Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary-Child (PAD-C) and Pediatric Asthma Diary-Observer (PAD-O).

Background: Pediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration's (FDA's) regulatory guidance for evaluating clinical benefit in treatment trials.

Measuring dengue illness intensity: Development and content validity of the dengue virus daily diary (DENV-DD).

Background: Dengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations.

Biochronology of South African hominin-bearing sites: A reassessment using cercopithecid primates.

Despite recent advances in chronometric techniques (e.g., Uranium-Lead [U-Pb], cosmogenic nuclides, electron spin resonance spectroscopy [ESR]), considerable uncertainty remains regarding the age of many Plio-Pleistocene hominin sites, including several in South Africa.

Evaluation of fluorescence-based viability stains in cells dissociated from scleractinian coral Pocillopora damicornis.

The application of established cell viability assays such as the commonly used trypan blue staining method to coral cells is not straightforward due to different culture parameters and different cellular features specific to mammalian cells compared to marine invertebrates. Using Pocillopora damicornis as a model, we characterized the autofluorescence and tested different fluorescent dye pair combinations to identify alternative viability indicators. The cytotoxicity of different representative molecules, namely small organic molecules, proteins and nanoparticles (NP), was measured after 24 h of exposure using the fluorescent dye pair Hoechst 33342 and SYTOX orange.

A comparison of faecal glucocorticoid metabolite concentration and gut microbiota diversity in bonobos ().

Sex, age, diet, stress and social environment have all been shown to influence the gut microbiota. In several mammals, including humans, increased stress is related to decreasing gut microbial diversity and may differentially impact specific taxa. Recent evidence from gorillas shows faecal glucocorticoid metabolite concentration (FGMC) did not significantly explain gut microbial diversity, but it was significantly associated with the abundance of the family Anaerolineaceae.

Lethal neonatal respiratory failure due to biallelic variants in BBS1 and monoallelic variant in TTC21B.

Background: Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive ciliopathy characterized by early onset retinal dystrophy, renal anomalies, postaxial polydactyly, and cognitive impairment with considerable phenotypic heterogeneity. BBS results from biallelic pathogenic variants in over 20 genes that encode key proteins required for the assembly or primary ciliary functions of the BBSome, a heterooctameric protein complex critical for homeostasis of primary cilia. While variants in BBS1 are most frequently identified in affected individuals, the renal and pulmonary phenotypes associated with BBS1 variants are reportedly less severe than those seen in affected individuals with pathogenic variants in the other BBS-associated genes.

Estimating bonobo () and chimpanzee () evolutionary history from nucleotide site patterns.

Admixture appears increasingly ubiquitous in the evolutionary history of various taxa, including humans. Such gene flow likely also occurred among our closest living relatives: bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). However, our understanding of their evolutionary history has been limited by studies that do not consider all Pan lineages or do not analyze all lineages simultaneously, resulting in conflicting demographic models.

Survey of current group demographics and management practices of bachelor groups of western lowland gorillas (Gorilla gorilla gorilla) across North America.

Recommendations for the successful management and maintenance of bachelor groups of western lowland gorillas (Gorilla gorilla gorilla) in zoological settings have been an increasingly prevalent focus within the zoological community. Over the past two decades, studies have examined the impact of various environmental factors on the stability of bachelor groups, proposed management strategies for bachelor groups, and compared behavioral trends between bachelor and mixed-sex groups. These studies have clearly demonstrated that bachelor groups are complex social units that require specialized management approaches.

Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins.

Lysosomal membrane permeabilization (LMP) and cathepsin release typifies lysosome-dependent cell death (LDCD). However, LMP occurs in most regulated cell death programs suggesting LDCD is not an independent cell death pathway, but is conscripted to facilitate the final cellular demise by other cell death routines. Previously, we demonstrated that Caenorhabditis elegans (C.

A Test of Foraging Models Using Dietary Diversity Indices for the Lomako Forest Bonobos.

Optimal diet and functional response models are used to understand the evolution of primate foraging strategies. The predictions of these models can be tested by examining the geographic and seasonal variation in dietary diversity. Dietary diversity is a useful tool that allows dietary comparisons across differing sampling locations and time periods.

Dominance rank, female choice, and reproductive success in semi-free ranging adult male Japanese macaques (Macaca fuscata).

The assumed evolutionary advantage of dominance is increased reproductive success. However, the efficacy of dominance as a mating strategy may be interrupted by any number of variables including female choice, estrous synchrony, and mating by non-troop males. In Japanese macaques (Macaca fuscata), there is evidence both for and against dominance as conferring reproductive success for adult males, with many discussions pointing to the importance of female choice in governing reproductive success in certain populations.

The common ABCA3 variant disrupts AT2 cell quality control and increases susceptibility to lung injury and aberrant remodeling.

ATP-binding cassette class A3 (ABCA3) is a lipid transporter that plays a critical role in pulmonary surfactant function. The substitution of valine for glutamic acid at codon 292 (E292V) produces a hypomorphic variant that accounts for a significant portion of mutations associated with lung disorders spanning from neonatal respiratory distress syndrome and childhood interstitial lung disease to diffuse parenchymal lung disease (DPLD) in adults including pulmonary fibrosis. The mechanisms by which this and similar mutations disrupt alveolar type 2 (AT2) cell homeostasis and cause DPLD are largely unclear.

