Electrical impedance spectroscopy detects skin barrier dysfunction in childhood atopic dermatitis.

BACKGROUND: Skin barrier dysfunction is associated with the development of atopic dermatitis (AD), however methods to assess skin barrier function are limited. We investigated the use of electrical impedance spectroscopy (EIS) to detect skin barrier dysfunction in children with AD of the CARE (Childhood AlleRgy, nutrition, and Environment) cohort. METHODS: EIS measurements taken at multiple time points from 4 months to 3-year-old children, who developed AD (n = 66) and those who did not (n = 49) were investigated. Using only the EIS measurement and the AD status, we developed a machine learning algorithm that produces a score (EIS/AD score) which reflects the probability that a given measurement is from a child with active AD. We investigated the diagnostic ability of this score and its association with clinical characteristics and age. RESULTS: Based on the EIS/AD score, the EIS algorithm was able to clearly discriminate between healthy skin and clinically unaffected skin of children with active AD (area under the curve 0.92, 95% CI 0.85-0.99). It was also able to detect a difference between healthy skin and AD skin when the child did not have active AD. There was no clear association between the EIS/AD score and the severity of AD or sensitisation to the tested allergens. The performance of the algorithm was not affected by age. CONCLUSIONS: This study shows that EIS can detect skin barrier dysfunction and differentiate skin of children with AD from healthy skin and suggests that EIS may have the ability to predict future AD development.

Prospective evaluation of ultrasound features of magnesium-based bioabsorbable screw resorption in pediatric fractures.

OBJECTIVE: Bioabsorbable magnesium-based alloy screws release gas upon resorption. The resulting findings in the adjacent soft tissues and joints may mimic infection. The aim of the study was to evaluate the ultrasound (US) findings in soft tissues and joints during screw resorption. METHODS: Prospectively acquired US studies from pediatric patients treated with magnesium screws were evaluated for screw head visibility, posterior acoustic shadowing, twinkling artifact, foreign body granuloma, gas (soft tissue, intra-articular), alterations of the skin and subcutaneous fat, perifascial fluid, localized fluid collections, hypervascularization, and joint effusion. RESULTS: Sixty-six US studies of 28 pediatric patients (nfemale = 9, nmale = 19) were included. The mean age of the patients at the time of surgery was 10.84 years; the mean time between surgery and ultrasound was 128.3 days (range = 6-468 days). The screw head and posterior acoustic shadowing were visible in 100% of the studies, twinkling artifact in 6.1%, foreign body granuloma in 92.4%, gas locules in soft tissue in 100% and intra-articular in 18.2%, hyperechogenicity of the subcutaneous fat in 90.9%, cobblestoning of the subcutaneous fat in 24.2%, loss of normal differentiation between the epidermis/dermis and the subcutaneous fat in 57.6%, localized fluid collection in 9.9%, perifascial fluid in 12.1%, hypervascularization in 27.3%, and joint effusion in 18.2%. CONCLUSION: US findings in pediatric patients treated with magnesium screws strongly resemble infection, but are normal findings in the setting of screw resorption. CLINICAL RELEVANCE STATEMENT: Bioabsorbable magnesium-based alloy screws release gas during resorption. The resulting US findings in the adjacent soft tissues and joints in pediatric patients may mimic infection, but are normal findings. KEY POINTS: • Bioabsorbable magnesium-based alloy screws release gas upon resorption. • The resulting ultrasound findings in children's soft tissues and joints closely resemble those of soft tissue infection or osteosynthesis-associated infection. • Be familiar with these ultrasound findings in order to avoid inadvertently misdiagnosing a soft tissue infection or osteosynthesis-associated infection.

Prospective measurement of the width of cerebrospinal fluid spaces by cranial ultrasound in neurologically healthy children aged 0-19 months.

BACKGROUND: Ultrasound (US) is often the first method used to look for brain or cerebrospinal fluid (CSF) space pathologies. Knowledge of normal CSF width values is essential. Most of the available US normative values were established over 20 years ago, were obtained with older equipment, and cover only part of the age spectrum that can be examined by cranial US. This prospective study aimed to determine the normative values of the widths of the subarachnoid and internal CSF spaces (craniocortical, minimal and maximal interhemispheric, interventricular, and frontal horn) for high-resolution linear US probes in neurologically healthy infants and children aged 0-19 months and assess whether subdural fluid collections can be delineated. METHODS: Two radiologists measured the width of the CSF spaces with a conventional linear probe and an ultralight hockey-stick probe in neurologically healthy children not referred for cranial or spinal US. RESULTS: This study included 359 neurologically healthy children (nboys = 178, 49.6%; ngirls = 181, 50.4%) with a median age of 46.0 days and a range of 1-599 days. We constructed prediction plots, including the 5th, 50th, and 95th percentiles, and an interactive spreadsheet to calculate normative values for individual patients. The measurements of the two probes and the left and right sides did not differ, eliminating the need for separate normative values. No subdural fluid collection was detected. CONCLUSION: Normative values for the widths of the subarachnoid space and the internal CSF spaces are useful for evaluating intracranial pathology, especially when determining whether an increase in the subarachnoid space width is abnormal.

Reconstructing the colonization history of Indo-Pacific bottlenose dolphins (Tursiops aduncus) in Northwestern Australia.

Bottlenose dolphins (Tursiops spp.) are found in waters around Australia, with T. truncatus typically occupying deeper, more oceanic habitat, while T. aduncus occur in shallower, coastal waters. Little is known about the colonization history of T. aduncus along the Western Australian coastline; however, it has been hypothesized that extant populations are the result of an expansion along the coastline originating from a source in the north of Australia. To investigate the history of coastal T. aduncus populations in the area, we generated a genomic SNP dataset using a double-digest restriction-site-associated DNA (ddRAD) sequencing approach. The resulting dataset consisted of 103,201 biallelic SNPs for 112 individuals which were sampled from eleven coastal and two offshore sites between Shark Bay and Cygnet Bay, Western Australia. Our population genomic analyses showed a pattern consistent with the proposed source in the north with significant isolation by distance along the coastline, as well as a reduction in genomic diversity measures along the coastline with Shark Bay showing the most pronounced reduction. Our demographic analysis indicated that the expansion of T. aduncus along the coastline began around the last glacial maximum and progressed southwards with the Shark Bay population being founded only 13 kya. Our results are in line with coastal colonization histories inferred for Tursiops globally, highlighting the ability of delphinids to rapidly colonize novel coastal niches as habitat is released during glacial cycle-related global sea level and temperature changes.

Alternative reproductive tactics of unflanged and flanged male orangutans revisited.

In many slowly developing mammal species, males reach sexual maturity well before they develop secondary sexual characteristics. Sexually mature male orangutans have exceptionally long periods of developmental arrest. The two male morphs have been associated with behavioral alternative reproductive tactics, but this interpretation is based on cross-sectional analyses predominantly of Northwest Sumatran populations. Here we present the first longitudinal analyses of behavioral changes of 10 adult males that have been observed in both unflanged and flanged morph. We also analyzed long-term behavioral data on an additional 143 individually identified males from two study sites, Suaq (Sumatra, Pongo abelii) and Tuanan (Borneo, Pongo pygmaeus wurmbii), to assess male mating tactics cross-sectionally in relation to population, male morph (unflanged and flanged), and other socio-ecological factors. Both our longitudinal and cross-sectional results confirm and refine previous cross-sectional accounts of the differences in mating tactics between the unflanged and the flanged male morphs. In the unflanged morph, males exhibit higher sociability, particularly with females, and higher rates of both copulation and sexual coercion than in the flanged morph. Based on our results and those of previous studies showing that females prefer flanged males, and that flanged males have higher reproductive success, we conclude that unflanged males face a trade-off between avoiding male-male contest competition and gaining mating access to females, and thus follow a "best-of-a-bad-job" mating strategy.

Pediatric reference values of anterior visual pathway structures measured with axis-correction on high-resolution 3D T2 fast spin echo sequences.

