Multi-year patterns in testosterone, cortisol and corticosterone in baleen from adult males of three whale species

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Conservation Physiology 6 (2018): coy049, doi:10.1093/conphys/coy049.Male baleen whales have long been suspected to have annual cycles in testosterone, but due to difficulty in collecting endocrine samples, little direct evidence exists to confirm this hypothesis. Potential influences of stress or adrenal stress hormones (cortisol, corticosterone) on male reproduction have also been difficult to study. Baleen has recently been shown to accumulate steroid hormones during growth, such that a single baleen plate contains a continuous, multi-year retrospective record of the whale’s endocrine history. As a preliminary investigation into potential testosterone cyclicity in male whales and influences of stress, we determined patterns in immunoreactive testosterone, two glucocorticoids (cortisol and corticosterone), and stable-isotope (SI) ratios, across the full length of baleen plates from a bowhead whale (Balaena mysticetus), a North Atlantic right whale (Eubalaena glacialis) and a blue whale (Balaenoptera musculus), all adult males. Baleen was subsampled at 2 cm (bowhead, right) or 1 cm (blue) intervals and hormones were extracted from baleen powder with methanol, followed by quantification of all three hormones using enzyme immunoassays validated for baleen extract of these species. Baleen of all three males contained regularly spaced peaks in testosterone content, with number and spacing of testosterone peaks corresponding well to SI data and to species-specific estimates of annual baleen growth rate. Cortisol and corticosterone exhibited some peaks that co-occurred with testosterone peaks, while other glucocorticoid peaks occurred independent of testosterone peaks. The right whale had unusually high glucocorticoids during a period with a known entanglement in fishing gear and a possible disease episode; in the subsequent year, testosterone was unusually low. Further study of baleen testosterone patterns in male whales could help clarify conservation- and management-related questions such as age of sexual maturity, location and season of breeding, and the potential effect of anthropogenic and natural stressors on male testosterone cycles.This work was supported by (1) the Arizona Board of Regents Technology Research Initiative Fund; (2) the Center for Bioengineering Innovation at Northern Arizona University; (3) the Greenland Institute of Natural Resources; (4) the Woods Hole Oceanographic Institution Ocean Life Institute and (5) Fisheries and Ocean Canada’s (DFO) Priorities and Partnership Strategic Initiatives Fund and Oceans Protection Plan

Changes in Human Fecal Microbiota Due to Chemotherapy Analyzed by TaqMan-PCR, 454 Sequencing and PCR-DGGE Fingerprinting

BACKGROUND: We investigated whether chemotherapy with the presence or absence of antibiotics against different kinds of cancer changed the gastrointestinal microbiota. METHODOLOGY/PRINCIPAL FINDINGS: Feces of 17 ambulant patients receiving chemotherapy with or without concomitant antibiotics were analyzed before and after the chemotherapy cycle at four time points in comparison to 17 gender-, age- and lifestyle-matched healthy controls. We targeted 16S rRNA genes of all bacteria, Bacteroides, bifidobacteria, Clostridium cluster IV and XIVa as well as C. difficile with TaqMan qPCR, denaturing gradient gel electrophoresis (DGGE) fingerprinting and high-throughput sequencing. After a significant drop in the abundance of microbiota (p = 0.037) following a single treatment the microbiota recovered within a few days. The chemotherapeutical treatment marginally affected the Bacteroides while the Clostridium cluster IV and XIVa were significantly more sensitive to chemotherapy and antibiotic treatment. DGGE fingerprinting showed decreased diversity of Clostridium cluster IV and XIVa in response to chemotherapy with cluster IV diversity being particularly affected by antibiotics. The occurrence of C. difficile in three out of seventeen subjects was accompanied by a decrease in the genera Bifidobacterium, Lactobacillus, Veillonella and Faecalibacterium prausnitzii. Enterococcus faecium increased following chemotherapy. CONCLUSIONS/SIGNIFICANCE: Despite high individual variations, these results suggest that the observed changes in the human gut microbiota may favor colonization with C. difficile and Enterococcus faecium. Perturbed microbiota may be a target for specific mitigation with safe pre- and probiotics

Demographic, ecological, and physiological responses of ringed seals to an abrupt decline in sea ice availability

