Reproductive tactics in baleen whales

Funding: FE is supported by a University of St Andrews School of Biology Ph.D. scholarship and a Royal Society Research Fellows Enhancement Award (RGF\EA \180213 to ECG), ECG is funded by a Royal Society University Research Fellowship (UF160081 & URF\R\221020), and ELC is funded by a Rutherford Discovery Fellowship from the Royal Society of New Zealand Te Apārangi.While a variety of reproductive tactics are readily witnessed in the odontocetes, such behaviors can be far more elusive, and in some cases, are yet to be observed, in baleen whales. This leads researchers to employ a variety of research methods, some of which have improved greatly in recent decades, to study reproductive behaviors in mysticetes. Genetics and genomics tools can provide invaluable information on maternity, paternity, age, diversity, and kinship, while acoustic tools can provide new insights into the function of sexual displays such as song. In this chapter, we explore what is known about the reproductive strategies and tactics of baleen whales, with a particular focus on the comparatively well-studied right whales (Eubalaena spp.) and humpback whales (Megaptera novaeangliae). Finally, we showcase that by integrating multiple data types, we can explore the interactions between anatomy, physiology, reproductive success, age, population dynamics, and acoustic displays to better understand the mating systems of baleen whales.Publisher PD

Phylogenetically controlled life history trait meta-analysis in cetaceans reveals unexpected negative brain size and longevity correlation

Funding: ELC was supported by a Rutherford Discovery Fellowship from the Royal Society of New Zealand Te Apārangi and EG was supported by a University Research Fellowship from the Royal Society of London.The identification of patterns in trait evolution is essential to understand the interaction of evolutionary forces, and provides useful information for species management. Cetaceans are a phylogenetically well-resolved infraorder that exhibit distinct trait variation across behavioural, molecular and life history dimensions, yet few researchers have applied a meta-analytic or comparative approach to these traits. To understand cetacean trait evolution, we used a phylogenetic generalised least squares approach to examine the cognitive buffer hypothesis (CBH). A large brain should buffer individuals against environmental challenges through increasing survival rates, and a longer lifespan should buffer individuals against the cost of extended development for larger brains according to the CBH, leading to an expected positive correlation between brain size and lifespan. In contrast to this expectation, previously observed in taxa including primates, we found a negative correlation between brain size and lifespan in cetaceans. This suggests cetaceans experience selective pressures different from most other mammals in these traits but may be more similar to some social mammalian carnivores that display alloparenting. We also provide a comprehensive dataset to explore additional aspects of trait evolution but which would greatly benefit from studies on behavioural ecology across cetaceans and increased focus on data deficient species.Publisher PDFPeer reviewe

A pan-cetacean MHC amplicon sequencing panel developed and evaluated in combination with genome assemblies

This study was funded by a Royal Society Research Grants for Research Fellows (RGF\R1\181014) to E.C.G. E.C.G. is funded by a Royal Society University Research Fellowship (UF160081 & URF\R\221020). F.E. is supported by a University of St Andrews School of Biology Ph.D. scholarship and a Royal Society Research Fellows Enhancement Award (RGF\EA\180213 to E.C.G). E.L.C. is funded by a Rutherford Discovery Fellowship from the Royal Society of New Zealand Te Apārangi.The major histocompatibility complex (MHC) is a highly polymorphic gene family that is crucial in immunity, and its diversity can be effectively used as a fitness marker for populations. Despite this, MHC remains poorly characterised in non-model species (e.g., cetaceans: whales, dolphins and porpoises) as high gene copy number variation, especially in the fast-evolving class I region, makes analyses of genomic sequences difficult. To date, only small sections of class I and IIa genes have been used to assess functional diversity in cetacean populations. Here, we undertook a systematic characterisation of the MHC class I and IIa regions in available cetacean genomes. We extracted full-length gene sequences to design pan-cetacean primers that amplified the complete exon2 from MHC class I and IIa genes in one combined sequencing panel. We validated this panel in 19 cetacean species and described 354 alleles for both classes. Furthermore, we identified likely assembly artefacts for many MHC class I assemblies based on the presence of class I genes in the amplicon data compared to missing genes from genomes. Finally, we investigated MHC diversity using the panel in 25 humpback and 30 southern right whales, including four paternity trios for humpback whales. This revealed copy-number variable class I haplotypes in humpback whales, which is likely a common phenomenon across cetaceans. These MHC alleles will form the basis for a cetacean branch of the Immuno-Polymorphism Database (IPD-MHC), a curated resource intended to aid in the systematic compilation of MHC alleles across several species, to support conservation initiatives.Peer reviewe

Structural optimization of MacPherson control arm under fatigue loading

U ovom istraživanju izvršena je optimizacija topologije i oblika MacPherson upravljačke poluge u svrhu postizanja manje težina. Postojeće automobilsko tržište traži dijelove niske cijene i male težine, a za potrebe energetski učinkovitog, a jeftinog vozila. To zahtijeva učinkovitiju uporabu materijala za automobilske dijelove koji mogu dovesti do smanjene mase vozila. Budući da su automobilski dijelovi izloženi dinamičkim opterećenjima koja uzrokuju oštećenja zbog zamora, uzimanje u obzir kriterija zamora čini se bitnim u dizajniranju automobilskih dijelova. Kako bi se stvorili što teži uvjeti opterećenja upravljačke poluge, najprije su spektralnom gustoćom snage generirane neravne ceste. Zatim su, dinamičkom analizom karoserije kompletnog modela vozila, dobiveni najkritičniji uvjeti opterećenja. Nakon toga, izvršena je optimizacija topologije pomoću kriterija vijeka trajanja do zamora primjenom HyperMesh softvera, što je rezultiralo smanjenjem mase od 50 %. U sljedećem koraku kreiran je CAD model primjenom CATIA softvera i provedena optimizacija oblika kako bi se dobile točne dimenzije s manje mase.In this research, the topology and shape optimization of a MacPherson control arm has been accomplished to achieve lighter weight. Present automotive market demands low cost and light weight component to meet the need of fuel efficient and cost effective vehicle. This in turn gives the rise to more effective use of materials for automotive parts which can reduce the mass of vehicle. Since automotive components are under dynamic loads which cause fatigue damage, considering fatigue criteria seems to be essential in designing automotive components. At first, in order to create severe loading condition for control arm some rough roads are generated through power spectral density. Then, the most critical loading conditions are obtained through multi body dynamics analysis of a full vehicle model. Then, the topology optimization is performed based on fatigue life criterion using HyperMesh software, which resulted in 50 % mass reduction. In the next step a CAD model is created using CATIA software and shape optimization is performed to achieve accurate dimensions with less mass

