Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer

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Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions

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A phylogeny of ranid frogs (Anura: Ranoidea: Ranidae), based on a simultaneous analysis of morphological and molecular data

During the last two decades, major taxonomic rearrangements were instituted in the anuran family Ranidae. Most of these changes were not based on phylogenetic analysis, and many are controversial. Addressing the phylogeny of Ranidae requires broader taxon sampling within the superfamily Ranoidea, the phylogenetic relationships and higher classification of which are also in a state of flux. No comprehensive attempt has yet been made to reconstruct ranid phylogeny using both morphological and molecular data. In the present contribution, data from 178 organismal characters were collated for 74 exemplar species representing the families Arthroleptidae, Hemisotidae, Hyperoliidae, Mantellidae Microhylidae, Petropedetidae, Rhacophoridae, Sooglossidae, and most subfamilies of Ranidae. These were combined with ～1 kb of DNA sequence from the mitochondrial 12S rDNA and 16S rDNA gene regions in a simultaneous parsimony analysis with direct optimization. Results support the classification of Hemisus with the brevicipitine microhylids, confirm that Arthroleptidae (and its two component subfamilies Astylosterninae and Arthroleptinae) are monophyletic, and advocate the recognition of Leptopelidae. Monophyly of Ranidae is compromised by recognition of Petropedetidae, Rhacophoridae and Mantellidae, which should be recognized as subfamilies of Ranidae at present. Furthermore, Petropedetidae was found to be grossly paraphyletic, comprising three clades which are all considered separate subfamilies of Ranidae, i.e., Petropedetinae, Phrynobatrachinae and Cacosterninae. Three well defined subfamilies of Ranidae were consistently retrieved as monophyletic in a sensitivity analysis, i.e., Tomopterninae, Ptychadeninae and Pyxicephalinae. However, Ptychadeninae and Pyxicephalinae were embedded in Raninae and Dicroglossinae, respectively. Ceratobatrachinae is removed from Dicroglossinae. Dicroglossinae is synonymized with Pyxicephalinae. A new subfamily Strongylopinae is proposed. Raninae should be conservatively treated as a “metataxon” (sensu Ford and Cannatella, 1993 ) until such time as it is fully revised. Tomopterninae is removed from synonymy with Cacosterninae. Morphological synapomorphies are reported for major monophyletic clades retrieved in the simultaneous analysis with equal weights. The present study found that many Old World clades appear to contain both African and Asian taxa, contrary to the findings of some recent biogeographical analyses. This study demonstrates the value of broad taxonomic sampling in ranid phylogeny, and highlights the immense contribution that can be made from detailed morphological data. © The Willi Hennig Society 2005.     

Measuring the Surface Roughness of Stream Stones

Measuring the fine-scale heterogeneity of stones and other substrates is a challenge for benthic ecologists. I describe a method for measuring the roughness of stones that is based on the ratio of two surface area measurements: one that follows substrate contours and one based on a similar-sized modified spheroid. This roughness index is easily measured, assesses the entire surface of stones, and enables the measurement of replicate stones. Roughness measurements of 14 rock types demonstrated that values obtained were consistent with perceived roughness and porosity. Application of the roughness index to a published data set produced a curvilinear relationship between stone roughness and the biomass of algae in roughness-associated crevices.     

Jumping spiders attend to context during learned avoidance of aposematic prey

A large number of studies on both animals and humans have demonstratedthat learning is influenced by context or secondary cues thatare present when an association is formed. Few studies, however,have examined the functional value of attending to context.We first demonstrated that jumping spiders, Phidippus princeps,could be trained to avoid aposematic, distasteful milkweed bugs,Oncopeltus fasciatus. Spiders readily attacked bugs on firstexposure but were significantly less likely to do so after eighttrials, although they subsequently attacked and ate crickets.Spiders exposed to nontoxic milkweed bugs reared on sunflowerseeds did not show the same decline in attack rate. We nextexamined the effects of secondary contextual cues on spiderlearning by training spiders to avoid milkweed bugs in one oftwo environments. When spiders were tested in an environmentdifferent from the one in which they were trained, attack ratesincreased, and spiders no longer demonstrated retention of theassociation. Spiders tested in the same environment in whichthey were trained continued to avoid attacking the bugs. Theseresults have potential consequences for the evolution of bothpredator and prey and point to the importance of studying context-dependentlearning.     

Predation by invertebrate predators on the colonial rotifer Sinantherina socialis