To assess whether demographic declines of Arctic species at the southern limit of their range will be gradual or punctuated, we compared large-scale environmental patterns including sea ice dynamics to ringed seal (Pusa hispida) reproduction, body condition, recruitment, and stress in Hudson Bay from 2003 to 2013. Aerial surveys suggested a gradual decline in seal density from 1995 to 2013, with the lowest density occurring in 2013. Body condition decreased and stress (cortisol) increased over time in relation to longer open water periods. The 2010 open water period in Hudson Bay coincided with extremes in large-scale atmospheric patterns (North Atlantic Oscillation, Arctic Oscillation, El Nino-Southern Oscillation) resulting in the earliest spring breakup and the latest ice formation on record. The warming event was coincident with high stress level, low ovulation rate, low pregnancy rate, few pups in the Inuit harvest, and observations of sick seals. Results provide evidence of changes in the condition of Arctic marine mammals in relation to climate mediated sea ice dynamics. We conclude that although negative demographic responses of Hudson Bay seals are occurring gradually with diminishing sea ice, a recent episodic environmental event played a significant role in a punctuated population decline

Reproductive Parameters for Female Beluga Whales (Delphinapterus leucas) of Baffin Bay and Hudson Bay, Canada

Monitoring marine mammal populations and their habitats is crucial for assessing population status and defining realistic management and conservation goals. Environmental and anthropogenic changes in the Arctic have prompted the pursuit for improved understanding of female beluga whale (Delphinapterus leucas) spatial and temporal reproductive patterns. There are relatively few estimates for female reproductive parameters of beluga whale populations across the Arctic, and those few that are available are outdated. Here we summarize female reproductive data from samples collected through Inuit subsistence hunts of three eastern Canadian Arctic beluga populations: High Arctic/Baffin Bay (HA), Western Hudson Bay (HB), and Cumberland Sound (CS) from 1989 to 2014. We grouped the CS and HA populations into a Baffin Bay region (BB) population based on similar body growth patterns and genetic similarity. Asymptotic body length of BB beluga whales (370.9 cm) was greater than HB whales (354.4 cm) as established from Gompertz growth curves fitted for whales ranging in age from 1 – 89 y. We did not detect a significant difference in average number of pseudocervices (8.6) between regions. Differences in average age of sexual maturity (ASM) and length at sexual maturity (LSM) were identified, with evidence of BB females maturing earlier than females from HB (probability method BB = 9.9 y versus HB = 11.0 and logistic method ASM50% HB = 9.99 and BB unresolved). BB females were also longer than HB females at maturing age (logistic LSM50%: BB = 314.5 cm vs HB = 290.3). Total corpora counts were strongly correlated with age, although the number of corpora (≥ 10 mm) suggests reproductive senescence between 40 and 50 y. Improved understanding of female reproductive patterns and knowledge of changes in the spatial and temporal timing of reproductive processes are fundamental for effective conservation and sustainable management of beluga whale populations.La surveillance des populations de mammifères marins et de leurs habitats joue un rôle crucial dans l’évaluation de l’état d’une population ainsi que dans la formulation d’objectifs réalistes en matière de gestion et de conservation. Dans l’Arctique, les changements environnementaux et anthropiques incitent à mieux comprendre les tendances spatiales et temporelles de reproduction du béluga femelle (Delphinapterus leucas). Il existe relativement peu d’estimations des paramètres de reproduction des femelles au sein des populations de bélugas de l’Arctique, et celles qui existent ne sont plus à jour. Nous résumons ici les données de reproduction des femelles en fonction d’échantillons recueillis à partir des chasses de subsistance d’Inuits parmi trois populations de bélugas de l’est de l’Arctique canadien : Extrême-Arctique et baie de Baffin (HA), ouest de la baie d’Hudson (HB) et détroit de Cumberland (CS), de 1989 à 2014. Nous avons regroupé les populations de CS et de HA dans une population de la région de la baie de Baffin (BB) en fonction de tendances de croissance corporelle semblables et de similarité génétique. La longueur corporelle asymptotique des bélugas de BB (370,9 cm) était plus grande que celle des baleines de HB (354,4 cm), ainsi déterminée à l’aide des courbes de croissance de Gompertz adaptées aux baleines, dont l’âge varie de un an à 89 ans. Nous n’avons pas détecté de différence importante dans le nombre moyen de « pseudo-cols de l’utérus » (8,6) entre les régions. Des différences dans l’âge moyen de la maturité sexuelle (ASM) et dans la longueur à la maturité sexuelle (LSM) ont été décelées, avec preuve que les femelles de BB arrivaient plus vite à maturité que les femelles de HB (méthode de probabilité de BB = 9,9 ans par opposition à HB = 11,0 et une méthode de logistique d’ASM50% HB = 9,99 et de BB non résolue). Par ailleurs, les femelles de BB étaient plus longues que les femelles de HB à l’âge de la maturité (logistique LSM50% : BB = 314,5 cm par opposition à HB = 290,3). Le nombre total de corps jaunes était fortement corrélé à l’âge, bien que le nombre de corps jaunes (≥ 10 mm) suggère une sénescence reproductive variant entre 40 et 50 ans. Une meilleure compréhension des tendances de reproduction des femelles et de meilleures connaissances des changements spatiaux et temporels des processus de reproduction revêtent une importance fondamentale pour la conservation efficace et la gestion durable des populations de bélugas

