Growth in fossil and extant deer and implications for body size and life history evolution

© Kolb et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The attached file is the published version of the article

BLISS: an artificial language for learnability studies

To explore neurocognitive mechanisms underlying the human language faculty, cognitive scientists use artificial languages to control more precisely the language learning environment and to study selected aspects of natural languages. Artificial languages applied in cognitive studies are usually designed ad hoc, to only probe a specific hypothesis, and they include a miniature grammar and a very small vocabulary. The aim of the present study is the construction of an artificial language incorporating both syntax and semantics, BLISS. Of intermediate complexity, BLISS mimics natural languages by having a vocabulary, syntax, and some semantics, as defined by a degree of non-syntactic statistical dependence between words. We quantify, using information theoretical measures, dependencies between words in BLISS sentences as well as differences between the distinct models we introduce for semantics. While modeling English syntax in its basic version, BLISS can be easily varied in its internal parametric structure, thus allowing studies of the relative learnability of different parameter sets

Correction : Transcriptome analysis of pigeon milk production - role of cornification and triglyceride synthesis genes

Stanley, D ORCiD: 0000-0001-7019-4726Background The pigeon crop is specially adapted to produce milk that is fed to newly hatched young. The process of pigeon milk production begins when the germinal cell layer of the crop rapidly proliferates in response to prolactin, which results in a mass of epithelial cells that are sloughed from the crop and regurgitated to the young. We proposed that the evolution of pigeon milk built upon the ability of avian keratinocytes to accumulate intracellular neutral lipids during the cornification of the epidermis. However, this cornification process in the pigeon crop has not been characterised. Results We identified the epidermal differentiation complex in the draft pigeon genome scaffold and found that, like the chicken, it contained beta-keratin genes. These beta-keratin genes can be classified, based on sequence similarity, into several clusters including feather, scale and claw keratins. The cornified cells of the pigeon crop express several cornification-associated genes including cornulin, S100-A9 and A16-like, transglutaminase 6-like and the pigeon ‘lactating’ crop-specific annexin cp35. Beta-keratins play an important role in ‘lactating’ crop, with several claw and scale keratins up-regulated. Additionally, transglutaminase 5 and differential splice variants of transglutaminase 4 are up-regulated along with S100-A10. Conclusions This study of global gene expression in the crop has expanded our knowledge of pigeon milk production, in particular, the mechanism of cornification and lipid production. It is a highly specialised process that utilises the normal keratinocyte cellular processes to produce a targeted nutrient solution for the young at a very high turnover. Background Pigeon lactation was first noted in the literature in 1786 when John Hunter described pigeon milk as being like “..granulated white curd” [1]. This curd-like substance is produced in the crop of male and female pigeons and regurgitated to the young. Like the mammary gland, the pigeon crop undergoes significant changes to the tissue structure during lactation. Several histological studies have characterised these changes and determined that pigeon milk consists of desquamated, sloughed crop epithelial cells [2, 3]. The process of pigeon milk production begins when the germinal cell layer of the crop rapidly proliferates in response to prolactin [4, 5], and this results in a convoluted, highly folded epithelial structure that then coalesces as it out-grows the vasculature, to form the nutritive cell layer that is sloughed off to produce the milk. This nutritive cell layer contains lipid-filled vacuoles [2, 3, 5, 6]. The lipid content of pigeon milk consists mainly of triglycerides, along with phospholipids, cholesterol, free fatty acids, cholesterol esters and diglycerides [7]. The triglyceride content decreases across the lactation period, from 81.2% of total lipid at day one, to 62.7% at day 19, whereas the other lipids increase, which suggests the cellular lipid content decreases towards the end of the lactation period, but the cell membrane-associated lipids remain constant [7]. Several studies have investigated the differences in gene expression between ‘lactating’ pigeon crop tissue and non-‘lactating’ crop tissue [6, 8, 9]. Nearly three decades ago, Horseman and Pukac were the first to identify that mRNA species differ in response to prolactin injection in the crop [8]. Specifically, they identified and characterised gene expression and protein translation of the prolactin-responsive mRNA anxI cp35 and the non-prolactin-responsive isoform, anxI cp37 [9, 10]. In addition, a recent global gene expression study in our laboratory [6] showed that genes encoding products involved in triglyceride synthesis and tissue signalling were up-regulated in the ‘lactating’ crop. We proposed that the evolution of the processes that result in the production of pigeon milk has built upon the more general ability of avian keratinocytes to accumulate intracellular neutral lipids during the cornification of the epidermis [11] in order to produce a nutritive substance for their young [6]. The mechanism of avian epidermal cornification and lipid accumulation is not well-characterised. However, studies have shown that antibodies against mammalian cornification proteins, which are relatively well-characterised, can cross-react with avian and reptilian species [12, 13], which suggests similarities in cornification proteins amongst vertebrate species. Cultured chicken keratinocytes have been shown to express beta-keratins (feather, scale and claw keratins), alpha-keratins (type I and II cytokeratins) and the cornified envelope precursor genes envoplakin and periplakin, as well as accumulating neutral lipids [11]. Mammalian keratinocytes differ from avian keratinocytes in that they are unable to accumulate intracellular neutral lipids [11], and can express alpha-keratins (cytokeratins) but not beta-keratins, which expanded from early archosaurians [14]. There are many cornification-associated proteins characterised from mammalian epidermal tissues. The proteins that form the cornified envelope include keratins, S100 proteins, small proline-rich proteins (SPRRs), late cornified envelope (LCE) proteins, annexins, involucrin, loricrin, filaggrin, desmoplakin, envoplakin, periplakin, trichohyalin, cystatin A, elafin and repetin [15]. Trans-glutaminase enzymes, some of which require cleavage by proteases and an increase in intracellular calcium concentration to become active, cross-link the cornified envelope proteins to form a ceramide lipid-coated protective barrier to the epidermis [16]. Many of the cornified envelope genes are present in the “epidermal differentiation complex” (EDC) which was first identified on chromosome 1q21 in humans [17]. Interestingly, the EDC region has been identified in an avian species (chicken), and is linked to the genes for beta-keratins, but lacks the LCE proteins [18]. Here we present an analysis of the pigeon crop transcriptome to show that pigeon milk production involves a specialised cornification process and de novo synthesis of lipids that accumulate intracellularly

