Abstract
Threespine stickleback populations are model systems for studying adaptive evolution and the underlying genetics. In lakes on the
H
aida
G
waii archipelago (off western
C
anada), stickleback ...have undergone a remarkable local radiation and show phenotypic diversity matching that seen throughout the species distribution. To provide a historical context for this radiation, we surveyed genetic variation at >1000 single nucleotide polymorphism (
SNP
) loci in stickleback from over 100 populations.
SNP
s included markers evenly distributed throughout genome and candidate
SNP
s tagging adaptive genomic regions. Based on evenly distributed
SNP
s, the phylogeographic pattern differs substantially from the disjunct pattern previously observed between two highly divergent mt
DNA
lineages. The
SNP
tree instead shows extensive within watershed population clustering and different watersheds separated by short branches deep in the tree. These data are consistent with separate colonizations of most watersheds, despite underlying genetic connections between some independent drainages. This supports previous suppositions that morphological diversity observed between watersheds has been shaped independently, with populations exhibiting complete loss of lateral plates and giant size each occurring in several distinct clades. Throughout the archipelago, we see repeated selection of
SNP
s tagging candidate freshwater adaptive variants at several genomic regions differentiated between marine–freshwater populations on a global scale (e.g.
EDA
,
Na/K
ATP
ase
). In estuarine sites, both marine and freshwater allelic variants were commonly detected. We also found typically marine alleles present in a few freshwater lakes, especially those with completely plated morphology. These results provide a general model for postglacial colonization of freshwater habitat by sticklebacks and illustrate the tremendous potential of genome‐wide
SNP
data sets hold for resolving patterns and processes underlying recent adaptive divergences.
It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage ...of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on 'HLA epitope' frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms-thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included.
Abstract Patients with chronic liver disease (CLD) often present with significant frailty, sarcopenia, and impaired immune function. However, the mechanisms driving the development of these ...age-related phenotypes are not fully understood. To determine whether accelerated biological aging may play a role in CLD, epigenetic, transcriptomic, and phenotypic assessments were performed on the skeletal muscle tissue and immune cells of CLD patients and age-matched healthy controls. Accelerated biological aging of the skeletal muscle tissue of CLD patients was detected, as evidenced by an increase in epigenetic age compared with chronological age (mean +2.2 ± 4.8 years compared with healthy controls at −3.0 ± 3.2 years, p = 0.0001). Considering disease etiology, age acceleration was significantly greater in both the alcohol-related (ArLD) ( p = 0.01) and nonalcoholic fatty liver disease (NAFLD) ( p = 0.0026) subgroups than in the healthy control subgroup, with no age acceleration observed in the immune-mediated subgroup or healthy control subgroup ( p = 0.3). The skeletal muscle transcriptome was also enriched for genes associated with cellular senescence. Similarly, blood cell epigenetic age was significantly greater than that in control individuals, as calculated using the PhenoAge ( p < 0.0001), DunedinPACE ( p < 0.0001), or Hannum ( p = 0.01) epigenetic clocks, with no difference using the Horvath clock. Analysis of the IMM-Age score indicated a prematurely aged immune phenotype in CLD patients that was 2-fold greater than that observed in age-matched healthy controls ( p < 0.0001). These findings suggested that accelerated cellular aging may contribute to a phenotype associated with advanced age in CLD patients. Therefore, therapeutic interventions to reduce biological aging in CLD patients may improve health outcomes.
Explaining consistent variation in the behaviour of individuals in terms of personality differences is one of the cornerstones of understanding human behaviour but is seldom discussed in behavioural ...ecology for fear of invoking anthropomorphism. Recently, however, interest has begun to focus on identifying personality traits in animals and examining their possible evolutionary consequences. One major axis used to define personality traits is the shyness–boldness continuum. We examined boldness in an in situ experiment using fish from eight populations of the poeciliid
Brachyraphis episcopi (also referred to as
Brachyrhaphis episcopi). Fish from high- and low-predation regions within four streams that run independently into the Panama Canal were tested. Boldness scores were strongly influenced by standard length and the relative level of predation pressure in the rivers. In all four rivers, fish from high-predation areas were bolder than those from low-predation areas. Fish became increasingly shy as they grew.
Despite the recent proliferation of scientific, clinical, and narrative accounts of auditory verbal hallucinations (AVHs), the phenomenology of voice hearing remains opaque and undertheorized. In ...this article, we outline an interdisciplinary approach to understanding hallucinatory experiences which seeks to demonstrate the value of the humanities and social sciences to advancing knowledge in clinical research and practice. We argue that an interdisciplinary approach to the phenomenology of AVH utilizes rigorous and context-appropriate methodologies to analyze a wider range of first-person accounts of AVH at 3 contextual levels: (1) cultural, social, and historical; (2) experiential; and (3) biographical. We go on to show that there are significant potential benefits for voice hearers, clinicians, and researchers. These include (1) informing the development and refinement of subtypes of hallucinations within and across diagnostic categories; (2) "front-loading" research in cognitive neuroscience; and (3) suggesting new possibilities for therapeutic intervention. In conclusion, we argue that an interdisciplinary approach to the phenomenology of AVH can nourish the ethical core of scientific enquiry by challenging its interpretive paradigms, and offer voice hearers richer, potentially more empowering ways to make sense of their experiences.
Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway ...is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a . Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.
Background
Negative experiences of needle procedures in childhood can lead to medical avoidance and vaccine hesitancy into adulthood. We evaluated the feasibility of two new interventions provided by ...clinical nurses to reduce the negative impact of vaccinations: divided attention (DA) and positive memory reframing (PMR).
Methods
Children (8–12 years) were randomized into four groups: usual care (UC), DA, PMR or combined (DA + PMR). To evaluate feasibility, we undertook in‐depth analysis of video‐recorded interventions, nurse experiences (phone interviews) and child/parent memory recall of interventions (phone interviews at 2 weeks post‐vaccination). Key clinical outcomes included child and parent ratings of needle‐related pain intensity and fear assessed at baseline, immediately post‐vaccination and 2 weeks post‐vaccination (recalled).
Results
A total of 54 child–parent dyads were screened, with 41 included (10/group, except PMR n = 11). The interventions were not always completed as intended: 10%–22% of participants received complete interventions and two had adverse events related to protocol breach. Preliminary within‐group analyses showed no effects on child/parent pain ratings. However, children in DA + PMR had reduced recalled fear (p = 0.008), and PMR (p = 0.025) and DA + PMR (p = 0.003) had reduced fear of future needles. Parent ratings of child fear were also reduced immediately post‐vaccination for UC (p = 0.035) and PMR (p = 0.035).
Conclusions
The interventions were feasible, although enhanced nurse training is required to improve fidelity. Preliminary clinical results appear promising, particularly for reducing needle‐related fear. Protocol registration: Protocol number ACTRN12618000687291 at ANZCTR.org.au
Significance
Two new nurse‐led interventions to reduce negative impacts of vaccinations in children, divided attention and positive memory reframing, were feasible and may reduce needle‐related fear. Nurses were able to deliver the interventions in various environments including non‐clinical settings (schools). These interventions have potential to facilitate broader dissemination of vaccinations for children in a manner that minimizes distress.
In estuaries throughout the northern hemisphere resident-freshwater forms of the threespined stickleback (Gasterosteus aculeatus) have undergone parallel divergence from their marine ancestors. ...Sticklebacks are useful for studies of reproductive isolation and speciation because divergent resident-freshwater and migratory anadromous forms exist in sympatry in the lower reaches of rivers. A great deal is already known about the evolutionary history of sticklebacks, however, little is known about reproductive isolation in wild populations. In this thesis, I investigate the nature of reproductive isolation in an anadromous-freshwater stickleback hybrid zone located in the River Tyne, Scotland and explore whether the same genes underlie variation in the same traits in different populations. 1. There was no evidence of morphotype-based assortative mating, in an experimental pond manipulation. Hybridisation between morphotypes occurred readily and this in part is due to the tendency of freshwater females to mate with large males. 2. In contrast, there is some evidence of premating isolation existing in the River Tyne wild population, and this is likely to be ecologically dependent assortative mating. Premating isolation is not strong, however, since hybrid juveniles represented 33% of the sample from sympatric sites. There was no evidence of hybridisation showing a directional bias. 3. Evidence suggests that morphological and genetic differences between anadromous and freshwater sticklebacks in the River Tyne are maintained by postmating isolation in the wild. Genetic hybrids had reduced probability of overwinter survival. There is also strong evidence for selection against intermediate morphotypes and this selection may be sex-biased against intermediate lateral plate morphs. 4. Statistical associations between loci and traits were detected and suggest both stability and flexibility in the underlying morphological divergence in sticklebacks.
In estuaries throughout the northern hemisphere resident-freshwater forms of the threespined stickleback (Gasterosteus aculeatus) have undergone parallel divergence from their marine ancestors. ...Sticklebacks are useful for studies of reproductive isolation and speciation because divergent resident-freshwater and migratory anadromous forms exist in sympatry in the lower reaches of rivers. A great deal is already known about the evolutionary history of sticklebacks, however, little is known about reproductive isolation in wild populations. In this thesis, I investigate the nature of reproductive isolation in an anadromous-freshwater stickleback hybrid zone located in the River Tyne, Scotland and explore whether the same genes underlie variation in the same traits in different populations. 1. There was no evidence of morphotype-based assortative mating, in an experimental pond manipulation. Hybridisation between morphotypes occurred readily and this in part is due to the tendency of freshwater females to mate with large males. 2. In contrast, there is some evidence of premating isolation existing in the River Tyne wild population, and this is likely to be ecologically dependent assortative mating. Premating isolation is not strong, however, since hybrid juveniles represented 33% of the sample from sympatric sites. There was no evidence of hybridisation showing a directional bias. 3. Evidence suggests that morphological and genetic differences between anadromous and freshwater sticklebacks in the River Tyne are maintained by postmating isolation in the wild. Genetic hybrids had reduced probability of overwinter survival. There is also strong evidence for selection against intermediate morphotypes and this selection may be sex-biased against intermediate lateral plate morphs. 4. Statistical associations between loci and traits were detected and suggest both stability and flexibility in the underlying morphological divergence in sticklebacks.
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