9):536−54

Embrüoselektsiooni uued võimalused – embrüodiagnostika

Viljatuse kõige tõhusamaks ravimeetodiks on kehaväline viljastamine, mida Eestis on rakendatud alates 90. aastate algusest. Kehavälise viljastamise õnnestumiseks on oluline embrüote selektsioon, et siirata kõige arenemisvõimelisem ja kromosomaalselt normaalne embrüo. Selektsiooni tulemuslikkuse parandamise uueks võimaluseks on embrüodiagnostika. Eesti Arst 2003; 82 (3): 188–19

Three Thousand Years of Continuity in the Maternal Lineages of Ancient Sheep (Ovis aries) in Estonia

lthough sheep (Ovis aries) have been one of the most exploited domestic animals in Estonia since the Late Bronze Age, relatively little is known about their genetic history. Here, we explore temporal changes in Estonian sheep populations and their mitochondrial genetic diversity over the last 3000 years. We target a 558 base pair fragment of the mitochondrial hypervariable region in 115 ancient sheep from 71 sites in Estonia (c. 1200 BC – AD 1900s), 19 ancient samples from Latvia, Russia, Poland and Greece (6800 BC – AD 1700), as well as 44 samples of modern Kihnu native sheep breed. Our analyses revealed: (1) 49 mitochondrial haplotypes, associated with sheep haplogroups A and B; (2) high haplotype diversity in Estonian ancient sheep; (3) continuity in mtDNA haplotypes through time; (4) possible population expansion during the first centuries of the Middle Ages (associated with the establishment of the new power regime related to 13th century crusades); (5) significant difference in genetic diversity between ancient populations and modern native sheep, in agreement with the beginning of large-scale breeding in the 19th century and population decline in local sheep. Overall, our results suggest that in spite of the observed fluctuations in ancient sheep populations, and changes in the natural and historical conditions, the utilisation of local sheep has been constant in the territory of Estonia, displaying matrilineal continuity from the Middle Bronze Age through the Modern Period, and into modern native sheep

Glial cell line-derived neurotrophic factor influences proliferation of osteoblastic cells

Little is known about the role of neurotrophic growth factors in bone metabolism. This study investigated the short-term effects of glial cell line-derived neurotrophic factor (GDNF) on calvarial-derived MC3T3-E1 osteoblasts. MC3T3-E1 expressed GDNF as well as its canonical receptors, GFRα1 and RET. Addition of recombinant GDNF to cultures in serum-containing medium modestly inhibited cell growth at high concentrations; however, under serum-free culture conditions GDNF dose-dependently increased cell proliferation. GDNF effects on cell growth were inversely correlated with its effect on alkaline phosphatase (ALP) activity showing a significant dose-dependent inhibition of relative ALP activity with increasing concentrations of GDNF in serum-free culture medium. Live/dead and lactate dehydrogenase assays demonstrated GDNF did not significantly affect cell death or survival under serum-containing and serum-free conditions. The effect of GDNF on cell growth was abolished in the presence of inhibitors to GFR α 1 and RET indicating that GDNF stimulated calvarial osteoblasts via its canonical receptors. Finally, this study found that GDNF synergistically increased tumor necrosis factor-α (TNF-α)-stimulated MC3T3-E1 cell growth suggesting that GDNF interacted with TNF-α-induced signaling in osteoblastic cells. In conclusion, this study provides evidence for a direct, receptor-mediated effect of GDNF on osteoblasts highlighting a novel role for GDNF in bone physiology. \ud \u

Tuning ribosomal elongation cycle by mutagenesis of 23S rRNA

http://www.ester.ee/record=b1053388~S58*es

To celebrate the 80th birthday of Klaus Unsicker : discovery of a new growth factor and studies on the effects of growth factors on adrenal chromaffin cells and neurons

Non peer reviewe

Combination of CDNF and Deep Brain Stimulation Decreases Neurological Deficits in Late-stage Model Parkinson's Disease

Several neurotrophic factors ( NTF) are shown to be neuroprotective and neurorestorative in pre-clinical animal models for Parkinson's disease ( PD), particularly in models where striatal dopamine neuron innervation partially exists. The results of clinical trials on late-stage patients have been modest. Subthalamic deep brain stimulation ( STN DBS) is a proven treatment for a selected group of advanced PD patients. The cerebral dopamine neurotrophic factor ( CDNF) is a promising therapeutic protein, but its effects in animal models of late-stage PD have remained under-researched. The interactions of NTF and STN DBS treatments have not been studied before. We found that a nigral CDNF protein alone had only a marginal effect on the behavioral deficits in a late-stage hemiparkinsonian rat model ( 6-OHDA MFB). However, CDNF improved the effect of acute STN DBS on front limb use asymmetry at 2 and 3 weeks after CDNF injection. STN lesion-modeling chronic stimulation-had an additive effect in reducing front limb use in the cylinder test and apomorphine-induced rotation. The combination of CDNF and acute STN DBS had a favorable effect on striatal tyrosine hydroxylase. This study presents a novel additive beneficial effect of NTF and STN DBS, which might be explained by the interaction of DBS-induced endogenous NTFs and exogenously injected CDNF. SNpc can be reached via similar trajectories used in clinical STN DBS, and this interaction is an important area for future studies. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Calibration of Nebular Emission-line Diagnostics: II. Abundances

(Abridged) We examine standard methods of measuring nebular chemical abundances, including estimates based on direct T_e measurements, and also bright-line diagnostics. We use observations of 4 LMC HII regions whose ionizing stars have classifications ranging from O7 to WN3. We assume a 2-zone T_e structure to compute ionic abundances. We compare with photoionization models tailored to the properties of the individual objects, and emphasize the importance of correctly relating T_e in the two zones, which can otherwise cause errors of ~0.2 dex in abundance estimates. There are no spatial variations to within 0.1 - 0.15 dex in any of the objects, even one hosting 3 WR stars. Our data agree with the modeled R23 and S23 diagnostics of O and S. We present the first theoretical tracks for S23, which are in excellent agreement with a larger dataset. However, contrary to earlier suggestions, S23 is much more sensitive to the ionization parameter than is R23, because S23 does not sample S IV. We therefore introduce S234 = ([SII]+[SIII]+[SIV])/H-beta. Predicted and observed spatial variations in S234 are dramatically reduced in contrast to S23. The intensity of [SIV]10.5 microns is easily estimated from a simple relation between [SIV]/[SIII] and [OIII]/[OII]. This method of estimating S234 yields excellent agreement with our models, hence we give a theoretical calibration for S234. The double-valued structure of S23 and S234 remains an important problem as for R23, and presently we consider the S diagnostics reliable only at Z < 0.5 Z_sol. However, the slightly larger dynamic range and excellent compatibility with theoretical predictions suggest the S diagnostics to be more effective abundance indicators than R23.Comment: Accepted to ApJ. 24 pages, 11 figures, uses emulateapj.st