Biologic and behavioral associations of estrogen receptor alpha positivity in head and neck squamous cell carcinoma

Oral oncology

2021 Jul 22

Drake, V;Bigelow, E;Fakhry, C;Windon, M;Rooper, LM;Ha, P;Miles, B;Gourin, C;Mandal, R;Mydlarz, W;London, N;Vosler, PS;Yavvari, S;Troy, T;Waterboer, T;Eisele, DW;D'Souza, G;
PMID: 34304004 | DOI: 10.1016/j.oraloncology.2021.105461

Tumor HPV status is an established independent prognostic marker for oropharynx cancer (OPC). Recent studies have reported that tumor estrogen receptor alpha (ERα) positivity is also associated with prognosis independent of HPV. Little is known about the biologic and behavioral predictors of ERα positivity in head and neck squamous cell cancer (HNSCC). We therefore explored this in a multicenter prospective cohort study.Participants with HNSCC completed a survey and provided a blood sample. Tumor samples were tested for ERα using immunohistochemistry. ERα positivity was defined as ≥1%, standardized by the American Society of Clinical Oncology/College of American Pathologists in breast cancer. Characteristics were compared with χ2 and Fisher's exact test. Odds ratios (OR) were calculated using logistic regression.Of 318 patients with HNSCC, one third had ERα positive tumors (36.2%, n = 115). Odds of ERα expression were significantly increased in those with HPV-positive tumors (OR = 27.5, 95% confidence interval[CI] 12.1-62), smaller tumors (≤T2, OR = 3.6, 95% CI 1.9-7.1), male sex (OR = 2.0, 95% CI 1.1-3.6), overweight/obesity (BMI ≥ 25, OR = 1.9, 95% CI 1.1-3.3), and those married/living with a partner (OR = 1.7, 95% CI 1.0-3.0). In a multivariate model, HPV-positivity (aOR = 27.5, 95% CI 11.4-66) and small tumor size (≤T2, aOR = 2.2, 95% CI 1.0-4.8) remained independently associated with ERα status. When restricted to OPC (n = 180), tumor HPV status (aOR = 17.1, 95% CI 2.1-137) and small tumor size (≤T2, aOR = 4.0 95% CI 1.4-11.3) remained independently associated with ERα expression.Tumor HPV status and small tumor size are independently associated with ERα expression in HNSCC.

Spike Generators and Cell Signaling in the Human Auditory Nerve: An Ultrastructural, Super-Resolution, and Gene Hybridization Study

Frontiers in Cellular Neuroscience

2021 Mar 16

Liu, W;Luque, M;Li, H;Schrott-Fischer, A;Glueckert, R;Tylstedt, S;Rajan, G;Ladak, H;Agrawal, S;Rask-Andersen, H;
| DOI: 10.3389/fncel.2021.642211

Background: The human auditory nerve contains 30,000 nerve fibers (NFs) that relay complex speech information to the brain with spectacular acuity. How speech is coded and influenced by various conditions is not known. It is also uncertain whether human nerve signaling involves exclusive proteins and gene manifestations compared with that of other species. Such information is difficult to determine due to the vulnerable, “esoteric,” and encapsulated human ear surrounded by the hardest bone in the body. We collected human inner ear material for nanoscale visualization combining transmission electron microscopy (TEM), super-resolution structured illumination microscopy (SR-SIM), and RNA-scope analysis for the first time. Our aim was to gain information about the molecular instruments in human auditory nerve processing and deviations, and ways to perform electric modeling of prosthetic devices.Material and Methods: Human tissue was collected during trans-cochlear procedures to remove petro-clival meningioma after ethical permission. Cochlear neurons were processed for electron microscopy, confocal microscopy (CM), SR-SIM, and high-sensitive in situ hybridization for labeling single mRNA transcripts to detect ion channel and transporter proteins associated with nerve signal initiation and conductance.Results: Transport proteins and RNA transcripts were localized at the subcellular level. Hemi-nodal proteins were identified beneath the inner hair cells (IHCs). Voltage-gated ion channels (VGICs) were expressed in the spiral ganglion (SG) and axonal initial segments (AISs). Nodes of Ranvier (NR) expressed Nav1.6 proteins, and encoding genes critical for inter-cellular coupling were disclosed.Discussion: Our results suggest that initial spike generators are located beneath the IHCs in humans. The first NRs appear at different places. Additional spike generators and transcellular communication may boost, sharpen, and synchronize afferent signals by cell clusters at different frequency bands. These instruments may be essential for the filtering of complex sounds and may be challenged by various pathological conditions.

