The distribution of South African loggerhead sea turtles (Caretta caretta) as indicated by epibionts and stable isotopes

Many marine species undertake long-distance migrations as part of their life history strategies, and so form an important part of marine ecosystems performing a range of functions, across many habitats. However, these migratory species, including sea turtles, face multiple threats and anthropogenic impacts across their ranges and knowing their movement and distribution patterns enables more effective and appropriate conservation strategies to be devised. Satellite telemetry has provided invaluable information on spatial distribution of marine migrants, but applying this approach to a large proportion of a population is often unfeasible and costly. This study aimed to identify alternative, more cost effective methods that could assist with tracking animal movements across a larger proportion of a population of marine focal species, such as sea turtles. This study used nesting loggerhead sea turtles (Caretta caretta) from the iSimangaliso Wetland Park, South Africa as a model species to test these alternative methods and subsequently combine body condition, habitat use, and distribution range in the South West Indian Ocean. First, epibiont community assemblages were investigated as a proxy to determine sea turtle body condition. A body condition index was created using plastron shape, injuries and skin deformities. Sixty turtles were classified into four body condition categories ranging from poor to very good and this was reflected in their epibiont communities as both species abundance and richness increased with a decline in body condition. A total of twenty-eight epibiont taxa were identified from a range of systematic groups including, but not limited to, Amphipoda, Cirripedia, Brachyura and Polychaeta. The barnacle Chelonibia testudinaria showed the greatest variation among different body conditions with an increase in abundance as turtle body condition deteriorated. These results suggest that epibiont load can be used as an indicator of body condition that is easy to implement in the field. Second, a combination of organic δ13C and δ15N isotopic signatures of turtle epidermis and epibiont communities was used to infer foraging habitat. One hundred and seventy turtles were sampled for stable isotope analysis. These turtles were clustered into two groups based on δ13C at -13.61 ‰ with relative depletion or enrichment indicating foraging in oceanic or neritic environments, respectively. The epibiont communities of IV 80 turtles closely followed this cluster grouping; turtles with depleted δ13C had a higher abundance and frequency of oceanic epibiont species, such Lepas spp. Similarly, three neritic epibionts (Hyale grandicornis, Hyachelia tortugae and Podocerus africanus) were the other habitat-specific species driving community assemblages, with higher occurrence and abundance on turtles in the enriched δ13C cluster. Additionally, the size of the dietary niche was determined by a Bayesian analysis of δ13C and δ15N for 46 turtles in different body condition categories. Although there was overlap among categories, individuals in very good body condition had the smallest dietary niche. These results show the complementarity of using epibionts and stable isotope analysis in determining foraging area. Third, Chelonibia testudinaria barnacles on sea turtles were analysed for δ18O and inorganic δ13C. The δ18O of expected calcite fractionation was mapped for the known migration routes of eight turtles in the South West Indian Ocean. The inorganic carbon values were not very informative on movement, however, the δ18O analysis of the barnacle showed the range of the turtle host moving through the isoscape. Most of the turtles migrated from the north in the Mozambique Channel, to the southern rookery in South Africa, which is in accordance with reports from tag recoveries and satellite telemetry studies. Using this approach to track migratory species that have epibiotic barnacles can provide complimentary approach to satellite tracking that can be used on more individuals within a population. This study aids in providing alternative methods to study body condition, habitat use and regional movement of loggerhead sea turtles. These approaches can be applied to other sea turtle species and migratory marine fauna to help better understand their movement patterns thereby promoting more effective conservation strategies. Future work should consider incorporating different cohorts, examining other epibionts such as meiofauna and diatoms, including additional isotope and trace elements for analysis on habitat and improving the resolution of the isoscape data for δ18O of seawater in the SWIO

