Search

Multiple sclerosis is a chronic disease characterized by inflammation, demyelination, and axonal damage in the central nervous system. Here, we established an induced pluripotent stem cell (iPSC) line METUi001-A from the peripheral blood mononuclear cells of a 25-year-old male individual with clinically diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS) using the integration-free Sendai reprogramming method. We demonstrated that the iPSCs are free of exogenous Sendai reprogramming vectors, have a normal male karyotype, express pluripotency markers, and differentiate into the three germ layers. The iPSC line can serve as a valuable resource to generate cellular model systems to investigate molecular mechanisms underlying RRMS.

This study makes a first attempt at a detailed estimation of the background radioactivity level and its distribution at the Sinop nuclear power plant site. The activity concentration levels of 226Ra, 232Th, 40K and 137Cs radionuclides in soil samples collected from 88 locations around Sinop Province, Turkey, in November 2016, were measured using gamma spectrometry. The distributions of radionuclide levels obtained from the results were evaluated using a geostatistical method, and the estimated radiation levels were determined using the ordinary kriging (OK) method, which is the best linear unbiased estimator (BLUE) for unmeasured points. Estimates of distribution results were evaluated using cross-validation diagrams, and it was shown that the OK method could predict radiological distributions for appropriate criteria. Finally, using the kriging parameters, distributions of radiation levels for the entire work area were mapped at a spatial resolution of 100 × 100 m2. These maps show that the natural radionuclides (226Ra, 232Th and 40K) are distributed at higher levels to the southeast of Sinop than in the other regions, and the activity of an artificial radionuclide (137Cs) is high in the interior and northern sections.

There is an urgent need to develop novel treatments to counter Botulinum neurotoxin (BoNT) poisoning. Currently, the majority of BoNT drug development efforts focus on directly inhibiting the proteolytic components of BoNT, i.e. light chains (LC). Although this is a rational approach, previous research has shown that LCs are extremely difficult drug targets and that inhibiting multi-serotype BoNTs with a single LC inhibitor may not be feasible. An alternative approach would target neuronal pathways involved in intoxication/recovery, rather than the LC itself. Phosphorylation-related mechanisms have been implicated in the intoxication pathway(s) of BoNTs. However, the effects of phosphatase inhibitors upon BoNT activity in the physiological target of BoNTs, i.e. motor neurons, have not been investigated. In this study, a small library of phosphatase inhibitors was screened for BoNT antagonism in the context of mouse embryonic stem cell-derived motor neurons (ES-MNs). Four inhibitors were found to function as BoNT/A antagonists. Subsequently, we confirmed that these inhibitors protect against BoNT/A in a dose-dependent manner in human ES-MNs. Additionally, these compounds provide protection when administered in post-intoxication scenario. Importantly, the inhibitors were also effective against BoNT serotypes B and E. To the best of our knowledge, this is the first study showing phosphatase inhibitors as broad-spectrum BoNT antagonists.

Sirin, Murat/0000-0001-6864-752X WOS: 000343763700041 Nine concrete samples with or without mineral admixtures have been analyzed for their naturally occurring radionuclide of Ra-226, Th-232 and K-40 using HPGe gamma spectrometry. Also, concrete raw materials such as aggregate, cement, fly ash and blast furnace slag have been measured. the radioactivity values of Ra-226, Th-232 and K-40 in fly ash and those of Ra-226 in blast furnace slag are higher than the corresponding world mean specific activities values which are 50, 50 and 500 Bq kg(-1) for Ra-226, Th-232 and K-40, respectively. the concretes activity concentrations have been found to change with supplementary cementitious materials of the concrete samples. This may be attributed to containing different proportions of different mineral additives such as fly ash and blast furnace slag which were found to contain high natural radionuclide concentrations according to the rest of raw material samples. in addition, radium equivalent activities (Ra-eq), gamma-index (I-gamma), alpha-index (I alpha), absorbed dose rate in air (D) and annual effective dose associated with the natural radionuclide were calculated to assess the radiation hazard of the natural radioactivity in the concrete mixture samples. the concentration of the natural radionuclides and the radium equivalent activity obtained in the present study are compared with the previous results. From these results, it can be seen that these building materials do not pose significant radiation hazards.

WOS: 000306646100019 PubMed: 22128356 Some building materials, regularly used in Turkey, such as sand, cement, gas concrete (lightweight, aerated concrete), tile and brick, have been investigated in terms of mass attenuation coefficient (mu/(rho)), effective atomic, numbers (Z(eff)), effective electron densities (N-e) and photon interaction cross section (sigma(a)) at 14 different energies from 81- to 1332-keV gamma-ray energies. The gamma rays were detected by using gamma-ray spectroscopy, a High Purity Germanium (HPGe) detector. The elemental compositions of samples were analysed using an energy dispersive X-ray fluorescence spectrometer. Mass attenuation coefficients of these samples have been compared with tabulations based upon the results of WinXcom. The theoretical mass attenuation coefficients were estimated using the mixture rule and the experimental values of investigated parameters were compared with the calculated values. The agreement of measured values of mass attenuation coefficient, effective atomic numbers, effective electron densities and photon interaction cross section with the theory has been found to be quite satisfactory.

