Strong Interactions Between Juvenile Caribbean Spiny Lobster (\u3ci\u3ePanulirus Argus\u3c/i\u3e) and Caribbean Reef Octopus (\u3ci\u3eOctopus Briareus\u3c/i\u3e) in the Florida Keys

Coexisting species may simultaneously compete for resources and interact as predator and prey, creating a strong interaction that can alter the structure of animal communities. This type of interaction potentially occurs between juvenile Caribbean spiny lobster (Panulirus argus) and Caribbean reef octopus (Octopus briareus) within hard-bottom habitats in the Florida Keys, FL (USA), where octopuses may consume juvenile lobsters and also compete with them for limited crevice shelters. I conducted a series of field and mesocosm studies to investigate the nature of octopus-lobster interactions and their implications for the structure of their populations in the wild. Six surveys (summer 2001, spring, summer, and fall 2002, and spring and summer 2003) of juvenile lobsters and octopuses occupying artificial shelters at 19 hard-bottom sites in the Florida Keys confirmed that lobsters do not cohabitate with octopuses. The number of juvenile lobsters on a site was negatively correlated with octopus abundance, although the frequency of injuries to lobsters was unrelated to the abundance of shelters, octopus, or conspecifics. Tethering of lobsters at seven sites that varied in octopus abundance revealed that significantly more juvenile lobsters were consumed on sites with more octopus. In contrast, the density of natural crevice shelters had no effect on the abundance of either species. Results from mesocosm experiments indicated that juvenile lobsters do not attain a size refuge from octopus predation and that octopus do not select dens in response to the chemical cues of lobster or other octopus. A separate set of mesocosm studies showed that the presence of alternative prey and lobster conspecifics reduced predation on lobster. Although lobsters were often displaced from dens by octopus, octopuses were never displaced from shelters by lobster. Thus, the negative association between lobster and octopus is driven largely by predation, not competition. Avoidance of octopus by lobster is of particular importance; direct predation probably plays a lesser role. The risk of predation by octopus on lobster depends strongly on the availability of alternative prey for octopus and the presence of lobster conspecifics that enhance group defense. Crevice shelters suitable for juvenile lobster are limited in many hard-bottom areas in the Florida Keys, so areas with abundant octopuses may further limit the local abundance and shelter use of juvenile spiny lobsters

Habitat-Based Intraguild Predation By Caribbean Reef Octopus Octopus Briareus on Juvenile Caribbean Spiny Lobster Panulirus Argus

Intraguild predation occurs when species simultaneously compete for resources and interact as predator and prey, which describes the interaction between juvenile Caribbean spiny lobster Panulirus argus and Caribbean reef octopus Octopus briareus in the Florida Keys, USA. Octopuses are notorious predators of decapod crustaceans, and their use of crevice shelters suggests that they may also compete for shelter with their lobster prey. Lobsters use mainly chemical cues to detect and avoid octopus, so we hypothesized that the negative association between these species may be as much the consequence of avoidance of a superior competitor as it is of direct predation. Surveys of lobsters and octopuses occupying artificial shelters at 19 hard-bottom sites confirmed that lobsters do not share dens with octopuses, and also show that lobster and octopus abundances are negatively correlated. Tethering experiments on a subset of those sites revealed that predation on lobster was indeed higher on sites with more octopuses. Results from mesocosm studies indicated that although juvenile lobsters do not attain a size refuge from octopus predation, the presence of alternative prey and lobster conspecifics reduces the risk of predation on lobster by octopus. Mesocosm experiments also showed that octopuses were the competitive dominants when shelter was limited. Thus, the negative association between lobster and octopus in the field appears to be driven by both predation and avoidance of octopus-rich sites by lobsters, rather than competition per se. However, crevice shelters suitable for juvenile lobster are limited in many hard-bottom areas in the Florida Keys, so areas where octopuses are abundant may further limit the local accessibility of shelters for juvenile spiny lobsters even if the direct effects of predation by octopus are minimal

Preventing placement disruption: how do foster carers experience and explain the process?