Demography and ecology of southern right whales Eubalaena australis wintering at sub-Antarctic Campbell Island, New Zealand

Since the decimation of the southern right whale Eubalaena australis population in New Zealand by whaling, research on its recovery has focused on the wintering ground at the Auckland Islands, neglecting potentially important wintering habitat at Campbell Island. For the first time in 20 years we conducted an expedition to sub-Antarctic Campbell Island to document and describe E. australis occupying this wintering habitat. We used a variety of methods including photo-identification, genetic and stable isotope analyses of tissue samples, and visual surveys of abundance and distribution, to provide details on the demography, population connectivity and ecology of E. australis wintering at Campbell Island. Our primary findings include (1) a lack of calves observed at Campbell Island, (2) an age-class bias toward sub-adults encountered at Campbell Island, (3) nine photo-identification matches between individuals observed at Campbell Island and previously documented elsewhere in New Zealand, (4) no genetic differentiation between E. australis at Campbell Island and the broader New Zealand population, (5) increased abundance estimates of E. australis at Campbell Island over the last 20 years, and (6) indications that E. australis forage within the sub-Antarctic region based on stable isotope analyses. Our results confirm that the Auckland Islands are currently the only significant calving area for E. australis in New Zealand, and therefore previous abundance estimates based on demographic data from the Auckland Islands are applicable to the entire New Zealand population of E. australis. However, future periodic surveys to Campbell Island are recommended to monitor population recovery and expansion.PostprintPeer reviewe

An unexpected link between fatty acid synthase and cholesterol synthesis in proinflammatory macrophage activation

Different immune activation states require distinct metabolic features and activities in immune cells. For instance, inhibition of fatty acid synthase (FASN), which catalyzes the synthesis of long-chain fatty acids, prevents the proinflammatory response in macrophages; however, the precise role of this enzyme in this response remains poorly defined. Consistent with previous studies, we found here that FASN is essential for lipopolysaccharide-induced, Toll-like receptor (TLR)-mediated macrophage activation. Interestingly, only agents that block FASN upstream of acetoacetyl-CoA synthesis, including the well-characterized FASN inhibitor C75, inhibited TLR4 signaling, while those acting downstream had no effect. We found that acetoacetyl-CoA could overcome C75's inhibitory effect, whereas other FASN metabolites, including palmitate, did not prevent C75-mediated inhibition. This suggested an unexpected role for acetoacetyl-CoA in inflammation that is independent of its role in palmitate synthesis. Our evidence further suggested that acetoacetyl-CoA arising from FASN activity promotes cholesterol production, indicating a surprising link between fatty acid synthesis and cholesterol synthesis. We further demonstrate that this process is required for TLR4 to enter lipid rafts and facilitate TLR4 signaling. In conclusion, we have uncovered an unexpected link between FASN and cholesterol synthesis that appears to be required for TLR signal transduction and proinflammatory macrophage activation

Genetic diversity and connectivity of southern right whales (Eubalaena australis) found in the Brazil and Chile-Peru wintering grounds and the South Georgia (Islas Georgias del Sur) feeding ground

As species recover from exploitation, continued assessments of connectivity and population structure are warranted to provide information for conservation and management. This is particularly true in species with high dispersal capacity, such as migratory whales, where patterns of connectivity could change rapidly. Here we build on a previous long-term, large-scale collaboration on southern right whales (Eubalaena australis) to combine new (nnew) and published (npub) mitochondrial (mtDNA) and microsatellite genetic data from all major wintering grounds and, uniquely, the South Georgia (Islas Georgias del Sur: SG) feeding grounds. Specifically, we include data from Argentina (npub mtDNA/microsatellite=208/46), Brazil (nnew mtDNA/microsatellite=50/50), South Africa (nnew mtDNA/microsatellite=66/77, npub mtDNA/microsatellite=350/47), Chile-Peru (nnew mtDNA/microsatellite=1/1), the Indo-Pacific (npub mtDNA/microsatellite=769/126), and SG (npub mtDNA/microsatellite=8/0, nnew mtDNA/microsatellite=3/11) to investigate the position of previously unstudied habitats in the migratory network: Brazil, SG and Chile-Peru. These new genetic data show connectivity between Brazil and Argentina, exemplified by weak genetic differentiation and the movement of one genetically identified individual between the South American grounds. The single sample from Chile-Peru had a mtDNA haplotype previously only observed in the Indo-Pacific and had a nuclear genotype that appeared admixed between the Indo-Pacific and South Atlantic, based on genetic clustering and assignment algorithms. The SG samples were clearly South Atlantic, and were more similar to the South American than the South African wintering grounds. This study highlights how international collaborations are critical to provide context for emerging or recovering regions, like the SG feeding ground, as well as those that remain critically endangered, such as Chile-Peru

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability