Evaluation of MERTK evolution and efferocytosis signalling

The TAM (TYRO3, AXL, and MERTK) family of receptor tyrosine kinases allow phagocytes to engage in the phagocytic removal of apoptotic cells. Although all three members of the TAM family are structurally homologous and function in a similar fashion, both human genome-wide association studies and knockout mice models have demonstrated that MERTK is the critical member of the TAM family for maintaining homeostasis. In this thesis, an evolutionary analysis was used to provide insight into the function of MERTK. Selection analysis in primates unexpectedly revealed a high degree of recent positive selection in MERTK’s signal peptide and transmembrane domain, absent from TYRO3 and AXL. Reconstruction of hominid and primate ancestral signal peptides revealed three nonsynonymous mutations in humans, with a G14C mutation producing a potential non-B DNA cruciform motif, which may regulate MERTK expression. Reconstruction of MERTK’s transmembrane domain determined that humans acquired three amino acid substitutions and two insertion/deletion mutations (INDELs) which added four amino acids. These new amino acids were largely leucines and isoleucines, and create a new interaction motif that increased self-clustering of MERTK. Although we found no significant difference among human MERTK and primate- or hominid-ancestral reconstructed signal peptides in expression levels or protein trafficking, recent evolutionary changes in MERTK’s transmembrane revealed significantly higher self-clustering with human MERTK, and hominid ancestral, compared to the reconstructed primate-ancestral transmembrane. This project highlights the importance of recent MERTK evolution, which has increased self-clustering

Increasing Resiliency in Students Using Coaching Skills

Before you can begin building resiliency with your students, they need to have trust and buy in with the relationship. The Coaching strategies involving Conversational Intelligence and Motivational Interviewing are proven methods in developing strong partnerships. These strategies decrease the anxiety that occurs when faced with new information and open the brain to engagement which can lead into increased motivation towards developing the skills needed to build resiliency

Distance-dependent duplex DNA destabilization proximal to G-quadruplex/i-motif sequences

G-quadruplexes and i-motifs are complementary examples of non-canonical nucleic acid substructure conformations. G-quadruplex thermodynamic stability has been extensively studied for a variety of base sequences, but the degree of duplex destabilization that adjacent quadruplex structure formation can cause has yet to be fully addressed. Stable in vivo formation of these alternative nucleic acid structures is likely to be highly dependent on whether sufficient spacing exists between neighbouring duplex- and quadruplex-/i-motif-forming regions to accommodate quadruplexes or i-motifs without disrupting duplex stability. Prediction of putative G-quadruplex-forming regions is likely to be assisted by further understanding of what distance (number of base pairs) is required for duplexes to remain stable as quadruplexes or i-motifs form. Using oligonucleotide constructs derived from precedented G-quadruplexes and i-motif-forming bcl-2 P1 promoter region, initial biophysical stability studies indicate that the formation of G-quadruplex and i-motif conformations do destabilize proximal duplex regions. The undermining effect that quadruplex formation can have on duplex stability is mitigated with increased distance from the duplex region: a spacing of five base pairs or more is sufficient to maintain duplex stability proximal to predicted quadruplex/i-motif-forming region

IVF or ICSI for fertility preservation?

In IVF, eggs and sperm are added together for fertilisation to occur whereas ICSI involves injecting a single sperm into each egg. ICSI is very effective where sperm count or swimming is poor (male infertility) but is slightly riskier than IVF in terms of health problems in children, although these risks are small. However, the risk of no eggs fertilising is higher for IVF compared to ICSI and couples undertaking fertility preservation, for example, before cancer treatment, usually only have time for one attempt. Using fertility preservation treatment cycle data reported to Human Fertilisation and Embryology Authority (HFEA), this study shows that ICSI results in higher number of fertilised eggs and embryos for storage or treatment compared to IVF. However, 19% of eggs are not used in ICSI treatment, so IVF appears to be better overall. Clinics should choose IVF or ICSI for fertility preservation depending on sperm characteristics rather than using ICSI for all

Interrelationship between insistence on sameness, effortful control and anxiety in adolescents and young adults with autism spectrum disorder (ASD)

Background Both self-regulation and insistence on sameness (IS) are related to anxiety, which is a common feature of individuals with autism spectrum disorder (ASD). Here, we aimed to characterise the IS-self-regulation-anxiety interrelationship by investigating the potential contribution made by self-regulation, assessed via effortful control (EC), to the IS-anxiety relationship in a sample of adolescents and young adults with ASD. Method Seventy-one older adolescents and younger adults with ASD (49 males, 22 females; M age = 18.71 years, SD = 2.51, range 14.42–24.81) completed the Adult Repetitive Behaviour Questionnaire-2, Effortful Control Scale of the Adult Temperament Questionnaire and the DSM-5 Dimensional Anxiety Scales. Results IS was associated with both EC (r = −.39, p = .001) and anxiety (r = .45, p < .001), and anxiety was in turn associated with EC (r = −.44, p < .001). To characterise the nature of this interrelationship, two mediation analyses were performed using the serial mediation model in PROCESS with 5000 resamples in bootstrapping. There was a significant indirect effect of EC on anxiety, through IS (b = −.06; BCa 95% CI [−.13, −.02]), and indirect effect on anxiety through EC (b = 1.62; BCa 95% CI [.59, 3.24]) with the mediators accounting for 29.07 and 26.04% of the total effect, respectively. Conclusions Our study provides the first exploration of the IS-anxiety-self-regulation link in ASD. The finding that lower levels of self-regulation are related both to anxiety and IS behaviours points to self-regulation as a viable intervention target for both anxiety and IS behaviours

