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BMJ Neurology Open 2024Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with...
BACKGROUND
Dystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation.
METHODOLOGY
Next-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.
RESULTS
We here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.
CONCLUSION
Dystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.
PubMed: 38912174
DOI: 10.1136/bmjno-2024-000710 -
Wellcome Open Research 2024We present a genome assembly from an individual male (the White-point; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 698.6 megabases in span....
We present a genome assembly from an individual male (the White-point; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence is 698.6 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.38 kilobases in length. Gene annotation of this assembly on Ensembl identified 13,679 protein coding genes.
PubMed: 38911902
DOI: 10.12688/wellcomeopenres.20682.1 -
Mitochondrial DNA. Part B, Resources 2024This study is the first to sequence the complete mitochondrial genome (mitogenome) of Bruguière, 1789 (Balanomorpha: Balanidae). The 15,536-bp long mitogenome...
This study is the first to sequence the complete mitochondrial genome (mitogenome) of Bruguière, 1789 (Balanomorpha: Balanidae). The 15,536-bp long mitogenome contained a typical set of animal mitochondrial genes, along with one control region. The mitogenome had an inverted gene block (-----) between (gct) and . This inverted gene block had been detected six species in three subfamilies of the Balanidae family (Balaninae, Acastinae and Megabalaninae), but our results show that it is also present in Concavinae, in which is included. The phylogenetic tree based on the concatenated sequences of the 13 protein-coding genes and two rRNA genes showed that is closely associated with and within Balanidae.
PubMed: 38911522
DOI: 10.1080/23802359.2024.2368727 -
Mitochondrial DNA. Part B, Resources 2024In this study, we assembled high-quality chloroplast genomes of through a reference-guided approach using high-throughput Illumina sequencing reads. The resulting...
In this study, we assembled high-quality chloroplast genomes of through a reference-guided approach using high-throughput Illumina sequencing reads. The resulting chloroplast genome assembly displayed a typical quadripartite structural organization, comprising a large single-copy (LSC) region of 85,233 bp, two inverted repeat (IR) regions of 25,685 bp each, and a small single-copy (SSC) region of 18,207 bp. The chloroplast genome harbored 141 complete genes, and its overall GC content was 38.0%. In maximum-likelihood (ML) and Bayesian inference (BI) trees, the 19 Solanaceae species formed a monophyletic group, dividing into two main clades. and formed a monophyletic group, suggesting a close relationship between the two species. The cp genome presented in this study lays a good foundation for further genetic and genomic studies of the Solanaceae.
PubMed: 38911521
DOI: 10.1080/23802359.2024.2368213 -
Mitochondrial DNA. Part B, Resources 2024Planchon. ex Franch 1886 is a plant with significant pharmacological effects and ornamental importance. This research unveiled the complete chloroplast (cp) genome...
Planchon. ex Franch 1886 is a plant with significant pharmacological effects and ornamental importance. This research unveiled the complete chloroplast (cp) genome sequence of . The study highlights that the cp genome of possesses a distinct tetrameric structure spanning 162,497 base pairs, comprising a small single-copy (SSC) region of 18,902 base pairs, a large single-copy (LSC) region of 90,441 base pairs, and two inverted-repeat regions (IRs), each 26,577 base pairs in length. The GC content of the SSC, LSC, and IR regions of the genome was 31.80%, 35.16%, and 42.82%, respectively, culminating in an overall GC content of 37.27%. The genome comprised 130 genes, which included eight rRNAs, 36 tRNAs, and 86 protein-coding genes. Through phylogenetic analysis utilizing the maximum-likelihood method, it was established that was closely related to var. , positioning it as a sister species. This report not only provides a scientific reference for understanding the phylogeny of the family Vitaceae but also enriches our genetic information of .
PubMed: 38911520
DOI: 10.1080/23802359.2024.2364753 -
Journal of Cancer 2024Colorectal cancer (CRC) ranks third in terms of cancer incidence and fourth in terms of cancer-related deaths worldwide. Identifying potential biomarkers of CRC is...
