Displaying publications 1 - 20 of 24 in total

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  1. Li N, Wang X, Lu X, Zhang P, Ong WJ
    Chemistry, 2021 Dec 20;27(71):17900-17909.
    PMID: 34714582 DOI: 10.1002/chem.202103218
    In this work, a series of non-noble metal single-atom catalysts of Mo2 CS2 -MXene for CO2 reduction were systematically investigated by well-defined density-functional-theory (DFT) calculations. It is found that nine types of transitional metal (TM) supported Mo2 CS2 (TM-Mo2 CS2 ) are very stable, while eight can effectively inhibit the competitive hydrogen evolution reaction (HER). After comprehensively comparing the changes of free energy for each pathway in CO2 reduction reaction (CO2 RR), it is found that the products of TM-Mo2 CS2 are not completely CH4 . Furthermore, Cr-, Fe-, Co- and Ni-Mo2 CS2 are found to render excellent CO2 RR catalytic activity, and their limiting potentials are in the range of 0.245-0.304 V. In particular, Fe-Mo2 CS2 with a nitrogenase-like structure has the lowest limiting potential and the highest electrocatalytic activity. Ab initio molecular dynamics (AIMD) simulations have also proven that these kinds of single-atom catalysts with robust performance could exist stably at room temperature. Therefore, these single TM atoms anchored on the surface of MXenes can be profiled as a promising catalyst for the electrochemical reduction of CO2 .
  2. Wu O, Lu X, Yeo KJ, Xiao Y, Yip P
    Int J Environ Res Public Health, 2022 Aug 30;19(17).
    PMID: 36078501 DOI: 10.3390/ijerph191710786
    BACKGROUND: University students with suicidal ideation are at high risk of suicide, which constitutes a significant social and public health problem in China. However, little is known about the prevalence and associated risk factors of suicidal ideation among first-year university students in China, especially during the COVID-19 pandemic.

    OBJECTIVES: To investigate the prevalence of suicidal ideation and its factors in first-year Chinese university students from a vocational college in Zhejiang during the COVID-19 pandemic.

    METHODS: Using a cluster sampling technique, a university-wide survey was conducted of 686 first-year university students from Hangzhou in March 2020 using University Personality Inventory (UPI). UPI includes an assessment for suicidal ideation and possible risk factors. Suicidal ideation prevalence was calculated for males and females. Univariate analysis and multivariable logistic regression models were conducted, adjusting for age and sex. Analyses were carried out using the SPSS version 22.0 software.

    RESULTS: The prevalence of 12-month suicidal ideation among first-year university students during March 2020 was 5.2%, and there was no significant difference between males and females (4.8% vs. 6.0%, x2 = 0.28, p = 0.597). Multivariable logistic regression analysis identified social avoidance (B = 0.78, OR = 2.17, p < 0.001) and emotional vulnerability (B = 0.71, OR = 2.02, p < 0.001) as positively associated with suicidal ideation.

    CONCLUSIONS: Social avoidance and emotional vulnerabilities are unique factors associated with greater suicidal ideation among first-year university students during the COVID-19 pandemic. UPI serves as a validated tool to screen suicide risks among Chinese university students. Encouraging social engagement and improving emotional regulation skills are promising targets to reduce suicidal ideation among first-year university students.

  3. Huang Z, Wang J, Lu X, Mohd Zain A, Yu G
    Brief Bioinform, 2023 Mar 19;24(2).
