Biomarkers in Carcinoma of Unknown Primary

2022 Jan 01

Talu, C;Ulukus, E;Zheng, W;
| DOI: 10.1007/978-3-030-84432-5_10

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A novel herpes-like virus inducing branchial lesions in a tiger shark (Galeocerdo cuvier)

Veterinary pathology

2021 Nov 18

Armwood, AR;Stilwell, JM;Ng, TFF;Clauss, TM;Leary, JH;Mader, D;Camus, AC;
PMID: 34794368 | DOI: 10.1177/03009858211052662

A juvenile, male tiger shark (Galeocerdo cuvier) developed illness after capture in Florida waters and was euthanized. Gross lesions included mild skin abrasions, hepatic atrophy, and coelomic fluid. Histologically, gills contained multifocal lamellar epithelial cell necrosis and thromboses. Scattered gill and esophageal epithelial cells had large, basophilic, intracytoplasmic, and intranuclear inclusions. Ultrastructurally, lamellar epithelial cells contained arrays of intracytoplasmic viral particles and scattered intranuclear nucleocapsids. Capsulated virions were 148 ± 11 nm with an 84 ± 8 nm icosahedral nucleocapsid and an electron-dense core. Next-generation sequencing, quantitative polymerase chain reaction, and in situ hybridization performed on formalin-fixed tissue confirmed a herpes-like viral infection. The viral polymerase shared 24% to 31% protein homology with other alloherpesviruses of fish, indicating a divergent virus. This report documents the pathologic findings associated with a molecularly confirmed novel herpes-like virus in an elasmobranch.

Single-cell omics: Overview, analysis, and application in biomedical science

Journal of cellular biochemistry

2021 Aug 30

Stein, CM;Weiskirchen, R;Damm, F;Strzelecka, PM;
PMID: 34459502 | DOI: 10.1002/jcb.30134

Single-cell sequencing methods provide the highest resolution insight into cellular heterogeneity. Owing to their rapid growth and decreasing cost, they are now widely accessible to scientists worldwide. Single-cell technologies enable analysis of a large number of cells, making them powerful tools to characterise rare cell types and refine our understanding of diverse cell states. Moreover, single-cell application in biomedical sciences helps to unravel mechanisms related to disease pathogenesis and outcome. In this Viewpoint, we briefly describe existing single-cell methods (genomics, transcriptomics, epigenomics, proteomics, and mulitomics), comment on available analysis tools, and give examples of method applications in the biomedical field.

Cell-cell contact and signaling in the muscle stem cell niche

Current opinion in cell biology

2021 Aug 02

Kann, AP;Hung, M;Krauss, RS;
PMID: 34352725 | DOI: 10.1016/j.ceb.2021.06.003

Muscle stem cells (also called satellite cells or SCs) rely on their local niche for regulatory signals during homeostasis and regeneration. While a number of cell types communicate indirectly through secreted factors, here we focus on the significance of direct contact between SCs and their neighbors. During quiescence, SCs reside under a basal lamina and receive quiescence-promoting signals from their adjacent skeletal myofibers. Upon injury, the composition of the niche changes substantially, enabling the formation of new contacts that mediate proliferation, self-renewal, and differentiation. In this review, we summarize the latest work in understanding cell-cell contact within the satellite cell niche and highlight areas of open questions for future studies.

Transcriptional and Anatomical Diversity of Medium Spiny Neurons in the Primate Striatum

SSRN Electronic Journal

2021 Apr 02

He, J;Kleyman, M;Chen, J;Alikaya, A;Rothenhoefer, K;Ozturk, B;Wirthlin, M;Fish, K;Byrne, L;Pfenning, A;Stauffer, W;
| DOI: 10.2139/ssrn.3815985

The striatum is the interface between dopamine reward signals and cortico-basal ganglia circuits that mediate diverse behavioral functions. Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and are traditionally classified as direct- or indirect-pathway neurons. However, that traditional model does not explain the anatomical and functional diversity of MSNs. Here, we defined molecularly distinct MSN types in the primate striatum, including (1) dorsal striatum MSN types associated with striosome and matrix compartments, (2) ventral striatum types associated with the nucleus accumbens shell and olfactory tubercle, and (3) an MSN-like type restricted to μ-opioid receptor rich islands in the ventral striatum. These results lay the foundation for achieving cell type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit-specific processing.

Single-cell sequencing in translational cancer research and challenges to meet clinical diagnostic needs

Genes, chromosomes & cancer

2021 Feb 21

Pfisterer, U;Bräunig, J;Brattås, P;Heidenblad, M;Karlsson, G;Fioretos, T;
PMID: 33611828 | DOI: 10.1002/gcc.22944

The ability to capture alterations in the genome or transcriptome by next-generation sequencing has provided critical insight into molecular changes and programs underlying cancer biology. With the rapid technological development in single-cell sequencing, it has become possible to study individual cells at the transcriptional, genetic, epigenetic, and protein level. Using single-cell analysis, an increased resolution of fundamental processes underlying cancer development is obtained, providing comprehensive insights otherwise lost by sequencing of entire (bulk) samples, in which molecular signatures of individual cells are averaged across the entire cell population. Here, we provide a concise overview on the application of single-cell analysis of different modalities within cancer research by highlighting key articles of their respective fields. We furthermore examine the potential of existing technologies to meet clinical diagnostic needs and discuss current challenges associated with this translation. This article is protected by

