Improved functions for nonlinear sequence comparison using SEEKR.

SEquence Evaluation through k-mer Representation (SEEKR) is a method of sequence comparison that uses sequence substrings called k-mers to quantify the nonlinear similarity between nucleic acid species. We describe the development of new functions within SEEKR that enable end-users to estimate P-values that ascribe statistical significance to SEEKR-derived similarities, as well as visualize different aspects of k-mer similarity. We apply the new functions to identify chromatin-enriched lncRNAs that contain XIST-like sequence features, and we demonstrate the utility of applying SEEKR on lncRNA fragments to identify potential RNA-protein interaction domains. We also highlight ways in which SEEKR can be applied to augment studies of lncRNA conservation, and we outline the best practice of visualizing RNA-seq read density to evaluate support for lncRNA annotations before their in-depth study in cell types of interest.

SAFB associates with nascent RNAs and can promote gene expression in mouse embryonic stem cells.

Scaffold attachment factor B (SAFB) is a conserved RNA-binding protein that is essential for early mammalian development. However, the functions of SAFB in mouse embryonic stem cells (ESCs) have not been characterized. Using RNA immunoprecipitation followed by RNA-seq (RIP-seq), we examined the RNAs associated with SAFB in wild-type and SAFB/SAFB2 double-knockout ESCs. SAFB predominantly associated with introns of protein-coding genes through purine-rich motifs. The transcript most enriched in SAFB association was the lncRNA Malat1, which also contains a purine-rich region in its 5' end. Knockout of SAFB/SAFB2 led to differential expression of approximately 1000 genes associated with multiple biological processes, including apoptosis, cell division, and cell migration. Knockout of SAFB/SAFB2 also led to splicing changes in a set of genes that were largely distinct from those that exhibited changes in expression level. The spliced and nascent transcripts of many genes whose expression levels were positively regulated by SAFB also associated with high levels of SAFB, implying that SAFB binding promotes their expression. Reintroduction of SAFB into double-knockout cells restored gene expression toward wild-type levels, an effect again observable at the level of spliced and nascent transcripts. Proteomics analysis revealed a significant enrichment of nuclear speckle-associated and RS domain-containing proteins among SAFB interactors. Neither Xist nor Polycomb functions were dramatically altered in SAFB/2 knockout ESCs. Our findings suggest that among other potential functions in ESCs, SAFB promotes the expression of certain genes through its ability to bind nascent RNA.

The Scandium(II) Carbonyl Complex (C5H2tBu3)2Sc(CO) and Its Isocyanide Analog (C5H2tBu3)2Sc(CNC6H3Me2-2,6).

Treatment of the scandium(II) metallocene Cpttt2Sc (Cpttt = C5H2tBu3) with CO or the isocyanide CNXyl (Xyl = C6H3Me2-2,6) yields the carbonyl complex Cpttt2Sc(CO), 1, or the isocyanide complex Cpttt2Sc(CNXyl), 2, which were identified by X-ray crystallography. Isotopic labeling with 13CO shows the CO stretch of 1 at 1875 cm-1 shifts to 1838 cm-1 in 1-13CO. The CN stretch in 2 is shifted to 1939 cm-1 compared to 2118 cm-1 for the free isocyanide. The 80.1 MHz (28.7 G) 45Sc hyperfine coupling in 1 and 74.7 MHz (26.8 G) in 2 are similar to the 82.6 MHz (29.6 G) coupling constant in Cpttt2Sc and indicate that 1 and 2 are Sc(II) complexes. A comprehensive analysis of the electronic structures of 1 and 2 using DFT calculations is reported.

A modest increase in fire weather overcomes resistance to fire spread in recently burned boreal forests.

Recently burned boreal forests have lower aboveground fuel loads, generating a negative feedback to subsequent wildfires. Despite this feedback, short-interval reburns (≤20 years between fires) are possible under extreme weather conditions. Reburns have consequences for ecosystem recovery, leading to enduring vegetation change. In this study, we characterize the strength of the fire-fuel feedback in recently burned Canadian boreal forests and the weather conditions that overwhelm resistance to fire spread in recently burned areas. We used a dataset of daily fire spread for thousands of large boreal fires, interpolated from remotely sensed thermal anomalies to which we associated local weather from ERA5-Land for each day of a fire's duration. We classified days with >3 ha of fire growth as spread days and defined burned pixels overlapping a fire perimeter ≤20 years old as short-interval reburns. Results of a logistic regression showed that the odds of fire spread in recently burned areas were ~50% lower than in long-interval fires; however, all Canadian boreal ecozones experienced short-interval reburning (1981-2021), with over 100,000 ha reburning annually. As fire weather conditions intensify, the resistance to fire spread declines, allowing fire to spread in recently burned areas. The weather associated with short-interval fire spread days was more extreme than the conditions during long-interval spread, but overall differences were modest (e.g. relative humidity 2.6% lower). The frequency of fire weather conducive to short-interval fire spread has significantly increased in the western boreal forest due to climate warming and drying (1981-2021). Our results suggest an ongoing degradation of fire-fuel feedbacks, which is likely to continue with climatic warming and drying.