    PMID: 36733262 DOI: 10.1093/bib/bbad040
    Single-cell RNA sequencing (scRNA-seq) data are typically with a large number of missing values, which often results in the loss of critical gene signaling information and seriously limit the downstream analysis. Deep learning-based imputation methods often can better handle scRNA-seq data than shallow ones, but most of them do not consider the inherent relations between genes, and the expression of a gene is often regulated by other genes. Therefore, it is essential to impute scRNA-seq data by considering the regional gene-to-gene relations. We propose a novel model (named scGGAN) to impute scRNA-seq data that learns the gene-to-gene relations by Graph Convolutional Networks (GCN) and global scRNA-seq data distribution by Generative Adversarial Networks (GAN). scGGAN first leverages single-cell and bulk genomics data to explore inherent relations between genes and builds a more compact gene relation network to jointly capture the homogeneous and heterogeneous information. Then, it constructs a GCN-based GAN model to integrate the scRNA-seq, gene sequencing data and gene relation network for generating scRNA-seq data, and trains the model through adversarial learning. Finally, it utilizes data generated by the trained GCN-based GAN model to impute scRNA-seq data. Experiments on simulated and real scRNA-seq datasets show that scGGAN can effectively identify dropout events, recover the biologically meaningful expressions, determine subcellular states and types, improve the differential expression analysis and temporal dynamics analysis. Ablation experiments confirm that both the gene relation network and gene sequence data help the imputation of scRNA-seq data.
  4. Wang Z, Ghaleb FA, Zainal A, Siraj MM, Lu X
    Sci Rep, 2024 Mar 25;14(1):7054.
    PMID: 38528084 DOI: 10.1038/s41598-024-57691-x
    Many intrusion detection techniques have been developed to ensure that the target system can function properly under the established rules. With the booming Internet of Things (IoT) applications, the resource-constrained nature of its devices makes it urgent to explore lightweight and high-performance intrusion detection models. Recent years have seen a particularly active application of deep learning (DL) techniques. The spiking neural network (SNN), a type of artificial intelligence that is associated with sparse computations and inherent temporal dynamics, has been viewed as a potential candidate for the next generation of DL. It should be noted, however, that current research into SNNs has largely focused on scenarios where limited computational resources and insufficient power sources are not considered. Consequently, even state-of-the-art SNN solutions tend to be inefficient. In this paper, a lightweight and effective detection model is proposed. With the help of rational algorithm design, the model integrates the advantages of SNNs as well as convolutional neural networks (CNNs). In addition to reducing resource usage, it maintains a high level of classification accuracy. The proposed model was evaluated against some current state-of-the-art models using a comprehensive set of metrics. Based on the experimental results, the model demonstrated improved adaptability to environments with limited computational resources and energy sources.
  5. Das R, Vecitis CD, Schulze A, Cao B, Ismail AF, Lu X, et al.
    Chem Soc Rev, 2017 Sep 29.
    PMID: 28959815 DOI: 10.1039/c6cs00921b
    The efficient handling of wastewater pollutants is a must, since they are continuously defiling limited fresh water resources, seriously affecting the terrestrial, aquatic, and aerial flora and fauna. Our vision is to undertake an exhaustive examination of current research trends with a focus on nanomaterials (NMs) to considerably improve the performance of classical wastewater treatment technologies, e.g. adsorption, catalysis, separation, and disinfection. Additionally, NM-based sensor technologies are considered, since they have been significantly used for monitoring water contaminants. We also suggest future directions to inform investigators of potentially disruptive NM technologies that have to be investigated in more detail. The fate and environmental transformations of NMs, which need to be addressed before large-scale implementation of NMs for water purification, are also highlighted.
  6. Zheng Y, Wang Q, Zhuang W, Lu X, Miron A, Chai TT, et al.
    Molecules, 2016 Nov 02;21(11).
    PMID: 27827862
    Lotus is an edible and medicinal plant, and the extracts from its different parts exhibit various bioactivities. In the present study, the hot water-soluble polysaccharides from lotus seeds (LSPS) were evaluated for their cancer cell cytotoxicity, immunomodulatory and antitumor activities. LSPS showed significant inhibitory effects on the mouse gastric cancer MFC cells, human liver cancer HuH-7 cells and mouse hepatocarcinoma H22 cells. The animal studies showed that LSPS inhibited tumor growth in H22 tumor-bearing mice with the highest inhibition rate of 45.36%, which is comparable to that induced by cyclophosphamide (30 mg/kg) treatment (50.79%). The concentrations of white blood cells were significantly reduced in cyclophosphamide-treated groups (p < 0.01), while LSPS showed much fewer side effects according to the hematology analysis. LSPS improved the immune response in H22 tumor-bearing mice by enhancing the spleen and thymus indexes, and increasing the levels of serum cytokines including tumor necrosis factor-α and interleukin-2. Moreover, LSPS also showed in vivo antioxidant activity by increasing superoxide dismutase activity, thus reducing the malondialdehyde level in the liver tissue. These results suggested that LSPS can be used as an antitumor and immunomodulatory agent.
