Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection.

Viruses that are typically benign sometimes invade the brainstem in otherwise healthy children. We report bi-allelic DBR1 mutations in unrelated patients from different ethnicities, each of whom had brainstem infection due to herpes simplex virus 1 (HSV1), influenza virus, or norovirus. DBR1 encodes the only known RNA lariat debranching enzyme. We show that DBR1 expression is ubiquitous, but strongest in the spinal cord and brainstem. We also show that all DBR1 mutant alleles are severely hypomorphic, in terms of expression and function. The fibroblasts of DBR1-mutated patients contain higher RNA lariat levels than control cells, this difference becoming even more marked during HSV1 infection. Finally, we show that the patients' fibroblasts are highly susceptible to HSV1. RNA lariat accumulation and viral susceptibility are rescued by wild-type DBR1. Autosomal recessive, partial DBR1 deficiency underlies viral infection of the brainstem in humans through the disruption of tissue-specific and cell-intrinsic immunity to viruses.

Herpesviruses assimilate kinesin to produce motorized viral particles.

Neurotropic alphaherpesviruses initiate infection in exposed mucosal tissues and, unlike most viruses, spread rapidly to sensory and autonomic nerves where life-long latency is established1. Recurrent infections arise sporadically from the peripheral nervous system throughout the life of the host, and invasion of the central nervous system may occur, with severe outcomes2. These viruses directly recruit cellular motors for transport along microtubules in nerve axons, but how the motors are manipulated to deliver the virus to neuronal nuclei is not understood. Here, using herpes simplex virus type I and pseudorabies virus as model alphaherpesviruses, we show that a cellular kinesin motor is captured by virions in epithelial cells, carried between cells, and subsequently used in neurons to traffic to nuclei. Viruses assembled in the absence of kinesin are not neuroinvasive. The findings explain a critical component of the alphaherpesvirus neuroinvasive mechanism and demonstrate that these viruses assimilate a cellular protein as an essential proviral structural component. This principle of viral assimilation may prove relevant to other virus families and offers new strategies to combat infection.

The HSV-1 pUL37 protein promotes cell invasion by regulating the kinesin-1 motor.

Neurotropic alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), recruit microtubule motor proteins to invade cells. The incoming viral particle traffics to nuclei in a two-step process. First, the particle uses the dynein-dynactin motor to sustain transport to the centrosome. In neurons, this step is responsible for long-distance retrograde axonal transport and is an important component of the neuroinvasive property shared by these viruses. Second, a kinesin-dependent mechanism redirects the particle from the centrosome to the nucleus. We have reported that the kinesin motor used during the second step of invasion is assimilated into nascent virions during the previous round of infection. Here, we report that the HSV-1 pUL37 tegument protein suppresses the assimilated kinesin-1 motor during retrograde axonal transport. Region 2 (R2) of pUL37 was required for suppression and functioned independently of the autoinhibitory mechanism native to kinesin-1. Furthermore, the motor domain and proximal coiled coil of kinesin-1 were sufficient for HSV-1 assimilation, pUL37 suppression, and nuclear trafficking. pUL37 localized to the centrosome, the site of assimilated kinesin-1 activation during infection, when expressed in cells in the absence of other viral proteins; however, pUL37 did not suppress kinesin-1 in this context. These results indicate that the pUL37 tegument protein spatially and temporally regulates kinesin-1 via the amino-terminal motor region in the context of the incoming viral particle.

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex.

Breathing behaviour involves the generation of normal breaths (eupnoea) on a timescale of seconds and sigh breaths on the order of minutes. Both rhythms emerge in tandem from a single brainstem site, but whether and how a single cell population can generate two disparate rhythms remains unclear. We posit that recurrent synaptic excitation in concert with synaptic depression and cellular refractoriness gives rise to the eupnoea rhythm, whereas an intracellular calcium oscillation that is slower by orders of magnitude gives rise to the sigh rhythm. A mathematical model capturing these dynamics simultaneously generates eupnoea and sigh rhythms with disparate frequencies, which can be separately regulated by physiological parameters. We experimentally validated key model predictions regarding intracellular calcium signalling. All vertebrate brains feature a network oscillator that drives the breathing pump for regular respiration. However, in air-breathing mammals with compliant lungs susceptible to collapse, the breathing rhythmogenic network may have refashioned ubiquitous intracellular signalling systems to produce a second slower rhythm (for sighs) that prevents atelectasis without impeding eupnoea. KEY POINTS: A simplified activity-based model of the preBötC generates inspiratory and sigh rhythms from a single neuron population. Inspiration is attributable to a canonical excitatory network oscillator mechanism. Sigh emerges from intracellular calcium signalling. The model predicts that perturbations of calcium uptake and release across the endoplasmic reticulum counterintuitively accelerate and decelerate sigh rhythmicity, respectively, which was experimentally validated. Vertebrate evolution may have adapted existing intracellular signalling mechanisms to produce slow oscillations needed to optimize pulmonary function in mammals.

