Molecular Context of Dopa Influences Adhesion of Mussel-Inspired Peptides

Chitinase-like proteins (CLPs) of the 18 glycosyl hydrolase family retain structural similarity to chitinases but lack enzymatic activity. Although CLPs are upregulated in several human disorders that affect regenerative and inflammatory processes, very little is known about their normal physiological function. We show that an insect CLP (Drosophila imaginal disc growth factor 3, IDGF3) plays an immune-protective role during entomopathogenic nematode (EPN) infections. During these infections, nematodes force their entry into the host via border tissues, thus creating wounds. Whole-genome transcriptional analysis of nematode-infected wild-type and Idgf3 mutant larvae have shown that, in addition to the regulation of genes related to immunity and wound closure, IDGF3 represses Jak/STAT and Wingless signaling. Further experiments have confirmed that IDGF3 has multiple roles in innate immunity. It serves as an essential component required for the formation of hemolymph clots that seal wounds, and Idgf3 mutants display an extended developmental delay during wound healing. Altogether, our findings indicate that vertebrate and invertebrate CLP proteins function in analogous settings and have a broad impact on inflammatory reactions and infections. This opens the way to further genetic analysis of Drosophila IDGF3 and will help to elucidate the exact molecular context of CLP function.

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Squamous Differentiation in the Thyroid: Metaplasia, Neoplasia, or Bystander?

International Journal of Surgical Pathology ◽

10.1177/10668969211065126 ◽

2021 ◽

pp. 106689692110651

Author(s):

Meagan A. Chambers ◽

Peter M. Sadow ◽

Darcy A. Kerr

Keyword(s):

Squamous Epithelium ◽

Clinical Information ◽

Follicular Cells ◽

Squamous Differentiation ◽

Neoplastic Processes ◽

Molecular Context ◽

Institutional Landscape ◽

Aggressive Tumors ◽

Pathology Reports ◽

Thyroid Malignancies

Background. Squamous differentiation within the thyroid is seen in a variety of settings. Squamous epithelium is non-native to the thyroid, and its debated origins span reactive metaplasia and developmental/embryologic remnants. Despite a lack of clarity as to its evolution, squamous epithelium may be associated with both neoplastic and non-neoplastic processes. Methods. Thyroid pathology reports spanning a 30-year period were reviewed for terms indicating squamous features. Associated diagnostic and clinical information was collated. Results. Four hundred and twenty seven of 17,452 (2.4%) thyroid surgical pathology cases during this period utilized terminology indicating squamous differentiation including 243 malignant (58%) and 178 benign (42%) diagnoses. There were 111 (26%) primary thyroid malignancies with squamous differentiation, 116 (28%) malignancies of non-thyroid origin including local extension from nearby cancers, and 16 (4%) malignancies of uncertain primary. Most benign lesions were non-neoplastic (84%). The minor subset representing benign neoplasia was interpreted as secondary reactive changes. Conclusion. While squamous differentiation is seen routinely in the thyroid, it is most commonly reported in malignancy. For primary thyroid malignancies reported to demonstrate a squamous component, biologically aggressive tumors were overrepresented. Available evidence suggests that multiple pathways may contribute to the presence of squamous epithelium in the thyroid including metaplasia of mature follicular cells, development from established embryonic remnants, or inception in putative, incompletely characterized stem-like cells. Our retrospective review presents an institutional landscape from which further investigation into the frequency and unique histologic and molecular context of intrathyroidal squamous differentiation as a driver or terminal event in thyroid pathophysiology.

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Abstract 972: Defining the molecular context of MYC and WDR5 at chromatin

10.1158/1538-7445.am2018-972 ◽

2018 ◽

Author(s):

Alissa D. Guarnaccia ◽

William P. Tansey

Keyword(s):

Molecular Context

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EXTH-55. TEMOZOLOMIDE-RESISTANT GLIOMA CELLS ARE SENSITIVE TO CHLOROETHYLATING NITROSOUREA COMPOUNDS IN COMBINATION WITH ATR INHIBITORS

Neuro-Oncology ◽

10.1093/neuonc/noz175.386 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi94-vi94

Author(s):

Christopher Jackson ◽

Aravind Kalathil ◽

Ranjit Bindra

Keyword(s):