  7. Lu X, Teh SY, Tay CJ, Abu Kassim NF, Fam PS, Soewono E
    Infect Dis Model, 2025 Mar;10(1):240-256.
    PMID: 39559512 DOI: 10.1016/j.idm.2024.10.007
    Despite the implementation of various initiatives, dengue remains a significant public health concern in Malaysia. Given that dengue has no specific treatment, dengue prediction remains a useful early warning mechanism for timely and effective deployment of public health preventative measures. This study aims to develop a comprehensive approach for forecasting dengue cases in Selangor, Malaysia by incorporating climate variables. An ensemble of Multiple Linear Regression (MLR) model, Long Short-Term Memory (LSTM), and Susceptible-Infected mosquito vectors, Susceptible-Infected-Recovered human hosts (SI-SIR) model were used to establish a relation between climate variables (temperature, humidity, precipitation) and mosquito biting rate. Dengue incidence subject to climate variability can then be projected by SI-SIR model using the forecasted mosquito biting rate. The proposed approach outperformed three alternative approaches and expanded the temporal horizon of dengue prediction for Selangor with the ability to forecast approximately 60 weeks ahead with a Mean Absolute Percentage Error (MAPE) of 13.97 for the chosen prediction window before the implementation of the Movement Control Order (MCO) in Malaysia. Extended validation across subsequent periods also indicates relatively satisfactory forecasting performance (with MAPE ranging from 13.12 to 17.09). This research contributed to the field by introducing a novel framework for the prediction of dengue cases over an extended temporal range.
  8. Guo J, Wu X, Too CL, Yin F, Lu X, He J, et al.
    PLoS One, 2012;7(7):e41228.
    PMID: 22829930 DOI: 10.1371/journal.pone.0041228
    OBJECTIVES: Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.

    METHODS: We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.

    RESULTS: DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).

    CONCLUSIONS: Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.
  9. Ying Y, Tu S, Ni J, Lu X, Hu X, Lei P, et al.
    Fitoterapia, 2023 Oct;170:105662.
    PMID: 37648028 DOI: 10.1016/j.fitote.2023.105662
    Two new terrein derivatives asperterreinones A-B (1-2), one new octahydrocoumarin derivative (±)-asperterreinin A (6), along with seventeen known compounds, were isolated from Aspergillus terreus F6-3, a marine fungus associated with Johnius belengerii. The structures of 1, 2, and 6 were established on the basis of 1D and 2D NMR, mass spectroscopy, comparative electronic circular dichroism (ECD) spectra analysis, density functional theory calculation of 13C NMR, and DP4+ probability analysis. Among all the isolates, eurylene (7), a constituent of the Malaysian medicinal plant Eurycoma longifolia, was obtained from a microbial source for first time. In the in vitro bioassay, 11 and 13 showed potent inhibitory activity against the Escherichia coli β-glucuronidase (EcGUS) with IC50 values of 27.75 ± 0.73 and 17.73 ± 0.81 μM, respectively. It was the first time that questinol (11) and (±)-aspertertone B (13) were reported as potent EcGUS inhibitors.
  10. Nie Y, Lau SYL, Tan X, Lu X, Liu S, Tahvanainen T, et al.
    Front Plant Sci, 2022;13:974251.