BACKGROUND: The size of the anterior visual pathway (AVP) structures is affected by patient age and pathology. Normative data is useful when determining whether pathology is present. AVP structures do not respect the standard planes of magnetic resonance (MR) imaging. The aim of this study was to produce normative age-related and axis-corrected data of the AVP structures using multiplanar reformation (MPR) of high-resolution 3D T2-weighted fast spin echo (3D T2w FSE) images. METHODS: For each patient 32 measurements of AVP structures were obtained in 145 children (2 months - 18 years) with normal brain MR studies on high-resolution 3D T2w FSE images adjusted to the axis of each AVP structure. Descriptive statistics were calculated for different age classes and growth models were fitted to the data and assessed for their performance to create a formal statistical model that allows inference beyond the sample. RESULTS: Descriptive statistics were compiled in a reference table and prediction plots in relation to age, height, and body surface area (BSA) were obtained from the best overall performing statistical model, also taking field strength (1.5 vs. 3 T) into account. Intraclass correlation coefficient values were calculated for all variables ranging from 0.474 to 0.967, the most reliable being the transverse diameter of the globe, the maximum diameter of the retrobulbar nerve sheath, the intracranial segment of the optic nerve and the transverse diameter of the chiasm. The maximum retrobulbar diameter of the optic nerve sheath and the lateral superoinferior diameter of the chiasm showed no statistically significant change with age. CONCLUSION: Detailed charts of reference values for AVP structures as well as prediction plots in relation to age, height and BSA were established using axis-corrected measurements from the MPR of high-resolution 3D T2w FSE images. Furthermore, an Excel spreadsheet that allows users to calculate normative values for the 9 AVP structures of key interest is provided as supplementary material.

To drum or not to drum: Selectivity in tree buttress drumming by chimpanzees (Pan troglodytes verus) in the Nimba Mountains, Guinea.

Chimpanzees live in fission-fusion social organizations, which means that party size, composition, and spatial distribution are constantly in flux. Moreover, chimpanzees use a remarkably extensive repertoire of vocal and nonvocal forms of communication, thought to help convey information in such a socially and spatially dynamic setting. One proposed form of nonvocal communication in chimpanzees is buttress drumming, in which an individual hits a tree buttress with its hands and/or feet, thereby producing a low-frequency acoustic signal. It is often presumed that this behavior functions to communicate over long distances and is, therefore, goal-oriented. If so, we would expect chimpanzees to exhibit selectivity in the choice of trees and buttresses used in buttress drumming. Selectivity is a key attribute of many other goal-directed chimpanzee behaviors, such as nut-cracking and ant dipping. Here, we investigate whether chimpanzees at the Seringbara study site in the Nimba Mountains, Guinea, West Africa, show selectivity in their buttress drumming behavior. Our results indicate that Seringbara chimpanzees are more likely to use larger trees and select buttresses that are thinner and have a greater surface area. These findings imply that tree buttress drumming is not a random act, but rather goal-oriented and requires knowledge of suitable trees and buttresses. Our results also point to long-distance communication as a probable function of buttress drumming based on selectivity for buttress characteristics likely to impact sound propagation. This study provides a foundation for further assessing the cognitive underpinnings and functions of buttress drumming in wild chimpanzees.

Radiographic features of magnesium-based bioabsorbable screw resorption in paediatric fractures.

BACKGROUND: Resorption of magnesium-based alloy bioabsorbable screws produces hydrogen gas, which can be mistaken as a sign of infection and may affect the physis or fixed bone fragment. OBJECTIVE: We evaluated the temporal and spatial occurrence of gas and the occurrence of a breakage of the fixed bone fragment or screw following magnesium screw fixation. MATERIALS AND METHODS: Radiographs of paediatric patients treated with magnesium screws were retrospectively reviewed. Temporal occurrence and distribution of gas in the bone, the physis and soft tissues, breakage of the screw or fixed bone fragment and joint effusion were assessed. RESULTS: One hundred and three radiographs in 35 paediatric patients were reviewed (mean age: 10.6 years). Follow-up ranged from 1 to 730 days. Gas in the bone increases up to week 5, remains constant up to week 16 and then decreases. Gas in soft tissues, intra-articular gas and joint effusions gradually reduce over time. In 1/23 (4.3%) patients with an open physis, gas intrusion into the physis occurred. Breakage of the bone fragment fixated by the screw was observed in 4/35 (11.4%) patients within the first 6 weeks. Screw breakage was observed in 16/35 (45.7%) patients, with a median time to first detection of 300 days. CONCLUSION: Gas bubbles in bone and soft tissue are normal findings in the context of screw resorption and should not be confused with soft-tissue infection or osteomyelitis. Gas is rarely visible in the physis. Breakage of the fixed bone fragment and/or screw can occur.

Association patterns and community structure among female bottlenose dolphins: environmental, genetic and cultural factors.

Social structuring from assortative associations may affect individual fitness, as well as population-level processes. Gaining a broader understanding of social structure can improve our knowledge of social evolution and inform wildlife conservation. We investigated association patterns and community structure of female Indo-Pacific bottlenose dolphins (Tursiops aduncus) in Shark Bay, Western Australia, assessing the role of kinship, shared culturally transmitted foraging techniques, and habitat similarity based on water depth. Our results indicated that associations are influenced by a combination of uni- and biparental relatedness, cultural behaviour and habitat similarity, as these were positively correlated with a measure of dyadic association. These findings were matched in a community level analysis. Members of the same communities overwhelmingly shared the same habitat and foraging techniques, demonstrating a strong homophilic tendency. Both uni- and biparental relatedness between dyads were higher within than between communities. Our results illustrate that intraspecific variation in sociality in bottlenose dolphins is influenced by a complex combination of genetic, cultural, and environmental aspects. Supplementary Information: The online version contains supplementary material available at 10.1007/s42991-022-00259-x.

SYNGAP1 Controls the Maturation of Dendrites, Synaptic Function, and Network Activity in Developing Human Neurons.

SYNGAP1 is a major genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy. De novo loss-of-function variants in this gene cause a neurodevelopmental disorder defined by cognitive impairment, social-communication disorder, and early-onset seizures. Cell biological studies in mouse and rat neurons have shown that Syngap1 regulates developing excitatory synapse structure and function, with loss-of-function variants driving formation of larger dendritic spines and stronger glutamatergic transmission. However, studies to date have been limited to mouse and rat neurons. Therefore, it remains unknown how SYNGAP1 loss of function impacts the development and function of human neurons. To address this, we used CRISPR/Cas9 technology to ablate SYNGAP1 protein expression in neurons derived from a commercially available induced pluripotent stem cell line (hiPSC) obtained from a human female donor. Reducing SynGAP protein expression in developing hiPSC-derived neurons enhanced dendritic morphogenesis, leading to larger neurons compared with those derived from isogenic controls. Consistent with larger dendritic fields, we also observed a greater number of morphologically defined excitatory synapses in cultures containing these neurons. Moreover, neurons with reduced SynGAP protein had stronger excitatory synapses and expressed synaptic activity earlier in development. Finally, distributed network spiking activity appeared earlier, was substantially elevated, and exhibited greater bursting behavior in SYNGAP1 null neurons. We conclude that SYNGAP1 regulates the postmitotic maturation of human neurons made from hiPSCs, which influences how activity develops within nascent neural networks. Alterations to this fundamental neurodevelopmental process may contribute to the etiology of SYNGAP1-related disorders.SIGNIFICANCE STATEMENTSYNGAP1 is a major genetic risk factor for global developmental delay, autism spectrum disorder, and epileptic encephalopathy. While this gene is well studied in rodent neurons, its function in human neurons remains unknown. We used CRISPR/Cas9 technology to disrupt SYNGAP1 protein expression in neurons derived from an induced pluripotent stem cell line. We found that induced neurons lacking SynGAP expression exhibited accelerated dendritic morphogenesis, increased accumulation of postsynaptic markers, early expression of synapse activity, enhanced excitatory synaptic strength, and early onset of neural network activity. We conclude that SYNGAP1 regulates the postmitotic differentiation rate of developing human neurons and disrupting this process impacts the function of nascent neural networks. These altered developmental processes may contribute to the etiology of SYNGAP1 disorders.

Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment.