Biallelic ASCC1 variants including a novel intronic variant result in expanded phenotypic spectrum of spinal muscular atrophy with congenital bone fractures 2 (SMABF2).

Spinal muscular atrophy with congenital bone fractures 2 (SMABF2), a type of arthrogryposis multiplex congenita (AMC), is characterized by congenital joint contractures, prenatal fractures of long bones, and respiratory distress and results from biallelic variants in ASCC1. Here, we describe an infant with severe, diffuse hypotonia, congenital contractures, and pulmonary hypoplasia characteristic of SMABF2, with the unique features of cleft palate, small spleen, transverse liver, and pulmonary thromboemboli with chondroid appearance. This infant also had impaired coagulation with diffuse petechiae and ecchymoses which has only been reported in one other infant with AMC.

Sex differences in bonobo (Pan paniscus) terrestriality: implications for human evolution.

Recent finds in hominin fossil environments place the transition to terrestriality in a wooded or forested habitat. Therefore, forest-dwelling apes can aid in understanding this important evolutionary transition. Sex differences in ape locomotion have been previously attributed to sexual dimorphism or ecological niche differences between males and females.

Variation in Adult Male-Juvenile Affiliative Behavior in Japanese Macaques (Macaca fuscata).

Adult males of some primate species are known to positively interact with juveniles. In cases where paternal certainty is high, these behaviors have been largely attributed to the paternal investment hypothesis. Males have also been observed to interact with nonkin juveniles, which has often been explained in terms of mating effort.

Functional Genomics of Variants.

Rare or private, biallelic variants in the (ATP-binding cassette transporter A3) gene are the most common monogenic cause of lethal neonatal respiratory failure and childhood interstitial lung disease. Functional characterization of fewer than 10% of over 200 disease-associated variants (majority missense) suggests either disruption of ABCA3 protein trafficking (type I) or of ATPase-mediated phospholipid transport (type II). Therapies remain limited and nonspecific.

Functional characterization of four ATP-binding cassette transporter A3 gene (ABCA3) variants.

ABCA3 transports phospholipids across lamellar body membranes in pulmonary alveolar type II cells and is required for surfactant assembly. Rare, biallelic, pathogenic ABCA3 variants result in lethal neonatal respiratory distress syndrome and childhood interstitial lung disease. Qualitative functional characterization of ABCA3 missense variants suggests two pathogenic classes: disrupted intracellular trafficking (type I mutant) or impaired ATPase-mediated phospholipid transport into the lamellar bodies (type II mutant).

Phenotypic expansion of KMT2D-related disorder: Beyond Kabuki syndrome.

Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature.

-Palmitoylation of junctophilin-2 is critical for its role in tethering the sarcoplasmic reticulum to the plasma membrane.

Junctophilins (JPH1-JPH4) are expressed in excitable and nonexcitable cells, where they tether endoplasmic/sarcoplasmic reticulum (ER/SR) and plasma membranes (PM). These ER/SR-PM junctions bring Ca-release channels in the ER/SR and Ca as well as Ca-activated K channels in the PM to within 10-25 nm. Such proximity is critical for excitation-contraction coupling in muscles, Ca modulation of excitability in neurons, and Ca homeostasis in nonexcitable cells.

New Observations of Meat Eating and Sharing in Wild Bonobos (Pan paniscus) at Iyema, Lomako Forest Reserve, Democratic Republic of the Congo.

Bonobos (Pan paniscus) consume a variety of vertebrates, although direct observations remain relatively rare compared to chimpanzees (Pan troglodytes). We report the first direct observations of meat eating and sharing among bonobos at Iyema, Lomako Forest, Democratic Republic of Congo. We collected meat consumption data ad libitum from June to November 2017 over 176.

Behavioral changes following alterations in the composition of a captive bachelor group of western lowland gorillas (Gorilla gorilla gorilla).

Western lowland gorillas (Gorilla gorilla gorilla) in zoos are housed in family or bachelor groups to maximize social opportunities. While wild bachelor groups are transient, all-male groups in zoos may be maintained for many years. Captive bachelor groups need to be carefully monitored, particularly during periods of demographic transition, due to the possibility for escalating aggression.

Coalitional Play Fighting and the Evolution of Coalitional Intergroup Aggression.

Dyadic play fighting occurs in many species, but only humans are known to engage in coalitional play fighting. Dyadic play fighting is hypothesized to build motor skills involved in actual dyadic fighting; thus, coalitional play fighting may build skills involved in actual coalitional fighting, operationalized as forager lethal raiding. If human psychology includes a motivational component that encourages engagement in this type of play, evidence of this play in forager societies is necessary to determine that it is not an artifact of agricultural or industrial conditions.

Infant handling in bonobos (Pan paniscus): Exploring functional hypotheses and the relationship to oxytocin.

Infant handling describes interactions between infants and non-maternal group members and is widespread across mammalian taxa. The expression of infant handling behaviors, defined as any affiliative or agonistic interaction between a group member and an infant, varies considerably among primate species. Several functional hypotheses may explain the adaptive value of infant handling including the Kin Selection hypothesis, which describes handling as a mechanism through which indirect fitness is increased and predicts a bias in handling behaviors directed toward related (genetic) infants; the Alliance Formation hypothesis, which describes handling as a social commodity and predicts females with infants will support handlers during conflict; and the Learning-to-Mother hypothesis, which describes handling as a mechanism through which handlers learn species-specific maternal behaviors and predicts that handling will occur most frequently in immature and nulliparous females.