Oncolytic adenoviral H101 synergizes with radiation in cervical cancer cells

Current cancer drug targets

2021 Mar 07

Duan, Y;Bai, H;Li, X;Wang, D;Wang, Y;Cao, M;Zhang, N;Chen, H;Wang, Y;
PMID: 33687882 | DOI: 10.2174/1568009621666210308103541

A major challenge in cervical cancer radiotherapy is to tailor the radiation doses efficiently to both eliminate malignant cells and to reduce the side effects to normal tissue. Oncolytic adenoviral drug H101 is recently tested and approved for topical adjuvant treatment of several malignancies. This study is to evaluate the potential neoadjuvant radiotherapy benefits of H101 by testing the inhibitory function of H101 combined with radiation in different cervical cancer cells. Human cervical cancer cells C33a, SiHa, CaSki, and Hela were treated with varying concentrations of H101 alone or combined with radiation (2Gy or 4Gy). Cell viability and apoptosis were measured at indicated time intervals. HPV16 E6 and cellular p53 mRNA expression alteration were measured by qRT-PCR. RNA scope in-situ detect HPV E6 status. P53 protein alteration are detected by Western blot. Cell viability and apoptosis show the combination of a high dose of H101 (MOI=1000, 10000) with radiation yielded a synergistic anti-cancer effect in all tested cervical cancer cell lines (P<0.05), with the greatest effect achieved in HPV negative C33a cells (P<0.05). Low HPV16 viral load SiHa cell was more sensitive to combination therapy than high HPV16 viral load CaSki cell (P<0.05). The combined treatment could reduce HPV16 E6 expression and increase cellular P53 level compared to radiation alone in SiHa and CaSki (P<0.05). Oncolytic adenoviral H101 effectively enhances the antitumor efficacy of radiation in cervical cancer cells and may serve as a novel combination therapy for cervical cancer.

MALAT1 maintains the intestinal mucosal homeostasis in Crohn\'s disease via the miR-146b-5p-CLDN11/NUMB pathway

Journal of Crohn's & colitis

2021 Mar 02

Li, Y;Zhu, L;Chen, P;Wang, Y;Yang, G;Zhou, G;Li, L;Feng, R;Qiu, Y;Han, J;Chen, B;He, Y;Zeng, Z;Chen, M;Zhang, S;
PMID: 33677577 | DOI: 10.1093/ecco-jcc/jjab040

Intestinal homeostasis disorder is critical for developing Crohn's disease (CD). Maintaining mucosal barrier integrity is essential for intestinal homeostasis, preventing intestinal injury and complications. Among the remarkably altered long non-coding RNAs (lncRNAs) in CD, we aimed to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) modulated CD and consequent disruption of intestinal homeostasis. Microarray analyses on intestinal mucosa of CD patients and controls were performed to identify dysregulated lncRNAs. MALAT1 expression was investigated via qRT-PCR and its distribution in intestinal tissues was detected using BaseScope. Intestines from MALAT1 knockout mice with colitis were investigated using histological, molecular and biochemical approaches. Effects of intestinal epithelial cells transfected with MALAT1 lentiviruses and Smart Silencer, on monolayer permeability and apical junction complex (AJC) proteins were analysed. MiR-146b-5p were confirmed as a critical MALAT1 mediator in cells transfected with miR-146b-5p mimic/inhibitor and in colitis mice administered with agomir-146b-5p/antagomir-146b-5p. Interaction between MALAT1 and miR-146b-5p was predicted via bioinformatics and validated using Dual-luciferase reporter assay and Ago2-RIP. MALAT1 was aberrantly downregulated in the intestine mucosa of CD patients and mice with experimental colitis. MALAT1 knockout mice were hypersensitive to DSS-induced experimental colitis. MALAT1 regulated intestinal mucosal barrier and regained intestinal homeostasis by sequestering miR-146b-5p and maintaining the expression of the AJC proteins NUMB and CLDN11. Downregulation of MALAT1 contributed to the pathogenesis of CD by disrupting AJC. Thus, a specific MALAT1-miR-146b-5p-NUMB/CLDN11 pathway that plays a vital role in maintaining intestinal mucosal homeostasis may serve as a novel target for CD treatment.