Abstract. Colonies of the freshwater colonial rotifer Sinantherina socialis (Monogononta, Flosculariidae) have been shown to be unpalatable to a variety of small-mouthed, zooplanktivorous fishes. To test whether invertebrate predators ingest the rotifer S. socialis , we conducted two types of experiments: (1) Microcosm experiments—in separate experiments, four invertebrate predators (i.e., dragonfly nymphs, damselfly nymphs, notonectids, and Hydra ) were offered prey either singly or in combination. Prey were comprised of S. socialis; Epiphanes senta , a solitary, free-swimming rotifer; and Daphnia magna , a microcrustacean. In each experiment, the percent of prey surviving after 12, 18, and 24 h was recorded. (2) Paired-feeding experiments—in separate experiments, predators were offered prey in a pairwise fashion, in which members of D. magna were alternated with a rotifer, either S. socialis or E. senta. The results of the microcosm experiments showed that, after 24 h, 60–100% prey items of S. socialis survived the predators, but significantly fewer individuals of E. senta (6–89%) and D. magna (<25%) survived. When offered rotifers and individuals of D. magna simultaneously, predators tested consistently consumed more specimens of Daphnia. However, predators significantly reduced percent survival in E. senta but not in S. socialis. Predators, given a choice between the two rotifer species, all consumed significantly more specimens of E. senta than S. socialis after 24 h. In the paired-feeding experiments, three of the four predators captured members of S. socialis , but these colonies were frequently released rather than ingested, although in some cases colony structure was seriously disrupted. Our results suggest that the unpalatable nature of members of S. socialis to certain fishes extends to several invertebrate predators, but the nature of the putative factor(s) responsible for this remains unknown.     

CD40L-Tri, a novel formulation of recombinant human CD40L that effectively activates B cells

CD40L has a well-established role in enhancing the immunostimulatory capacity of normal and malignant B cells, but a formulation suitable for clinical use has not been widely available. Like other TNF family members, in vivo and in vitro activity of CD40L requires a homotrimeric configuration, and growing evidence suggests that bioactivity depends on higher-order clustering of CD40. We generated a novel formulation of human recombinant CD40L (CD40L-Tri) in which the CD40L extracellular domain and a trimerization motif are connected by a long flexible peptide linker. We demonstrate that CD40L-Tri significantly expands normal CD19+ B cells by over 20- to 30-fold over 14 days and induces B cells to become highly immunostimulatory antigen-presenting cells (APCs). Consistent with these results, CD40L-Tri-activated B cells could effectively stimulate antigen-specific T responses (against the influenza M1 peptide) from normal volunteers. In addition, CD40L-Tri could induce malignant B cells to become effective APCs, such that tumor-directed immune responses could be probed. Together, our studies demonstrate the potent immune-stimulatory effects of CD40L-Tri on B cells that enable their expansion of antigen-specific human T cells. The potent bioactivity of CD40L-Tri is related to its ability to self-multimerize, which may be facilitated by its long peptide linker.     

Determination and quantification of sinigrin glucosinolates in Alternaria solani susceptible tomato (Solanum lycopersicum) leaves treated with moringa (Moringa oleifera) leaf extract

Abstract

The study investigates the presence and quantity of antimicrobial sinigrin glucosinolates in tomato leaves after spraying them with moringa (Moringa oleifera) leaf extract (MLAE). Moringa concentrates (0.5, 0.75, 1.00 and 1.5?kg?L^?1 (w v^?1)) were prepared. Distilled water was the control. Sampled tomato leaves were air-dried, freeze-dried and extracted firstly using pure methanol in a hot water bath and then pellet re-extracted using 5?mL of hot aqueous methanol (70% v v^?1). An ion exchange column, and sulphatase was used to achieve glucosiodesulphonation. High performance liquid chromatography (HPLC) was employed in the identification and quantitative analysis of the sinigrin glucosinolates. Tomato (Solanum lycopersicum) leaves treated with MLAE revealed highly significant (p?<?.001) content of sinigrin glucosinolates. The sinigrin standard and the desulphated sinigrin glucosinolates had a 7?s retention time difference; 5?kg?L^?1 (w v^?1) resulted in a superior amount of sinigrin in tomato leaves as compared to all the other MLAE concentrations. The study reveals that spraying MLAE on putatively diseased tomato leaves donates specific quantifiable glucosinolates like sinigrin, which may be involved in defense against tomato diseases and, hence, recommends use of 5?kg?L^?1 (w v^?1) for the highest sinigrin defense tag.     

Lymphatic Endothelial Differentiation in Pulmonary Lymphangioleiomyomatosis Cells

Pulmonary lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm affecting almost exclusively women of childbearing age. LAM belongs to the family of perivascular epithelioid cell tumors, characterized by spindle and epithelioid cells with smooth muscle and melanocytic differentiation. LAM cells infiltrate the lungs, producing multiple, bilateral lesions rich in lymphatic channels and forming cysts, leading to respiratory insufficiency. Here we used antibodies against four lymphatic endothelial markers—podoplanin (detected by D2-40), prospero homeobox 1 (PROX1), vascular endothelial growth factor receptor 3 (VEGFR-3), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1)—to determine whether LAM cells show lymphatic differentiation. Twelve of 12 diagnostic biopsy specimens (early-stage LAM) and 19 of 19 explants (late-stage LAM) showed immunopositivity for D2-40 in most neoplastic cells. PROX1, VEGFR-3, and LYVE1 immunoreactivity varied from scarce in the early stage to abundant in the late stage. Lymphatic endothelial, smooth muscle, and melanocytic markers were partially co-localized. These findings indicate that lymphatic endothelial differentiation is a feature of LAM and provide evidence of a previously unidentified third lineage of differentiation in this neoplasm. This study has implications for the histological diagnosis of LAM, the origin of the neoplastic cells, and potential future treatment with drugs targeting lymphangiogenesis.