Hibernating female big brown bats (Eptesicus fuscus) adjust huddling and drinking behaviour, but not arousal frequency, in response to low humidity.

Many mammals hibernate during winter, reducing energy expenditure via bouts of torpor. The majority of a hibernator's energy reserves are used to fuel brief, but costly, arousals from torpor. Although arousals likely serve multiple functions, an important one is to restore water stores depleted during torpor. Many hibernating bat species require high humidity, presumably to reduce torpid water loss, but big brown bats (Eptesicus fuscus) appear tolerant of a wide humidity range. We tested the hypothesis that hibernating female E. fuscus use behavioural flexibility during torpor and arousals to maintain water balance and reduce energy expenditure. We predicted: (1) E. fuscus hibernating in dry conditions would exhibit more compact huddles during torpor and drink more frequently than bats in high humidity conditions; and (2) the frequency and duration of torpor bouts and arousals, and thus total loss of body mass would not differ between bats in the two environments. We housed hibernating E. fuscus in temperature- and humidity-controlled incubators at 50% or 98% relative humidity (8°C, 110 days). Bats in the dry environment maintained a more compact huddle during torpor and drank more frequently during arousals. Bats in the two environments had a similar number of arousals, but arousal duration was shorter in the dry environment. However, total loss of body mass over hibernation did not differ between treatments, indicating that the two groups used similar amounts of energy. Our results suggest that behavioural flexibility allows hibernating E. fuscus to maintain water balance and reduce energy costs across a wide range of hibernation humidities.

Assessing contact dermatitis risk among Manitoba workers in the Manitoba Occupational Disease Surveillance System.

INTRODUCTION: This exploratory study aimed to assess contact dermatitis (CD) risk among workers using the Manitoba Occupational Disease Surveillance System (MODSS). METHODS: The MODSS linked accepted time-loss claims from the Workers' Compensation Board of Manitoba (2006-2019), with administrative health data from medical and hospital records (1996-2020). CD risk by occupation and industry (hazard ratio, 95% confidence intervals) was estimated using Cox proportional hazard models, adjusted for age and stratified by sex. RESULTS: Increased risk of new onset CD was observed among some occupations and industries with known skin irritants and allergens. Some occupations with known increased risks of CD remained elevated when removing the accepted WCB cases was performed, suggesting that all CD cases in these occupations may not show up in WCB statistics. Increased risk was also observed for occupations and industries with unknown exposures related to CD, whereas some groups known to be at risk of CD were not observed to have elevated risks in this cohort. DISCUSSION: The MODSS successfully identified some occupations and industries known to be at high risk of occupational CD, but not others. Some occupations not typically associated with work-related CD were also identified, which warrants further investigation.

Surviving winter on the Qinghai-Tibetan Plateau: Pikas suppress energy demands and exploit yak feces to survive winter.

The Qinghai-Tibetan Plateau, with low precipitation, low oxygen partial pressure, and temperatures routinely dropping below -30 °C in winter, presents several physiological challenges to its fauna. Yet it is home to many endemic mammalian species, including the plateau pika (Ochotona curzoniae). How these small animals that are incapable of hibernation survive the winter is an enigma. Measurements of daily energy expenditure (DEE) using the doubly labeled water method show that pikas suppress their DEE during winter. At the same body weight, pikas in winter expend 29.7% less than in summer, despite ambient temperatures being approximately 25 °C lower. Combined with resting metabolic rates (RMRs), this gives them an exceptionally low metabolic scope in winter (DEE/RMRt = 1.60 ± 0.30; RMRt is resting metabolic rate at thermoneutrality). Using implanted body temperature loggers and filming in the wild, we show that this is achieved by reducing body temperature and physical activity. Thyroid hormone (T3 and T4) measurements indicate this metabolic suppression is probably mediated via the thyroid axis. Winter activity was lower at sites where domestic yak (Bos grunniens) densities were higher. Pikas supplement their food intake at these sites by eating yak feces, demonstrated by direct observation, identification of yak DNA in pika stomach contents, and greater convergence in the yak/pika microbiotas in winter. This interspecific coprophagy allows pikas to thrive where yak are abundant and partially explains why pika densities are higher where domestic yak, their supposed direct competitors for food, are more abundant.

