Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a rare paediatric lysosomal storage disorder, caused by the progressive accumulation of heparan sulphate, resulting in neurocognitive decline and behavioural abnormalities. Anecdotal reports from paediatricians indicate a more severe neurodegeneration in MPS IIIA patients, following infection, suggesting inflammation as a potential driver of neuropathology. To test this hypothesis, we performed acute studies in which WT and MPS IIIA mice were challenged with the TLR3-dependent viral mimetic poly(I:C). The challenge with an acute high poly(I:C) dose exacerbated systemic and brain cytokine expression, especially IL-1ß in the hippocampus. This was accompanied by an increase in caspase-1 activity within the brain of MPS IIIA mice with concomitant loss of hippocampal GFAP and NeuN expression. Similar levels of cell damage, together with exacerbation of gliosis, were also observed in MPS IIIA mice following low chronic poly(I:C) dosing. While further investigation is warranted to fully understand the extent of IL-1ß involvement in MPS IIIA exacerbated neurodegeneration, our data robustly reinforces our previous findings, indicating IL-1ß as a pivotal catalyst for neuropathological processes in MPS IIIA.

Sustainability of exercise-induced benefits on circulating MicroRNAs and physical fitness in community-dwelling older adults: a randomized controlled trial with follow up.

BACKGROUND: Circulating miRNAs (c-miR) have been shown to be potential biomarkers in sarcopenia, but the miRNAs response to aerobic exercise in older people remains inconclusive. We sought to examine the exercise benefits on physical fitness and miRNAs, and to explore the mediating effect of miRNAs on training-induced fitness changes. METHODS: This controlled trial recruited 58 community-dwelling older adults and randomized them into exercise group (EX) and control group (CON). EX received 8-week supervised moderate intensity cycling training 3x/week. C-miR expression (c-miR-21, c-miR-126, c-miR-146a, c-miR-222), physical fitness (body composition, cardiorespiratory fitness, muscular fitness) and physical activity level (PAL, measured as in daily step counts) were evaluated at baseline, post-training, and post-16-week follow-up. The mediating effect of miRNA expression onto exercise-induced physical fitness change was determined by causal mediation analysis (CMA). RESULTS: Exercise significantly improved body fat and cardiorespiratory fitness in older people while maintaining muscle mass and strength, and augmented expression of c-miR-126, c-miR-146a, and c-miR-222 for up to 16 weeks post-training. Notably, older people in EX had substantially higher daily step counts than CON throughout the study even after the active training period. However, CMA revealed no significant indirect effect but a potential mediating effect of c-miR-21, but not the rest, onto the body composition, cardiorespiratory fitness, and lower limb strength. CONCLUSION: An eight-week supervised MICT program promoted a higher level of physical activity up to 16 weeks post-training, which induces better cardiorespiratory fitness and resists decline in muscular measures. C-miRNA, especially c-miR-21, potentially mediates the training effect upon fitness.

A mitochondrial targeted dual ratiometric near-infrared fluorescent probe based on ICT effect for the detection of SO2 derivative and its bioimaging.

SO2 derivatives play an important role in many metabolic processes, excessive ingestion of them can lead to serious complications of various diseases. In this work, a novel dual ratiometric NIR fluorescent probe XT-CHO based on ICT effect was synthesized for detecting SO2 derivative. In the design of the probe, the α, ß-unsaturated bond formed between benzopyran and coumarin was used as the reaction site for SO2, meanwhile, the extended π-conjugate system promoted maximum emission wavelength of the probe up to 708 nm. Notably, the probe exhibited high selectivity and sensitivity for detecting SO2, the limit of detection reached 2.13 nM and 58.5 nM in fluorescence spectra and UV-Vis absorption spectra, respectively. The reaction mechanism of SO2 and XT-CHO had been verified by 1H NMR, ESI-MS spectra and DFT calculation. Moreover, the probe was successfully applied in detecting endogenous and exogenous SO2 in living cells and proved possessed the mitochondrial targeted ability.

A dual-response NIR fluorescent probe for separately and continuously recognizing H2S and Cys with different fluorescence signals and its applications.