Chronic venous insufficiency: Clinical and duplex correlations. The Edinburgh Vein Study of venous disorders in the general population

AbstractObjective: The objective of this study was to determine the prevalence of chronic venous insufficiency (CVI) in the general population and to correlate its clinical features with sonographically proven venous reflux. Design of Study: The study design was a cross-sectional survey of the general population. Subjects and Method: Ambulatory men and women, aged 18-64 years, were selected randomly from 12 general practices. Subjects were examined for CVI. Eight segments of the deep and superficial veins were assessed for reflux by means of duplex scanning. Results: A total of 1566 subjects were screened (867 women, mean age 44.8 years; 699 men, mean age 45.8 years) of whom 124 were diagnosed as having CVI: 95, grade 1; 19, grade 2; and 10, grade 3. The age-adjusted prevalence for the whole population was 9.4% in men and 6.6% in women. Prevalence of CVI correlated closely with age and sex, being 21.2% in men >50 years and 12.0% in women >50 years. Heaviness and tension, and a feeling of swelling, aching, and itching, were significantly associated with worsening grade of CVI. CVI was significantly associated with reflux in all deep and superficial segments. The frequency of reflux in both superficial and deep segments increased with the clinical severity of disease. In 30.8% of subjects with CVI in the left leg, reflux was limited to the superficial system. Conclusions: The prevalence of CVI rises steeply with age. There is a strong correlation between venous symptoms and the presence and severity of CVI. CVI is associated in approximately one third of the subjects with incompetence limited to the superficial system and in these a good therapeutic outcome could be expected from surgery to the superficial veins. The severity of clinical features, including Basle CVI grade 1, correlates significantly with prevalence of valvular reflux in the deep and superficial systems. If leg ulcers are to be prevented by timely intervention, a better understanding of the natural history of the association between presenting features and disordered hemodynamics is required. (J Vasc Surg 2002;36:520-5.

Assessment of the LeadCare® Plus for Use on Scandinavian Brown Bears (Ursus arctos)

publishedVersio

Singing teaching as a therapy for chronic respiratory disease - a randomised controlled trial and qualitative evaluation

<p>Abstract</p> <p>Background</p> <p>Despite optimal pharmacological therapy and pulmonary rehabilitation, patients with COPD continue to be breathless. There is a need to develop additional strategies to alleviate symptoms. Learning to sing requires control of breathing and posture and might have benefits that translate into daily life.</p> <p>Methods</p> <p>To test this hypothesis we performed a randomised controlled trial, comparing a six week course of twice weekly singing classes to usual care, in 28 COPD patients. The experience of singing was assessed in a qualitative fashion, through interviews with a psychologist. In addition, we surveyed patients with chronic respiratory conditions who participated in a series of open singing workshops.</p> <p>Results</p> <p>In the RCT, the physical component score of the SF36 improved in the singers (n = 15) compared to the controls (n = 13); +7.5(14.6) vs. -3.8(8.4) p = 0.02. Singers also had a significant fall in HAD anxiety score; -1.1(2.7) vs. +0.8(1.7) p = 0.03. Singing did not improve single breath counting, breath hold time or shuttle walk distance. In the qualitative element, 8 patients from the singing group were interviewed. Positive effects on physical sensation, general well-being, community/social support and achievement/efficacy emerged as common themes. 150 participants in open workshops completed a questionnaire. 96% rated the workshops as "very enjoyable" and 98% thought the workshop had taught them something about breathing in a different way. 81% of attendees felt a "marked physical difference" after the workshop.</p> <p>Conclusion</p> <p>Singing classes can improve quality of life measures and anxiety and are viewed as a very positive experience by patients with respiratory disease; no adverse consequences of participation were observed.</p> <p>Trial Registration</p> <p>Current Controlled Trials - ISRCTN17544114.</p

Particulate oxidative burden as a predictor of exhaled nitric oxide in children with asthma

Background: Epidemiological studies have provided strong evidence that fine particulate matter (PM2.5; aerodynamic diameter ≤ 2.5 μm) can exacerbate asthmatic symptoms in children. Pro-oxidant components of PM2.5 are capable of directly generating reactive oxygen species. Oxidative burden is used to describe the capacity of PM2.5 to generate reactive oxygen species in the lung. Objective: In this study we investigated the association between airway inflammation in asthmatic children and oxidative burden of PM2.5 personal exposure. Methods: Daily PM2.5 personal exposure samples (n = 249) of 62 asthmatic school-aged children in Montreal were collected over 10 consecutive days. The oxidative burden of PM2.5 samples was determined in vitro as the depletion of low-molecular-weight antioxidants (ascorbate and glutathione) from a synthetic model of the fluid lining the respiratory tract. Airway inflammation was measured daily as fractional exhaled nitric oxide (FeNO). Results: A positive association was identified between FeNO and glutathione-related oxidative burden exposure in the previous 24 hr (6.0% increase per interquartile range change in glutathione). Glutathione-related oxidative burden was further found to be positively associated with FeNO over 1-day lag and 2-day lag periods. Results further demonstrate that corticosteroid use may reduce the FeNO response to elevated glutathione-related oxidative burden exposure (no use, 15.8%; irregular use, 3.8%), whereas mold (22.1%), dust (10.6%), or fur (13.1%) allergies may increase FeNO in children with versus children without these allergies (11.5%). No association was found between PM2.5 mass or ascorbate-related oxidative burden and FeNO levels. Conclusions: Exposure to PM2.5 with elevated glutathione-related oxidative burden was associated with increased FeNO