Colorectal cancer (CRC) ranks third in terms of cancer incidence and fourth in terms of cancer-related deaths worldwide. Identifying potential biomarkers of CRC is crucial for treatment and drug development. In this study, we established a C57B/6N mouse model of colon carcinogenesis using azoxymethane-dextran sodium sulfate (AOM-DSS) treatment for 14 weeks to identify proteins associated with colon cancer. An isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis was conducted on the cell membrane components enriched in the colonic mucosa. Additionally, tumor tissues and adjacent normal colon tissues were collected from patients with colon cancer for comparative protein and metabolite analyses. In total, 74 differentially expressed proteins were identified in the tumor tissue samples from AOM/DSS-treated mice compared to both the adjacent tissue samples from AOM/DSS-treated mice and tissue samples from saline-treated control mice. Bioinformatics analysis revealed eight downregulated proteins enriched in the branched-chain amino acids pathway (valine, leucine, and isoleucine degradation). Moreover, these proteins are already known to be associated with the survival rate of patients with cancer. Targeted metabolomics showed increased levels of valine, leucine, and isoleucine in tumor tissues compared to those in adjacent normal tissues in patients with colon cancer. Furthermore, a real-time PCR experiment demonstrated that Aldehyde dehydrogenase, mitochondrial (short protein name ALDH2, gene name ) and Hydroxyacyl-coenzyme A dehydrogenase, mitochondrial (short protein name HCDH, gene name ) (two genes) in the pathway of branched-chain amino acids) were downregulated in patients with colon cancer (colon tumor tissues vs. their adjacent colon tissues). ALDH2 expression was further validated by western blotting in AOM/DSS-treated mouse model and in clinical samples. This study highlighted the inactivation of the branched-chain amino acid degradation pathway in colon cancer and identified ALDH2 and HCDH as potential biomarkers for diagnosing colon cancer and developing new therapeutic strategies.
PubMed: 38911385
DOI: 10.7150/jca.95454 -
Journal of Cancer 2024DNA damage-inducible transcript 3 (DDIT3) is a transcription factor central to apoptosis, differentiation, and stress response. DDIT3 has been extensively studied in...
DNA damage-inducible transcript 3 (DDIT3) is a transcription factor central to apoptosis, differentiation, and stress response. DDIT3 has been extensively studied in cancer biology. However, its precise implications in breast cancer progression and its interaction with the immune microenvironment are unclear. In this study, we utilized a novel multi-omics integration strategy, combining bulk RNA sequencing, single-cell sequencing, spatial transcriptomics and immunohistochemistry, to explore the role of DDIT3 in breast cancer and establish the correlation between DDIT3 and poor prognosis in breast cancer patients. We identified a robust prognostic signature, including six genes (unc-93 homolog B1, TLR signaling regulator, anti-Mullerian hormone, DCTP pyrophosphatase 1, mitochondrial ribosomal protein L36, nuclear factor erythroid 2, and Rho GTPase activating protein 39), associated with DDIT3. This signature stratified the high-risk patient groups, characterized by increased infiltration of the regulatory T cells and M2-like macrophages and fibroblast growth factor (FGF)/FGF receptor signaling activation. Notably, the high-risk patient group demonstrated enhanced sensitivity to immunotherapy, presenting novel therapeutic opportunities. Integrating multi-omics data helped determine the spatial expression pattern of DDIT3 in the tumor microenvironment and its correlation with immune cell infiltration. This multi-dimensional analysis provided a comprehensive understanding of the intricate interplay between DDIT3 and the immune microenvironment in breast cancer. Overall, our study not only facilitates understanding the role of DDIT3 in breast cancer but also offers innovative insights for developing prognostic models and therapeutic strategies. Identifying the DDIT3-related prognostic signature and its association with the immune microenvironment provided a promising avenue for personalized breast cancer treatment.
PubMed: 38911383
DOI: 10.7150/jca.96491 -
Journal of Cancer 2024In this study, we aimed to elucidate the role of mitochondrial calcium uptake 1/2 (MiCU1/2) in breast cancer (BRCA) by employing a comprehensive multi-omics approach....