Botulinum neurotoxins (BoNTs) inhibit cholinergic synaptic transmission by specifically cleaving proteins that are crucial for neurotransmitter exocytosis. Due to the lethality of these toxins, there are elevated concerns regarding their possible use as bioterrorism agents. Moreover, their widespread use for cosmetic purposes, and as medical treatments, has increased the potential risk of accidental overdosing and environmental exposure. Hence, there is an urgent need to develop novel modalities to counter BoNT intoxication. Mammalian motoneurons are the main target of BoNTs; however, due to the difficulty and poor efficiency of the procedures required to isolate the cells, they are not suitable for high-throughput drug screening assays. Here, we explored the suitability of embryonic stem (ES) cell-derived motoneurons as a renewable, reproducible, and physiologically relevant system for BoNT studies. We found that the sensitivity of ES-derived motoneurons to BoNT/A intoxication is comparable to that of primary mouse spinal motoneurons. Additionally, we demonstrated that several BoNT/A inhibitors protected SNAP-25, the BoNT/A substrate, in the ES-derived motoneuron system. Furthermore, this system is compatible with immunofluorescence-based high-throughput studies. These data suggest that ES-derived motoneurons provide a highly sensitive system that is amenable to large-scale screenings to rapidly identify and evaluate the biological efficacies of novel therapeutics.

Background The dynamic growing and shortening behaviors of microtubules are central to the fundamental roles played by microtubules in essentially all eukaryotic cells. Traditionally, microtubule behavior is quantified by manually tracking individual microtubules in time-lapse images under various experimental conditions. Manual analysis is laborious, approximate, and often offers limited analytical capability in extracting potentially valuable information from the data. Results In this work, we present computer vision and machine-learning based methods for extracting novel dynamics information from time-lapse images. Using actual microtubule data, we estimate statistical models of microtubule behavior that are highly effective in identifying common and distinct characteristics of microtubule dynamic behavior. Conclusion Computational methods provide powerful analytical capabilities in addition to traditional analysis methods for studying microtubule dynamic behavior. Novel capabilities, such as building and querying microtubule image databases, are introduced to quantify and analyze microtubule dynamic behavior.

Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from αβ heterodimeric tubulin. A variety of microtubule-associated-proteins (MAPs) bind to tubulin subunits and regulate microtubule dynamics, although the process in which this occurs is not well understood. In mature neurons MAP tau promotes MT assembly while in developing neurons MAP tau also plays a critical role in axonogensis [1]. Furthermore, aberrant tau function has been implicated in numerous neurodegenerative diseases, such as Alzheimer's, Pick's, and supranuclear palsy. Understanding the interactions between MAP tau and MTs will be critical in further elucidating the role that MAP tau plays in neurodegenerative diseases. We examined the effects of the human MAP tau on the assembled structure of taxol-stabilized MTs under osmotic pressure (mimicking the crowded environment of axonal neurons) using synchrotron small angle x-ray scattering (SAXS) and binding assays [2, 3]. Previous work had shown that MAP tau isoforms regulate the distribution of protofilament numbers in MTs resulting in an increase in the average MT radius with increasing tau [4]. Significantly, the pressure-tau concentration phase diagram (using the SAXS-osmotic pressure technique) reveal that tau does indeed modify the interactions between MTs in an isoform dependent manner.Supported by DOE DE-FG02-06ER46314, NSF DMR-0803103, NIH NS35010, NIH NS13560.1. B. Esmaeli-Azad, J. H. McCarty, and S. C. Feinstein. J. Cell Sci. 107; 869 (1994).2. V. A. Parsegian, R.P. Rand, and D.C. Rau. Methods Enzymol. 259; 43 (1995).3. D.J. Needleman et al. Phys. Rev. Lett. 93; 198104 (2004).4. M.C. Choi, U. Raviv et al. Biophys. J. 97; 519 (2009).

Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from αβ heterodimeric tubulin. In neural cells, different isoforms of the microtubule-associated-protein (MAP) tau regulate tubulin assembly and MT stability. Using synchrotron small angle x-ray scattering (SAXS) and binding assay, we examine the effects of human MAP tau on the assembly structure of taxol-stabilized MTs. We find that tau regulates the distribution of protofilament numbers in MTs as reflected in the observed increase in the average radius of MTs with increasing the tau/tubulin molar ratio. Further, we describe that tau-MT interactions are mediated to a large extent via electrostatic interactions: the binding affinity of tau to MTs is ionic strength dependent. Supported by DOE DE-FG02-06ER46314, NSF DMR-0803103, NIH NS35010, NIH NS13560. (Ref) M.C. Choi, S.C. Feinstein, and C.R. Safinya et al. Biophys. J. 97; 519 (2009).