Given the significant interactions between hydrogen sulfide (H2S) and cysteine (Cys) in organisms, a dual-site multi-purpose fluorescent probe (Cy-NP) for H2S and Cys was synthesized. Cy-NP is composed of two fluorophores: naphthalimide that emits in the visible region of 500-600 nm, and cyanine dye that emits in the NIR region of 700-800 nm. Cy-NP showed admirable sensitivity and selectivity for identifying H2S and Cys by fluorescent signals with limits of detection as low as 0.15 µM and 1.4 µM, respectively. Furthermore, other biological thiols (especially GSH and Hcy) showed no positive response to Cy-NP compared with H2S and Cys. The chemical mechanism of Cy-NP with H2S and Cys in DMF/PBS (1/1, v/v, pH = 7.4) solution was verified by HRMS and DFT calculations. Further, Cy-NP was successfully applied to monitor H2S released in raw meat and adapted to detect H2S and Cys in MCF-7 cells independently and continuously.

A novel diarylethene-based fluorescence sensor for Zn2+ detection and its application.

A series of fluorometric sensors of Zn2+ have been synthesized due to the significant function of Zn2+ in the human body and environment. However, most of probes reported for detecting Zn2+ have high detection limit or low sensitivity. In this paper, an original Zn2+ sensor, namely 1o, was synthesized by diarylethene and 2-aminobenzamide. When Zn2+ was added, the fluorescence intensity of 1o increased by 11 times within 10 s, along with a fluorescence color change from dark to bright blue, and the detection limit (LOD) was calculated to be 0.329 µM. According to Job's plot curves, the binding mode of 1o and Zn2+ was measured as 1:1, which was further proved by 1H NMR spectra, HRMS and FT-IR spectra. The logic circuit was designed to take advantage of the fact that the fluorescence intensity of 1o can be controlled by Zn2+, EDTA, UV and Vis. In addition, Zn2+ in actual water samples were tested, in which the recovery rate of Zn2+ was between 96.5 % and 109 %. Furthermore, 1o was successfully made into a fluorescent test strip, which could be used to detect Zn2+ in the environment economically and conveniently.

A "Turn-on" Fluorescent Probe Based on Phenothiazine for Selectively Recognizing ClO- and its Practical Applications.

Hypochlorous acid (HClO), a highly reactive oxygen species, has important effects on human health. High selectivity and sensitivity remain challenges of fluorescent probes for detection of ClO- with a large Stokes shift. This work designed and synthesized a novel phenothiazine-based fluorescent probe TF which can detect ClO- by colorimetric and fluorescent dual signals. TF displayed turn-on fluorescence effect toward ClO- with high selectivity (≥ 28-folds) and sensitivity (LOD = 0.472 µM), fast response time (< 1 min) and large Stokes shift (150 nm) in PBS (pH = 7.4, 40% DMSO). Meanwhile, TF can visualize ClO- on the mung bean sprouts model and apply as testing strips for portable and rapid detecting ClO- by the naked eyes. A phenothiazine-based fluorescent probe with large Stokes shift was synthesized and its responding rapidly ability to detect ClO- was studied.

The Effects of Exercise Training on Mitochondrial Function in Cardiovascular Diseases: A Systematic Review and Meta-Analysis.

Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included "mitochondria", "exercise", "aerobic capacity", and "cardiovascular disease" in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I2 = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.

Association of sports vision with age, gender, and static visual acuity among nonathletic population.