An Ontological Model of User Preferences

The notion of preferences plays an important role in many disciplines including service robotics which is concerned with scenarios in which robots interact with humans. These interactions can be favored by robots taking human preferences into account. This raises the issue of how preferences should be represented to support such preference-aware decision making. Several formal accounts for a notion of preferences exist. However, these approaches fall short on defining the nature and structure of the options that a robot has in a given situation. In this work, we thus investigate a formal model of preferences where options are non-atomic entities that are defined by the complex situations they bring about

a protocol for developing a patient-reported outcome measurement instrument

Introduction: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions. Methods and analysis: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established through the use of focus groups. If patients deem necessary, we will develop new items based on the patients' input. We will examine whether it is valid to score all selected and developed items on the same scale as the original items from the PROMIS PF item bank. Our analyses will follow the methods used for calibrating the original PROMIS PF item bank in US samples, which were largely based on the general PROMIS approach. Ethics and dissemination: This study will be carried out in accordance with the Helsinki Declaration. Ethics approvals will be obtained where necessary, and signed informed consent will be obtained from all participants. We aim to disseminate the results of the study through publication in international peer-reviewed journals and at international conferences

Hand-related physical function in rheumatic hand conditions:a protocol for developing a patient-reported outcome measurement instrument

Introduction: There is no consensus about what constitutes the most appropriate patient-reported outcome measurement (PROM) instrument for measuring physical function in patients with rheumatic hand conditions. Existing instruments lack psychometric testing and vary in feasibility and their psychometric qualities. We aim to develop a PROM instrument to assess hand-related physical function in rheumatic hand conditions. Methods and analysis: We will perform a systematic search to identify existing PROMs to rheumatic hand conditions, and select items relevant for hand-related physical function as well as those items from the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) item bank that are relevant to patients with rheumatic hand conditions. Selection will be based on consensus among reviewers. Content validity of selected items will be established through the use of focus groups. If patients deem necessary, we will develop new items based on the patients' input. We will examine whether it is valid to score all selected and developed items on the same scale as the original items from the PROMIS PF item bank. Our analyses will follow the methods used for calibrating the original PROMIS PF item bank in US samples, which were largely based on the general PROMIS approach. Ethics and dissemination: This study will be carried out in accordance with the Helsinki Declaration. Ethics approvals will be obtained where necessary, and signed informed consent will be obtained from all participants. We aim to disseminate the results of the study through publication in international peer-reviewed journals and at international conferences

Biophysical Characterization of Pro-apoptotic BimBH3 Peptides Reveals an Unexpected Capacity for Self-Association

Bcl-2 proteins orchestrate the mitochondrial pathway of apoptosis, pivotal for cell death. Yet, the structural details of the conformational changes of pro- and antiapoptotic proteins and their interactions remain unclear. Pulse dipolar spectroscopy (double electron-electron resonance [DEER], also known as PELDOR) in combination with spin-labeled apoptotic Bcl-2 proteins unveils conformational changes and interactions of each protein player via detection of intra- and inter-protein distances. Here, we present the synthesis and characterization of pro-apoptotic BimBH3 peptides of different lengths carrying cysteines for labeling with nitroxide or gadolinium spin probes. We show by DEER that the length of the peptides modulates their homo-interactions in the absence of other Bcl-2 proteins and solve by X-ray crystallography the structure of a BimBH3 tetramer, revealing the molecular details of the inter-peptide interactions. Finally, we prove that using orthogonal labels and three-channel DEER we can disentangle the Bim-Bim, Bcl-xL-Bcl-xL, and Bim-Bcl-xL interactions in a simplified interactome.This work was funded by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2033—Projektnummer 390677874, the DFG Priority Program SPP1601 “New Frontiers in Sensitivity in EPR Spectroscopy” (to E.B.), DFG BO 3000/5-1 (to E.B.), SFB958 – Z04 (to E.B.), DFG grant INST 130/972-1 FUGG (to E.B.). P.E.C. is supported by an Australian NHMRC fellowship (1079700

Deviant reporter expression and P2X4 passenger gene overexpression in the soluble EGFP BAC transgenic P2X7 reporter mouse model