    PMID: 36160957 DOI: 10.3389/fpls.2022.974251
    Melting permafrost mounds in subarctic palsa mires are thawing under climate warming and have become a substantial source of N2O emissions. However, mechanistic insights into the permafrost thaw-induced N2O emissions in these unique habitats remain elusive. We demonstrated that N2O emission potential in palsa bogs was driven by the bacterial residents of two dominant Sphagnum mosses especially of Sphagnum capillifolium (SC) in the subarctic palsa bog, which responded to endogenous and exogenous Sphagnum factors such as secondary metabolites, nitrogen and carbon sources, temperature, and pH. SC's high N2O emission activity was linked with two classes of distinctive hyperactive N2O emitters, including Pseudomonas sp. and Enterobacteriaceae bacteria, whose hyperactive N2O emitting capability was characterized to be dominantly pH-responsive. As the nosZ gene-harboring emitter, Pseudomonas sp. SC-H2 reached a high level of N2O emissions that increased significantly with increasing pH. For emitters lacking the nosZ gene, an Enterobacteriaceae bacterium SC-L1 was more adaptive to natural acidic conditions, and N2O emissions also increased with pH. Our study revealed previously unknown hyperactive N2O emitters in Sphagnum capillifolium found in melting palsa mound environments, and provided novel insights into SC-associated N2O emissions.
  11. Wang Y, Zhang J, Yuan J, Li Q, Zhang S, Wang C, et al.
    Sci Rep, 2024 Jul 29;14(1):17403.
    PMID: 39075134 DOI: 10.1038/s41598-024-65755-1
    Traumatic cervical spinal cord injury (TCSCI) often causes varying degrees of motor dysfunction, common assessed by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), in association with the American Spinal Injury Association (ASIA) Impairment Scale. Accurate prediction of motor function recovery is extremely important for formulating effective diagnosis, therapeutic and rehabilitation programs. The aim of this study is to investigate the validity of a novel nested ensemble algorithm that uses the very early ASIA motor score (AMS) of ISNCSCI examination to predict motor function recovery 6 months after injury in TCSCI patients. This retrospective study included complete data of 315 TCSCI patients. The dataset consisting of the first AMS at ≤ 24 h post-injury and follow-up AMS at 6 months post-injury was divided into a training set (80%) and a test set (20%). The nested ensemble algorithm was established in a two-stage manner. Support Vector Classification (SVC), Adaboost, Weak-learner and Dummy were used in the first stage, and Adaboost was selected as second-stage model. The prediction results of the first stage models were uploaded into second-stage model to obtain the final prediction results. The model performance was evaluated using precision, recall, accuracy, F1 score, and confusion matrix. The nested ensemble algorithm was applied to predict motor function recovery of TCSCI, achieving an accuracy of 80.6%, a F1 score of 80.6%, and balancing sensitivity and specificity. The confusion matrix showed few false-negative rate, which has crucial practical implications for prognostic prediction of TCSCI. This novel nested ensemble algorithm, simply based on very early AMS, provides a useful tool for predicting motor function recovery 6 months after TCSCI, which is graded in gradients that progressively improve the accuracy and reliability of the prediction, demonstrating a strong potential of ensemble learning to personalize and optimize the rehabilitation and care of TCSCI patients.
  12. Adedze YMN, Lu X, Xia Y, Sun Q, Nchongboh CG, Alam MA, et al.
    Sci Rep, 2021 02 16;11(1):3872.
    PMID: 33594240 DOI: 10.1038/s41598-021-83313-x
    Insertion and Deletion (InDel) are common features in genomes and are associated with genetic variation. The whole-genome re-sequencing data from two parents (X1 and X2) of the elite cucumber (Cucumis sativus) hybrid variety Lvmei No.1 was used for genome-wide InDel polymorphisms analysis. Obtained sequence reads were mapped to the genome reference sequence of Chinese fresh market type inbred line '9930' and gaps conforming to InDel were pinpointed. Further, the level of cross-parents polymorphism among five pairs of cucumber breeding parents and their corresponding hybrid varieties were used for evaluating hybrid seeds purity test efficiency of InDel markers. A panel of 48 cucumber breeding lines was utilized for PCR amplification versatility and phylogenetic analysis of these markers. In total, 10,470 candidate InDel markers were identified for X1 and X2. Among these, 385 markers with more than 30 nucleotide difference were arbitrary chosen. These markers were selected for experimental resolvability through electrophoresis on an Agarose gel. Two hundred and eleven (211) accounting for 54.81% of markers could be validated as single and clear polymorphic pattern while 174 (45.19%) showed unclear or monomorphic genetic bands between X1 and X2. Cross-parents polymorphism evaluation recorded 68 (32.23%) of these markers, which were designated as cross-parents transferable (CPT) InDel markers. Interestingly, the marker InDel114 presented experimental transferability between cucumber and melon. A panel of 48 cucumber breeding lines including parents of Lvmei No. 1 subjected to PCR amplification versatility using CPT InDel markers successfully clustered them into fruit and common cucumber varieties based on phylogenetic analysis. It is worth noting that 16 of these markers were predominately associated to enzymatic activities in cucumber. These agarose-based InDel markers could constitute a valuable resource for hybrid seeds purity testing, germplasm classification and marker-assisted breeding in cucumber.