Alkylating Agents ◽

Methylation Status ◽

Promoter Hypermethylation ◽

Common Mechanism ◽

Repair System ◽

Drug Of Choice ◽

Mismatch Repair System ◽

Molecular Context ◽

Future Work ◽

Recurrent Gbm

Abstract BACKGROUND Despite decades of research, nearly all patients with glioblastoma (GBM) face recurrent disease. Temozolomide (TMZ), the drug of choice for GBM, methylates guanine bases at the O6 position (O6meG). These lesions are normally repaired by O6meG-methyltransferase (MGMT). When MGMT is deficient (e.g. in the case of promoter hypermethylation), O6meG lesions generate mispairs with thymine and activate the mismatch repair system (MMR), which is thought to be critical for the cytotoxicity of TMZ. Numerous studies have established that acquired MMR deficiency is a common mechanism of TMZ resistance that emerges in recurrent GBM. However, reversion of MGMT-methylation status is not common in recurrent GBM. Recent work from our group demonstrated that TMZ synergizes with ATR inhibitors (ATRi’s) in MGMT-methylated GBM cells. The goal of this project was to identify the specific types of alkylating agents that synergize with ATRi’s in an MGMT-methylated, MMR-deficient molecular context. RESULTS We used GBM cell lines U251 and LN229, which are both MGMT-methylated and exquisitely sensitive to TMZ in combination with ATRi at baseline, and created MMR-deficient versions through stable knockdown of MSH2. We determined that MSH2 knockdown conferred remarkable resistance in U251 and LN229 to TMZ treatment in comparison to their respective MMR-proficient counterparts. In addition, we were unable to detect synergy between ATRi’s and TMZ in the setting of MSH2 knockdown. In contrast to TMZ, we found that treatment with chloroethyl nitrosourea (CNU) alkylating agents--including lomustine--with ATRi’s was extremely effective in killing MGMT-methylated, MMR-deficient GBM cells. CONCLUSION Here, we report an exquisite synergistic interaction between ATRi’s and CNU agents in MMR-deficient, MGMT-methylated GBM cells. Future work in the lab will examine the interaction of CNU and ATRi’s with radiation therapy (RT). Because ATRi’s are known radiosensitizers, we believe that novel combinations of ATRi’s, lomustine, and re-RT may have promise in recurrent GBM.

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104 The molecular context of vulnerability for CDK9 suppression in melanoma

Journal of Investigative Dermatology ◽

10.1016/j.jid.2020.03.107 ◽

2020 ◽

Vol 140 (7) ◽

pp. S12

Author(s):

S.M. Guhan ◽

M. Shaughnessy ◽

A. Rajadurai ◽

R. Kumar ◽

Z. Ji ◽

...

Keyword(s):

Molecular Context

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Revision of Neacomys spinosus (Thomas, 1882) (Rodentia: Cricetidae) with emphasis on Peruvian populations and the description of a new species

Zootaxa ◽

10.11646/zootaxa.4242.3.1 ◽

2017 ◽

Vol 4242 (3) ◽

pp. 401 ◽

Cited By ~ 11

Author(s):

NATALI HURTADO ◽

VÍCTOR PACHECO

Keyword(s):

New Species ◽

Taxonomic Revision ◽

Molecular Evidence ◽

Cloud Forests ◽

Qualitative And Quantitative ◽

Candidate Species ◽

Molecular Context ◽

Northern Peru ◽

Species Groups ◽

A New Species

The large spiny mouse Neacomys spinosus (Thomas, 1882) has been considered the widest ranging species of the genus, occurring in southern Colombia, eastern Peru, western Brazil and northern Bolivia. The morphological variation between subspecies and populations of N. spinosus has been noted; nonetheless, this variation has not been assessed in a morphological or molecular context. Here, we present a taxonomic revision of Neacomys spinosus s.l. using qualitative and quantitative morphological analyses. These analyses were complemented with molecular analysis to reconstruct the phylogenetic relationships among species of Neacomys, based on sequences of the cytochrome b gene. Our results reveal that N. spinosus s.l. is a monophyletic group, and morphological and molecular evidence to differentiate three taxa: N. spinosus s.s., an endemic species from mountain cloud forests in Peru; N. amoenus s.l. from the Cerrado between Bolivia and Brazil to the Amazonia between Ecuador and northern Peru, and Neacomys sp. nov. from mountain cloud forests from southern Peru to Bolivia. Also, our molecular results indicate that Neacomys is still far from being completely known. For instance, there are three candidate species pending of taxonomic revision. Finally, we propose three species groups within Neacomys: “paracou”, “tenuipes” and “spinosus”, and discuss biogeographical scenarios of the genus within South America.

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Pseudolagarobasidium (Basidiomycota): on the reinstatement of a genus of parasitic, saprophytic, and endophytic resupinate fungi

Botany ◽

10.1139/b08-088 ◽

2008 ◽

Vol 86 (11) ◽

pp. 1319-1325 ◽

Cited By ~ 13

Author(s):

Nils Hallenberg ◽

Martin Ryberg ◽

R. Henrik Nilsson ◽

Alan R. Wood ◽

Sheng-Hua Wu

Keyword(s):

Theobroma Cacao ◽

Monophyletic Group ◽

Leguminous Trees ◽

Molecular Context ◽

Cacao Tree ◽

Theobroma Cacao L ◽

Ecological Range

The small resupinate genus Pseudolagarobasidium (Polyporales, Basidiomycota) presently comprises less than five species, all of which were described from tropical to subtropical regions, and two of which are root parasites on leguminous trees. The genus has recently been synonymized with Radulodon on morphological grounds, and the present study evaluates this proposal in a molecular context. Pseudolagarobasidium was found to constitute a well supported, monophyletic group excluding Radulodon and this synonymy is rejected. The ecological range of the genus spans saprotrophy to parasitism, and this study presents evidence that at least one lineage in Pseudolagarobasidium is endophytic in the cacao tree ( Theobroma cacao L.).

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