In this study, we aimed to elucidate the role of mitochondrial calcium uptake 1/2 (MiCU1/2) in breast cancer (BRCA) by employing a comprehensive multi-omics approach. Unlike previous research, we utilized a novel web application tailored for whole tumor tissue, single-cell, and spatial transcriptomics analysis to investigate the association between MiCU1/2 and the tumor immune microenvironment (TIME). Our gene set enrichment analysis (GSEA) provided insights into the primary biological effects of MiCU1/2, while our CRISPR-based drug screening repository identified potential effective drugs. Our study revealed that high MiCU1/2 expression serves as an independent diagnostic biomarker, correlating with advanced clinical status and indicating poorer recurrence-free survival (RFS) rates in BRCA patients. Additionally, spatial transcriptome analysis highlighted the heightened expression of MiCU1/2 in tumors and its relevance in surrounding immune cells. Furthermore, using the CIBERSORT algorithm, we discovered a positive correlation between MiCU1/2 levels and macrophage infiltration, underscoring their potential impact on immune infiltration. We also identified expression patterns of immune-related genes associated with responses against various immune cell types, including CXCL, MIF, GDF, SPP1, and IL16. Finally, our pharmacogenomic screening identified potential small molecule drugs capable of effectively targeting breast cancer cells with elevated MiCU1/2 expression. Overall, our study establishes MiCU1/2 as a promising novel biomarker for BRCA diagnosis and prognostic prediction, as well as a potential therapeutic target, highlighting the importance of exploring these pathways to advance patient care and outcomes in BRCA treatment.
PubMed: 38911376
DOI: 10.7150/jca.95979 -
Wellcome Open Research 2023We present a genome assembly from an individual male (the Ochreous Pearl; Arthropoda; Insecta; Lepidoptera; Crambidae). The genome sequence is 624.0 megabases in span....
We present a genome assembly from an individual male (the Ochreous Pearl; Arthropoda; Insecta; Lepidoptera; Crambidae). The genome sequence is 624.0 megabases in span. Most of the assembly is scaffolded into 29 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.33 kilobases in length. Gene annotation of this assembly on Ensembl identified 20,293 protein coding genes.
PubMed: 38911283
DOI: 10.12688/wellcomeopenres.20573.1 -
Frontiers in Pharmacology 2024Cisplatin-induced acute kidney injury (AKI) increases the patient mortality dramatically and results in an unfavorable prognosis. A strong correlation between AKI and...
Cisplatin-induced acute kidney injury (AKI) increases the patient mortality dramatically and results in an unfavorable prognosis. A strong correlation between AKI and ferroptosis, which is a notable type of programmed cell death, was found in recent studies. Myricitrin is a natural flavonoid compound with diverse pharmacological properties. To investigate the protective effect of myricitrin against cisplatin induced human tubular epithelium (HK-2) cell injury and the underlying anti-ferroptic mechanism by this study. Firstly, a pharmacology network analysis was proposed to explore the myricitrin's effect. HK-2 cells were employed for experiments. Ferroptosis was detected by cell viability, quantification of iron, malondialdehyde, glutathione, lipid peroxidation fluorescence, and glutathione peroxidase (GPX4) expression. Ferritinophagy was detected by related protein expression (NCOA4, FTH, LC3II/I, and SQSTM1). In our study, GO enrichment presented that myricitrin might be effective in eliminating ferroptosis. The phenomenon of ferroptosis regulated by ferritinophagy was observed in cisplatin-activated HK-2 cells. Meanwhile, pretreatment with myricitrin significantly rescued HK-2 cells from cell death, reduced iron overload and lipid peroxidation biomarkers, and improved GPX4 expression. In addition, myricitrin downregulated the expression of LC3II/LC3I and NCOA4 and elevated the expression of FTH and SQTM. Furthermore, myricitrin inhibited ROS production and preserved mitochondrial function with a lower percentage of green JC-1 monomers. However, the protection could be reserved by the inducer of ferritinophagy rapamycin. Mechanically, the Hub genes analysis reveals that AKT and NF-κB are indispensable mediators in the anti-ferroptic process. In conclusion, myricitrin ameliorates cisplatin induced HK-2 cells damage by attenuating ferritinophagy mediated ferroptosis.
PubMed: 38910888
DOI: 10.3389/fphar.2024.1372094