Activity behavior of goitered gazelles in an arid environment.

The daily activity pattern in ruminants consists mainly of alternating foraging with bouts of resting, while other behaviors usually play a minor role in the daily activity budgets of ungulates most of the year. Interactions of both intrinsic and extrinsic factors force animals to adopt compromises to form optimal time proportions for foraging and resting to satisfy their daily energy demands. This paper considers the impact of ambient temperature, pasture conditions, body-size, and the effects of lactation and animal growth on the daily activities of goitered gazelles (Gazella subgutturosa). My study found: 1) temperature was the most significant factor leading to the greatest daily hour-to-hour variations in activity, as well as significant monthly changes in activity fluctuations; 2) seasonal improvement of forage conditions did not have a distinctive effect on daily activity; 3) the effect of body size, lactation and fawn growth also did not noticeably change activity fluctuations; but 4) factors related to hiding behavior had a significant impact on goitered gazelle activity. Though goitered gazelles are a sexually dimorphic species, they did not demonstrate any significant deviation between males and females in their daily activities in contrast to typical dimorphic ruminants. The goitered gazelles' hiding behavior may provide a possible explanation for this distinction, as other previously observed dimorphic ungulates were mainly species where fawns followed their mothers from birth. Among other influences, ambient temperature and features of their hiding behavior were the most significant factors influencing diurnal activity of goitered gazelles, while age and sex had a weaker impact on daily behaviors.

Ontogeny of audible squeaks in yellow steppe lemming Eolagurus luteus: trend towards shorter and low-frequency calls is reminiscent of those in ultrasonic vocalization.

BACKGROUND: Rodents are thought to be produced their human-audible calls (AUDs, below 20 kHz) with phonation mechanism based on vibration of the vocal folds, whereas their ultrasonic vocalizations (USVs, over 20 kHz) are produced with aerodynamic whistle mechanism. Despite of different production mechanisms, the acoustic parameters (duration and fundamental frequency) of AUDs and USVs change in the same direction along ontogeny in collared lemming Dicrostonyx groenlandicus and fat-tailed gerbil Pachyuromys duprasi. We hypothesize that this unidirectional trend of AUDs and USVs is a common rule in rodents and test whether the AUDs of yellow steppe lemmings Eolagurus luteus would display the same ontogenetic trajectory (towards shorter and low-frequency calls) as their USVs, studied previously in the same laboratory colony. RESULTS: We examined for acoustic variables 1200 audible squeaks emitted during 480-s isolation-and-handling procedure by 120 individual yellow steppe lemmings (at 12 age classes from neonates to breeding adults, 10 individuals per age class, up to 10 calls per individual, each individual tested once). We found that the ontogenetic pathway of the audible squeaks, towards shorter and lower frequency calls, was the same as the pathway of USVs revealed during 120-s isolation procedure in a previous study in the same laboratory population. Developmental milestone for the appearance of mature patterns of the squeaks (coinciding with eyes opening at 9-12 days of age), was the same as previously documented for USVs. Similar with ontogeny of USVs, the chevron-like squeaks were prevalent in neonates whereas the squeaks with upward contour were prevalent after the eyes opening. CONCLUSION: This study confirms a hypothesis of common ontogenetic trajectory of call duration and fundamental frequency for AUDs and USVs within species in rodents. This ontogenetic trajectory is not uniform across species.

Clinical Trial Simulations and Pharmacometric Analysis in Pediatrics: Application to Inhaled Loxapine in Children and Adolescents.

BACKGROUND AND OBJECTIVES: Loxapine for inhalation is a drug-device combination product approved in adults for the acute treatment of agitation associated with schizophrenia or bipolar I disorder. The primary objective of this study was to develop a clinical trial protocol to support a phase I pharmacokinetic study in children aged 10 years and older. In addition, this report details the results of the clinical study in relation to the predicted likelihood of achieving the target exposure associated with therapeutic effect in adults. METHODS: A nonlinear mixed-effects population pharmacokinetic model was developed using adult data and was adjusted for the targeted pediatric age groups by applying allometric scaling to account for body size effects. Based on this pediatric model, age-appropriate regimens to achieve loxapine exposures similar to the ones associated with therapeutic effect in the adult studies were identified via trial simulation. D-optimal design and power analysis were conducted to identify optimal pharmacokinetic sampling times and sample size, respectively. RESULTS: The developed clinical trial design formed the basis of a phase I study to assess the safety and pharmacokinetics of loxapine for inhalation in children aged 10 years and older (ClinicalTrials.gov ID: NCT02184767). CONCLUSION: The results of the study indicated that overall loxapine exposures were consistent with what had been predicted by the trial simulations. The presented approach illustrates how modeling and simulation can assist in the design of informative clinical trials to identify safe and effective doses and dose ranges in children and adolescents.

Rearrangement and evolution of mitochondrial genomes in parrots.

Mitochondrial genome rearrangements that result in control region duplication have been described for a variety of birds, but the mechanisms leading to their appearance and maintenance remain unclear, and their effect on sequence evolution has not been explored. A recent survey of mitochondrial genomes in the Psittaciformes (parrots) found that control region duplications have arisen independently at least six times across the order. We analyzed complete mitochondrial genome sequences from 20 parrot species, including representatives of each lineage with control region duplications, to document the gene order changes and to examine effects of genome rearrangements on patterns of sequence evolution. The gene order previously reported for Amazona parrots was found for four of the six independently derived genome rearrangements, and a previously undescribed gene order was found in Prioniturus luconensis, representing a fifth clade with rearranged genomes; the gene order resulting from the remaining rearrangement event could not be confirmed. In all rearranged genomes, two copies of the control region are present and are very similar at the sequence level, while duplicates of the other genes involved in the rearrangement show signs of degeneration or have been lost altogether. We compared rates of sequence evolution in genomes with and without control region duplications and did not find a consistent acceleration or deceleration associated with the duplications. This could be due to the fact that most of the genome rearrangement events in parrots are ancient, and additionally, to an effect of body size on evolutionary rate that we found for mitochondrial but not nuclear sequences. Base composition analyses found that relative to other birds, parrots have unusually strong compositional asymmetry (AT- and GC-skew) in their coding sequences, especially at fourfold degenerate sites. Furthermore, we found higher AT skew in species with control region duplications. One potential cause for this compositional asymmetry is that parrots have unusually slow mtDNA replication. If this is the case, then any replicative advantage provided by having a second control region could result in selection for maintenance of both control regions once duplicated.