Osborneborregaard3005

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by polyglutamine expansion mutations in the huntingtin protein. Despite its ubiquitous distribution, expression of mutant huntingtin (mHtt) is particularly detrimental to medium spiny neurons within the striatum. Mitochondrial dysfunction has been associated with HD pathogenesis. Here we review the current evidence for mHtt-induced abnormalities in mitochondrial dynamics and quality control, with a particular focus on brain and neuronal data pertaining to striatal vulnerability. We address mHtt effects on mitochondrial biogenesis, protein import, complex assembly, fission and fusion, mitochondrial transport, and on the degradation of damaged mitochondria via autophagy (mitophagy). For an integrated perspective on potentially converging pathogenic mechanisms, we also address impaired autophagosomal transport and abnormal mHtt proteostasis in HD.The lysosomal hydrolase glucocerebrosidase (GCase) is encoded for by the GBA gene. Homozygous GBA mutations cause Gaucher disease (GD), a lysosomal storage disorder. Furthermore, homozygous and heterozygous GBA mutations are numerically the greatest genetic risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. The loss of GCase activity results in impairment of the autophagy-lysosome pathway (ALP), which is required for the degradation of macromolecules and damaged organelles. Aberrant protein handling of α-synuclein by the ALP occurs in both GD and PD. α-synuclein is the principle component of Lewy bodies, a defining hallmark of PD. Mitochondrial dysfunction is also observed in both GD and PD. In this review we will describe how mitochondria are affected following loss of GCase activity. The pathogenic mechanisms leading to mitochondria dysfunction will also be discussed, focusing on the likely inhibition of the degradation of mitochondria by the ALP, also termed mitophagy. Other pathogenic cellular processes associated with GBA mutations that might contribute, such as the unfolding of GCase in the endoplasmic reticulum, calcium dysregulation and neuroinflammation will also be described. Impairment of the ALP and mitochondria dysfunction are common pathogenic themes between GD and PD and probably explain why GBA mutations increase the risk of developing PD that is very similar to sporadic forms of the disease.Neurotoxicity following paradichlorobenzene (PDCB) exposure is rare and can occur in patients with pica and mothball or toilet cake ingestion. selleck products We present a rare case of toxic encephalopathy due to PDCB mothball inhalation and ingestion and describe the rapidly progressive leukoencephalopathy seen on computed tomography, magnetic resonance, and magnetic resonance spectroscopy. Given the nonspecificity of clinical and imaging findings, it is important for radiologists to maintain a high index of suspicion for toxic encephalopathy.A new analytical method based on capillary zone electrophoresis-tandem mass spectrometry is proposed and validated for the identification and simultaneous quantification of nine aminoglycosides in honey samples. Detection using an ion trap mass analyzer operating in the multiple reaction monitoring mode was used. Different parameters were optimized in order to obtain an adequate separation combined with the highest sensitivity. In order to achieve high selectivity in the sample treatment, a commercially-available molecularly imprinted polymer has been used for the solid phase extraction of the analytes. Under optimum conditions, recoveries for fortified samples ranged from 88.2 to 99.8%, with relative standard deviations lower than 8%. The limits of detection ranged from 0.4 to 28.5 μg kg(-1). Furthermore, the decision limit and the detection capability were evaluated, ranging from 3.5 to 60.5 μg kg(-1) and from 6.0 to 103.1 μg kg(-1), respectively, demonstrating the sensitivity and applicability of this fast and simple method.In this study, we have performed the preparation of over-oxidized poly(3,4-ethylenedioxythiophene) nanofibers modified pencil graphite electrode (Ox-PEDOT-nf/PGE) to develop a selective and sensitive voltammetric uric acid (UA) sensor. It was noted that the over-oxidation potential and time had a prominent effect on the UA response of the Ox-PEDOT-nf/PGE. Characterizations of PEDOT-nf/PGE and Ox-PEDOT-nf/PGE have been performed by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy, Fourier transform infrared spectroscopy and Raman spectroscopy. The highest voltammetric response of UA was obtained at pH 2.0. A linear relationship between the concentration of UA and oxidation peak currents was observed in the concentration range of 0.01-20.0 μM. The detection limit (1.3 nM according to S/N = 3) and reproducibility (RSD 4.6 % for N10) have also been determined. The effects of different substances on the determination of UA have been investigated. A very high peak separation value of 423 mV was obtained between UA and ascorbic acid which is the major interfering substance for UA. The use of Ox-PEDOT-nf/PGE has been successfully tested in the determination of UA in human blood serum and urine samples for the first time in the literature.In this study, we investigated the effect of yttrium content on the structural properties and sensing characteristics of YbYxOy sensing membranes for electrolyte-insulator-semiconductor (EIS) sensors to detect the rheumatoid factor (RF). The YbYxOy EIS device prepared at the 60 W plasma condition exhibited a higher sensitivity of 65.77 mV/pH, a lower hysteresis voltage of ∼1 mV, and a smaller drift rate of 0.14 mV/h than did those prepared