Endosperm-based incompatibilities in hybrid monkeyflowers.

Endosperm is an angiosperm innovation central to their reproduction whose development, and thus seed viability, is controlled by genomic imprinting, where expression from certain genes is parent-specific. Unsuccessful imprinting has been linked to failed inter-specific and inter-ploidy hybridization. Despite their importance in plant speciation, the underlying mechanisms behind these endosperm-based barriers remain poorly understood. Here, we describe one such barrier between diploid Mimulus guttatus and tetraploid Mimulus luteus. The two parents differ in endosperm DNA methylation, expression dynamics, and imprinted genes. Hybrid seeds suffer from underdeveloped endosperm, reducing viability, or arrested endosperm and seed abortion when M. guttatus or M. luteus is seed parent, respectively, and transgressive methylation and expression patterns emerge. The two inherited M. luteus subgenomes, genetically distinct but epigenetically similar, are expressionally dominant over the M. guttatus genome in hybrid embryos and especially their endosperm, where paternal imprints are perturbed. In aborted seeds, de novo methylation is inhibited, potentially owing to incompatible paternal instructions of imbalanced dosage from M. guttatus imprints. We suggest that diverged epigenetic/regulatory landscapes between parental genomes induce epigenetic repatterning and global shifts in expression, which, in endosperm, may uniquely facilitate incompatible interactions between divergent imprinting schemes, potentially driving rapid barriers.

Mononuclear η6-arene ruthenium(II) complexes with pyrazolyl-pyridazine ligands: synthesis, CT-DNA binding, reactivity towards glutathione, and cytotoxicity.

Organometallic η6-arene ruthenium(II) complexes with 3-chloro-6-(1H-pyrazol-1-yl)pyridazine (Ru1, Ru2, and Ru5) and 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (Ru3-4) N,N' heterocyclic and η6-arene (cymene (Ru1-4) or toluene (Ru 5)) have been synthesized. The ruthenium(II) complexes have common "three-legged piano-stool" pseudo-octahedral structures known for half-sandwich complexes. Evolution of their UV-Visible absorption spectra in PBS buffer or DMSO over 24 h confirmed their good solvolysis stability. Titrations of the complexes with the calf thymus DNA (CT-DNA) were monitored using UV-Visible absorption and fluorescence spectroscopies. The complexes interact moderately with CT-DNA and their binding constants are in the order of 104 M-1. Competitive binding of the complexes to a DNA-Hoechst 33,258 depicted competitive displacement of Hoechst from DNA's minor grooves. These complexes bind to glutathione forming GSH-adducts through S coordination by replacement of a halide, with the iodo-analogues having higher binding constants than the chloro-complexes. Cyclic voltammograms of the complexes exhibited one electron-transfer quasi-reversible process. Trends in the molecular docking data of Ru1-5/DNA were similar to those for DNA binding constants. Of the five, only Ru1, Ru3 and Ru5 showed some activity (moderate) against the MCF-7 breast cancer cells with IC50 values in the range of 59.2-39.9 for which Ru5 was the most active. However, the more difficult-to-treat cell line, MDA-MB 231 cell was recalcitrant to the treatment by these complexes.

Epilepsy phenotype and its reproducibility after lateral fluid percussion-induced traumatic brain injury in rats: Multicenter EpiBioS4Rx study project 1.

OBJECTIVE: This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites. METHODS: A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis. RESULTS: A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites). SIGNIFICANCE: The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.

Longitudinal transactions between negative urgency and fasting predict binge eating.