The ATP-gated P2X7 receptor is highly expressed in microglia and has been involved in diverse brain diseases. P2X7 effects were also described in neurons and astrocytes but its localisation and function in these cell types has been challenging to demonstrate in situ. BAC transgenic mouse lines have greatly advanced neuroscience research and two BAC-transgenic P2X7 reporter mouse models exist in which either a soluble EGFP (sEGFP) or an EGFP-tagged P2X7 receptor (P2X7-EGFP) is expressed under the control of a BAC-derived P2rx7 promoter. Here we evaluate both mouse models and find striking differences in both P2X expression levels and EGFP reporter expression patterns. Most remarkably, the sEGFP model overexpresses a P2X4 passenger gene and sEGFP shows clear neuronal localisation but appears to be absent in microglia. Preliminary functional analysis in a status epilepticus model suggests functional consequences of the observed P2X receptor overexpression. In summary, an aberrant EGFP reporter pattern and possible effects of P2X4 and/or P2X7 protein overexpression need to be considered when working with this model. We further discuss reasons for the observed differences and possible caveats in BAC transgenic approaches

Thyroid function and risk of all-cause and cardiovascular mortality:a prospective population-based cohort study

PURPOSE Although thyroid hormones are irrefutably implicated in cardiovascular physiology, the impact of within-reference range variations of thyroid function on cardiovascular disease (CVD) remains unclear. Elucidating this is important, since it could foster preventive treatment and reduce global CVD burden. We therefore investigated the impact of within-reference range variations of thyroid function on all-cause and cardiovascular mortality. METHODS We included community-dwelling individuals aged 28-75 years from a prospective cohort study, without known use of thyroid-affecting therapy and with thyrotropin within reference range. Associations of thyroid function with mortality were quantified using Cox models and adjusted for sociodemographic and cardiovascular risk factors. RESULTS Mean (SD) age of the 6,054 participants (52.0% male) was 53.3 (12.0) years. During 47,594 person-years of follow-up, we observed 380 deaths from all causes and 103 from CVDs. Although higher thyrotropin was not associated with all-cause mortality (adjusted HR 1.02, 95% CI 0.92-1.14), point estimates for cardiovascular mortality diverged toward increased risk in younger (<72 years) participants (1.31, 1.00-1.72) and decreased risk in elderly (≥72 years) (0.77, 0.56-1.06). Higher free thyroxine (FT4) was associated with all-cause mortality (1.18, 1.07-1.30) and with cardiovascular mortality only in elderly (1.61, 1.19-2.18), but not in younger participants (1.03, 0.78-1.34). Higher free triiodothyronine (FT3) was associated with all-cause mortality in females only (1.18, 1.02-1.35). FT3 was not associated with cardiovascular mortality (0.91, 0.70-1.18). CONCLUSIONS Community-dwelling elderly individuals with high-normal thyroid function are at increased risk of all-cause and cardiovascular mortality, reinforcing the need of redefining the current reference ranges of thyroid function

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Auditory cortical delta-entrainment interacts with oscillatory power in multiple fronto-parietal networks

The timing of slow auditory cortical activity aligns to the rhythmic fluctuations in speech. This entrainment is considered to be a marker of the prosodic and syllabic encoding of speech, and has been shown to correlate with intelligibility. Yet, whether and how auditory cortical entrainment is influenced by the activity in other speech–relevant areas remains unknown. Using source-localized MEG data, we quantified the dependency of auditory entrainment on the state of oscillatory activity in fronto-parietal regions. We found that delta band entrainment interacted with the oscillatory activity in three distinct networks. First, entrainment in the left anterior superior temporal gyrus (STG) was modulated by beta power in orbitofrontal areas, possibly reflecting predictive top-down modulations of auditory encoding. Second, entrainment in the left Heschl's Gyrus and anterior STG was dependent on alpha power in central areas, in line with the importance of motor structures for phonological analysis. And third, entrainment in the right posterior STG modulated theta power in parietal areas, consistent with the engagement of semantic memory. These results illustrate the topographical network interactions of auditory delta entrainment and reveal distinct cross-frequency mechanisms by which entrainment can interact with different cognitive processes underlying speech perception