Zinc Dependent Regulation of ZEB1 and YAP1 Co-activation Promotes EMT Plasticity and Metastasis in Pancreatic Cancer

Gastroenterology

2021 Jan 06

Liu, M;Zhang, Y;Yang, J;Zhan, H;Zhou, Z;Jiang, Y;Shi, X;Fan, X;Zhang, J;Luo, W;Fung, KA;Xu, C;Bronze, MS;Houchen, CW;Li, M;
PMID: 33421513 | DOI: 10.1053/j.gastro.2020.12.077

Pancreatic cancer is characterized by extensive metastasis. EMT plasticity plays a critical role in tumor progression and metastasis by maintaining the transition between EMT and MET states. Our aim is to understand the molecular events regulating metastasis and EMT plasticity in pancreatic cancer. The interactions between a cancer promoting zinc transporter ZIP4, a zinc dependent EMT transcriptional factor ZEB1, a co-activator YAP1, and integrin α3 (ITGA3) were examined in human pancreatic cancer cells, clinical specimens, spontaneous mouse models (KPC and KPCZ) and orthotopic xenografts, and 3D spheroid and organoid models. Correlations between ZIP4, miR-373, and its downstream targets were assessed by RNA in situ hybridization and IHC staining. The transcriptional regulation of ZEB1, YAP1, ITGA3 by ZIP4 was determined by ChIP, Co-IP and luciferase reporter assays. The Hippo pathway effector YAP1 is a potent transcriptional co-activator and forms a complex with ZEB1 to activate ITGA3 transcription through the YAP1/TEAD binding sites in human pancreatic cancer cells and KPC derived mouse cells. ZIP4 upregulated YAP1 expression via activation of miR-373 and inhibition of the YAP1 repressor LATS2. Furthermore, upregulation of ZIP4 promoted EMT plasticity, cell adhesion, spheroid formation and organogenesis both in human pancreatic cancer cells, 3D spheroid model, xenograft model, and spontaneous mouse models (KPC and KPCZ) through ZEB1/YAP1-ITGA3 signaling axis. We demonstrated that ZIP4 activates ZEB1 and YAP1 through distinct mechanisms. The ZIP4-miR-373-LATS2-ZEB1/YAP1-ITGA3 signaling axis has a significant impact on pancreatic cancer metastasis and EMT plasticity.

Single-cell transcriptomics identifies limbal stem cell population and cell types mapping its differentiation trajectory in limbal basal epithelium of human cornea

The Ocular Surface

2021 Jan 01

Li, D;Kim, S;Li, J;Gao, Q;Choi, J;Bian, F;Hu, J;Zhang, Y;Li, J;Lu, R;Li, Y;Pflugfelder, S;Miao, H;Chen, R;
| DOI: 10.1016/j.jtos.2020.12.004

Purpose This study aimed to uncover novel cell types in heterogenous basal limbus of human cornea for identifying LSC at single cell resolution. Methods Single cells of human limbal basal epithelium were isolated from young donor corneas. Single-cell RNA-Sequencing was performed using 10x Genomics platform, followed by clustering cell types through the graph-based visualization method UMAP and unbiased computational informatic analysis. Tissue RNA in situ hybridization with RNAscope, immunofluorescent staining and multiple functional assays were performed using human corneas and limbal epithelial culture models. Results Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters belonging to three lineages. A smallest cluster (0.4% of total cells) was identified as LSCs based on their quiescent and undifferentiated states with enriched marker genes for putative epithelial stem cells. TSPAN7 and SOX17 are discovered and validated as new LSC markers based on their exclusive expression pattern and spatial localization in limbal basal epithelium by RNAscope and immunostaining, and functional role in cell growth and tissue regeneration models with RNA interference in cultures. Interestingly, five cell types/states mapping a developmental trajectory of LSC from quiescence to proliferation and differentiation are uncovered by Monocle3 and CytoTRACE pseudotime analysis. The transcription factor networks linking novel signaling pathways are revealed to maintain LSC stemness. Conclusions This human corneal scRNA-Seq identifies the LSC population and uncovers novel cell types mapping the differentiation trajectory in heterogenous limbal basal epithelium. The findings provide insight into LSC concept and lay the foundation for understanding the corneal homeostasis and diseases.

Colonic epithelial-derived Selenoprotein P is the source for antioxidant-mediated protection in colitis-associated cancer

Gastroenterology

2021 Jan 01

Short, S;Pilat, J;Barrett, C;Reddy, V;Haberman, Y;Hendren, J;Marsh, B;Keating, C;Motley, A;Hill, K;Zemper, A;Washington, M;Shi, C;Chen, X;Wilson, K;Hyams, J;Denson, L;Burk, R;Rosen, M;Williams, C;
| DOI: 10.1053/j.gastro.2020.12.059

