In vivo phage display identifies novel peptides for cardiac targeting.

Heart failure remains a leading cause of mortality. Therapeutic intervention for heart failure would benefit from targeted delivery to the damaged heart tissue. Here, we applied in vivo peptide phage display coupled with high-throughput Next-Generation Sequencing (NGS) and identified peptides specifically targeting damaged cardiac tissue.

Global species delimitation of the cosmopolitan marine littoral earthworm Pontodrilus litoralis (Grube, 1855).

The marine littoral earthworm Pontodrilus litoralis (Grube, 1855) is widely distributed and is reported as a single species. This study utilized an integrative taxonomic approach based upon morphological examination, phylogenetic reconstruction, and molecular species delimitation, to test whether the taxon is a single species or a species complex. For this, a total of 114 P.

Cryptic carnivores: Intercontinental sampling reveals extensive novel diversity in a genus of freshwater annelids.

Freshwater annelids are globally widespread in aquatic ecosystems, but their diversity is severely underestimated. Obvious morphological features to define taxa are sparse, and molecular phylogenetic analyses regularly discover cryptic diversity within taxa. Despite considerable phylogenetic work on certain clades, many groups of freshwater annelids remain poorly understood.

Psychedelic drug use and schizotypy in young adults.

Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n = 1032) with a special focus on young (18-35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders.

Testing species hypotheses for Fridericia magna, an enchytraeid worm (Annelida: Clitellata) with great mitochondrial variation.

Background: Deep mitochondrial divergences were observed in Scandinavian populations of the terrestrial to semi-aquatic annelid Fridericia magna (Clitellata: Enchytraeidae). This raised the need for testing whether the taxon is a single species or a complex of cryptic species.

Results: A total of 62 specimens from 38 localities were included in the study, 44 of which were used for species delimitation.

Aligned nanofiber scaffolds improve functionality of cardiomyocytes differentiated from human induced pluripotent stem cell-derived cardiac progenitor cells.

Cardiac progenitor cells (CPCs), capable of differentiating into multiple cardiac cell types including cardiomyocytes (CMs), endothelial cells, and smooth muscle cells, are promising candidates for cardiac repair/regeneration. In vitro model systems where cells are grown in a more in vivo-like environment, such as 3D cultures, have been shown to be more predictive than 2D culture for studying cell biology and disease pathophysiology. In this report, we focused on using Wnt inhibitors to study the differentiation of human iPSC-CPCs under 2D or 3D culture conditions by measuring marker protein and gene expression as well as intracellular Ca oscillation.

A high-content, in vitro cardiac fibrosis assay for high-throughput, phenotypic identification of compounds with anti-fibrotic activity.

A key feature in the pathogenesis of heart failure is cardiac fibrosis, but effective treatments that specifically target cardiac fibrosis are currently not available. A major impediment to progress has been the lack of reliable in vitro models with sufficient throughput to screen for activity against cardiac fibrosis. Here, we established cell culture conditions in micro-well format that support extracellular deposition of mature collagen from primary human cardiac fibroblasts - a hallmark of cardiac fibrosis.

Identification and analyses of inhibitors targeting apolipoprotein(a) kringle domains KIV-7, KIV-10, and KV provide insight into kringle domain function.

Increased plasma concentrations of lipoprotein(a) (Lp(a)) are associated with an increased risk for cardiovascular disease. Lp(a) is composed of apolipoprotein(a) (apo(a)) covalently bound to apolipoprotein B of low-density lipoprotein (LDL). Many of apo(a)'s potential pathological properties, such as inhibition of plasmin generation, have been attributed to its main structural domains, the kringles, and have been proposed to be mediated by their lysine-binding sites.

Discovery of retinoic acid receptor agonists as proliferators of cardiac progenitor cells through a phenotypic screening approach.

Identification of small molecules with the potential to selectively proliferate cardiac progenitor cells (CPCs) will aid our understanding of the signaling pathways and mechanisms involved and could ultimately provide tools for regenerative therapies for the treatment of post-MI cardiac dysfunction. We have used an in vitro human induced pluripotent stem cell-derived CPC model to screen a 10,000-compound library containing molecules representing different target classes and compounds reported to modulate the phenotype of stem or primary cells. The primary readout of this phenotypic screen was proliferation as measured by nuclear count.

Effect of clinically relevant doses of vortioxetine and citalopram on serotonergic PET markers in the nonhuman primate brain.

Vortioxetine is a multimodal antidepressant approved for treatment of major depressive disorder. Preclinical studies have demonstrated that the mechanism of action of vortioxetine might be different from selective serotonin reuptake inhibitors (SSRIs), including larger serotonin (5-HT) release and direct modulation of several 5-HT receptors. In the current positron emission tomography (PET) study, we evaluated the mechanism of action of vortioxetine by comparing its effect to the SSRI citalopram on the binding of [C]AZ10419369 to the 5-HT receptor in the nonhuman primate brain.

Promoting intestinal lymphatic transport targets a liver-X receptor (LXR) agonist (WAY-252,623) to lymphocytes and enhances immunomodulation.

Lymphocytes play a central role in the pathology of a range of chronic conditions such as autoimmune disease, transplant rejection, leukemia, lymphoma HIV/AIDs and cardiometabolic diseases such as atherosclerosis. Current treatments for lymphocyte-associated conditions are incompletely effective and/or complicated by a range of off-target toxicities. One major challenge is poor drug access to lymphocytes via the systemic blood and this may be attributed, at least in part, to the fact that lymphocytes are concentrated within lymph fluid and lymphoid tissues, particularly in gut-associated lymphatics.

