Phylogenetic and taxonomic revisions of Jurassic sea stars support a delayed evolutionary origin of the Asteriidae.

Background: The superorder Forcipulatacea is a major clade of sea stars with approximately 400 extant species across three orders (Forcipulatida, Brisingida, Zorocallida). Over the past century, the systematics of Forcipulatacea have undergone multiple revisions by various authors, with some considering numerous families such as Asteriidae, Zoroasteridae, Pedicellasteridae, Stichasteridae, Heliasteridae, Labidiasteridae, and Neomorphasteridae, while others recognized only two families (., Asteriidae and Zoroasteridae).

Transposon-sequencing (Tn-seq) of the Candida glabrata reference strain CBS138 reveals epigenetic plasticity, structural variation, and intrinsic mechanisms of resistance to micafungin.

Candida glabrata (also called Nakaseomyces glabratus) is an opportunistic pathogen that can resist common antifungals and rapidly acquire multidrug resistance. A large amount of genetic variation exists between isolates, which complicates generalizations. Portable transposon-sequencing (Tn-seq) methods can efficiently provide genome-wide information on strain differences and genetic mechanisms.

Tn-seq of the reference strain CBS138 reveals epigenetic plasticity, structural variation, and intrinsic mechanisms of resistance to micafungin.

Unlabelled: is an opportunistic pathogen that can resist common antifungals and rapidly acquire multidrug resistance. A large amount of genetic variation exists between isolates, which complicates generalizations. Portable Tn-seq methods can efficiently provide genome-wide information on strain differences and genetic mechanisms.

Calcineurin-dependent contributions to fitness in the opportunistic pathogen .

The protein phosphatase calcineurin is vital for the virulence of the opportunistic fungal pathogen . The host-induced stresses that activate calcineurin signaling are unknown, as are the targets of calcineurin relevant to virulence. To potentially shed light on these processes, millions of transposon insertion mutants throughout the genome of were profiled for fitness defects in the presence of FK506, a specific inhibitor of calcineurin.

Redefining pleiotropic drug resistance in a pathogenic yeast: Pdr1 functions as a sensor of cellular stresses in .

is a prominent opportunistic fungal pathogen of humans. The increasing incidence of infections is attributed to both innate and acquired resistance to antifungals. Previous studies suggest the transcription factor Pdr1 and several target genes encoding ABC transporters are critical elements of pleiotropic defense against azoles and other antifungals.

Redefining Pleiotropic Drug Resistance in a Pathogenic Yeast: Pdr1 Functions as a Sensor of Cellular Stresses in .

Unlabelled: is a prominent opportunistic fungal pathogen of humans. The increasing incidence of infections is attributed to both innate and acquired resistance to antifungals. Previous studies suggest the transcription factor Pdr1 and several target genes encoding ABC transporters are critical elements of pleiotropic defense against azoles and other antifungals.

Ontogeny, evolution and palaeogeographic distribution of the world's largest ammonite Parapuzosia (P.) seppenradensis (Landois, 1895).

The world's largest ammonite, Parapuzosia (P.) seppenradensis (Landois, 1895), fascinated the world ever since the discovery, in 1895, of a specimen of 1.74 metres (m) diameter near Seppenrade in Westfalia, Germany, but subsequent findings of the taxon are exceedingly rare and its systematic position remains enigmatic.

Genome and transcriptome of a pathogenic yeast, Candida nivariensis.

We present a highly contiguous genome and transcriptome of the pathogenic yeast, Candida nivariensis. We sequenced both the DNA and RNA of this species using both the Oxford Nanopore Technologies and Illumina platforms. We assembled the genome into an 11.

The fossil record of the asteroid (Echinodermata) family Chaetasteridae Sladen, 1889 and subfamily Hyalothricinae Fisher, 1911.

The Cretaceous asteroid Arthraster is referred to the living family Chaetasteridae on the basis of similarities in ossicular arrangement in the abactinal disc and arms. Chaetasterina, previously identified as a chaetasterid, is transferred to the family Asterinidae, subfamily Hyalothricinae, and constitutes the first fossil record of the subfamily.

A new comb-star (Asteroidea, Astropectinidae) from the Upper Triassic (Carnian) of China.

A new astropectinid asteroid, Eoastropecten sechuanensis gen. et sp. nov.

Identification of Essential Genes and Fluconazole Susceptibility Genes in by Profiling Transposon Insertions.