Background and Aims Patients with inflammatory bowel disease (IBD) demonstrate nutritional selenium deficiencies and are at greater risk for colon cancer. Previously, we determined that global reduction of the secreted antioxidant selenium-containing protein, Selenoprotein P (SELENOP), substantially increased tumor development in an experimental colitis-associated cancer (CAC) model. We next sought to delineate tissue-specific contributions of SELENOP to intestinal inflammatory carcinogenesis and define clinical context. Methods Selenop floxed mice crossed with Cre driver lines to delete Selenop from the liver, myeloid lineages, or intestinal epithelium were placed on an azoxymethane/dextran sodium sulfate (AOM/DSS) experimental CAC protocol. SELENOP loss was assessed in human ulcerative colitis (UC) organoids, and expression was queried in human and adult UC samples. Results Although large sources of SELENOP, both liver- and myeloid-specific Selenop deletion failed to modify AOM/DSS-mediated tumorigenesis. Instead, epithelial-specific deletion increased CAC tumorigenesis, likely due to elevated oxidative stress with a resulting increase in genomic instability and augmented tumor initiation. SELENOP was downregulated in UC colon biopsies and levels were inversely correlated with endoscopic disease severity and tissue S100A8 (calprotectin) gene expression. Conclusions While global selenium status is typically assessed by measuring liver-derived plasma SELENOP levels, our results indicate that the peripheral SELENOP pool is dispensable for CAC. Colonic epithelial SELENOP is the main contributor to local antioxidant capabilities. Thus, colonic SELENOP is the most informative means to assess selenium levels and activity in IBD patients and may serve as a novel biomarker for UC disease severity and identify patients most predisposed to CAC development.

Skin-dependent morphological and molecular maturation of specialized mechanosensory neurons (S34.005)

Wednesday, April 26

2023 Apr 25

Koutsioumpa, C;Santiago, C;Jacobs, K;Lehnert, B;Ginty, D;
| DOI: 10.1212/wnl.0000000000203780

Objective: Identification of the developmental steps leading to somatosensory neuron development. Background: Our sense of touch is essential for life and relies on Low-Threshold Mechanoreceptors (LTMRs). LTMR subtypes characterized by early embryonic expression of Ntrk2 (TrkB) and Ret exhibit distinct properties depending on the skin region they innervate - hairy skin or glabrous(hairless) skin. In glabrous skin, TrkB+ and Ret+ LTMRs form Meissner corpuscles, while in hairy skin they form longitudinal lanceolate endings around hair follicles. These morphological features reflect the physiological properties and specialized functions of these neurons. The developmental steps leading to glabrous and hairy skin LTMR properties are largely unknown, in particular whether they are genetically pre-specified or whether interactions with different target skin regions define their unique features. Design/Methods: Sparse genetic labeling experiments demonstrate that morphological specialization of glabrous- and hairy paw skin-innervating TrkB+ and Ret+ LTMRs arise at nearly identical times during postnatal development. Interestingly, we find that individual neurons that terminate along the border of glabrous and hairy skin, termed “border neurons”, exhibit branches that form both lanceolate endings and Meissner corpuscle endings. Additionally, transcriptomic profiling and RNAscope experiments show that neonatal glabrous skin-and hairy skin-innervating TrkB+ and Ret+ neurons are transcriptionally similar, although distinct from other DRG neuron types. Lastly, using mouse mutants that have either ectopic glabrous skin or ectopic hairy skin we find that neurons that innervate ectopic skin regions of these mutants form ending types (either lanceolate or Meissner corpuscle endings) in accordance with the ectopic skin type. Results: These findings support a model in which embryonic TrkB+ and Ret+ LTMRs are able to form either Meissner corpuscle or lanceolate endings, and that the skin target region differentially instructs morphological maturation of these LTMR types. Conclusions: This model implies that neuronal identity in the peripheral nervous system is flexibly determined by target tissue.

Radiotherapy exposure directly damages the uterus and causes pregnancy loss

JCI insight

2023 Mar 22

Griffiths, MJ;Marshall, SA;Cousins, FL;Alesi, LR;Higgins, J;Giridharan, S;Sarma, UC;Menkhorst, E;Zhou, W;Care, AS;Donoghue, JF;Holdsworth-Carson, SJ;Rogers, PA;Dimitriadis, E;Gargett, CE;Robertson, SA;Winship, AL;Hutt, KJ;
PMID: 36946464 | DOI: 10.1172/jci.insight.163704

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma-/-) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.

