Evolutionary problems in centrosome and centriole biology

Centrosomes have been an enigma to evolutionary biologists. Either they have been the subject of ill‐founded speculation or they have been ignored. Here, we highlight evolutionary paradoxes and problems of centrosome and centriole evolution and seek to understand them in the light of recent advances in centrosome biology. Most evolutionary accounts of centrosome evolution have been based on the hypothesis that centrosomes are replicators, independent of the nucleus and cytoplasm. It is now clear, however, that this hypothesis is not tenable. Instead, centrosomes are formed de novo each cell division, with the presence of an old centrosome regulating, but not essential for, the assembly of a new one. Centrosomes are the microtubule‐organizing centres of cells. They can potentially affect sensory and motor characters (as the basal body of cilia), as well as the movements of chromosomes during cell division. This latter role does not seem essential, however, except in male meiosis, and the reasons for this remain unclear. Although the centrosome is absent in some taxa, when it is present, its structure is extraordinarily conserved: in most taxa across eukaryotes, it does not appear to evolve at all. And yet a few insect groups display spectacular hypertrophy of the centrioles. We discuss how this might relate to the unusual reproductive system found in these insects. Finally, we discuss why the fate of centrosomes in sperm and early embryos might differ between different groups of animals

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Multi-tissue DNA methylation aging clocks for sea lions, walruses and seals.

Age determination of wild animals, including pinnipeds, is critical for accurate population assessment and management. For most pinnipeds, current age estimation methodologies utilize tooth or bone sectioning which makes antemortem estimations problematic. We leveraged recent advances in the development of epigenetic age estimators (epigenetic clocks) to develop highly accurate pinniped epigenetic clocks. For clock development, we applied the mammalian methylation array to profile 37,492 cytosine-guanine sites (CpGs) across highly conserved stretches of DNA in blood and skin samples (n = 171) from primarily three pinniped species representing the three phylogenetic families: Otariidae, Phocidae and Odobenidae. We built an elastic net model with Leave-One-Out-Cross Validation (LOOCV) and one with a Leave-One-Species-Out-Cross-Validation (LOSOCV). After identifying the top 30 CpGs, the LOOCV produced a highly correlated (r = 0.95) and accurate (median absolute error = 1.7 years) age estimation clock. The LOSOCV elastic net results indicated that blood and skin clock (r = 0.84) and blood (r = 0.88) pinniped clocks could predict age of animals from pinniped species not used for clock development to within 3.6 and 4.4 years, respectively. These epigenetic clocks provide an improved and relatively non-invasive tool to determine age in skin or blood samples from all pinniped species

Cultured proteins: An analysis of the policy and regulatory environment in selected geographies

The global burden of malnutrition is unacceptably high. Animal-source foods are important components of diverse diets and provide high-quality proteins and other essential nutrients that promote optimal growth and development. The global demand for animal-source foods is projected to increase substantially, particularly in many low- and lower-middle income countries (LMICs). However, cost is a significant barrier to access and meeting this growing demand through livestock production will be highly resource intensive. As such, sustainable, high-quality alternatives to protein from livestock have the potential for significant transformative impact for both people and the planet. Through a process known as fermentation-based cellular agriculture, animal proteins found in milk and eggs can be produced without animals. According to this method, a gene encoded with an animal protein is introduced into a starter culture of microflora (e.g., fungi or yeast). This culture is grown in controlled fermentation tanks, where it expresses the desired protein. Finally, the protein is separated from the microflora, generally producing a purified protein powder. These resulting “cultured” proteins are designed to be identical to the corresponding animal-source proteins produced through traditional livestock farming and can be used as ingredients in existing or new food products. Although there are many potential sustainability and nutritionrelated benefits of these nnovations, they also face several challenges to commercialization and market uptake