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BackgroundIn a large pedigree with an unusual phenotype of spastic paraplegia or dystonia and autosomal dominant inheritance, linkage analysis previously mapped the disease to chromosome 2q24-2q31.ObjectiveThe aim of this study is to identify the genetic cause and molecular basis of an unusual autosomal dominant spastic paraplegia and dystonia.MethodsWhole exome sequencing following linkage analysis was used to identify the genetic cause in a large family. Cosegregation analysis was also performed. An additional 384 individuals with spastic paraplegia or dystonia were screened for pathogenic sequence variants in the adenosine triphosphate (ATP) synthase membrane subunit C locus 3 gene (ATP5MC3). The identified variant was submitted to the "GeneMatcher" program for recruitment of additional subjects. Mitochondrial functions were analyzed in patient-derived fibroblast cell lines. Transgenic Drosophila carrying mutants were studied for movement behavior and mitochondrial function.ResultsExome analysis revealed a variant (c.318C > G; p.Asn106Lys) (NM_001689.4) in ATP5MC3 in a large family with autosomal dominant spastic paraplegia and dystonia that cosegregated with affected individuals. No variants were identified in an additional 384 individuals with spastic paraplegia or dystonia. GeneMatcher identified an individual with the same genetic change, acquired de novo, who manifested upper-limb dystonia. Patient fibroblast studies showed impaired complex V activity, ATP generation, and oxygen consumption. Drosophila carrying orthologous mutations also exhibited impaired mitochondrial function and displayed reduced mobility.ConclusionA unique form of familial spastic paraplegia and dystonia is associated with a heterozygous ATP5MC3 variant that also reduces mitochondrial complex V activity.

Neurodegeneration occurs naturally as humans age, but the presence of additional pathogenic mechanisms yields harmful and consequential effects on the brain. Alzheimer's disease (AD), the most common form of dementia, is a composite of such factors. Despite extensive research to identify the exact causes of AD, therapeutic approaches for treating the disease continue to be ineffective, indicating important gaps in our understanding of disease mechanisms. Long non-coding RNAs (lncRNAs) are an endogenous class of regulatory RNA transcripts longer than 200 nucleotides, involved in various regulatory networks, whose dysregulation is evident in several neural and extraneural diseases. LncRNAs are ubiquitously expressed across all tissues with a wide range of functions, including controlling cell differentiation and development, responding to environmental stimuli, and other physiological processes. Several lncRNAs have been identified as potential contributors in worsening neurodegeneration due to altered regulation during abnormal pathological conditions. Within neurological disease, lncRNAs are prime candidates for use as biomarkers and pharmacological targets. Gender-associated lncRNA expression is altered in a gender-dependent manner for AD, suggesting more research needs to be focused on this relationship. Overall, research on lncRNAs and their connection to neurodegenerative disease is growing exponentially, as commercial enterprises are already designing and employing RNA therapeutics. In this review we offer a comprehensive overview of the current state of knowledge on the role of lncRNAs in AD and discuss the potential implications of lncRNA as potential therapeutic targets and diagnostic biomarkers in patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The production of polymer‐stabilized vertically aligned (PSVA) displays requires two UV processes for liquid crystal (LC) alignments. UV1 is usually short for pre‐tilt angle formation, while UV2 takes approximately 90 minutes to consume the remaining reactive monomers (RMs). Therefore, shortening the UV2 process can significantly reduce the power consumption and maintenance costs of UV lamps during LCD fabrication. Herein, we report a novel LC material consisting of fast‐reaction RMs. With the addition of fast‐reaction RMs, the UV2 process can be dramatically decreased from 90 min to 20 min. Furthermore, the reduction of the UV2 process shows competitive optical properties, reliabilities and pre‐tilt angle stabilities compared with the reference. Overall, new fast‐reaction LC materials are beneficial to energy saving and the cost competitiveness of the company. [ABSTRACT FROM AUTHOR]

The development of power grid system not only increases voltage and capacity, but also increases power risk. This paper briefly introduces the feature extraction method of the vibration signal of high voltage circuit breaker and support vector machine (SVM) algorithm and then analyzed the high voltage circuit breaker in three states: normal operation, fixed screw loosening and falling of opening spring, using the SVM based on the above feature extraction method. The results showed that the accuracy and precision rates of fault identification of circuit breaker were the highest by using the wavelet packet energy entropy extraction features, the false alarm rate was the lowest, and the detection time was the shortest.

Pulse injection hydraulic fracturing (HF) can release high-energy peak pressure in a split-second, forming a complex hydraulic fracture network in shale reservoirs. However, the initiation and propagation of multiple fractures in the horizontal well of shale reservoirs under pulse injection HF have been inadequately studied. Hence, in this study, a HF model coupling the fracturing fluid flow along the fracture and the rock deformation was adopted, and the effect of the pulsed injection method on multistage HF of horizontal wells was determined. The results show that the pulsed injection HF can improve the fracturing effect of horizontal wells. However, no matter how the injection displacement and pulse frequency change, the propagation length of cracks at both ends seriously disturbed by stress almost remains unchanged. When the dominant fracture is temporarily shielded, the fluid pressure of the non-dominant fractures at both ends disturbed by stress compression increases, and the non-dominant fractures can be further expanded. Thus, a new composite multistaged HF scheme suitable for horizontal wells with pulse-temporary shielding in shale reservoirs was proposed. The method presented here can be adopted to optimize the fracture growth regime and provide a scientific basis for the fracturing operation of the horizontal well in shale reservoirs. [ABSTRACT FROM AUTHOR]