Fasting and negative urgency (the disposition to act rashly when distressed) are risk factors for binge eating. It may be that each influences the other over time to predict binge eating. OBJECTIVE: This study tested whether (1) fasting predicts binge eating through negative urgency, and (2) negative urgency predicts binge eating through fasting. METHOD: Path analysis and mediation tests were used to investigate objectives in n = 302 college women assessed three times over eight months. We controlled for each variable at the previous time point, and concurrent negative affect and body mass index at each time point. RESULTS: Time 1 (T1) fasting predicted elevated negative urgency three months later at Time 2 (T2) and T2 negative urgency predicted increases in binge eating five months later at Time 3 (T3). T2 negative urgency mediated the relationship between T1 fasting and T3 binge eating. T1 negative urgency predicted increases in T2 fasting, which then predicted increases in T3 binge eating. T2 fasting mediated the relationship between T1 negative urgency and T3 binge eating. DISCUSSION: Findings suggest fasting and negative urgency transact to predict binge eating among college women. Interventions targeting negative urgency may prevent or reduce both fasting and binge eating.

Mono- and bilayer smectic liquid crystal ordering in dense solutions of "gapped" DNA duplexes.

Although its mesomorphic properties have been studied for many years, only recently has the molecule of life begun to reveal the true range of its rich liquid crystalline behavior. End-to-end interactions between concentrated, ultrashort DNA duplexes-driving the self-assembly of aggregates that organize into liquid crystal phases-and the incorporation of flexible single-stranded "gaps" in otherwise fully paired duplexes-producing clear evidence of an elementary lamellar (smectic-A) phase in DNA solutions-are two exciting developments that have opened avenues for discovery. Here, we report on a wider investigation of the nature and temperature dependence of smectic ordering in concentrated solutions of various "gapped" DNA (GDNA) constructs. We examine symmetric GDNA constructs consisting of two 48-base pair duplex segments bridged by a single-stranded sequence of 2 to 20 thymine bases. Two distinct smectic layer structures are observed for DNA concentration in the range [Formula: see text] mg/mL. One exhibits an interlayer periodicity comparable with two-duplex lengths ("bilayer" structure), and the other has a period similar to a single-duplex length ("monolayer" structure). The bilayer structure is observed for gap length ≳10 bases and melts into the cholesteric phase at a temperature between 30 °C and 35 °C. The monolayer structure predominates for gap length ≲10 bases and persists to [Formula: see text]C. We discuss models for the two layer structures and mechanisms for their stability. We also report results for asymmetric gapped constructs and for constructs with terminal overhangs, which further support the model layer structures.

The role of parental maladaptive emotion socialization in the risk process for negative urgency and drinking behavior in adolescence.

INTRODUCTION: Negative urgency (the tendency to act rashly when experiencing negative emotions) is a robust risk factor for a number of problem behaviors, including early adolescent drinking. Little is known about the factors that precede the development of negative urgency, and hence the full etiology of this component of risk. The current study aimed to investigate the possibility that facets of childhood maladaptive emotion socialization (the tendency for children's expressions of emotions to be met with punishment, minimized, or invoke a reaction of distress from their parents/caretakers) increases risk for the development of negative urgency and drinking behavior. METHOD: Self-report measures of negative urgency, subfacets of maladaptive emotion socialization, and drinking behavior were collected during the 2021-2022 academic year from a sample of 428 high school students (mean age = 14.7, SD = 0.09, 44% female), assessed twice over the course of a semester, reflecting a 4-month longitudinal window. RESULTS: Distress emotion socialization predicted increases in negative urgency, minimizing predicted decreases in negative urgency, and punitive did not provide significant prediction. Additionally, results found that higher levels of both negative urgency and distress emotion socialization increased adolescents' likelihood of having tried alcohol. These processes were invariant across race and gender. CONCLUSIONS: The present study may inform the future creation of prevention and intervention efforts aimed at reducing maladaptive emotion socialization and increasing adaptive emotion socialization. Successful reductions in negative urgency as a consequence of increased adaptive emotion socialization may then lead to decreases in adolescent drinking and other impulsigenic behaviors.

Ontogeny of the Cytochrome P450 Superfamily in the Ornate Spiny Lobster (Panulirus ornatus).

Cytochrome P450s (CYP450s) are a versatile superfamily of enzymes known to undergo rapid evolution. They have important roles across growth and development pathways in crustaceans, although it is difficult to characterise orthologs between species due to their sequence diversity. Conserved CYP450s enzymes in crustaceans are those associated with ecdysteroidogenesis: synthesising and breaking down the active moult hormone, 20-hydroxyecdysone. The complex life cycle of the ornate spiny lobster, Panulirus ornatus, relies on moulting in order to grow and develop. Many of these diverse life stages have been analysed to establish a comprehensive transcriptomic database for this species. The transcripts putatively encoding for CYP450s were mapped using transcriptomic analysis and identified across growth and development stages. With the aid of phylogeny, 28 transcripts of 42 putative P. ornatus CYP450s were annotated, including the well conserved Halloween genes, which are involved in ecdysteroidogenesis. Expression patterns across the life stages determined that only a subset of the CYP450s can be detected in each life stage or tissue. Four Shed transcripts show overlapping expression between metamorphosis and adult tissues, suggesting pleotropic functions of the multiple Shed orthologs within P. ornatus.

Quinolyl-Based PGM Metallarectangles: Antiproliferative Activity, DNA and BSA Protein Interactions, and a Molecular Docking Perspective.

The increased success of small metal-containing molecules as pharmaceutical agents has prompted investigations into the pharmacological activity of a different class of metal-based compounds; supramolecular coordination complexes (SCCs). Such complexes have been extensively investigated for their anticancer activity, with many displaying activities comparable or superior to available clinical chemotherapeutic drugs. Here, we evaluated a series of quinoline-containing binuclear complexes and metallarectangles for their in vitro anticancer activity in the hormone receptor positive MCF-7 and triple negative MDA-MB-231 breast cancer cell lines. The preliminary cytotoxic screen, in the MCF-7 cell line, revealed that the ligand (7-chloro-4-(pyridin-4-yl)quinoline, L) and metallarectangle [{Ir(µ-Cl)(Cp*)}4 (µ-L)2 ](OTf)4 display superior activity to cisplatin, while [{Ru(p-cymene)}4 (µ-η2 -η2 -C2 O4 )2 (µ-L)2 ](OTf)4 was more potent than cisplatin in the triple-negative MDA-MD-231 cell line. Upon evaluation in a multidose screen, ligand L and metallarectangle [{Ir(µ-Cl)(Cp*)}4 (µ-L)2 ](OTf)4 displayed antiproliferative activity almost two-fold greater than cisplatin in the MCF-7 cell line, while [{Ru(p-cymene)}4 (µ-η2 -η2 -C2 O4 )2 (µ-L)2 ](OTf)4 was over two-times more active than cisplatin in the MDA-MB-231 cell line. Additionally, using the non-tumorigenic MCF-12 A breast epithelial cell line, the compounds demonstrate increased selectivity toward breast cancer cells over non-tumorigenic cells. Furthermore, investigations into the interactions of ligand L and selected complexes with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) indicate favourable binding.

Bovine Herpesvirus 1 Invasion of Sensory Neurons by Retrograde Axonal Transport Is Dependent on the pUL37 Region 2 Effector.

Following exposure and replication at mucosal surfaces, most alphaherpesviruses invade the peripheral nervous system by retrograde axonal transport and establish lifelong latent infections in the peripheral ganglia. Reactivation of ganglionic infections is followed by anterograde axonal transport of virions back to body surfaces where viral replication results in disease that can range from moderate to severe in presentation. In the case of bovine herpesvirus 1 (BoHV-1), replication in the epithelial mucosa presents as infectious bovine rhinotracheitis (IBR), a respiratory disease of significant economic impact. In this study, we provide a live-cell analysis of BoHV-1 retrograde axonal transport relative to the model alphaherpesvirus pathogen pseudorabies virus (PRV) and demonstrate that this critical neuroinvasive step is conserved between the two viruses. In addition, we report that the BoHV-1 pUL37 tegument protein supports processive retrograde motion in infected axons and invasion of the calf peripheral nervous system. IMPORTANCE A molecular and cellular understanding of the retrograde axonal transport process that underlies the neuroinvasive properties of the alphaherpesviruses is established from studies of herpes simplex virus and pseudorabies virus. The degree to which this phenotype is conserved in other related viruses has largely not been examined. We provide a time-lapse analysis of the retrograde axonal transport kinetics of bovine herpesvirus 1 and demonstrate that mutation of the pUL37 region 2 effector affords a strategy to produce live-attenuated vaccines for enhanced protection of cattle.

Protective effects of inhaled antioxidants against air pollution-induced pathological responses.