Within the budding yeasts, the opportunistic pathogen and other members of the clade have developed virulence traits independently from and To begin exploring the genetic basis of virulence and its innate resistance to antifungals, we launched the transposon from a plasmid and sequenced more than 500,000 different semi-random insertions throughout the genome. With machine learning, we identified 1278 protein-encoding genes (25% of total) that could not tolerate transposon insertions and are likely essential for fitness Interestingly, genes involved in mRNA splicing were less likely to be essential in than their orthologs in , whereas the opposite is true for genes involved in kinetochore function and chromosome segregation. When a pool of insertion mutants was challenged with the first-line antifungal fluconazole, insertions in several known resistance genes (, , , , , , , ) and 15 additional genes (including , , ) became hypersensitive to fluconazole.

An engineered factor Va prevents bleeding induced by direct-acting oral anticoagulants by different mechanisms.

Control of bleeding with direct-acting oral anticoagulants (DOACs) remains an unmet clinical need. Activated superFactor V (superFVa) is an engineered activated protein C (APC)-resistant FVa variant with enhanced procoagulant activity resulting from an A2/A3 domain disulfide bond and was studied here for control of DOAC-induced bleeding. SuperFVa reversed bleeding induced by FXa inhibitors (rivaroxaban, apixaban), and the FIIa inhibitor dabigatran in BalbC mice.

Comparing the utility of in vivo transposon mutagenesis approaches in yeast species to infer gene essentiality.

In vivo transposon mutagenesis, coupled with deep sequencing, enables large-scale genome-wide mutant screens for genes essential in different growth conditions. We analyzed six large-scale studies performed on haploid strains of three yeast species (Saccharomyces cerevisiae, Schizosaccaromyces pombe, and Candida albicans), each mutagenized with two of three different heterologous transposons (AcDs, Hermes, and PiggyBac). Using a machine-learning approach, we evaluated the ability of the data to predict gene essentiality.

Enhanced SLAMF7 Homotypic Interactions by Elotuzumab Improves NK Cell Killing of Multiple Myeloma.

Elotuzumab (Elo) is an IgG monoclonal antibody targeting SLAMF7 (CS1, CRACC, and CD319), which is highly expressed on multiple myeloma (MM) cells, natural killer (NK) cells, and subsets of other leukocytes. By engaging with FcγRIIIA (CD16), Elo promotes potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and macrophage-mediated antibody-dependent cellular phagocytosis (ADCP) toward SLAMF7 MM tumor cells. Relapsed/refractory MM patients treated with the combination of Elo, lenalidomide, and dexamethasone have improved progression-free survival.

Auxin-Inducible Depletion of the Essentialome Suggests Inhibition of TORC1 by Auxins and Inhibition of Vrg4 by SDZ 90-215, a Natural Antifungal Cyclopeptide.

Gene knockout and knockdown strategies have been immensely successful probes of gene function, but small molecule inhibitors (SMIs) of gene products allow much greater time resolution and are particularly useful when the targets are essential for cell replication or survival. SMIs also serve as lead compounds for drug discovery. However, discovery of selective SMIs is costly and inefficient.

Augmentation of Human Monocyte Responses to Lipopolysaccharide by the Protein S and Mer/Tyro3 Receptor Tyrosine Kinase Axis.

Resolution of the inflammatory response requires coordinated regulation of pro- and anti-inflammatory mediator production, together with clearance of recruited inflammatory cells. Many different receptors have been implicated in phagocytosis of apoptotic cells (efferocytosis), including Mer, a receptor tyrosine kinase that can mediate recognition and subsequent internalization of apoptotic cells. In this manuscript, we examine the expression and function of the Tyro3/Axl/Mer (TAM) family of receptors by human monocytes.

Heparin Binding to an Engineered Virus-like Nanoparticle Antagonist.

The anticoagulant activity of heparin administered during medical interventions must be reversed to restore normal clotting, typically by titrating with protamine. Given the acute toxicity associated with protamine, we endeavored to generate safer heparin antagonists by engineering bacteriophage Qβ virus-like particles (VLPs) to display motifs that bind heparin. A particle bearing a single amino acid change from wild-type (T18R) was identified as a promising candidate for heparin antagonism.

Sensitive Visualization of Breast Cancer Using Ratiometric Protease-activatable Fluorescent Imaging Agent, AVB-620.

