Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral ...organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
A highly efficient rhodium(III)‐catalyzed synthesis of novel functionalized indene derivatives has been achieved via C−H activation/intramolecular aldol condensation. This cascade reaction is an atom ...economical protocol which could be further applied to build more complex compounds.
Essential tremor is one of the most common movement disorders. Despite its high prevalence and heritability, the genetic aetiology of essential tremor remains elusive. Up to now, only a few ...genes/loci have been identified, but these genes have not been replicated in other essential tremor families or cohorts. Here we report a genetic study in a cohort of 197 Chinese pedigrees clinically diagnosed with essential tremor. Using a comprehensive strategy combining linkage analysis, whole-exome sequencing, long-read whole-genome sequencing, repeat-primed polymerase chain reaction and GC-rich polymerase chain reaction, we identified an abnormal GGC repeat expansion in the 5' region of the NOTCH2NLC gene that co-segregated with disease in 11 essential tremor families (5.58%) from our cohort. Clinically, probands that had an abnormal GGC repeat expansion were found to have more severe tremor phenotypes, lower activities of daily living ability. Obvious genetic anticipation was also detected in these 11 essential tremor-positive families. These results indicate that abnormal GGC repeat expansion in the 5' region of NOTCH2NLC gene is associated with essential tremor, and provide strong evidence that essential tremor is a family of diseases with high clinical and genetic heterogeneities.
I am very emo Ying Qi Wu; Sun, Qi
English today,
03/2024, Letnik:
40, Številka:
1
Journal Article
Recenzirano
The contemporary expansion of English is becoming remarkably rapid and exceptionally global (Ostler, 2011). In present-day China, English has gained unprecedented popularity, fueled by the nation's ...current political and social development (Bolton & Graddol, 2012). There is a notable trend of bilingual education using English as a medium of instruction in Chinese schools (Wei, 2013). Therefore, an increasing number of Chinese are enthusiastic about learning and using English in communication. With the active participation of youths, ‘Internet English’ has been used widely in social networking spaces. The practice of ‘English mixing’ in various Chinese homegrown social networking sites has become the most remarkable intranational use of English in today's mainland China (Zhang, 2012). Interestingly, youngsters1 often create novel meanings when using languages on the Internet as ‘teenagers are well-known for introducing innovations into language, and indeed are generally regarded as prime agents of language change’ (Palacios Martínez, 2018: 363). Many linguistic studies have dealt with the mechanisms of the evolution of word meanings in past decades (Kachru, 1983; Qin & Guo, 2020; Tan, 2009; Yang, 2005). Much evidence indicates that meanings and usages of words are variable and composite, and may turn out differently depending on how words are used in contexts.
Secondary organic aerosol (SOA) is an important component of fine particular matter (PM2.5). Most air quality models use an equilibrium partitioning method along with the saturation vapor ...pressure (SVP) of semivolatile organic compounds (SVOCs) to predict SOA formation. However, the models typically assume that the organic particulate matter (OPM) is an ideal mixture and ignore the partitioning of water vapor to OPM. In this study, the Community Multiscale Air Quality model (CMAQ) is updated to investigate the impacts of water vapor partitioning and nonideality of the
organic–water mixture on SOA formation during winter (January) and summer
(July) of 2013 over eastern China. The updated model treats the partitioning of water vapor molecules into OPM and uses the universal functional activity coefficient (UNIFAC) model to estimate the activity coefficients of species in the organic–water mixture. The modified model can generally capture the observed surface organic carbon (OC) with a correlation coefficient R of 0.7 and the surface organic aerosol (OA) with the mean fractional bias (MFB) and mean fractional error (MFE) of −0.28 and 0.54, respectively. SOA concentration shows significant seasonal and spatial variations, with high concentrations in the North China Plain (NCP), central China, and the Sichuan Basin (SCB) regions during winter (up to 25 µg m−3) and in the Yangtze River Delta (YRD) during summer (up to 16 µg m−3). In winter, SOA decreases slightly in the updated model, with a monthly averaged relative change of 10 %–20 % in the highly concentrated areas, mainly due to organic–water interactions. The monthly averaged concentration of SOA increases greatly in summer, by 20 %–50 % at the surface and 30 %–60 % in the whole column. The increase in SOA is mainly due
to the increase in biogenic SOA in inland areas and anthropogenic SOA in
coastal areas. As a result, the averaged aerosol optical depth (AOD) is
increased by up to 10 %, and the cooling effect of aerosol radiative
forcing (ARF) is enhanced by up to 15 % over the YRD in summer. The aerosol
liquid water content associated with OPM (ALWorg) at the surface is relatively high in inland areas in winter and over the ocean in summer, with a monthly averaged concentration of 0.5–3.0 and 5–7 µg m−3, respectively. The hygroscopicity parameter κ of OA based on the κ–Köhler theory is determined using the modeled ALWorg. The correlation of κ with the O:C ratio varies significantly across
different cities and seasons. Analysis of two representative cities, Jinan
(in the NCP) and Nanjing (in the YRD), shows that the impacts of water partitioning
and nonideality of the organic–water mixture on SOA are sensitive to
temperature, relative humidity (RH), and the SVP of SVOCs. The two processes exhibit opposite impacts on SOA in eastern China. Water uptake increases SOA by up to 80 % in the organic phase, while including nonunity activity coefficients decreases SOA by up to 50 %. Our results indicate that both water partitioning into OPM and the activity coefficients of the condensed organics should be considered in simulating SOA formation from gas–particle partitioning, especially in hot and humid environments.
Increasing evidences have demonstrated that long noncoding RNAs (LncRNAs) play a significant role in the development of tumor. However, the role of metastasis-associated lung adenocarcinoma ...transcript 1 (MALAT1) in uveal melanoma remains unknown. In this study, we demonstrated that the expression of MALAT1 was upregulated in the uveal melanoma tissues compared to normal tissues. Among them, MALAT1 was upregulated in 72% (18/25) uveal melanoma tissues compared to their paired normal tissues. Knockdown of MALAT1 suppressed uveal melanoma cell proliferation, colony information, invasion and migration. Moreover, we showed that knockdown of MALAT1 promoted miR-140 expression and suppressed Slug and ADAM10 expression in the MUM-2C cell. In addition, we demonstrated that miR-140 was downregulated in the uveal melanoma tissues compared to normal tissues and cell lines. The expression level of MALAT1 was inversely correlated with the expression level of miR-140 in uveal melanoma tissues. These results suggested that MALAT1 served as an oncogenic LncRNA in the development of uveal melanoma.
The impact of chlorine (Cl) chemistry on the formation of secondary organic aerosol (SOA) during a severe wintertime air pollution episode is investigated in this study. The Community Multiscale Air ...Quality (CMAQ) model v5.0.1 with a modified SAPRC-11 gas-phase mechanism and heterogeneous reactions for reactive chlorine species is updated to include the formation of chlorine radical (Cl•)-initiated SOA (Cl-SOA) from aromatic compounds, terpenes, and isoprene. Reported SOA yield data on Cl-SOA formation from environmental chamber studies are used to derive the mass yield and volatility data for the two-product equilibrium-partitioning model. The heterogeneous reaction of particulate chloride (pCl–) leads to a significant increase in the Cl• and hydroxyl radical (OH) concentrations throughout the domain. Monthly Cl-SOA concentrations range from 0.7 to 3.0 μg m–3, with increasing anthropogenic Cl emissions leading to higher Cl-SOA concentrations. Indirectly, this also leads to an increase of monthly SOA by up to 2.5–3.0 g μm–3 from the traditional OH oxidation pathways as well as the surface uptake of glyoxal and methylglyoxal. Increased OH concentrations, however, do not always lead to higher overall SOA concentrations in the entire domain. High OH reduces the lifetime of glyoxal/methylglyoxal (GLY/MGLY), making them less available to form SOA. In the Sichuan Basin (SCB) and part of Southwest China where high O3 concentrations meet high pCl emissions, a higher Cl•/OH ratio leads to net O3 loss from the Cl• + O3 reaction, thus reducing SOA formation from the O3 oxidation of volatile organic compounds (VOCs). Also, the competition between Cl• and OH for VOCs could lead to lower overall SOA because the molar yields of the semivolatile products in Cl-VOC reactions are lower than their OH + VOC reaction counterparts. When Cl• concentrations are further increased with higher emissions of Cl, precursor gases can be depleted and become the limiting factor in SOA formation. This study reveals the direct and indirect impacts of chlorine chemistry on SOA in polluted winter conditions, which are greatly affected by the Cl emissions, the ambient O3 level, and the availability of SOA precursors.
Fracture reduction quality is of paramount importance for osteosynthesis. The aim of this study was to report the outcome of an inferior cortical buttress non-anatomic reduction pattern and internal ...fixation for displaced femoral neck fractures (Garden types III and IV) in young adults.
A retrospective analysis of 46 displaced femoral neck fractures was performed, which were treated by closed reduction and internal fixation with parallel cannulated screws. There were 20 males and 26 females, with an average age of 50.3 years (19-60). According to the inferior cortical reduction quality seen in recorded intraoperative fluoroscopy, the patients were divided into two groups. Group I (n = 30) was anatomic cortical apposition as the two inferior cortices were smoothly contacted, and group II (n = 16) was buttress cortical apposition as the two inferior cortices were located in positive support contact (Gotfried reduction pattern). With a mean follow-up of 22.0 months, femoral neck length, neck-shaft angle, and clinical outcomes were compared.
Thirty-nine patients (84.8%) achieved uneventful fracture union. Complications occurred in seven patients, six in group I (20%) and one in group II (6.3%), including displacement to varus, neck shortening, early fixation failure, nonunion, and avascular necrosis of the femoral head. No significant difference existed in the complication rate between the two groups (p = 0.216). Four patients (13.3%) in group I were converted to prosthetic replacement, but none in group II.
For closed reduction and fixation of displaced femoral neck fractures in young adults, an inferior cortical buttress reduction pattern, though non-anatomic, can produce sustainable fracture stability and predictable clinical outcomes.
The correct understanding of the behavior of highly stripped ions immersed in a dense plasma environment is a hitherto challenge for theory and it is of importance in various applications. Here, we ...developed four kinds of novel theoretical models to the determination of the spectral properties and collision dynamics of H‐like ions in dense and hot plasmas by employing the analytical potential Li et al., Phys. Plasmas 2019, 26, 033301 to describe the interactions among the charged particles: (i) The electron photon processes in plasma model within the relativistic scheme; (ii) The multiconfiguration Dirac–Fock model within the framework of relativistic self‐consistent iteration approximation; (iii) The generalized pseudospectral method within the relativistic framework; and (iv) An analytic formula based on the Hartree–Fock method and the irreducible tensor theory within the non‐relativistic regime, derived from a solution of Schrödinger equation. As a typical example, energy eigenvalues, radiative transition properties, spectral line shifts, and electron impact excitation and ionization cross sections of the selected N6+ and Ne9+ ions are determined for several temperature‐density cases, characteristic of inertial confinement fusion plasmas. A comparison of these results with each other and the results from earlier calculations as well as with the available experimental data is provided. Systematic trend is determined for all the properties under study concerning increased screening. The present study not only extends our understanding of the dense plasma shielding effects, but also opens the way for future investigations allowing accurate predictions of spectral properties of ions in dense and hot plasmas aimed at providing precision data for various practical applications.
The paper presents an investigation of the atomic structure and collisional cross section of H‐like ions embedded in hot and dense plasmas. The strength of the work is that four different theoretical approaches were used and compared. The presentation of the results as well as their comparison are detailed and the conclusions as well as the perspectives of improvement of the calculations are drawn.
PDF