  13. Djandja OS, Liew RK, Liu C, Liang J, Yuan H, He W, et al.
    Sci Total Environ, 2023 May 15;873:162119.
    PMID: 36773913 DOI: 10.1016/j.scitotenv.2023.162119
    Hydrothermal carbonization has gained attention in converting wet organic solid waste into hydrochar with many applications such as solid fuel, energy storage material precursor, fertilizer or soil conditioner. Recently, various catalysts such as organic and inorganic catalysts are employed to guide the properties of the hydrochar. This review presents a summarize and a critical discussion on types of catalysts, process parameters and catalytic mechanisms. The catalytic impact of carboxylic acids is related to their acidity level and the number of carboxylic groups. The catalysis level with strong mineral acids is likely related to the number of hydronium ions liberated from their hydrolysis. The impact of inorganic salts is determined by the Lewis acidity of the cation. The metallic ions in metallic salts may incorporate into the hydrochar and increase the ash of the hydrochar. The selection of catalysts for various applications of hydrochars and the environmental and the techno-economic aspects of the process are also presented. Although some catalysts might enhance the characteristics of hydrochar for various applications, these catalysts may also result in considerable carbon loss, particularly in the case of organic acid catalysts, which may potentially ruin the overall advantage of the process. Overall, depending on the expected application of the hydrochar, the type of catalyst and the amount of catalyst loading requires careful consideration. Some recommendations are made for future investigations to improve laboratory-scale process comprehension and understanding of pathways as well as to encourage widespread industrial adoption.
  14. Li T, Heenan TMM, Rabuni MF, Wang B, Farandos NM, Kelsall GH, et al.
    Nat Commun, 2019 04 02;10(1):1497.
    PMID: 30940801 DOI: 10.1038/s41467-019-09427-z
    Ceramic fuel cells offer a clean and efficient means of producing electricity through a variety of fuels. However, miniaturization of cell dimensions for portable device application remains a challenge, as volumetric power densities generated by readily-available planar/tubular ceramic cells are limited. Here, we demonstrate a concept of 'micro-monolithic' ceramic cell design. The mechanical robustness and structural integrity of this design is thoroughly investigated with real-time, synchrotron X-ray diffraction computed tomography, suggesting excellent thermal cycling stability. The successful miniaturization results in an exceptional power density of 1.27 W cm-2 at 800 °C, which is among the highest reported. This holistic design incorporates both mechanical integrity and electrochemical performance, leading to mechanical property enhancement and representing an important step toward commercial development of portable ceramic devices with high volumetric power (>10 W cm-3), fast thermal cycling and marked mechanical reliability.
  15. Li Y, Ouyang Y, Wu H, Wang P, Huang Y, Li X, et al.
    Eur J Med Chem, 2022 Jan 15;228:113979.
    PMID: 34802838 DOI: 10.1016/j.ejmech.2021.113979
    The shortage of new antibiotics makes infections caused by gram-negative (G-) bacteria a significant clinical problem. The key enzymes involved in folate biosynthesis represent important targets for drug discovery, and new antifolates with novel mechanisms are urgently needed. By targeting to dihydrofolate reductase (DHFR), a series of 1,3-diamino-7H-pyrrol[3,2-f]quinazoline (PQZ) compounds were designed, and exhibited potent antibacterial activities in vitro, especially against multi-drug resistant G- strains. Multiple experiments indicated that PQZ compounds contain a different molecular mechanism against the typical DHFR inhibitor, trimethoprim (TMP), and the thymidylate synthase (TS) was identified as another potential but a relatively weak target. A significant synergism between the representative compound, OYYF-175, and sulfamethoxazole (SMZ) was observed with a strong cumulative and significantly bactericidal effect at extremely low concentrations (2 μg/mL for SMZ and 0.03 pg/mL for OYYF-175), which could be resulted from the simultaneous inhibition of dihydropteroate synthase (DHPS), DHFR and TS. PQZ compounds exhibited therapeutic effects in a mouse model of intraperitoneal infections caused by Escherichia coli (E. coli). The co-crystal structure of OYYF-175-DHFR was solved and the detailed interactions were provided. The inhibitors reported represent innovative chemical structures with novel molecular mechanism of action, which will benefit the generation of new, efficacious bactericidal compounds.