PURPOSE: Excellent vision is essential to performing well in sports. Sports vision includes visual, perceptual, cognitive, and oculomotor tasks that enable athletes to process and respond to what is seen. We aimed to examined how sports vision parameters - dynamic visual acuity (DVA), eye movement (EM), peripheral vision (PV), and momentary vision (MV) - varied with age and sex and assessed how static visual acuity (SVA) affect sports vision performance. MATERIALS AND METHODS: Sports vision was assessed at 45 cm distance at best-corrected SVA in 310 nonathletic participants (age, 6-60 years). Among these 310 participants, 108 university students underwent their sports vision test at 45 cm and 2.5 m distance, with and without glasses. The 4 sports vision parameters were measured by Athlevision software package installed to a laptop. Two-way analysis of variance (ANOVA) was used to compare sports vision performance in relation to age group and sex. Repeated-measures ANOVA with 1 within-factor (4 conditions) were used to analyze how sports vision varied among the near/far distance with/without glasses conditions. RESULTS: DVA increased during childhood, peaked during the 20s or 30s, and gradually decreased during middle age (P < 0.0001). DVA was significantly better in males than in females (P = 0.0001). The other 3 sport vision parameters - EM, PV, and MV - exhibited similar age trends (P < 0.001) but did not differ between two sexes. The university students with mild myopia had similar DVA, EM, and PV at both near and far distances, with and without correction; but moderate or severe myopic students with uncorrected vision had worse DVA, EM, and PV at 2.5 m than at 45 cm. CONCLUSION: Low SVA in uncorrected myopia significantly interferes the performance in sport vision tests applied in this study, especially in far distance. Improve static vision, such as myopic correction, may significantly improve sports vision, which is important in athletic performance and safety.

Large Optical Nonlinearity of Dielectric Nanocavity-Assisted Mie Resonances Strongly Coupled to an Epsilon-near-Zero Mode.

Strong coupling provides a powerful way to modify the nonlinear optical properties of materials. The coupling strength of the state-of-the-art strongly coupled systems is restricted by a weak-field confinement of the cavity, which limits the enhancement of the optical nonlinearity. Here, we investigate a strong coupling between Mie resonant modes of high-index dielectric nanocavities and an epsilon-near-zero mode of an ultrathin indium tin oxide film and obtain an anticrossing splitting of 220 meV. Static nonlinear optical measurements reveal a large enhancement in the intensity-independent effective optical nonlinear coefficients, reaching more than 3 orders of magnitude at the coupled resonance. In addition, we observe a transient response of ∼300 fs for the coupled system. The ultrafast and large optical nonlinear coefficients presented here offer a new route towards strong coupling-assisted high-speed photonics.

Stereopsis and Response Times between Collegiate Table Tennis Athletes and Non-Athletes.

Table tennis athletes and non-athletes potentially differ in stereopsis and eye-hand response times (RT), but whether stereopsis correlates with response time has scarcely been discussed. We aimed to compare stereopsis and RT between collegiate table tennis athletes and non-athletes and to examine the correlation between stereopsis and RT. From December 2016 to October 2019, table tennis athletes (n = 80) and non-athletes (n = 56) were recruited. Stereopsis was measured in four modes (A25, A50, R25, R50: approaching and receding directions at 25 mm/s or 50 mm/s). RT was measured with simple and choice tasks at zero, shoulder, and random distance. For stereopsis, the judged deviations were smaller during the approaching phases. Men had smaller A25 than women (p =0.012), whereas table tennis athletes showed smaller R25 and A50 than non-athletes (p = 0.03, 0.01, respectively). RT increased from simple to choice conditions and from zero to random, followed by shoulder distance. Men were significantly faster than women in choice tasks (p < 0.01). Table tennis athletes performed better in RT than the non-athletes (p < 0.05). No correlation was observed between stereopsis and RT (r = -0.01 to 0.12). In conclusion, athletes from table tennis sports showed better stereopsis and RT than non-athletes. Men had better stereopsis and RT than women. There was no correlation between stereopsis and RT.

Moderated Mediation Model from Stress to Burnout among Health Professionals.

Objectives: It is unclear whether poor health is a contributing factor or a consequence of burn-out. We aimed to explore the relationship among job stress, physical health, mental health, burnout, and coping strategies among health professionals using a moderated mediation model. Methods: Health professionals in Taiwan were invited using a stratified and probability proportional to size sampling. A structure equation model (SEM) was used to examine relationships among job stress, burnout, and physical/mental health. The bootstrapping approach for moderated mediation analysis was then used to explore the role of coping strategies. Results: Totally 935 health professionals participated. The SEM model revealed that job stress was inversely associated with physical and mental health. The direct association between job stress and burn-out was insignificant. Moderated mediation analysis revealed that job stress influenced burnout through physical health and mental health, and that the coping strategy of support-seeking moderated the indirect effect only through mental health. Conclusions: Support-seeking is a good coping strategy for health professionals to buffer the harmful effects of job stress on mental health.

Opto-thermal oscillation and trapping of light absorbing particles.

We present an experimental study on opto-thermal oscillation and trapping of light absorbing particles. The oscillation is a three-dimensional motion in the solution. The particles at the lower substrate of the sample cell are driven towards the center of optical trap by the optical force. When the particles arrive at the location near the trap center, the laser heating on the particles results in a strong thermal gradient force that repels the particles to leave the focus spot. Next, the particles slow down under the viscous drag force. At last, the particles settle to the lower substrate of sample cell due to gravity, and restart the new oscillation process. For opto-thermal trapping of the absorbing particles, the particles are dispersed in a thin cell to compress the convention and enhance the viscous resistance. The particles can be trapped close to the spot due to the balance of optical and thermal gradient forces.

Post-transplant laronidase augmentation for children with Hurler syndrome: biochemical outcomes.

Allogeneic hematopoietic cell transplantation (HCT) benefits children with Hurler syndrome (MPS-IH). However, survivors remain burdened by substantial MPS-IH related residual disease. We studied the feasibility, safety and biochemical impact of augmentative recombinant intravenous enzyme replacement therapy (IV-ERT) post transplantation. Ten children with MPS-IH and ≥2 years from successful HCT underwent IV-ERT for 2 years' duration. Patients were monitored for anti-drug antibody (ADA) development, including inhibitory capacity and changes in urinary excretion of glycosaminoglycans (uGAG). Three patients demonstrated low-level ADA at baseline, though all children tolerated IV-ERT well. Eight patients developed ADA over the 2-year study, with 3 (38%) meeting criteria for an inhibitory ADA response. The aggregate cohort experienced a reduction in uGAG from baseline to study end, which was enhanced in children with low or no ADA response. Conversely, children with inhibitory ADA showed increase in uGAG over time. IV-ERT in previously transplanted children with MPS-IH appears safe and can reduce uGAG, although this is reversed by the presence of inhibitory ADA. These data show a biochemical change after initiation of post-HCT IV-ERT, but the occurrence of ADA and inhibitory antibodies are a concern and should be monitored in future efficacy trials. This trial was registered at www.clinicaltrials.gov , NCT01173016, 07/30/2010.

An Assessment of Heavy Metals Toxicity in Asian Clam, Corbicula fluminea, from Mekong River, Pa Sak River, and Lopburi River, Thailand.

High population density and economic development attributing to the changes in water quality in Pa Sak River, Lopburi River, and Mekong River have attracted great attention. This research aimed to determine the pollution of heavy metals in collected clams at three different study sites. Bioaccumulation of heavy metals in Asian clam (Corbicula fluminea) may be likely to cause serious health effects on human beings. The clams sampled from three different rivers (Mekong, Pa Sak, and Lopburi) from Thailand were analyzed for the presence of heavy metals (Zn, Cu, Cd, Cr, Mn, and Pb) with an air-acetylene flame atomic absorption spectrophotometer (AAS). Among the heavy metals studied, Zn was recorded as having the highest concentration (127.33-163.65 µg/g) among the three rivers. The observed mean concentration of Cu was in the range of 84.61-127.15 µg/g followed by Mn (13.96-100.63 µg/g), Cr (5.79-15.00 µg/g), Pb (3.43-8.55 µg/g), and Cd (0.88-1.95 µg/g). Overall, Asian clam from Pa Sak River was found to contain high concentrations of Zn, Cu, Cd, Cr, and Pb compared to Mekong and Lopburi River.

Survey on Heavy Metals Contamination and Health Risk Assessment in Commercially Valuable Asian Swamp Eel, Monopterus albus from Kelantan, Malaysia.