Do intraspecific life history patterns follow interspecific predictions? A test using latitudinal variation in ringed seals

Mammals adapted to unpredictable and low-energy environments often evolve a “bet-hedging” life history strategy characterized by less costly reproductive outputs over a longer and slower-growing life. In contrast, species adapted to more predictable (i.e., low variation) and higher energy environments may evolve greater fecundity over a shorter and faster-growing life. We tested whether this known interspecific pattern also occurs within a species. We compared life history traits of the ringed seal (Pusa hispida) in the Canadian High Arctic to those closer to the southern limit of the species\u27 circumpolar distribution. We found that northern seals grew slower than southern seals (Brody growth coefficient), achieved a greater asymptotic body weight (82 and 69 kg vs. 74 and 54 kg female and male, respectively), reached sexual maturity later (6.1 years vs. 4.5 years), had lower fecundity (1.8 years vs. 1.3 years interbirth interval), longer average lifespan (5 years vs. 3 years median age), and greater movements (1,269 vs. 681 km). Mating systems also likely differed with northern seals showing morphological evidence of a promiscuous mating system with potential sperm competition as indicated by greater relative testes size. The northern region was also characterized by more unpredictable environmental timing of seasonal events, such as spring sea ice breakup. Life history variation between the intraspecific groups of seals appears to agree with interspecific patterns and provides a better understanding of how species\u27 life history parameters shift in concert with environmental conditions

Neuroblastoma Risk Assessment and Treatment Stratification with Hybrid Capture-Based Panel Sequencing

For many years, the risk-based therapy stratification of children with neuroblastoma has relied on clinical and molecular covariates. In recent years, genome analysis has revealed further alterations defining risk, tumor biology, and therapeutic targets. The implementation of a robust and scalable method for analyzing traditional and new molecular markers in routine diagnostics is an urgent clinical need. Here, we investigated targeted panel sequencing as a diagnostic approach to analyze all relevant genomic neuroblastoma risk markers in one assay. Our neuroblastoma hybrid capture sequencing panel (NB-HCSP) assay employs a technology for the high-coverage sequencing (>1000x) of 55 selected genes and neuroblastoma-relevant genomic regions, which allows for the detection of single nucleotide changes, structural rearrangements, and copy number alterations. We validated our assay by analyzing 15 neuroblastoma cell lines and a cohort of 20 neuroblastomas, for which reference routine diagnostic data and genome sequencing data were available. We observed a high concordance for risk markers identified by the NB-HSCP assay, clinical routine diagnostics, and genome sequencing. Subsequently, we demonstrated clinical applicability of the NB-HCSP assay by analyzing routine clinical samples. We conclude that the NB-HCSP assay may be implemented into routine diagnostics as a single assay that covers all essential covariates for initial neuroblastoma classification, extended risk stratification, and targeted therapy selection

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

International audienc

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted.Accepted version (6 month embargo), submitted versio