White-Nose Syndrome Disrupts the Splenic Lipidome of Little Brown Bats (Myotis lucifugus) at Early Disease Stages.

White-nose syndrome (WNS)-positive little brown bats (Myotis lucifugus) may exhibit immune responses including increased cytokine and pro-inflammatory mediator gene levels. Bioactive lipid mediators (oxylipins) formed by enzymatic oxidation of polyunsaturated fatty acids can contribute to these immune responses, but have not been investigated in WNS pathophysiology. Nonenzymatic conversion of polyunsaturated fatty acids can also occur due to reactive oxygen species, however, these enantiomeric isomers will lack the same signaling properties. In this study, we performed a series of targeted lipidomic approaches on laboratory Pseudogymnoascus destructans-inoculated bats to assess changes in their splenic lipidome, including the formation of lipid mediators at early stages of WNS. Hepatic lipids previously identified were also resolved to a higher structural detail. We compared WNS-susceptible M. lucifugus to a WNS-resistant species, the big brown bat (Eptesicus fuscus). Altered splenic lipid levels were only observed in M. lucifugus. Differences in splenic free fatty acids included both omega-3 and omega-6 compounds. Increased levels of an enantiomeric monohydroxy DHA mixture were found, suggesting nonenzymatic formation. Changes in previously identified hepatic lipids were confined to omega-3 constituents. Together, these results suggest that increased oxidative stress, but not an inflammatory response, is occurring in bats at early stages of WNS that precedes fat depletion. These data have been submitted to metabolomics workbench and assigned a study number ST002304.

Broadleaf tree phenology and springtime wildfire occurrence in boreal Canada.

Although broadleaf tree species of the boreal biome have a lower flammability compared to conifers, there is a period following snow melt and prior to leaf flush (i.e., greenup), termed the "spring window" by fire managers, when these forests are relatively conducive to wildfire ignition and spread. The goal of this study was to characterize the duration, timing, and fire proneness of the spring window across boreal Canada and assess the link between these phenological variables and the incidence of springtime wildfires. We used remotely sensed snow cover and greenup data to identify the annual spring window for five boreal ecozones from 2001 to 2021 and then compared seasonality of wildfire starts (by cause) and fire-conducive weather in relation to this window, averaged over the 21-year period. We conducted a path analysis to concomitantly evaluate the influence of the spring window's duration, the timing of greenup, and fire-conducive weather on the annual number and the seasonality of spring wildfires. Results show that the characteristics of spring windows vary substantially from year to year and among geographic zones, with the interior west of Canada having the longest and most fire-conducive spread window and, accordingly, the greatest springtime wildfire activity. We also provide support for the belief that springtime weather generally promotes wind-driven, rather than drought-driven wildfires. The path analyses show idiosyncratic behavior among ecozones, but, in general, the seasonality of the wildfire season is mainly driven by the timing of the greenup, whereas the number of spring wildfires mostly responds to the duration of the spring window and the frequency of fire-conducive weather. The results of this study allows us to better understand and anticipate the biome-wide changes projected for the northern forests of North America.

Experimental and Theoretical Exploration of the Kinetics and Thermodynamics of the Nucleophile-Induced Fragmentation of Ylidenenorbornadiene Carboxylates.

Ylidenenorbornadienes (YNDs), prepared by [4 + 2] cycloadditions between fulvenes and acetylene carboxylates, react with thiol nucleophiles to yield mixtures of four to eight diastereomers depending on the symmetry of the YND substrate. The mixtures of diastereomers fragment via a retro-[4 + 2] cycloaddition with a large variation in rate, with half-lives ranging from 16 to 11,000 min at 80 °C. The diastereomer-enriched samples of propane thiol adducts [YND-propanethiol (PTs)] were isolated and identified by nuclear Overhauser effect spectroscopy (NOESY) correlations. Simulated kinetics were used to extrapolate the rate constants of individual diastereomers from the observed rate data, and it correlated well with rate constants measured directly and from isolated diastereomer-enriched samples. The individual diastereomers of a model system fragment at differing rates with half-lives ranging from 5 to 44 min in CDCl3. Density functional theory calculations were performed to investigate the mechanism of fragmentation and support an asynchronous retro-[4 + 2] cycloaddition transition state. The computations generally correlated well with the observed free energies of activation for four diastereomers of the model system as a whole, within 2.6 kcal/mol. However, the observed order of the fragmentation rates across the set of diastereomers deviated from the computational results. YNDs display wide variability in the rate of fragmentation, dependent on the stereoelectronics of the ylidene substituents. A Hammett study showed that the electron-rich aromatic rings attached to the ylidene bridge increase the fragmentation rate, while electron-deficient systems slow fragmentation rates.