A new Scandinavian Chamaedrilus species (Clitellata: Enchytraeidae), with additional notes on others.

Chamaedrilus (earlier referred to as Cognettia) is a well-known genus of terrestrial and limnic enchytraeids, currently with 19 known species in the world. Some of its species are morphologically cryptic and can only be identified using genetic (DNA) information. Many of them reproduce asexually, and the prevalence of sexual mature individuals is generally low in the populations.

Green light to an integrative view of Microscolex phosphoreus (Dugès, 1837) (Annelida: Clitellata: Acanthodrilidae).

The small synanthropic and peregrine earthworm Microscolex phosphoreus (Dugès, 1837) is reported for the first time from Siberia. Morphological and DNA barcode (COI) analyses of this and widely separate samples worldwide demonstrate that, as currently identified, M. phosphoreus is a heterogeneous taxon, with divergent lineages occurring often in the same locality and hardly providing geographically structured genetic signals.

Biocompatible, Purified mRNA Improves Cardiac Function after Intracardiac Injection 1 Week Post-myocardial Infarction in Swine.

mRNA can direct dose-dependent protein expression in cardiac muscle without genome integration, but to date has not been shown to improve cardiac function in a safe, clinically applicable way. Herein, we report that a purified and optimized mRNA in a biocompatible citrate-saline formulation is tissue specific, long acting, and does not stimulate an immune response. In small- and large-animal, permanent occlusion myocardial infarction models, mRNA improves systolic ventricular function and limits myocardial damage.

Fenfluramine Reduces [11C]Cimbi-36 Binding to the 5-HT2A Receptor in the Nonhuman Primate Brain.

Background: [11C]Cimbi-36 is a serotonin 2A receptor agonist positron emission tomography radioligand that has recently been examined in humans. The binding of agonist radioligand is expected to be more sensitive to endogenous neurotransmitter concentrations than antagonist radioligands. In the current study, we compared the effect of serotonin releaser fenfluramine on the binding of [11C]Cimbi-36, [11C]MDL 100907 (a serotonin 2A receptor antagonist radioligand), and [11C]AZ10419369 (a serotonin 1B receptor partial agonist radioligand with established serotonin sensitivity) in the monkey brain.

Multi-locus phylogenetic analysis of the genus Limnodrilus (Annelida: Clitellata: Naididae).

Limnodrilus species are annelid worms distributed worldwide in various freshwater sediments. The systematics of Limnodrilus has chiefly been based on morphology, but the genus has not been subject to any closer phylogenetic studies over the past two decades. To reconstruct the evolutionary history of Limnodrilus, and to assess the monophyly of this genus and its systematic position within the subfamily Tubificinae (Annelida: Clitellata: Naididae), 45 Limnodrilus specimens, representing 19 species, and 35 other naidid species (representing 24 genera) were sampled.

Characterization of [C]Lu AE92686 as a PET radioligand for phosphodiesterase 10A in the nonhuman primate brain.

Purpose: [C]Lu AE92686 is a positron emission tomography (PET) radioligand that has recently been validated for examining phosphodiesterase 10A (PDE10A) in the human striatum. [C]Lu AE92686 has high affinity for PDE10A (IC  = 0.39 nM) and may also be suitable for examination of the substantia nigra, a region with low density of PDE10A.

Cryptic speciation and limited hybridization within Lumbricus earthworms (Clitellata: Lumbricidae).

Cryptic mitochondrial (mt) lineages are known to exist in the earthworm morphospecies Lumbricus rubellus and L. terrestris. The latter was recently split into two species, L.

Barcoding gap, but no support for cryptic speciation in the earthworm Aporrectodea longa (Clitellata: Lumbricidae).

DNA-barcoding, using the mitochondrial marker COI, has been found successful for the identification of specimens in many animal groups, but may not be suited for species discovery and delimitation if used alone. In this study, we investigate whether two observed COI haplogroups in the earthworm Aporrectodea longa correspond to two cryptic species or if the variation is intraspecific. This is done by complementing COI with two nuclear markers, ITS2 and Histone 3.

Corrigenda: Martinsson S, Rota E, Erséus C (2015) On the identity of Chamaedrilusglandulosus (Michaelsen, 1888) (Clitellata, Enchytraeidae), with the description of a new species. ZooKeys 501: 1-14. doi: 10.3897/zookeys.501.9279.

[This corrects the article DOI: 10.3897/zookeys.501.

On the identity of Chamaedrilusglandulosus (Michaelsen, 1888) (Clitellata, Enchytraeidae), with the description of a new species.

The taxonomy of Chamaedrilusglandulosus (Michaelsen, 1888) s. l., most commonly known previously as Cognettiaglandulosa, is revised.

Ancistrocerus waldenii waldenii (Viereck 1906) (Hymenoptera: Vespidae, Eumeninae), a new addition to the fauna of Greenland.

Ancistrocerus waldenii waldenii (Viereck 1906) is newly recorded from West Greenland. This is a new northern limit for the species.

A simple method for assessing free brain/free plasma ratios using an in vitro model of the blood brain barrier.

Historically, the focus has been to use in vitro BBB models to optimize rate of drug delivery to the CNS, whereas total in vivo brain/plasma ratios have been used for optimizing extent. However, these two parameters do not necessarily show good correlations with receptor occupancy data or other pharmacological readouts. In line with the free drug hypothesis, the use of unbound brain concentrations (Cu,br) has been shown to provide the best correlations with pharmacological data.