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Tau pathogenesis is a hallmark of many neurodegenerative diseases, including Alzheimers disease (AD). Although the events leading to initial tau misfolding and subsequent tau spreading in patient brains are largely unknown, traumatic brain injury (TBI) may be a risk factor for tau-mediated neurodegeneration. Using a repetitive TBI (rTBI) paradigm, we report that rTBI induced somatic accumulation of phosphorylated and misfolded tau, as well as neurodegeneration across multiple brain areas in 7-month-old tau transgenic PS19 mice but not wild-type (WT) mice. rTBI accelerated somatic tau pathology in younger PS19 mice and WT mice only after inoculation with tau preformed fibrils and AD brain-derived pathological tau (AD-tau), respectively, suggesting that tau seeds are needed for rTBI-induced somatic tau pathology. rTBI further disrupted axonal microtubules and induced punctate tau and TAR DNA binding protein 43 (TDP-43) pathology in the optic tracts of WT mice. These changes in the optic tract were associated with a decline of visual function. Treatment with a brain-penetrant microtubule-stabilizing molecule reduced rTBI-induced tau, TDP-43 pathogenesis, and neurodegeneration in the optic tract as well as visual dysfunction. Treatment with the microtubule stabilizer also alleviated rTBI-induced tau pathology in the cortices of AD-tau-inoculated WT mice. These results indicate that rTBI facilitates abnormal microtubule organization, pathological tau formation, and neurodegeneration and suggest microtubule stabilization as a potential therapeutic avenue for TBI-induced neurodegeneration.

This qualitative study explored perspectives of college students with learning disabilities (LD) regarding their self-determination and parental influences on student self-determination during students' transition from high school to postsecondary education. Data were collected from in-depth interviews with 12 college students with LD. Qualitative analyses were conducted to examine students' participation in secondary transition, self-determination behaviors, and parental influences on students' self-determination. The findings identified five important self-determination behaviors (i.e., postsecondary education goal setting and attainment, self-advocacy, being autonomous, self-awareness, and decision-making) students demonstrated in secondary transition. Four themes pertain to parental influences on student self-determination, including encouraging students to be advocates, fostering students' academic competency, showing moral support and high expectations, and providing opportunities for students to make decisions. Recommendations for engaging parents to promote student self-determination are provided.

Based on the principle of the rich-burn/quench/lean-burn (RQL) technology, a low emission combustion chamber for gas turbine was designed. The effects of different heights of quenching structure and distribution ratios of the air flow on the flow field, temperature field, and pollutant formation characteristics of combustion chamber were studied under the premise of keeping the inlet parameters of combustion chamber unchanged. The results show that the height of quenching structure and the proportion of air distribution are important parameters affecting the combustion performance of the combustion chamber. With the decrease of the height of quenching structure, the NOx emission increases at the exit of the combustion chamber. The NOx emission from combustion chamber outlet first decreases and then increases with the decrease of the proportion of air mass flow from the main combustion hole to the fired air mass flow in oil-rich areas, and an optimal proportion of air mass flow makes the NOx minimum. The production of thermal NOx is directly related to the size of the region with a temperature higher than 1 900 K and the maximum gas temperature. The designed combustion chamber has a minimum NOx emission of less than 35 mg/m3 under the studied working conditions, which achieves the emission standard of a low pollution combustion chamber.

BackgroundViral tracers are important tools for mapping brain connectomes. The feature of predominant anterograde transneuronal transmission offers herpes simplex virus-1 (HSV-1) strain H129 (HSV1-H129) as a promising candidate to be developed as anterograde viral tracers. In our earlier studies, we developed H129-derived anterograde polysynaptic tracers and TK deficient (H129-dTK) monosynaptic tracers. However, their broad application is limited by some intrinsic drawbacks of the H129-dTK tracers, such as low labeling intensity due to TK deficiency and potential retrograde labeling caused by axon terminal invasion. The glycoprotein K (gK) of HSV-1 plays important roles in virus entry, egress, and virus-induced cell fusion. Its deficiency severely disables virus egress and spread, while only slightly limits viral genome replication and expression of viral proteins. Therefore, we created a novel H129-derived anterograde monosynaptic tracer (H129-dgK) by targeting gK, which overcomes the limitations of H129-dTK.MethodsUsing our established platform and pipeline for developing viral tracers, we generated a novel tracer by deleting the gK gene from the H129-G4. The gK-deleted virus (H129-dgK-G4) was reconstituted and propagated in the Vero cell expressing wildtype H129 gK (gKwt) or the mutant gK (gKmut, A40V, C82S, M223I, L224V, V309M), respectively. Then the obtained viral tracers of gKmut pseudotyped and gKwt coated H129-dgK-G4 were tested in vitro and in vivo to characterize their tracing properties.ResultsH129-dgK-G4 expresses high levels of fluorescent proteins, eliminating the requirement of immunostaining for imaging detection. Compared to the TK deficient monosynaptic tracer H129-dTK-G4, H129-dgK-G4 labeled neurons with 1.76-fold stronger fluorescence intensity, and visualized 2.00-fold more postsynaptic neurons in the downstream brain regions. gKmut pseudotyping leads to a 77% decrease in retrograde labeling by reducing axon terminal invasion, and thus dramatically improves the anterograde-specific tracing of H129-dgK-G4. In addition, assisted by the AAV helper trans-complementarily expressing gKwt, H129-dgK-G4 allows for mapping monosynaptic connections and quantifying the circuit connectivity difference in the Alzheimer's disease and control mouse brains.ConclusionsgKmut pseudotyped H129-dgK-G4, a novel anterograde monosynaptic tracer, overcomes the limitations of H129-dTK tracers, and demonstrates desirable features of strong labeling intensity, high tracing efficiency, and improved anterograde specificity.