Globally, songs and instrumental melodies are slower and higher and use more stable pitches than speech: A Registered Report.

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness.

Concurrent prenatal drinking and smoking increases risk for SIDS: Safe Passage Study report.

Background: Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality. Although the rate has plateaued, any unexpected death of an infant is a family tragedy thus finding causes and contributors to risk remains a major public health concern. The primary objective of this investigation was to determine patterns of drinking and smoking during pregnancy that increase risk of SIDS.

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities.

Importance: Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples.

Objective: To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States.

Drinking and smoking patterns during pregnancy: Development of group-based trajectories in the Safe Passage Study.

Precise identification of drinking and smoking patterns during pregnancy is crucial to better understand the risk to the fetus. The purpose of this manuscript is to describe the methodological approach used to define prenatal drinking and smoking trajectories from a large prospective pregnancy cohort, and to describe maternal characteristics associated with different exposure patterns. In the Safe Passage Study, detailed information regarding quantity, frequency, and timing of exposure was self-reported up to four times during pregnancy and at 1 month post-delivery.

A modified Timeline Followback assessment to capture alcohol exposure in pregnant women: Application in the Safe Passage Study.

Prenatal alcohol exposure (PAE) has been linked to poor pregnancy outcomes, yet there is no recognized standard for PAE assessment, and the specific effects of quantity, frequency, and timing remain largely unknown. The Safe Passage Study was designed to investigate the role of PAE in a continuum of poor peri- and postnatal outcomes. The objective of this manuscript is to describe the rationale for, and feasibility of, modifications to the traditional Timeline Followback (TLFB) for collecting PAE information in a large cohort of pregnant women.

Clinical sensitivity and specificity of meconium fatty acid ethyl ester, ethyl glucuronide, and ethyl sulfate for detecting maternal drinking during pregnancy.

Background: We investigated agreement between self-reported prenatal alcohol exposure (PAE) and objective meconium alcohol markers to determine the optimal meconium marker and threshold for identifying PAE.

Methods: Meconium fatty acid ethyl esters (FAEE), ethyl glucuronide (EtG), and ethyl sulfate (EtS) were quantified by LC-MS/MS in 0.1 g meconium from infants of Safe Passage Study participants.

The safe passage study: design, methods, recruitment, and follow-up approach.

Background: The Safe Passage Study is a large, prospective, multidisciplinary study designed to (1) investigate the association between prenatal alcohol exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine the biological basis of the spectrum of phenotypic outcomes from exposure, as modified by environmental and genetic factors that increase the risk of stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders.

Methods: The results provided are based on an interim assessment of 6004 women enrolled, out of the 12,000 projected, from the Northern Plains, US, and Cape Town, South Africa, areas known to be of high risk for maternal drinking during pregnancy. Research objectives, study design, and descriptive statistics, including consent, recruitment, and retention information, are provided.

Quantification of GPCR internalization by single-molecule microscopy in living cells.

Receptor internalization upon ligand stimulation is a key component of a cell's response and allows a cell to correctly sense its environment. Novel fluorescent methods have enabled the direct visualization of the agonist-stimulated G-protein-coupled receptors (GPCR) trafficking in living cells. However, it is difficult to observe internalization of GPCRs in vivo due to intrinsic autofluorescence and cytosolic signals of fluorescently labeled GPCRs.

MicroRNAs: master regulators of ethanol abuse and toxicity?

Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss, and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol's deleterious effects leading to the suggestion that ethanol is a "dirty drug.

Fluorescence resonance energy transfer imaging reveals that chemokine-binding modulates heterodimers of CXCR4 and CCR5 receptors.

Background: Dimerization has emerged as an important feature of chemokine G-protein-coupled receptors. CXCR4 and CCR5 regulate leukocyte chemotaxis and also serve as a co-receptor for HIV entry. Both receptors are recruited to the immunological synapse during T-cell activation.

How human leukocytes track down and destroy pathogens: lessons learned from the model organism Dictyostelium discoideum.

Human leukocytes, including macrophages and neutrophils, are phagocytic immune cells that capture and engulf pathogens and subsequently destroy them in intracellular vesicles. To accomplish this vital task, these leukocytes utilize two basic cell behaviors-chemotaxis for chasing down infectious pathogens and phagocytosis for destroying them. The molecular mechanisms controlling these behaviors are not well understood for immune cells.

Chemotaxis, chemokine receptors and human disease.

Cell migration is involved in diverse physiological processes including embryogenesis, immunity, and diseases such as cancer and chronic inflammatory disease. The movement of many cell types is directed by extracellular gradients of diffusible chemicals. This phenomenon, referred to as "chemotaxis", was first described in 1888 by Leber who observed the movement of leukocytes toward sites of inflammation.

Slamming the DOR on chemokine receptor signaling: heterodimerization silences ligand-occupied CXCR4 and delta-opioid receptors.

Dimerization has emerged as a common mechanism for regulating the function of G protein-coupled receptors (GPCR). Among these are chemokine receptors, which detect various chemokines and regulate a range of physiological process, including immune cell trafficking, cancer cell migration, and neuronal patterning. Homo- and heterodimerization in response to chemokine binding has been shown to be required for the initiation or alteration of signaling by a number of chemokine receptors.