This work investigates the metals concentration in the tissues of Asian swamp eel, Monopterus albus. Five selected tissues, including liver, gill, bone, skin, and muscle were examined for the concentration of Zn, Cu, Cd, Pb, and Ni. The concentrations of Cd and Pb were found high in the muscle tissues of the eels. Additionally, high amounts of Zn and Cu metals were observed in the liver, whereas the Cd, Pb, and Ni metals were highly detected in gill. The accumulation of Zn, Cu, Cd, Pb, and Ni in both skin and bone of the eel seems to vary between seasons. Low levels of Zn, Cu, and Ni were identified in the muscle tissues of the eels. This study revealed that the concentration of Cd and Pb in the muscle tissues of Asian swamp eels exceeded the permissible limits by the US EPA, suggesting the consumption of the muscle may be hazardous and can severely affect one's health.

Seasonal variation of heavy metals and metallothionein contents in Asian swamp eels, Monopterus albus (Zuiew, 1793) from Tumpat, Kelantan, Malaysia.

BACKGROUND: Levels of toxic metal exposure in indigenous inhabitants are key bioindicators of the severity of environmental contamination. This study measured the seasonal variation of heavy metals and metallothionein (MT) contents in Asian swamp eels (Monopterus albus) from a paddy field situated in Tumpat, Kelantan, Malaysia, to identify prevalence, patterns and associations and togain insight on the suitability of MT as a biomarker for metal exposure. METHODS: Gill, muscle and liver tissues of M. albus (n = 50) sampled during the ploughing, seedling, growing and harvesting phases of rice growing were collected. The concentrations of copper (Cu), zinc (Zn), lead (Pb), nickel (Ni), and cadmium (Cd) in these tissues were determined by flame atomic absorption spectrometry. MT from each sample was isolated and purified, and subsequently quantitated using UV spectrophotometry. Associations between metal and MT concentrations, season and tissue type were evaluated using Pearson correlation and ANOVA with post-hoc Tukey HSD analysis. RESULTS: Zn was present in higher quantities in gill and liver tissues, while Cu levels were elevated solely in liver. Patterns of non-essential metal accumulation were varied: Cd was detected in low concentrations in all tissues, while Pb and Ni were abundant in gill tissues across all seasons. MT concentration in liver tissue was consistently higher than that found in muscle or gill tissue, except during the growing phase. Moreover, significant correlations (P < 0.05) were observed for Cd, Ni, and Zn when MT was employed as metal exposure biomarker. However, no significant association was found between high Pb and Ni levels and MT concentration in gill tissue.Variation of bioaccumulation rates of heavy metals among the different tissues was observed. Some of these metal concentration differences were found to be associated with MT concentration and, by extension, to its high metal-binding capacity. CONCLUSIONS: Significant liver MT-Zn, MT-Cd, and MT-Ni correlations found in this study emphasised the role of metallothionein as a biomarker for exposure of zinc, cadmium and nickel metals in M. albus.

The Effectiveness of a Virtual Reality-Based Tai Chi Exercise on Cognitive and Physical Function in Older Adults with Cognitive Impairment.

BACKGROUND: Tai Chi (TC) is a Chinese mind-body exercise with proven physical and psychological benefits. A modified TC via virtual reality (VR) may be suitable for the elderly owing to the immediate guidance and feedback regarding movement accuracy. This study explored the cognitive and physical effects of a VR-based TC (VRTC) exercise program on older adults with cognitive impairment (CI). METHODS: Sixty older adults with CI were cluster-assigned to either the VRTC or the control group; the intervention was conducted twice weekly for 6 months. Outcomes included cognitive and physical functions. The movement accuracy score and attendance were recorded. Generalized estimating equation (GEE) and multiple regression analyses were performed. RESULTS: Adjusted GEE analysis showed significant interaction effects in the 6-min walk test, 30-s sit-to-stand test, functional reach, 5-m gait speed, and abstract thinking and judgment. Overall, medium to large effect sizes (d = 0.50-0.82) were found in favor of the VRTC group. The average movement accuracy score in the first 3 months significantly predicted improvement in cognitive performance (p = 0.011). CONCLUSIONS: The VRTC exercise posed a protective effect for some cognitive and physical functions in older adults with CI. The more engaging the program, the greater the improvement in the cognitive performance.

Lead Concentration in Long-Tailed Macaque (Macaca fascicularis) Hair in Kuala Selangor, Malaysia.

Long-tailed macaque (Macaca fascicularis) has the potential to be a good biological indicator for toxic exposure because they have an almost similar physiology and behaviour to humans. The objective of this study is to determine the concentration of lead (Pb) in hair samples of long-tailed macaques which were found in and out of the Kuala Selangor Nature Park (KSNP) area. The hypothesis is long-tailed macaques that live in the anthropogenic area (outside KSNP) may be exposed to high levels of lead compared to long-tailed macaques living in the forest area (inside KSNP). Analysis of hair samples were carried out using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The study found that the average mean of lead concentration in the anthropogenic area is 6.31 µg/g while for the forest area it is 3.16 µg/g. Lead concentration in the two areas are statistically insignificant. Nevertheless, lead concentration in the anthropogenic area recorded a slightly higher mean concentration than in the forest area. Even so, results of this study indicate that long-tailed macaques in Kuala Selangor are not exposed to high levels of lead. This study is the first in Malaysia to utilise long-tailed macaques as a biological indicator for testing the concentration of toxic substances in the environment. This study is still in its early stages; thus, future research requires improvements.

Brain-targeted stem cell gene therapy corrects mucopolysaccharidosis type II via multiple mechanisms.

The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS.ApoEII) compared to a lentivirus expressing normal IDS or a normal bone marrow transplant. In mucopolysaccharidosis II mice, all treatments corrected peripheral disease, but only IDS.ApoEII mediated complete normalization of brain pathology and behavior, providing significantly enhanced correction compared to IDS. A normal bone marrow transplant achieved no brain correction. Whilst corrected macrophages traffic to the brain, secreting IDS/IDS.ApoEII enzyme for cross-correction, IDS.ApoEII was additionally more active in plasma and was taken up and transcytosed across brain endothelia significantly better than IDS via both heparan sulfate/ApoE-dependent receptors and mannose-6-phosphate receptors. Brain-targeted hematopoietic stem cell gene therapy provides a promising therapy for MPS II patients.

A novel adeno-associated virus capsid with enhanced neurotropism corrects a lysosomal transmembrane enzyme deficiency.

Recombinant adeno-associated viruses (AAVs) are popular in vivo gene transfer vehicles. However, vector doses needed to achieve therapeutic effect are high and some target tissues in the central nervous system remain difficult to transduce. Gene therapy trials using AAV for the treatment of neurological disorders have seldom led to demonstrated clinical efficacy. Important contributing factors are low transduction rates and inefficient distribution of the vector. To overcome these hurdles, a variety of capsid engineering methods have been utilized to generate capsids with improved transduction properties. Here we describe an alternative approach to capsid engineering, which draws on the natural evolution of the virus and aims to yield capsids that are better suited to infect human tissues. We generated an AAV capsid to include amino acids that are conserved among natural AAV2 isolates and tested its biodistribution properties in mice and rats. Intriguingly, this novel variant, AAV-TT, demonstrates strong neurotropism in rodents and displays significantly improved distribution throughout the central nervous system as compared to AAV2. Additionally, sub-retinal injections in mice revealed markedly enhanced transduction of photoreceptor cells when compared to AAV2. Importantly, AAV-TT exceeds the distribution abilities of benchmark neurotropic serotypes AAV9 and AAVrh10 in the central nervous system of mice, and is the only virus, when administered at low dose, that is able to correct the neurological phenotype in a mouse model of mucopolysaccharidosis IIIC, a transmembrane enzyme lysosomal storage disease, which requires delivery to every cell for biochemical correction. These data represent unprecedented correction of a lysosomal transmembrane enzyme deficiency in mice and suggest that AAV-TT-based gene therapies may be suitable for treatment of human neurological diseases such as mucopolysaccharidosis IIIC, which is characterized by global neuropathology.