As the public health burden of air pollution continues to increase, new strategies to mitigate harmful health effects are needed. Dietary antioxidants have previously been explored to protect against air pollution-induced lung injury producing inconclusive results. Inhaled (pulmonary or nasal) administration of antioxidants presents a more promising approach as it could directly increase antioxidant levels in the airway surface liquid (ASL), providing protection against oxidative damage from air pollution. Several antioxidants have been shown to exhibit antioxidant, anti-inflammatory, and anti-microbial properties in in vitro and in vivo models of air pollution exposure; however, little work has been done to translate these basic research findings into practice. This narrative review summarizes these findings and data from human studies using inhaled antioxidants in response to air pollution, which have produced positive results, indicating further investigation is warranted. In addition to human studies, cell and murine studies should be conducted using more relevant models of exposure such as air-liquid interface (ALI) cultures of primary cells and non-aqueous apical delivery of antioxidants and pollutants. Inhalation of antioxidants shows promise as a protective intervention to prevent air pollution-induced lung injury and exacerbation of existing lung disease.

Collaborative cross strain CC011/UncJ as a novel mouse model of T2-high, severe asthma.

Among asthmatics, there is significant heterogeneity in the clinical presentation and underlying pathophysiological mechanisms, leading to the recognition of multiple disease endotypes (e.g., T2-high vs. T2-low). This heterogeneity extends to severe asthmatics, who may struggle to control symptoms even with high-dose corticosteroid treatment and other therapies. However, there are limited mouse models available to model the spectrum of severe asthma endotypes. We sought to identify a new mouse model of severe asthma by first examining responses to chronic allergen exposure among strains from the Collaborative Cross (CC) mouse genetics reference population, which contains greater genetic diversity than other inbred strain panels previously used for models of asthma. Mice from five CC strains and the often-used classical inbred strain BALB/cJ were chronically exposed to house dust mite (HDM) allergen for five weeks followed by measurements of airway inflammation. CC strain CC011/UncJ (CC011) exhibited extreme responses to HDM including high levels of airway eosinophilia, elevated lung resistance, and extensive airway wall remodeling, and even fatalities among ~ 50% of mice prior to study completion. Compared to BALB/cJ mice, CC011 mice had stronger Th2-mediated airway responses demonstrated by significantly elevated total and HDM-specific IgE and increased Th2 cytokines during tests of antigen recall, but not enhanced ILC2 activation. Airway eosinophilia in CC011 mice was completely dependent upon CD4+ T-cells. Notably, we also found that airway eosinophilia in CC011 mice was resistant to dexamethasone steroid treatment. Thus, the CC011 strain provides a new mouse model of T2-high, severe asthma driven by natural genetic variation likely acting through CD4+ T-cells. Future studies aimed at determining the genetic basis of this phenotype will provide new insights into mechanisms underlying severe asthma.

Structure Property Relationship of Micellar Waterborne Poly(Urethane-Urea): Tunable Mechanical Properties and Controlled Release Profiles with Amphiphilic Triblock Copolymers.

Waterborne polyurethane (WPU) has attracted significant interest as a promising alternative to solvent-based polyurethane (SPU) due to its positive impact on safety and sustainability. However, significant limitations of WPU, such as its weaker mechanical strength, limit its ability to replace SPU. Triblock amphiphilic diols are promising materials to enhance the performance of WPU due to their well-defined hydrophobic-hydrophilic structures. Yet, our understanding of the relationship between the hydrophobic-hydrophilic arrangements of triblock amphiphilic diols and the physical properties of WPU remains limited. In this study, we show that by controlling the micellar structure of WPU in aqueous solution via the introduction of triblock amphiphilic diols, the postcuring efficiency and the resulting mechanical strength of WPU can be significantly enhanced. Small-angle neutron scattering confirmed the microstructure and spatial distribution of hydrophilic and hydrophobic segments in the engineered WPU micelles. In addition, we show that the control of the WPU micellar structure through triblock amphiphilic diols renders WPU attractive in the applications of controlled release, such as drug delivery. Here, curcumin was used as a model hydrophobic drug, and the drug release behavior from WPU-micellar-based drug delivery systems was characterized. It was found that curcumin-loaded WPU drug delivery systems were highly biocompatible and exhibited antibacterial properties in vitro. Furthermore, the sustained release profile of the drug was found to be dependent on the structure of the triblock amphiphilic diols, suggesting the possibility of controlling the drug release profile via the selection of triblock amphiphilic diols. This work shows that by shedding light on the structure-property relationship of triblock amphiphilic diol-containing WPU micelles, we may enhance the applicability of WPU systems and move closer to realizing their promising potential in real-life applications.

Pairing statistics and melting of random DNA oligomers: Finding your partner in superdiverse environments.