A critical but molecularly uncharacterized step in heart formation and regeneration is the process that commits progenitor cells to differentiate into cardiomyocytes. Here, we show that the endoderm-derived dual Nodal/bone morphogenetic protein (BMP) antagonist Cerberus-1 (Cer1) in embryonic stem cell cultures orchestrates two signaling pathways that direct the SWI/SNF chromatin remodeling complex to cardiomyogenic loci in multipotent (KDR/Flk1+) progenitors, activating lineage-specific transcription. Transient inhibition of Nodal by Cer1 induces Brahma-associated factor 60c (Baf60c), one of three Baf60 variants (a, b, and c) that are mutually exclusively assembled into SWI/SNF. Blocking Nodal and BMP also induces lineage-specific transcription factors Gata4 and Tbx5, which interact with Baf60c. siRNA to Cer1, Baf60c, or the catalytic SWI/SNF subunit Brg1 prevented the developmental opening of chromatin surrounding the Nkx2.5 early cardiac enhancer and cardiomyocyte differentiation. Overexpression of Baf60c fully rescued these deficits, positioning Baf60c and SWI/SNF function downstream from Cer1. Thus, antagonism of Nodal and BMP coordinates induction of the myogenic Baf60c variant and interacting transcription factors to program the developmental opening of cardiomyocyte-specific loci in chromatin. This is the first demonstration that cues from the progenitor cell environment direct the subunit variant composition of SWI/SNF to remodel the transcriptional landscape for lineage-specific differentiation.

Male monkeys use punishment and coercion to de-escalate costly intergroup fights.

In numerous social species, males direct aggression towards female group members during intergroup fights, and this behaviour is commonly thought to function as mate guarding, even though males often target non-receptive females. In studying intergroup fights in a wild population of vervet monkeys, we found that male intragroup aggression was primarily directed towards individuals who had either just finished exhibiting, or were currently attempting to instigate intergroup aggression. Targeted females were less likely to instigate intergroup aggression in the future, indicating that male intragroup aggression functioned as coercion (when directed towards those who were currently trying to instigate a fight) and punishment (when directed towards those who had recently fought). These manipulative tactics effectively prevented intergroup encounters from escalating into fights and often de-escalated ongoing conflicts. Males who were likely sires were those most likely to use punishment/coercion, particularly when they were wounded, and, therefore, less able to protect vulnerable offspring should a risky intergroup fight erupt. This work, along with our previous finding that females use punishment and rewards to recruit males into participating in intergroup fights, highlights the inherent conflict of interest that exists between the sexes, as well as the role that social incentives can play in resolving this conflict. Furthermore, unlike other studies which have found punishment to be used asymmetrically between partners, these works represent a novel example of reciprocal punishment in a non-human animal.

The slow ape: High infant survival and long interbirth intervals in wild orangutans.

Orangutans (Pongo spp.) are reported to have extremely slow life histories, including the longest average interbirth intervals of all mammals. Such slow life history can be viable only when unavoidable mortality is kept low. Thus, orangutans' survivorship under natural conditions is expected to be extremely high. Previous estimates of orangutan life history were based on captive individuals living under very different circumstances or on small samples from wild populations. Here, we combine birth data from seven field sites, each with demographic data collection for at least 10 years (range 12-43 years) on wild orangutans to better document their life history. Using strict criteria for data inclusion, we calculated infant survival, interbirth intervals and female age at first reproduction, across species, subspecies and islands. We found an average closed interbirth interval of 7.6 years, as well as consistently very high pre-weaning survival for males and females. Female survival of 94% until age at first birth (at around age 15 years) was higher than reported for any other mammal species under natural conditions. Similarly, annual survival among parous females is very high, but longevity remains to be estimated. Current data suggest no major life history differences between Sumatran and Bornean orangutans. The high offspring survival is remarkable, noting that modern human populations seem to have reached the same level of survival only in the 20th century. The orangutans' slow life history illustrates what can be achieved if a hominoid bauplan is exposed to low unavoidable mortality. Their high survival is likely due to their arboreal and non-gregarious lifestyle, and has allowed them to maintain viable populations, despite living in low-productivity habitats. However, their slow life history also implies that orangutans are highly vulnerable to a catastrophic population crash in the face of drastic habitat change.

The social organization of Homo ergaster: Inferences from anti-predator responses in extant primates.