Cognitive decrements in 1991 Gulf War veterans: associations with Gulf War illness and neurotoxicant exposures in the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) cohorts.

BACKGROUND: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. METHODS: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. RESULTS: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. CONCLUSIONS: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.

Human Milk Oligosaccharide Compositions Illustrate Global Variations in Early Nutrition.

BACKGROUND: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. OBJECTIVES: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. METHODS: LC-MS-based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. RESULTS: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. CONCLUSIONS: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.

Radial scars and complex sclerosing lesions on core needle biopsy of the breast: upgrade rates and long-term outcomes.

PURPOSE: Radial scars and complex sclerosing lesions of the breast are part of a group of "indeterminate" breast lesions, which are excised due to risk of coexistent carcinoma. The aim of this study was to assess rate of upgrade of these lesions to invasive and in situ carcinoma and to quantify the risk of development of subsequent cancer in women diagnosed with these lesions. METHODS: A retrospective review of a prospectively maintained breast screening database was performed. All patients with radial scar identified at either core biopsy or final excision biopsy between January 2006 and July 2012 were identified. Full pathological reports for both core biopsy and final excision biopsy were reviewed. Patient outcomes were followed for a mean of 117.1 months. RESULTS: Of 451 B3 biopsies performed at our screening unit, 95 (22%) were found to have a radial scar or complex sclerosing lesion (CSL) on core needle biopsy. Within this group, 77 had no atypia on CNB, with 7 (9%) upgraded to invasive/in situ carcinoma on final excision. Of nine with definite atypia on CNB, 3 (33%) were upgraded. In those patients without atypia or malignancy on final excision, 7.5% developed cancer during 10-year follow-up. CONCLUSION: Patients with radial scar with atypia have a higher risk of upgrade to malignancy. Further research is needed to identify which patients may safely avoid excision of radial scar. Patients with a diagnosis of radial scar on CNB are at increased subsequent risk of breast cancer and may benefit from additional screening.

Detection of haplosporidian protistan parasites supports an increase to their known diversity, geographic range and bivalve host specificity.

Haplosporidian protist parasites are a major concern for aquatic animal health, as they have been responsible for some of the most significant marine epizootics on record. Despite their impact on food security, aquaculture and ecosystem health, characterizing haplosporidian diversity, distributions and host range remains challenging. In this study, water filtering bivalve species, cockles Cerastoderma edule, mussels Mytilus spp. and Pacific oysters Crassostrea gigas, were screened using molecular genetic assays using deoxyribonucleic acid (DNA) markers for the Haplosporidia small subunit ribosomal deoxyribonucleic acid region. Two Haplosporidia species, both belonging to the Minchinia clade, were detected in C. edule and in the blue mussel Mytilus edulis in a new geographic range for the first time. No haplosporidians were detected in the C. gigas, Mediterranean mussel Mytilus galloprovincialis or Mytilus hybrids. These findings indicate that host selection and partitioning are occurring amongst cohabiting bivalve species. The detection of these Haplosporidia spp. raises questions as to whether they were always present, were introduced unintentionally via aquaculture and or shipping or were naturally introduced via water currents. These findings support an increase in the known diversity of a significant parasite group and highlight that parasite species may be present in marine environments but remain undetected, even in well-studied host species.

Among-population divergence in personality is linked to altitude in plateau pikas (Ochotona curzoniae ).

BACKGROUND: Animals inhabiting high altitudes consistently show slow life-histories. The pace-of-life syndrome (POLS) hypothesis posits behavioural, physiological and/or morphological traits that mediate the trade-off between current and future reproduction or survival, which have coevolved along a slow-fast life history continuum. Previous studies have shown that the life histories of plateau pikas varied across altitude, high-altitude individuals showed slow pace of life which were characterized by few litters per year with small litter sizes. Thus, we hypothesized that pikas populations at higher altitudes would also express personalities characteristic associated with slow life history, such as high sociability, low activity or aggressiveness. We tested this hypothesis by comparing the activity and docility of three plateau pika (Ochotona curzoniae) populations distributed along an altitudinal gradient of the Tibetan Plateau. We predicted that high-altitude pika would be more docile and less active. RESULTS: The behaviour of 556 pikas, from which 120 individuals were measured at least twice, was quantified. We observed that plateau pikas at high altitudes were less active and more docile than pika at lower altitudes. Activity and docility were significantly and negatively correlated in populations from high altitudes but not in populations from low altitudes. CONCLUSIONS: Our results support the POLS hypothesis, highlight the existence of personality variation among populations distributed along an altitudinal gradient and emphasise the importance of environmental selection on personality divergence.