  16. Hu J, Pradit S, Loh PS, Chen Z, Guo C, Le TPQ, et al.
    Mar Pollut Bull, 2024 Jan 29;200:116064.
    PMID: 38290368 DOI: 10.1016/j.marpolbul.2024.116064
    Mangrove forests can help to mitigate climate change by storing a significant amount of carbon (C) in soils. Planted mangrove forests have been established to combat anthropogenic threats posed by climate change. However, the efficiency of planted forests in terms of soil organic carbon (SOC) storage and dynamics relative to that of natural forests is unclear. We assessed SOC and nutrient storage, SOC sources and drivers in a natural and a planted forest in southern Thailand. Although the planted forest stored more C and nutrients than the natural forest, the early-stage planted forest was not a strong sink relative to mudflat. Both forests were predominated by allochthonous organic C and nitrogen limited, with total nitrogen being a major driver of SOC in both cases. SOC showed a significant decline along land-to-sea and depth gradients as a result of soil texture, nutrient availability, and pH in the natural forest.
  17. Shi Y, Deng C, Lu X, Wang Y, Pan Y, Su D, et al.
    Cell Rep, 2025 Feb 25;44(2):115258.
    PMID: 39891905 DOI: 10.1016/j.celrep.2025.115258
    Cuticles protect plants from water loss and pathogen attack. We address here the functional significance of SlGRAS9, SlZHD17, and SlMBP3 in regulating cutin formation in tomato fruit. The study unveils the role of the multipartite "SlGRAS9-SlZHD17-SlMBP3-SlMIXTA-like" transcription factor module in cutin biosynthesis. Plants deficient in SlGRAS9, SlZHD17, or SlMBP3 exhibit thickened cuticles and a higher accumulation of cutin monomers, conferring extended fruit shelf life and higher tolerance to postharvest fungal infection. SlGRAS9 regulation of cutin is mediated by SlZHD17, a negative regulator of SlCYP86A69. SlZHD17 acts synergistically with SlMBP3 to repress SlCYP86A69, and its interaction with SlMIXTA-like prevents the binding to the SlCYP86A69 promoter, thereby releasing the repression of cutin biosynthesis. SlZHD17 and SlMBP3 synergistically repress cutin biosynthesis, while SlMIXTA-like and SlCD2 act antagonistically to SlZHD17 and SlMBP3 on this metabolic pathway. The study defines targets for breeding strategies aimed at improving cuticle-associated traits in tomato and potentially other crops.
  18. Zak J, Vives V, Szumska D, Vernet A, Schneider JE, Miller P, et al.
    Cell Death Differ, 2016 Dec;23(12):1973-1984.
    PMID: 27447114 DOI: 10.1038/cdd.2016.76
    Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities. Consistent with this, Trp53bp2-deficient mice show dilation of lateral ventricles resembling the phenotype of 1q41q42 microdeletion patients. Trp53bp2 deficiency causes 100% neonatal lethality in the C57BL/6 background associated with a high incidence of neural tube defects and a range of developmental abnormalities such as congenital heart defects, coloboma, microphthalmia, urogenital and craniofacial abnormalities. Interestingly, abnormalities show a high degree of overlap with 1q41q42 microdeletion-associated abnormalities. These findings identify TP53BP2 as a strong candidate causative gene for central nervous system (CNS) defects in 1q41q42 microdeletion syndrome, and open new avenues for investigation of the mechanisms underlying CNS abnormalities.
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