A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.

BACKGROUND: Hereditary spastic paraplegia (HSP) represents a group of monogenic neurodegenerative disorders characterized by high clinical and genetic heterogeneity. HSP is characterized by slowly progressing hypertonia of both lower extremities, spastic gait, and myasthenia. The most prevalent autosomal dominant form of HSP, known as spastic paraplegia 4 (SPG4), is attributed to variants in the spastin (SPAST) gene. METHODS AND RESULTS: Here, a Chinese family presenting with spasticity in both legs and a shuffling gait participated in our investigation. Whole exome sequencing of the proband was utilized to identify the genetic lesion in the family. Through data filtering, Sanger sequencing validation, and co-separation analysis, a novel variant (NM_014946.3: c.1669G > C:p.A557P) of SPAST was identified as the genetic lesion of this family. Furthermore, bioinformatic analysis revealed that this variant was deleterious and located in a highly evolutionarily conserved site. CONCLUSION: Our study confirmed the diagnosis of SPG4 in this family, contributing to genetic counseling for families affected by SPG4. Additionally, our study broadened the spectrum of SPAST variants and highlighted the importance of ATPases associated with various cellular activity domains of SPAST.

[A Method for Fine Mapping of Carbon Emissions from Regional Land Use Change and Its Application].

Land use changes are always patchy and widespread within a region, making it a challenge to identify the point-scale pressure of reducing carbon emissions from land use/cover change （LUCC）. The carbon emission observation index （CEOI） was thus proposed to conduct the point-scale comparability analysis, which was based on the unique net C flux effects of conversions between two different land use types. Then, the spatial-temporal characteristics of land use changes and the resulting pressure of reducing carbon emissions were studied in the Weihe River Basin of China, which adopted the LUCC data from 2000 to 2020 and models of the Markov transition matrix （MTM）, compound carbon emission coefficients （CEC） of various types of land use changes, and the CEOI-based classification method on point-scale pressure of reducing carbon emissions. The results showed that： ① The net C flux was from 3.551 Tg C （2000-2010） to 7.031 Tg C （2010-2020）, and the pressure of reducing carbon emissions from LUCC had been continuously increasing, which was mainly driven by the significant increase in change-spots with the super-strong ability to reduce carbon emissions. ② Due to contributions from change spots with carbon uptake ability, the amount of carbon released to the atmosphere was eliminated by approximately 19.21% over the period 2000-2020 and approximately 37.4% during 2000-2010. ③ Change spots on various pressure levels for reducing carbon emissions were distributed unevenly in the basin, with their gravity points in the previous 10 years （2010-2020） far away from those during 2000-2010. Additionally, the gravity points of change-spots with a strong ability to reduce carbon emissions from conversions of grassland into forestland moved northeastward from Tianshui City to Pingliang City, whereas the gravity points of other change-spots with different abilities to reduce carbon emissions were mostly northwestward to the north-central region with higher elevations from the Middle and Lower Reaches of the Weihe River Basin with low elevations.

Development and evaluation of a bivalent vaccine based on recombinant newcastle disease virus expressing infectious bursal disease virus VP2L-CH3-CH4 in SPF chickens.

Newcastle disease (ND) and infectious bursal disease (IBD) are two viral infectious diseases that are extremely damaging to the poultry industry and are widespread throughout the world. It is necessary to develop a safe and effective vaccine against IBD and ND because vaccination is an effective preventive measure. It has been discovered that recombinant proteins expressed by an expression system in which a fragment of mammalian Immunoglobulin G (IgG) Fragment crystallizable (Fc) is linked to a segment of a gene have antibody-like properties that increase the exogenous protein's serum half-life. Heavy chain constant region 3 and heavy chain constant region 4 (CH3-CH4) of Avian Immunoglobulin Y (IgY) is structurally very similar to mammalian Ig G Fc. In this study, a bivalent vaccine rClone30-VP2L-CH3-CH4-GMCSF was developed by using NDV rClone30-chGM-CSF vector to produce VP2L-CH3-CH4 fusion protein. The vaccine has been given to 14-day-old specific pathogen free (SPF) free chickens to test whether it has the potential to prevent IBD and ND. Anti-IBDV and anti-NDV antibody levels in serum were evaluated using ELISA and HI, respectively, and the contents of CD4+ T, CD8+ T, and B cells in leukocytes were determined via flow cytometry. The contents and mRNA transcription levels of four inflammatory factors, IL-1ß, IL-4, IFN-γ and chGM-CSF, were detected by ELISA and real-time PCR respectively. The results showed that after vaccination with the rClone30-VP2L-CH3-CH4-GMCSF vaccine, the levels of anti NDV and anti IBDV antibodies in chickens were significantly higher than those of the rClone30 vaccine and commercial vaccines. Meanwhile, the contents and transcription levels of inflammatory factors in chickens inoculated with rClone30-VP2L-CH3-CH4-GMCSF were significantly increased, and the proliferation response of B cells, CD4+ and CD8+ T cells was also stronger. However, the rClone30-VP2L-CH3-CH4-GMCSF vaccine had no significant advantage over the rClone30-VP2L-GMCSF vaccine in any of the above-mentioned features. In summary, rClone30-VP2L-CH3-CH4-GMCSF can stimulate the body to produce a stronger immune response, showing its potential to be considered as vaccine against IBD and ND, but the addition of CH3-CH4 did not improve the vaccine's immune effect as expected. The research lays the foundation for developing vaccines for other infectious viral diseases and avoids a unrealistic vaccine optimization method.