Persistence in diving American mink

Background American mink forage on land and in water, with aquatic prey often constituting a large proportion of their diet. Their long, thin body shape and relatively poor insulation make them vulnerable to heat loss, particularly in water, yet some individuals dive over 100 times a day. At the level of individual dives, previous research found no difference in dive depth or duration, or the total number of dives per day between seasons, but mink did appear to make more dives per active hour in winter than in summer. There was also no difference in the depth or duration of individual dives between the sexes, but there was some evidence that females made more dives per day than males. However, because individual mink dives tend to be extremely short in duration, persistence (quantified as the number of consecutive dives performed) may be a more appropriate metric with which to compare diving behaviour under different scenarios. Results Mink performed up to 28 consecutive dives, and dived continually for up to 36 min. Periods of more loosely aggregated diving (termed ‘aquatic activity sessions’) comprised up to 80 dives, carried out over up to 162.8 min. Contrary to our predictions, persistence was inversely proportional to body weight, with small animals more persistent than large ones, and (for females, but not for males) increased with decreasing temperature. For both sexes, persistence was greater during the day than during the night. Conclusions The observed body weight effect may point to inter-sexual niche partitioning, since in mink the smallest animals are females and the largest are males. The results may equally point to individual specialism’s, since persistence was also highly variable among individuals. Given the energetic costs involved, the extreme persistence of some animals observed in winter suggests that the costs of occasional prolonged activity in cold water are outweighed by the energetic gains. Analysing dive persistence can provide information on an animal’s physical capabilities for performing multiple dives and may reveal how such behaviour is affected by different conditions. Further development of monitoring and biologging methodology to allow quantification of hunting success, and thus the rewards obtained under alternative scenarios, would be insightful

The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) Study: Trial Design and Baseline Characteristics

INTRODUCTION: Despite optimal current care, up to 30% of individuals suffering from immunoglobulin A nephropathy (IgAN) will develop kidney failure requiring dialysis or kidney transplantation. The Therapeutic Evaluation of STeroids in IgA Nephropathy Global (TESTING) study was designed to assess the benefits and risks of steroids in people with IgAN. We report the trial design as well as the baseline characteristics of study participants. METHODS: It is an investigator-initiated, multicenter, double-blind, placebo-controlled, randomized trial of individuals with kidney biopsy-confirmed IgAN, proteinuria ≥1 g/day, and an estimated GFR of 20-120 mL/min/1.73 m2, following at least 3 months of standard of care including maximum labelled (or tolerated) dose of renin-angiotensin system blockade. The original study design randomized participants 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/day, maximum 48 mg/day) for 2 months, with subsequent weaning by 8 mg/day/month over 6-8 months, or matching placebo. The intervention was modified in 2016 (due to an excess of serious infection) to low-dose methylprednisolone (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo. Participants recruited after 2016 also received prophylaxis against Pneumocystis jirovecii pneumonia during the first 12 weeks of treatment. RESULTS: The study recruitment period extended from May 2012 to November 2019. By the time the excess of serious infections was observed, 262 participants had been randomized to the original full-dose treatment algorithm, and an interim analysis was reported in 2016. Subsequently, 241 additional participants were randomized to a revised low-dose protocol, for a total of 503 participants from China (373), India (78), Canada (24), Australia (18), and Malaysia (10). The mean age of randomized participants was 38, 39% were female, mean eGFR at randomization was 62.7 mL/min/1.73 m2, and mean 24-h urine protein 2.54 g. The primary endpoint is a composite of 40% eGFR decline from baseline or kidney failure (dialysis, transplantation, or death due to kidney disease), and participants will be followed until the primary outcome has been observed in at least 160 randomized participants. Analyses will also be made across predefined subgroups. Effects on eGFR slope and albuminuria will also be assessed overall, as well as by the steroid dosing regimen. CONCLUSIONS: The TESTING study (combined full and low dose) will define the benefits of corticosteroid use on major kidney outcomes, as well as the risks of therapy, and provide data on the relative effects of different doses, in individuals with high-risk IgAN

What drives sound symbolism? Different acoustic cues underlie sound-size and sound-shape mappings

Sound symbolism refers to the non-arbitrary mappings that exist between phonetic properties of speech sounds and their meaning. Despite there being an extensive literature on the topic, the acoustic features and psychological mechanisms that give rise to sound symbolism are not, as yet, altogether clear. The present study was designed to investigate whether different sets of acoustic cues predict size and shape symbolism, respectively. In two experiments, participants judged whether a given consonant-vowel speech sound was large or small, round or angular, using a size or shape scale. Visual size judgments were predicted by vowel formant F1 in combination with F2, and by vowel duration. Visual shape judgments were, however, predicted by formants F2 and F3. Size and shape symbolism were thus not induced by a common mechanism, but rather were distinctly affected by acoustic properties of speech sounds. These findings portray sound symbolism as a process that is not based merely on broad categorical contrasts, such as round/unround and front/back vowels. Rather, individuals seem to base their sound-symbolic judgments on specific sets of acoustic cues, extracted from speech sounds, which vary across judgment dimensions

Sexual Size Dimorphism and Body Condition in the Australasian Gannet

Funding: The research was financially supported by the Holsworth Wildlife Research Endowment. Acknowledgments We thank the Victorian Marine Science Consortium, Sea All Dolphin Swim, Parks Victoria, and the Point Danger Management Committee for logistical support. We are grateful for the assistance of the many field volunteers involved in the study.Peer reviewedPublisher PD

Treating frailty-a practical guide

Frailty is a common syndrome that is associated with vulnerability to poor health outcomes. Frail older people have increased risk of morbidity, institutionalization and death, resulting in burden to individuals, their families, health care services and society. Assessment and treatment of the frail individual provide many challenges to clinicians working with older people. Despite frailty being increasingly recognized in the literature, there is a paucity of direct evidence to guide interventions to reduce frailty. In this paper we review methods for identification of frailty in the clinical setting, propose a model for assessment of the frail older person and summarize the current best evidence for treating the frail older person. We provide an evidence-based framework that can be used to guide the diagnosis, assessment and treatment of frail older people

Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25 mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months' streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the molecular and functional expression of TRPV4 channels in retinal microvascular endothelial cells. These changes may contribute to diabetes induced endothelial dysfunction and retinopathy