at the other conditions. We attribute this behavior to the optimal yttrium content in the YbYxOy film forming a smooth surface. Furthermore, we used a novel YbTixOy EIS biosensor to measure the RF antigen in human serum because of its rapid and label-free detection. Two different techniques were used for the immobilization of RF antibody onto the surface of an YbTixOy EIS sensor. The RF antibody was directly immobilized on the EIS surface modified with 3-aminopropyltriethoxysilane (APTES) followed by glutaraldehyde (GA). In contrast, a mixture of 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) solution was used to functionalize the carboxyl groups at the tail of RF antibodies. RF antibodies functionalized with the active NHS esters were covalently immobilized on the APTES-modified YbTixOy surface. The immobilized RF antibodies on the EIS that are functionalized with the EDC and NHS exhibit higher (41.11mV/pCRF) for detection of serum RF antigen in the range 10(-7) to 10(-3) M, compared to traditional antibody immobilization technique via APTES and GA linkage. The YbTixOy EIS biosensor is a promising analytical tool for RF antigen monitoring due to its good sensitivity, stability and repeatability.In this work, a novel colorimetric detection method for kanamycin (Kana), a widely used aminoglycoside antibiotic, has been developed using unmodified silver nanoparticles (AgNPs) as sensing probe. The method is designed based on the finding that the analyte (Kana) can protect AgNPs against salt-induced aggregation, and nucleic acid aptamers can decrease the risk of false positives through an aptamer-selective sensing mechanism. By use of the proposed method, selective quantification of Kana can be achieved over the concentration range from 0.05 to 0.6 μg mL(-1) within 20 min. The detection limit is estimated to be 2.6 ng mL(-1), which is much lower than the allowed maximum residue limit. Further studies also demonstrate the applicability of the proposed method in milk samples, revealing that the method may possess enormous potential for practical detection of Kana in the future.A nanomaterials-based novel molecular beacon has attracted growing attentions in fluorescent assays as many nanomaterials possess excellent quenching efficiency. In this work, a gold-based nanobeacon probe was established to detect organophosphorus pesticides for the first time. The constructed gold-based nanobeacon acted as a signal indicator and could display the decreasing of the intensity in the presence of targets, which competitively bound to single strand DNA. To achieve a high sensitive probe, some parameters including solution pH, temperature and reaction time were investigated and optimized. The gold-based nanobeacon probe assay was proved to be rapid and sensitive to achieve a detection limit of 0.035 μM for isocarbophos, 0.134 μM for profenofos, 0.384 μM for phorate and 2.35 μM for omethoate, respectively. The prepared nanobeacon effectively reduced the background and improved the detection sensitivity and selectivity. The probe is stable, easy to operate and does not need sophisticated instruments. These features makes the probe feasible for screening trace organophosphorus pesticides in real samples.Inhibitors of Rho-associated protein kinase (ROCK) enzymatic activity have been shown to reduce the invasive phenotype observed in metastatic hepatocellular carcinoma (HCC). We describe the design, synthesis, and evaluation of a direct probe for ROCK activity utilizing a phosphorylation-sensitive sulfonamido-oxine fluorophore, termed Sox. The Sox fluorophore undergoes an increase in fluorescence upon phosphorylation of a proximal amino acid via chelation-enhanced fluorescence (CHEF, ex. = 360 nm and em. = 485 nm), allowing for the direct visualization of the rate of phosphate addition to a peptide substrate over time. Our optimal probe design, ROCK-S1, is capable of sensitively reporting ROCK activity with a limit of detection of 10 pM and a high degree of reproducibility (Z'-factor = 0.6 at 100 pM ROCK2). As a proof-of-principle for high-throughput screening (HTS) we demonstrate the ability to rapidly assess the efficacy of a 78 member, small molecule library against ROCK2 using a robotics platform. We identify two previously unreported ROCK2 inhibitor scaffolds, PHA665752 and IKK16, with IC50 values of 3.6 μM and 247 nM respectively. Lastly, we define conditions for selectively monitoring ROCK activity in the presence of potential off-target enzymes (PKCα, PKA, and PAK) with similar substrate specificities.Alpha-fetoprotein (AFP), a primary marker for many diseases including various cancers, is important in clinical tumor diagnosis and antenatal screening. Most immunoassays provide high sensitivity and accuracy for determining AFP, but they are expensive, often complex, time-consuming procedures. A simple and rapid point-of-care system that integrates Eu (III) chelate microparticles with lateral flow immunoassay (LFIA) has been developed to determine AFP in serum with an assay time of 15 min. The approach is based on a sandwich immunoassay performed on lateral flow test strips. A fluorescence strip reader was used to measure the fluorescence peak heights of the test line (HT) and the control line (HC); the HT/HC ratio was used for quantitation. The Eu (III) chelate microparticles-based LFIA assay exhibited a wide linear range (1.0-1000 IU mL(-1)) for AFP with a low limit of detection (0.1 IU mL(-1)) based on 5ul of serum. Satisfactory specificity and accuracy were demonstrated and the intra- and inter-assay coefficients of variation (CV) for AFP were both less then 10%.