Regulation of G protein-coupled cAMP receptor activation by a hydrophobic residue in transmembrane helix 3.

cAR1, a G protein-coupled cAMP receptor, is essential for multicellular development of Dictyostelium. We previously identified a cAR1-Ile(104) mutant that appeared to be constitutively activated based on its constitutive phosphorylation, elevated affinity for cAMP, and dominant-negative effects on development as well as specific cAR1 pathways that are subject to adaptation. To investigate how Ile(104) might regulate cAR1 activation, we assessed the consequences of substituting it with all other amino acids.

Moving toward understanding eukaryotic chemotaxis.

The discovery in 1947 of directed cell movement in Dictyostelium discoideum quietly gave a birth to a new line of investigation into the molecular basis of chemotaxis. Some 60 years later, D. discoideum continues to be a key model system for the study of eukaryotic chemotaxis as well as an array of other important biological processes.

Constitutively active G protein-coupled receptor mutants block dictyostelium development.

cAR1, a G protein-coupled receptor (GPCR) for cAMP, is required for the multicellular development of Dictyostelium. The activation of multiple pathways by cAR1 is transient because of poorly defined adaptation mechanisms. To investigate this, we used a genetic screen for impaired development to isolate four dominant-negative cAR1 mutants, designated DN1-4.

A cAMP receptor-like G protein-coupled receptor with roles in growth regulation and development.

Dictyostelium discoideum uses G protein-mediated signal transduction for many vegetative and developmental functions, suggesting the existence of G protein-coupled receptors (GPCRs) other than the four known cyclic adenosine monophosphate (cAMP) receptors (cAR1-4). Sequences of the cAMP receptors were used to identify Dictyostelium genes encoding cAMP receptor-like proteins, CrlA-C. Limited sequence identity between these putative GPCRs and the cAMP receptors suggests the Crl receptors are unlikely to be receptors for cAMP.

Two Dictyostelium orthologs of the prokaryotic cell division protein FtsZ localize to mitochondria and are required for the maintenance of normal mitochondrial morphology.

In bacteria, the protein FtsZ is the principal component of a ring that constricts the cell at division. Though all mitochondria probably arose through a single, ancient bacterial endosymbiosis, the mitochondria of only certain protists appear to have retained FtsZ, and the protein is absent from the mitochondria of fungi, animals, and higher plants. We have investigated the role that FtsZ plays in mitochondrial division in the genetically tractable protist Dictyostelium discoideum, which has two nuclearly encoded FtsZs, FszA and FszB, that are targeted to the inside of mitochondria.

The phosphorylated C-terminus of cAR1 plays a role in cell-type-specific gene expression and STATa tyrosine phosphorylation.

cAMP receptors mediate some signaling pathways via coupled heterotrimeric G proteins, while others are G-protein-independent. This latter class includes the activation of the transcription factors GBF and STATa. Within the cellular mounds formed by aggregation of Dictyostelium, micromolar levels of cAMP activate GBF function, thereby inducing the transcription of postaggregative genes and initiating multicellular differentiation.

Phosphorylation of chemoattractant receptors is not essential for chemotaxis or termination of G-protein-mediated responses.

In several G-protein-coupled signaling systems, ligand-induced receptor phosphorylation by specific kinases is suggested to lead to desensitization via mechanisms including receptor/G-protein uncoupling, receptor internalization, and receptor down-regulation. We report here that elimination of phosphorylation of a chemoattractant receptor of Dictyostelium, either by site-directed substitution of the serines or by truncation of the C-terminal cytoplasmic domain, completely prevented agonist-induced loss of ligand binding but did not impair the adaptation of several receptor-mediated responses including the activation of adenylyl and guanylyl cyclases and actin polymerization. In addition, the phosphorylation-deficient receptors were capable of mediating chemotaxis, aggregation, and differentiation.

Agonist-induced loss of ligand binding is correlated with phosphorylation of cAR1, a G protein-coupled chemoattractant receptor from Dictyostelium.

The parallel agonist-induced phosphorylation, alteration in electrophoretic mobility, and loss of ligand binding of a guanine nucleotide-binding regulatory protein (G protein)-coupled chemoattractant receptor from Dictyostelium (cAR1) depend upon a cluster of five C-terminal domain serine residues (Caterina, M. J., Hereld, D.

Occupancy of the Dictyostelium cAMP receptor, cAR1, induces a reduction in affinity which depends upon COOH-terminal serine residues.

Many G-protein-coupled receptors display a rapid decrease in ligand binding following pretreatment with agonist. cAR1, a cAMP receptor expressed early in the developmental program of Dictyostelium, mediates chemotaxis, activation of adenylyl cyclase, and gene expression changes that bring about the aggregation of 10(5) amoebae to form a multicellular structure. Occupancy of cAR1 by cAMP initiates multiple desensitization processes, one of which is an apparent reduction in binding sites.

Localization of ligand-induced phosphorylation sites to serine clusters in the C-terminal domain of the Dictyostelium cAMP receptor, cAR1.

When Dictyostelium cells are stimulated with cyclic adenosine 3',5'-monophosphate (cAMP), the major surface cAMP receptor expressed in early development, cAR1, undergoes a rapid phosphorylation and parallel decrease in electrophoretic mobility which may serve to regulate the activity of this G protein-coupled receptor. Biochemical analyses indicate the electrophoretic mobility shift is caused by phosphorylation of serine residues within the C-terminal cytoplasmic domain. The 18 serines of this domain are grouped in four clusters, designated 1 to 4 (in N- to C-terminal order).