Multiomics Technologies Capture More Particulars, Reveal More Grandeur

Genetic Engineering & Biotechnology News

2023 Jun 01

LeMieux, J;
| DOI: 10.1089/gen.43.06.13

A patient's genome, Van Eyk noted, contains information about that patient's disease predispositions and drug responses. She added, however, that better information about disease risks and drug responses could be gleaned from the proteome. Although there are only so many protein-encoding genes, the intricacies of protein expression generate various kinds of proteomic information in abundance. According to Van Eyk, information about disease-induced modifications, isoforms, concentration changes, and chemical complexity can inform predictions of what will happen in the body, in the context of the body and the environment. She suggests that a proteomics approach—one that would involve monitoring of not just one protein at a time, but thousands—could generate valuable clinical insights.

Elucidating the structure and function of the nucleus-The NIH Common Fund 4D Nucleome program

Molecular cell

2023 Jan 06

Roy, AL;Conroy, RS;Taylor, VG;Mietz, J;Fingerman, IM;Pazin, MJ;Smith, P;Hutter, CM;Singer, DS;Wilder, EL;
PMID: 36640770 | DOI: 10.1016/j.molcel.2022.12.025

Genomic architecture appears to play crucial roles in health and a variety of diseases. How nuclear structures reorganize over different timescales is elusive, partly because the tools needed to probe and perturb them are not as advanced as needed by the field. To fill this gap, the National Institutes of Health Common Fund started a program in 2015, called the 4D Nucleome (4DN), with the goal of developing and ultimately applying technologies to interrogate the structure and function of nuclear organization in space and time.

Multiscale microscopy to decipher plant cell structure and dynamics

The New phytologist

2022 Dec 07

Cui, Y;Zhang, X;Li, X;Lin, J;
PMID: 36477856 | DOI: 10.1111/nph.18641

New imaging methodologies with high contrast and molecular specificity allow researchers to analyze dynamic processes in plant cells at multiple scales, from single protein and RNA molecules to organelles and cells, to whole organs and tissues. These techniques produce informative images and quantitative data on molecular dynamics to address questions that cannot be answered by conventional biochemical assays. Here, we review selected microscopy techniques, focusing on their basic principles and applications in plant science, discussing the pros and cons of each technique, and introducing methods for quantitative analysis. This review thus provides guidance for plant scientists in selecting the most appropriate techniques to decipher structures and dynamic processes at different levels, from protein dynamics to morphogenesis.

Gene expression data visualization tool on the o²S²PARC platform

F1000Research

2022 Nov 07

Ben Aribi, H;Ding, M;Kiran, A;
| DOI: 10.12688/f1000research.126840.1

Background: The identification of differentially expressed genes and their associated biological processes, molecular function, and cellular components are important for genetic diseases studies because they present potential biomarkers and therapeutic targets. Methods: In this study, we developed an o²S²PARC template representing an interactive pipeline for the gene expression data visualization and ontologies data analysis and visualization. To demonstrate the usefulness of the tool, we performed a case study on a publicly available dataset. Results: The tool enables users to identify the differentially expressed genes (DEGs) and visualize them in a volcano plot format. The ontologies associated with the DEGs are determined and visualized in barplots. Conclusions: The “Expression data visualization” template is publicly available on the o²S²PARC platform.

Cross-species single-cell transcriptomic analysis reveals factors limiting human Müller glial-derived retinal regeneration

Investigative Ophthalmology & Visual Science

2022 Jan 01

Dhodapkar, R;Martell, D;Calapkulu, E;

RESULTS : After quality control and data integration, 17,401 nuclei were isolated from 26,471 original droplets, derived from macular samples of 4 patients without retinal disease and 3 patients with POAG. The proportion of retinal ganglion cells in glaucomatous retina was significantly lower than that in healthy retina (p=0.024). An activated subpopulation of Müller glia was identified in both healthy and glaucomatous retina by cell clustering. Cross-species analysis comparing zebrafish and humans identified YAP1 activation as a differentiator between zebrafish and human glial activation. Human retinal explants cultured with N3B1P3C demonstrated significant proliferation of GS+ Muller cells (p=0.044).

Immune-guided therapy of COVID-19

Cancer immunology research

2022 Jan 24

Ferraccioli, G;Gremese, E;Goletti, D;Petrone, L;Cantini, F;Ugel, S;Canè, S;Bronte, V;
PMID: 35074758 | DOI: 10.1158/2326-6066.CIR-21-0675

Vaccination has been a game changer in our efforts to address the coronavirus disease 2019 (COVID-19) pandemic. However, the disease might still represent a clinical crisis for several more years, in part because of the inevitable emergence of variants capable of evading the pre-existing immunity. Drugs affecting viral spread will help curtail transmission, but therapeutics are needed to treat the more severe cases requiring hospitalization. A deep analysis of the evolving immune landscape of COVID-19 suggests that understanding the molecular bases of the distinct clinical stages is paramount if we are to limit the burden of inflammation, which can lead to death in frail individuals, according to age, sex and comorbidities. Different phases can be defined using immune biomarkers and need specific therapeutic approaches, tailored to the underlying immune contexture.

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	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

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