Understanding of the pairing statistics in solutions populated by a large number of distinct solute species with mutual interactions is a challenging topic, relevant in modeling the complexity of real biological systems. Here we describe, both experimentally and theoretically, the formation of duplexes in a solution of random-sequence DNA (rsDNA) oligomers of length L = 8, 12, 20 nucleotides. rsDNA solutions are formed by 4L distinct molecular species, leading to a variety of pairing motifs that depend on sequence complementarity and range from strongly bound, fully paired defectless helices to weakly interacting mismatched duplexes. Experiments and theory coherently combine revealing a hybridization statistics characterized by a prevalence of partially defected duplexes, with a distribution of type and number of pairing errors that depends on temperature. We find that despite the enormous multitude of inter-strand interactions, defectless duplexes are formed, involving a fraction up to 15% of the rsDNA chains at the lowest temperatures. Experiments and theory are limited here to equilibrium conditions.

Unravelling the neuropeptidome of the ornate spiny lobster Panulirus ornatus: A focus on peptide hormones and their processing enzymes expressed in the reproductive tissues.

Neuropeptides are commonly produced in the neural tissues yet can have effects on far-reaching targets, with varied biological responses. We describe here the neuropeptidome of the ornate spiny lobster, Panulirus ornatus, a species of emerging importance to closed-system aquaculture, with a focus on peptide hormones produced by the reproductive tissues. Transcripts for a precursor to one neuropeptide, adipokinetic hormone/corazonin-related peptide (ACP) were identified in high numbers in the sperm duct of adult spiny lobsters suggesting a role for ACP in the reproduction of this species. Neuropeptide production in the sperm duct may be linked with physiological control of spermatophore production in the male, or alternatively may function in signalling to the female. The enzymes which process nascent neuropeptide precursors into their mature, active forms have seldom been studied in decapods, and never before at the multi-tissue level. We have identified transcripts for multiple members of the proprotein convertase subtisilin/kexin family in the ornate spiny lobster, with some enzymes showing specificity to certain tissues. In addition, other enzyme transcripts involved with neuropeptide processing are identified along with their tissue and life stage expression patterns.

Pathways of personality and learning risk for addictive behaviors: A systematic review of mediational research on the acquired preparedness model.

OBJECTIVE: The Acquired Preparedness (AP) model proposes that impulsive personality traits predispose some individuals to learn certain behavior-outcome associations (expectancies), and that these expectancies in turn influence the escalation of risky behaviors. This theory has been applied to the development of behaviors such as drinking, drug use, gambling, and disordered eating. In the current study, we aimed to summarize empirical tests of this model over the 20 years since it was proposed. METHOD: We used a descriptive approach to summarize tests of mediation across 50 studies involving n = 21,715 total participants. RESULTS: We observed a consistent effect of personality on expectancies (median effect size = .22), of expectancies on behavior (.24), and a small mediated effect (.05) of personality on behavior via expectancies. Impulsive traits that involve positive or negative affect showed the most consistent support for AP, as did positive expectancies. Most studies testing AP focused on alcohol, but research on other behaviors also showed support for AP. CONCLUSIONS: The literature appears to support a small mediated effect consistent with the AP model. Future research should continue to clarify which AP pathways are most influential in explaining risky behaviors, and supplement correlational research with experimental and quasi-experimental designs.

Heterogeneous origins and functions of mouse skeletal muscle-resident macrophages.

Tissue-resident macrophages can originate from embryonic or adult hematopoiesis. They play important roles in a wide range of biological processes including tissue remodeling during organogenesis, organ homeostasis, repair following injury, and immune response to pathogens. Although the origins and tissue-specific functions of resident macrophages have been extensively studied in many other tissues, they are not well characterized in skeletal muscle. In the present study, we have characterized the ontogeny of skeletal muscle-resident macrophages by lineage tracing and bone marrow transplant experiments. We demonstrate that skeletal muscle-resident macrophages originate from both embryonic hematopoietic progenitors located within the yolk sac and fetal liver as well as definitive hematopoietic stem cells located within the bone marrow of adult mice. Single-cell-based transcriptome analyses revealed that skeletal muscle-resident macrophages are distinctive from resident macrophages in other tissues as they express a distinct complement of transcription factors and are composed of functionally diverse subsets correlating to their origins. Functionally, skeletal muscle-resident macrophages appear to maintain tissue homeostasis and promote muscle growth and regeneration.