New technologies to study helminth development and host-parasite interactions

International journal for parasitology

2023 Mar 16

Britton, C;Laing, R;McNeilly, TN;Perez, MG;Otto, TD;Hildersley, KA;Maizels, RM;Devaney, E;Gillan, V;
PMID: 36931423 | DOI: 10.1016/j.ijpara.2022.11.012

How parasites develop and survive, and how they stimulate or modulate host immune responses are important in understanding disease pathology and for the design of new control strategies. Microarray analysis and bulk RNA sequencing have provided a wealth of data on gene expression as parasites develop through different life-cycle stages and on host cell responses to infection. These techniques have enabled gene expression in the whole organism or host tissue to be detailed, but do not take account of the heterogeneity between cells of different types or developmental stages, nor the spatial organisation of these cells. Single-cell RNA-seq (scRNA-seq) adds a new dimension to studying parasite biology and host immunity by enabling gene profiling at the individual cell level. Here we review the application of scRNA-seq to establish gene expression cell atlases for multicellular helminths and to explore the expansion and molecular profile of individual host cell types involved in parasite immunity and tissue repair. Studying host-parasite interactions in vivo is challenging and we conclude this review by briefly discussing the applications of organoids (stem-cell derived mini-tissues) to examine host-parasite interactions at the local level, and as a potential system to study parasite development in vitro. Organoid technology and its applications have developed rapidly, and the elegant studies performed to date support the use of organoids as an alternative in vitro system for research on helminth parasites.

Effective Marketing and Corporate Governance Contribute to Entrepreneurial Success: Case Study of India’s Most Trusted Diagnostics—Healthians

Indian Journal of Corporate Governance

2022 Dec 01

Jain, A;Jain, P;
| DOI: 10.1177/09746862221142332

The increased awareness surrounding health is a significant factor contributing to the trend of health awareness. People are showing extra care with changing lifestylesleading to more proactive care toward their health. There was an immense need to fill this gap. The founders of Healthians, India’s most trusted diagnostics, sensed this need and converted that into a successful business model. This article analyses Healthians governance and brand strategy making it one of the largest players in the Indian market. The article begins by describing the initial journey of Healthians and its founder. The article also highlights the financial strategy of the company along with the funding details. The industry analysis had also been done along with an analysis of major players in the diagnostic industry, followed by a discussion on the expansion strategy of the company. The business model, corporate governance, and marketing strategy of the company have been discussed in detail, followed by the brand strategy, in order to derive useful learning from the journey of this company. Adequate discussion on the products of the company had been done, along with the mentioning opportunities waiting to be explored by the company. With the highest competitive and volatile market of the healthcare industry, this company ensures that the highest standards in corporate governance and business ethics are being followed in the company. The article concludes with some dilemmas being faced by the company which may decide its future course of action and the various alternatives available to the company.

P.190 Congenital muscular dystrophy associated to conserved oligomeric Golgi complex subunit 1 homozygous mutation

Neuromuscular Disorders

2022 Oct 01

Balkenhol, J;Araneda, P;Suarez, B;Jofre, J;Martinez-Jalilie, M;De la Fuente, M;Fattori, F;Bertini, E;Serrano, M;Castiglioni, C;
| DOI: 10.1016/j.nmd.2022.07.333

Congenital disorders of glycosylation (CDG) are a group of clinically and genetically heterogeneous diseases caused by disorders of glycoproteins synthesis. Patients manifest a wide range of symptoms, phenotypes, and severity, usually with neurological compromise. The conserved oligomeric Golgi (COG) complex plays an important role in vesicular tethering in retrograde Golgi transport. Mutation in this complex is considered a multiple-pathway CDG. Only 6 cases of pathogenic variants of COG1 have been reported in the literature. We present a 10 year-old-female born at term to healthy non-consanguineous Chilean parents. At birth, the main findings were weak suction, hypotonia, and high creatine kinase (CK). Due to development delay, hypotonia, and persistently elevated CK levels, sometimes over 10 times normal values, electromyography was performed, suggestive of a predominantly proximal myopathic compromise. Muscle biopsy revealed dystrophic changes and abnormal alpha-dystroglycan immunohistochemistry. The patient's symptoms progressed, and she currently continues with motor difficulties, muscle weakness, joint hypermobility, recurrent patellar dislocation, and severe progressive kyphoscoliosis. A lower limb muscular magnetic resonance image revealed mild fat replacement mainly on soleus and gastrocnemius muscles. No cognitive impairment or additional neurological symptoms have appeared, but persistent thrombocytopenia and intermittent leukopenia appeared after age 6 years. A neuromuscular NGS panel was negative, and exome sequencing revealed a homozygous frameshift mutation in COG1 gene (c.2665dupC, p.Arg889Profs*12). This mutation has been previously reported and is considered pathogenic. However, this is the first report of a COG1 mutation manifesting mainly as congenital muscular dystrophy with a musculoskeletal phenotype and without the intellectual phenotype expected due to the COG1 mutation. This communication expands the COG1 clinical spectrum, including muscle compromise and COG1 mutations as a potential gene candidate in the differential diagnosis of congenital muscular dystrophies.

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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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