With the goal of improving intraoperative cancer visualization, we have developed AVB-620, a novel intravenously administered, fluorescent peptide dye conjugate that highlights malignant tissue and is optimized for human use. Matrix metalloproteinases (MMPs) hydrolyze AVB-620 triggering tissue retention and a ratiometric fluorescence color change which is visualized using camera systems capable of imaging fluorescence and white light simultaneously. AVB-620 imaging visualizes primary tumors and demonstrated high diagnostic sensitivity and specificity (both >95%) for identifying breast cancer metastases to lymph nodes in two immunocompetent syngeneic mouse models.

Selective factor VIII activation by the tissue factor-factor VIIa-factor Xa complex.

Safe and effective antithrombotic therapy requires understanding of mechanisms that contribute to pathological thrombosis but have a lesser impact on hemostasis. We found that the extrinsic tissue factor (TF) coagulation initiation complex can selectively activate the antihemophilic cofactor, FVIII, triggering the hemostatic intrinsic coagulation pathway independently of thrombin feedback loops. In a mouse model with a relatively mild thrombogenic lesion, TF-dependent FVIII activation sets the threshold for thrombus formation through contact phase-generated FIXa.

Activation-resistant homozygous protein C R229W mutation causing familial perinatal intracranial hemorrhage and delayed onset of thrombosis.

Introduction: We describe a family with two first-degree cousins who presented with similar phenotypes characterized by neonatal intracranial hemorrhage and subsequent onset of thrombosis.

Patients/methods: We enrolled the two affected patients, five unaffected family members and fifty-five normal controls. Clinical, laboratory, and radiological characteristics of patients were obtained.

Safety, Stability and Pharmacokinetic Properties of (super)Factor Va, a Novel Engineered Coagulation Factor V for Treatment of Severe Bleeding.

Purpose: Activated (super)Factor V ((super)FVa) is a novel engineered FV with excellent prohemostatic efficacy. (Super)FVa has three APC cleavage site mutations and an interdomain disulfide bond. Stability, pharmacokinetics, and immunogenic and thrombogenic potential are reported here.

Phylogeny of the deep-sea cirripede family Scalpellidae (Crustacea, Thoracica) based on shell capitular plate morphology.

A cladistic analysis of 23 extant species of the deep-sea pedunculate cirripede family Scalpellidae was undertaken, based on 61 shell plate characters, and taking the Jurassic-Cretaceous scalpellomorph genus as an out-group. The consensus tree shows progressive morphological change from basal to more derived taxa, but a derived group is marked by major morphological innovation, including 27 character state changes that permit subdivision of the family into two sharply demarcated clades - the more basal group is here placed within a redefined Scalpellinae ( , , , , , and ), and a more derived group named that shows numerous progressive trends in morphology, permitting the recognition of three genera ( , , and ). The phylogeny is independently supported by a recently published multiple DNA marker-based molecular phylogeny.

Improved coagulation and haemostasis in haemophilia with inhibitors by combinations of superFactor Va and Factor VIIa.

Bypassing inhibitors in haemophilia patients is limited to activated (a) Factor(F)VII products. We introduced "FVa activity augmentation" as another bypassing strategy and studied effects of an engineered FVa variant designated superFVa. Procoagulant and clot stabilising properties of superFVa and recombinant human (rh)FVIIa, either alone or in combination, were studied in thrombin generation and clot lysis assays in normal human plasma (NHP) with or without anti-FVIII inhibitors, in haemophilia plasma, and in FVIII-deficient mice or in wild-type mice with anti-FVIII inhibitors.

An engineered factor Va prevents bleeding induced by anticoagulant wt activated protein C.

Objective: An increased risk of bleeding is observed in patients receiving activated protein C (APC), which may be a limiting factor for the application of novel APC therapies. Since APC's therapeutic effects often require its cytoprotective activities on cells but not APC's anticoagulant activities, an agent that specifically antagonizes APC's anticoagulant effects but not its cytoprotective effects could provide an effective means to control concerns for risk of bleeding. We hypothesized that superFVa, an engineered activated FVa-variant that restores hemostasis in hemophilia could reduce APC-induced bleeding.

Chryseobacterium angstadtii sp. nov., isolated from a newt tank.

As part of an undergraduate microbiology course, a yellow-orange-pigmented, Gram-staining negative, rod-shaped, non-motile bacterial strain was isolated from a glass tank housing several red-spotted newts (Notophthalmus viridescens). The sequence of the 16S rRNA gene of this strain, designated KM(T), was 97.4-98.