Despite the importance of placement stability in promoting positive outcomes for looked after children, the number of foster placement disruptions continues to be high. Existing research has identified factors which contribute to placement disruption and success. However, the experiences of foster carers who are able to create stable placements are less well understood. The aim of this study was to examine what can be learnt from the experience of long-term, mainstream foster carers, who had been providing placements that were at risk of disruption, but which eventually became stable. The study explored how foster carers experience and explain recovery from a threatened placement, how and why they make the decision to maintain difficult placements and what processes and factors influence this. It also aimed to understand how theories of attachment and resilience contribute to the understanding of foster carers' experiences. Seven foster carers were recruited from across two Local Authorities. They each took part in a semi-structured interview which was transcribed and subjected to a grounded theory lite methodology. The analysis generated one super-ordinate theme (layers of protection) and seven core themes (fragile context, personal investment and affirmations, expectations, special kind of love, strengthening experiences and feelings, adapt and take action and collective vs isolated). A visual model of the data was produced which represented the protective layers, which collectively mitigated the threatening elements associated with difficult placements. The findings suggested that not all participants needed or experienced all of the layers and that the importance of each layer, in maintaining the placement, was variable, depending on the situation. Clinical implications can be drawn from this study including: the importance of foster carers investment in the role, participants mixed feelings about the full disclosure of information on the child and the importance of balancing realistic expectations and maintaining hope

Phenotypic Characterization of EIF2AK4 Mutation Carriers in a Large Cohort of Patients Diagnosed Clinically With Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

A type III complement factor D deficiency: Structural insights for inhibition of the alternative pathway.

Abstract Background: Complement factor D (FD) is the rate-limiting enzyme of the alternative complement pathway. Previous reports of FD deficiency featured absent plasma FD (type I deficiency) and susceptibility to meningococcal infection. A new FD mutant, which is non-functional but fully expressed, was identified in a patient with invasive meningococcal disease. Objectives: We sought to investigate the molecular features of this novel FD mutant. Methods: We performed complement haemolytic assays, western blot analysis of serum FD and Sanger sequencing of the CFD gene. Recombinant mutant FD was assessed by in vitro catalytic assays, circular dichroism, thermal shift assays, esterolytic assays and surface plasmon resonance. Molecular dynamics simulation was used to visualise the structural changes in mutant FD. Results: A homozygous single-nucleotide variation of the CFD gene in the patient and their sibling resulted in an arginine to proline (R176P) substitution in FD. While R176P FD was stable and fully expressed in blood, it had minimal catalytic activity. Mutation R176P caused key FD-C3bB binding exosite loop 156-162 to lose its binding-competent conformation and stabilised the inactive conformation of FD. Consequently, R176P FD was unable to bind its natural substrate, C3bB. Neither patient nor sibling demonstrated the glucose homeostasis impairment that occurs in FD-null mice. Conclusions: Here, we report the first genetically confirmed functional, or type III, deficiency of an activating complement serine protease. This novel mechanism of FD inhibition can inform further development of alternative pathway inhibitors to treat common inflammatory diseases such as age-related macular degeneration

Neonatal cerebrovascular autoregulation.

Cerebrovascular pressure autoregulation is the physiologic mechanism that holds cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure (CPP). Cerebral vasoreactivity refers to the vasoconstriction and vasodilation that occur during fluctuations in arterial blood pressure (ABP) to maintain autoregulation. These are vital protective mechanisms of the brain. Impairments in pressure autoregulation increase the risk of brain injury and persistent neurologic disability. Autoregulation may be impaired during various neonatal disease states including prematurity, hypoxic-ischemic encephalopathy (HIE), intraventricular hemorrhage, congenital cardiac disease, and infants requiring extracorporeal membrane oxygenation (ECMO). Because infants are exquisitely sensitive to changes in cerebral blood flow (CBF), both hypoperfusion and hyperperfusion can cause significant neurologic injury. We will review neonatal pressure autoregulation and autoregulation monitoring techniques with a focus on brain protection. Current clinical therapies have failed to fully prevent permanent brain injuries in neonates. Adjuvant treatments that support and optimize autoregulation may improve neurologic outcomes

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype