Resolution of hypereosinophilic syndrome following resection of a schwannoma

The journal of allergy and clinical immunology. In practice

2023 Jan 05

Ware, JM;Folio, LR;Pittaluga, S;Klion, A;Khoury, P;
PMID: 36621605 | DOI: 10.1016/j.jaip.2022.12.028

The technological landscape and applications of single-cell multi-omics

Nature reviews. Molecular cell biology

2023 Jun 06

Baysoy, A;Bai, Z;Satija, R;Fan, R;
PMID: 37280296 | DOI: 10.1038/s41580-023-00615-w

Single-cell multi-omics technologies and methods characterize cell states and activities by simultaneously integrating various single-modality omics methods that profile the transcriptome, genome, epigenome, epitranscriptome, proteome, metabolome and other (emerging) omics. Collectively, these methods are revolutionizing molecular cell biology research. In this comprehensive Review, we discuss established multi-omics technologies as well as cutting-edge and state-of-the-art methods in the field. We discuss how multi-omics technologies have been adapted and improved over the past decade using a framework characterized by optimization of throughput and resolution, modality integration, uniqueness and accuracy, and we also discuss multi-omics limitations. We highlight the impact that single-cell multi-omics technologies have had in cell lineage tracing, tissue-specific and cell-specific atlas production, tumour immunology and cancer genetics, and in mapping of cellular spatial information in fundamental and translational research. Finally, we discuss bioinformatics tools that have been developed to link different omics modalities and elucidate functionality through the use of better mathematical modelling and computational methods.

[Not Available]

Actas dermo-sifiliograficas

2023 Jun 16

Llamas-Velasco, M;Fraga, J;Lario, AR;Catalá, A;Pérez-González, YC;Galván, C;Ruiz-Villaverde, R;Sánchez-Pérez, J;Wiesner, T;Metze, D;
PMID: 37331619 | DOI: 10.1016/j.ad.2023.05.024

Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies.After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated.Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopatic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

AT2 Cell-Derived IgA Trapped by the Extracellular Matrix and Promoted Pulmonary Fibrosis

Available at SSRN

2023 May 03

Chen, M;Wang, J;Yuan, M;Long, M;Sun, Y;Wang, S;Luo, W;Zhang, W;Jiang, W;Chao, J;
| DOI: 10.2139/ssrn.4431410

Pulmonary fibrosis is an interstitial lung disease caused by various factors such as exposure to workplace environmental contaminants, drugs, or X-rays. Epithelial cells are among the driving factors of pulmonary fibrosis. Immunoglobulin A (IgA), traditionally thought to be secreted by B cells, is an important immune factor involved in COVID-19 infection and vaccination. In current study, we found lung epithelial cells were involved in IgA secretion which, in turn, promoted pulmonary fibrosis. The spatial transcriptomics and single-cell sequencing suggests that Igha transcripts were highly expressed in the fibrotic lesion areas of lungs from silica-treated mice. Reconstruction of B-cell receptor (BCR) sequences revealed a new cluster of AT2-like epithelial cells with a shared BCR and high expression of genes related to IgA production. Furthermore, the secretion of IgA by AT2-like cells were trapped by extracellular matrix and aggravated pulmonary fibrosis by activating fibroblasts. Targeted blockade of IgA secretion by pulmonary epithelial cells may be a potential strategy for treating pulmonary fibrosis.

Bridging clinic and wildlife care with AI-powered pan-species computational pathology

Nature communications

2023 Apr 26

AbdulJabbar, K;Castillo, SP;Hughes, K;Davidson, H;Boddy, AM;Abegglen, LM;Minoli, L;Iussich, S;Murchison, EP;Graham, TA;Spiro, S;Maley, CC;Aresu, L;Palmieri, C;Yuan, Y;
PMID: 37100774 | DOI: 10.1038/s41467-023-37879-x

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We build a pan-species cancer digital pathology atlas (panspecies.ai) and conduct a pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). In 18 other vertebrate species (mammalia = 11, reptilia = 4, aves = 2, and amphibia = 1), accuracy (range 0.57-0.94) is influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. Furthermore, a spatial immune score based on artificial intelligence and spatial statistics is associated with prognosis in canine melanoma and prostate tumours. A metric, named morphospace overlap, is developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on understanding of morphological conservation, which could vastly accelerate developments in veterinary medicine and comparative oncology.

Small RNA shuffling between murine sperm and their cytoplasmic droplets during epididymal maturation

Developmental cell

2023 Mar 28

Wang, H;Wang, Z;Zhou, T;Morris, D;Chen, S;Li, M;Wang, Y;Zheng, H;Fu, W;Yan, W;
PMID: 37023748 | DOI: 10.1016/j.devcel.2023.03.010

Reports that mouse sperm gain small RNAs from the epididymosomes secreted by epididymal epithelial cells and that these "foreign" small RNAs act as an epigenetic information carrier mediating the transmission of acquired paternal traits have drawn great attention because the findings suggest that heritable information can flow from soma to germ line, thus invalidating the long-standing Weismann's barrier theory on heritable information flow. Using small RNA sequencing (sRNA-seq), northern blots, sRNA in situ hybridization, and immunofluorescence, we detected substantial changes in the small RNA profile in murine caput epididymal sperm (sperm in the head of the epididymis), and we further determined that the changes resulted from sperm exchanging small RNAs, mainly tsRNAs and rsRNAs, with cytoplasmic droplets rather than the epididymosomes. Moreover, the murine sperm-borne small RNAs were mainly derived from the nuclear small RNAs in late spermatids. Thus, caution is needed regarding sperm gaining foreign small RNAs as an underlying mechanism of epigenetic inheritance.

IRX5 promotes DNA damage repair and activation of hair follicle stem cells

Stem cell reports

2023 Apr 07

Chen, JK;Wiedemann, J;Nguyen, L;Lin, Z;Tahir, M;Hui, CC;Plikus, MV;Andersen, B;
PMID: 37084727 | DOI: 10.1016/j.stemcr.2023.03.013

The molecular mechanisms allowing hair follicles to periodically activate their stem cells (HFSCs) are incompletely characterized. Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice have delayed anagen onset, with increased DNA damage and diminished HFSC proliferation. Open chromatin regions form near cell cycle progression and DNA damage repair genes in Irx5-/- HFSCs. DNA damage repair factor BRCA1 is an IRX5 downstream target. Inhibition of FGF kinase signaling partially rescues the anagen delay in Irx5-/- mice, suggesting that the Irx5-/- HFSC quiescent phenotype is partly due to failure to suppress Fgf18 expression. Interfollicular epidermal stem cells also show decreased proliferation and increased DNA damage in Irx5-/-mice. Consistent with a role for IRX5 as a promoter of DNA damage repair, we find that IRX genes are upregulated in many cancer types and that there is a correlation between IRX5 and BRCA1 expression in breast cancer.

Prenatal CFAP53-related laterality defect: case report and review of the literature

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

2023 Dec 01

Mastromoro, G;Guadagnolo, D;Novelli, A;Torres, B;Piane, M;Magliozzi, M;Bernardini, L;Ventriglia, F;Pizzuti, A;Petrucci, S;
PMID: 37041101 | DOI: 10.1080/14767058.2023.2201653

Laterality defects include morphological anomalies with impaired left-right asymmetry induction, such as dextrocardia, situs inversus abdominis, situs inversus totalis and situs ambiguus. The different arrangement of major organs is called heterotaxy. We describe for the first time a fetus with situs viscerum inversus and azygos continuation of the inferior vena cava, due to previously unreported variants in compound heterozygosity in the CFAP53 gene, whose product is implied in cilial motility. Prenatal trio exome sequencing was performed with turn-around time during the pregnancy. The fetuses with laterality defects are suitable candidates for prenatal exome sequencing due to the emerging high diagnostic rate of this group of morphological anomalies. A timely molecular diagnosis plays a fundamental role in genetic counseling, regarding couple decisions on the ongoing pregnancy, providing recurrence risks, and in predicting possible respiratory complications due to ciliary dyskinesia.

Molecular mechanisms of cardiac complications associated with COVID-19

Biophysical Journal

2023 Feb 01

Reiken, S;Dridi, H;Sittenfeld, L;Liu, Y;Marks, A;
| DOI: 10.1016/j.bpj.2022.11.1388

The COVID-19 pandemic has had a devastating global impact, resulting in over 5,000,000 deaths. In the United States alone, over 1,000,000 individuals have died from COVID-19. Cardiovascular complications of COVID-19 include arrhythmias, heart failure, and myocardial infarction and COVID-19 has differentially impacted racial and ethnic groups. Ethnic minority groups, including African Americans and Hispanics, have a higher risk of COVID-19 hospitalization and death, independent of their socioeconomic, lifestyle and health-related factors. Our data indicate substantial proteomic remodeling of cardiac tissues from SARS-CoV-2 infected mice including upregulation of arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy and dilated cardiomyopathy pathways. Markers of collagen deposition were significantly enriched in the COVID-19 group and confirmed by Masson’s trichrome staining in the hearts of SARS-CoV-2 infected mice. Inflammatory cell infiltration, rupture of cardiomyocytes and significantly increased thrombotic events were also observed. Cardiac tissues of COVID-19 patients exhibited oxidative stress, inflammatory and adrenergic signaling, and calcium dyshomeostasis. Furthermore, we have observed posttranslational modifications of cardiac RyR2 calcium release channels from human COVID-19 hearts including increased PKA phosphorylation and oxidation of RyR2 known as the “leaky phenotype” of these channels. These biochemical changes correlated with the cardiomyopathic pathways activation identified by whole cell proteomic analyses in the hACE2 mouse model of COVID-19.

Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology

2023 Feb 27

Caprini, E;D'Agnese, G;Brennan, PA;Rahimi, S;
PMID: 36847112 | DOI: 10.1111/jop.13419

The increase of the incidence of Human Papilloma Virus (HPV) dependent oropharyngeal squamous cell carcinoma (OPSCC) is alarming, although we have greatly progressed in the classification and staging of this disease. We now know that OPSCC-HPV+ is a sub-type of head and neck squamous cell carcinoma with favourable prognosis and good response to therapy that needs a proper system of classification and staging. Thus, in routine practice it is essential to test patients for the presence of HPV. The most popular technique to assess HPV status is immunohistochemistry on biopsy samples with p16, which is an excellent surrogate for high-risk HPV infection. Another highly sensitive and specific tissue-based technique for the detection of HPV is RNAscope In Situ Hybridization (ISH) that has a prohibitive cost, limiting its use in routine practice. Radiomic is an artificial intelligence based non-invasive method of computational analysis of computed tomography, magnetic resonance imaging, positron emission tomography, and ultrasound images. A growing body of evidence suggest that radiomics is able to characterise and detect early relapse after treatment, and enable development of tailored therapy of HPV-positive OPSCC. In this review, we summarise the last findings of radiomic applied to HPV-associated OPSCC.This article is protected by

Distinct biogenesis pathways may have led to functional divergence of the human and Drosophila Arglu1 sisRNA

EMBO reports

2022 Dec 19

Chan, SN;Pek, JW;
PMID: 36533631 | DOI: 10.15252/embr.202154350

Stable intronic sequence RNAs (sisRNAs) are stable, long noncoding RNAs containing intronic sequences. While sisRNAs have been found across diverse species, their level of conservation remains poorly understood. Here we report that the biogenesis and functions of a sisRNA transcribed from the highly conserved Arglu1 locus are distinct in human and Drosophila melanogaster. The Arglu1 genes in both species show similar exon-intron structures where the intron 2 is orthologous and positionally conserved. In humans, Arglu1 sisRNA retains the entire intron 2 and promotes host gene splicing. Mechanistically, Arglu1 sisRNA represses the splicing-inhibitory activity of ARGLU1 protein by binding to ARGLU1 protein and promoting its localization to nuclear speckles, away from the Arglu1 gene locus. In contrast, Drosophila dArglu1 sisRNA forms via premature cleavage of intron 2 and represses host gene splicing. This repression occurs through a local accumulation of dARGLU1 protein and inhibition of telescripting by U1 snRNPs at the dArglu1 locus. We propose that distinct biogenesis of positionally conserved Arglu1 sisRNAs in both species may have led to functional divergence.

Safety De-risking Approaches for Advanced Modalities

pharmafocusasia.com

2022 Jan 01

Gaskin, P;Singh, P;

Artificial intelligence (AI) is now a powerful tool which can be applied to significantly improve the safety de-risking process early in discovery, with AI-driven pipelines of biotechs expanding at a very fast rate. Data from screening studies with DNA-encoded libraries together with high throughput in silico data are screened through AI-enabled computational platforms. These platforms leverage a wide range of in vitro and in vivo models and along with computational predictive models to help identify targets, predicting ‘druggable’ characteristics and target selectivity of molecules from a vast space. In terms of safety, AI can also be used to predict potential interactions and by leveraging publicly available data or proprietary databases can predict potential on- and off-target safety liabilities. A major advantage of AI systems is that they include an active learning loop, referred to as machine learning, which helps to improve the accuracy of prediction and to identify advanceable lead series or candidate molecules leading to a very high success rate, which improves as more data is gathered. Critically AI can also be used to screen billions of molecules virtually, reducing costs and resource requirements and improving the discovery process by more efficient use of molecular biology, public and private databases and other resources.

Pages

	Description
sense Example: Hs-LAG3-sense	Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe.
Intron# Example: Mm-Htt-intron2	Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G)	A mixture of multiple probe sets targeting multiple genes or transcripts
No-XSp Example: Hs-PDGFB-No-XMm	Does not cross detect with the species (Sp)
XSp Example: Rn-Pde9a-XMm	designed to cross detect with the species (Sp)
O# Example: Mm-Islr-O1	Alternative design targeting different regions of the same transcript or isoforms
CDS Example: Hs-SLC31A-CDS	Probe targets the protein-coding sequence only
EnEm	Probe targets exons n and m
En-Em	Probe targets region from exon n to exon m
Retired Nomenclature
tvn Example: Hs-LEPR-tv1	Designed to target transcript variant n
ORF Example: Hs-ACVRL1-ORF	Probe targets open reading frame
UTR Example: Hs-HTT-UTR-C3	Probe targets the untranslated region (non-protein-coding region) only
5UTR Example: Hs-GNRHR-5UTR	Probe targets the 5' untranslated region only
3UTR Example: Rn-Npy1r-3UTR	Probe targets the 3' untranslated region only
Pan Example: Pool	A mixture of multiple probe sets targeting multiple genes or transcripts

Search form

Probes for INS

Content for comparison

Gene

Product

Research area

Category

Pages

Advanced Cell Diagnostics

Bio-Techne

Advanced Cell Diagnostics China