Patterns of primate socioecology have been used to suggest that the first truly savanna-dwelling hominin, Homo ergaster, lived in sizeable groups. Here, we revisit these estimates and infer additional features of the social organization of these early hominins based on anti-predator responses observed across the primate taxon. We first show that the effect of habitat on primate group size, composition, and sexual dimorphism is negligible after controlling for substrate use and phylogeny: terrestrial species live in larger groups with more and bigger males than arboreal taxa. We next hypothesize that groups can only survive in open habitats if males are able to engage in joint counter-attacks against the large carnivorans typical of such environments. To test this, we analyze reports on primate counter-attacks against known predators and find these are indeed disproportionately frequent in terrestrial taxa living in open habitats, sometimes even involving the use of tentative weapons. If we subsequently only examine the taxa that are particularly adept at this (chimpanzees and baboons), we find an effect of habitat type on group size: groups on the savanna are larger than those in the forest. We thus infer that H. ergaster lived in very large groups with many males that jointly defended the group against carnivorans, and argue that these counter-attacks will readily have turned into confrontational scavenging and cooperative hunting, allowing Homo to move into the niche of social carnivore. These two features (life in very large multi-male groups and a switch to persistent carnivory) shaped the evolution of our lineage to such an extent that the social organization of H. ergaster may already have contained many key elements characterizing modern day foragers: male bonding, incipient male-female friendships with food sharing, a tendency toward endogamy, and the presence of large communities that eventually turned into the ethno-linguistic units we can still recognize today.

Female monkeys use both the carrot and the stick to promote male participation in intergroup fights.

Group-level cooperation often poses a social dilemma in which joint action may be difficult to achieve. Theoretical models and experimental work on humans show that social incentives, such as punishment of defectors and rewarding of cooperators, can promote cooperation in groups of unrelated individuals. Here, we demonstrate that these processes can operate in a non-human animal species, and be used to effectively promote the production of a public good. We took advantage of the fact that intergroup fights in vervet monkeys (Chlorocebus aethiops pygerythrus) are characterized by episodes of intergroup aggression with pauses in-between. During pauses, females selectively groomed males that had participated in the previous aggressive episode, but aggressed male group members that had not. In subsequent (i.e. future) episodes, males who had received either aggression or grooming participated above their personal base-line level. Therefore, female-male aggression and grooming both appear to function as social incentives that effectively promote male participation in intergroup fights. Importantly, females stood to gain much from recruiting males as the probability of winning intergroup fights was dependent on the number of active participants, relative to the number of fighters in the opposing group. Furthermore, females appear to maximize the benefits gained from recruiting males as they primarily used social incentives where and when high-quality food resources, which are the resources primarily limiting to female fitness, were at stake.

Cyclic stretch of embryonic cardiomyocytes increases proliferation, growth, and expression while repressing Tgf-ß signaling.

Perturbed biomechanical stimuli are thought to be critical for the pathogenesis of a number of congenital heart defects, including Hypoplastic Left Heart Syndrome (HLHS). While embryonic cardiomyocytes experience biomechanical stretch every heart beat, their molecular responses to biomechanical stimuli during heart development are poorly understood. We hypothesized that biomechanical stimuli activate specific signaling pathways that impact proliferation, gene expression and myocyte contraction. The objective of this study was to expose embryonic mouse cardiomyocytes (EMCM) to cyclic stretch and examine key molecular and phenotypic responses. Analysis of RNA-Sequencing data demonstrated that gene ontology groups associated with myofibril and cardiac development were significantly modulated. Stretch increased EMCM proliferation, size, cardiac gene expression, and myofibril protein levels. Stretch also repressed several components belonging to the Transforming Growth Factor-ß (Tgf-ß) signaling pathway. EMCMs undergoing cyclic stretch had decreased Tgf-ß expression, protein levels, and signaling. Furthermore, treatment of EMCMs with a Tgf-ß inhibitor resulted in increased EMCM size. Functionally, Tgf-ß signaling repressed EMCM proliferation and contractile function, as assayed via dynamic monolayer force microscopy (DMFM). Taken together, these data support the hypothesis that biomechanical stimuli play a vital role in normal cardiac development and for cardiac pathology, including HLHS.

Induced pluripotent stem cells in cardiovascular drug discovery.

The unexpected discovery that somatic cells can be reprogrammed to a pluripotent state yielding induced pluripotent stem cells has made it possible to produce cardiovascular cells exhibiting inherited traits and disorders. Use of these cells in high throughput analyses should broaden our insight into fundamental disease mechanisms and provide many benefits for patients, including new therapeutics and individually tailored therapies. Here we review recent progress in generating induced pluripotent stem cell-based models of cardiovascular disease and their multiple applications in drug development.

Validation of an acoustic location system to monitor Bornean orangutan (Pongo pygmaeus wurmbii) long calls.

The long call is an important vocal communication signal in the widely dispersed, semi-solitary orangutan. Long calls affect individuals' ranging behavior and mediate social relationships and regulate encounters between dispersed individuals in a dense rainforest. The aim of this study was to test the utility of an Acoustic Location System (ALS) for recording and triangulating the loud calls of free-living primates. We developed and validated a data extraction protocol for an ALS used to record wild orangutan males' long calls at the Tuanan field site (Central Kalimantan). We installed an ALS in a grid of 300 ha, containing 20 SM2+ recorders placed in a regular lattice at 500 m intervals, to monitor the distribution of calling males in the area. The validated system had the following main features: (i) a user-trained software algorithm (Song Scope) that reliably recognized orangutan long calls from sound files at distances up to 700 m from the nearest recorder, resulting in a total area of approximately 900 ha that could be monitored continuously; (ii) acoustic location of calling males up to 200 m outside the microphone grid, which meant that within an area of approximately 450 ha, call locations could be calculated through triangulation. The mean accuracy was 58 m, an error that is modest relative to orangutan mobility and average inter-individual distances. We conclude that an ALS is a highly effective method for detecting long-distance calls of wild primates and triangulating their position. In combination with conventional individual focal follow data, an ALS can greatly improve our knowledge of orangutans' social organization, and is readily adaptable for studying other highly vocal animals.

Endocrinological correlates of male bimaturism in wild Bornean orangutans.

Among primates, orangutans are unique in having pronounced male bimaturism leading to two fully adult morphs that differ in both physical appearance and behavior. While unflanged males have a female-like appearance, flanged males have the full suite of secondary sexual characteristics, including cheek flanges and a large throat sac. So far, hormonal correlates of arrested development in unflanged males and the expression of secondary sexual characteristics in flanged males have only been studied in zoo-housed individuals. In this study, we investigated fecal androgen and glucocorticoid metabolites as hormonal correlates of male bimaturism in 17 wild adult Bornean orangutans (Pongo pygmaeus) in Central Kalimantan, Indonesia. We predicted and found higher androgen levels in flanged males compared to unflanged males, probably due to ongoing strong competition among flanged males who meet too infrequently to establish a clear linear dominance hierarchy. Furthermore, we found no difference in fecal glucocorticoid metabolite concentrations between flanged and unflanged males, indicating that social stress is unlikely to explain arrested development in unflanged wild orangutans. The only actively developing male in our study showed significantly higher androgen levels during the period of development than later as a fully flanged male. This supports earlier findings from zoo studies that elevated androgen levels are associated with the development of secondary sexual characteristics.

A Nodal-to-TGFß cascade exerts biphasic control over cardiopoiesis.

RATIONALE: The transforming growth factor-ß (TGFß) family member Nodal promotes cardiogenesis, but the mechanism is unclear despite the relevance of TGFß family proteins for myocardial remodeling and regeneration. OBJECTIVE: To determine the function(s) of TGFß family members during stem cell cardiogenesis. METHODS AND RESULTS: Murine embryonic stem cells were engineered with a constitutively active human type I Nodal receptor (caACVR1b) to mimic activation by Nodal and found to secrete a paracrine signal that promotes cardiogenesis. Transcriptome and gain- and loss-of-function studies identified the factor as TGFß2. Both Nodal and TGFß induced early cardiogenic progenitors in embryonic stem cell cultures at day 0 to 2 of differentiation. However, Nodal expression declines by day 4 due to feedback inhibition, whereas TGFß persists. At later stages (days 4-6), TGFß suppresses the formation of cardiomyocytes from multipotent Kdr(+) progenitors while promoting the differentiation of vascular smooth muscle and endothelial cells. CONCLUSIONS: Nodal induces TGFß, and both stimulate the formation of multipotent cardiovascular Kdr(+) progenitors. TGFß, however, becomes uniquely responsible for controlling subsequent lineage segregation by stimulating vascular smooth muscle and endothelial lineages and simultaneously blocking cardiomyocyte differentiation.