Seven cases of probable endotoxin poisoning related to contaminated glutathione infusions.

We report seven cases of probable endotoxin poisoning linked to contaminated compounded glutathione. Five of the cases were using the infusions for treatment of Lyme disease highlighting the risks of using compounded sterile preparations for unapproved indications, especially if the quality of source products cannot be assured.

Enhancing the get healthy information and coaching service for Aboriginal adults: evaluation of the process and impact of the program.

BACKGROUND: Non-communicable chronic diseases in Australia contribute to approximately 85% of the total burden of disease; this proportion is greater for Aboriginal communities. The Get Healthy Service (GHS) is effective at reducing lifestyle-based chronic disease risk factors among adults and was enhanced to facilitate accessibility and ensure Aboriginal cultural appropriateness. The purpose of this study is to detail how formative research with Aboriginal communities was applied to guide the development and refinement of the GHS and referral pathways; and to assess the reach and impact of the GHS (and the Aboriginal specific program) on the lifestyle risk factors of Aboriginal participants. METHODS: Formative research included interviews with Aboriginal participants, leaders and community members, healthcare professionals and service providers to examine acceptability of the GHS; and contributed to the redesign of the GHS Aboriginal program. A quantitative analysis employing a pre-post evaluation design examined anthropometric measures, physical activity and fruit and vegetable consumption of Aboriginal participants using descriptive and chi square analyses, t-tests and Wilcoxon signed-rank tests. RESULTS: Whilst feedback from the formative research was positive, Aboriginal people identified areas for service enhancement, including improving program content, delivery and service promotion as well as ensuring culturally appropriate referral pathways. Once these changes were implemented, the proportion of Aboriginal participants increased significantly (3.2 to 6.4%). There were significant improvements across a number of risk factors assessed after six months (average weight loss: 3.3 kg and waist circumference reduction: 6.2 cm) for Aboriginal participants completing the program. CONCLUSIONS: Working in partnership with Aboriginal people, Elders, communities and peak bodies to enhance the GHS for Aboriginal people resulted in an enhanced culturally acceptable and tailored program which significantly reduced chronic disease risk factors for Aboriginal participants. Mainstream telephone based services can be modified and enhanced to meet the needs of Aboriginal communities through a process of consultation, community engagement, partnership and governance.

Quantitative measures of meniscus extrusion predict incident radiographic knee osteoarthritis--data from the Osteoarthritis Initiative.

OBJECTIVE: To test the hypothesis that quantitative measures of meniscus extrusion predict incident radiographic knee osteoarthritis (KOA), prior to the advent of radiographic disease. METHODS: 206 knees with incident radiographic KOA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline, developing KLG 2 or greater with a definite osteophyte and joint space narrowing (JSN) grade ≥1 by year 4) were matched to 232 control knees not developing incident KOA. Manual segmentation of the central five slices of the medial and lateral meniscus was performed on coronal 3T DESS MRI and quantitative meniscus position was determined. Cases and controls were compared using conditional logistic regression adjusting for age, sex, BMI, race and clinical site. Sensitivity analyses of early (year [Y] 1/2) and late (Y3/4) incidence was performed. RESULTS: Mean medial extrusion distance was significantly greater for incident compared to non-incident knees (1.56 mean ± 1.12 mm SD vs 1.29 ± 0.99 mm; +21%, P < 0.01), so was the percent extrusion area of the medial meniscus (25.8 ± 15.8% vs 22.0 ± 13.5%; +17%, P < 0.05). This finding was consistent for knees restricted to medial incidence. No significant differences were observed for the lateral meniscus in incident medial KOA, or for the tibial plateau coverage between incident and non-incident knees. Restricting the analysis to medial incident KOA at Y1/2 differences were attenuated, but reached significance for extrusion distance, whereas no significant differences were observed at incident KOA in Y3/4. CONCLUSION: Greater medial meniscus extrusion predicts incident radiographic KOA. Early onset KOA showed greater differences for meniscus position between incident and non-incident knees than late onset KOA.

Velocity of climate change algorithms for guiding conservation and management.

The velocity of climate change is an elegant analytical concept that can be used to evaluate the exposure of organisms to climate change. In essence, one divides the rate of climate change by the rate of spatial climate variability to obtain a speed at which species must migrate over the surface of the earth to maintain constant climate conditions. However, to apply the algorithm for conservation and management purposes, additional information is needed to improve realism at local scales. For example, destination information is needed to ensure that vectors describing speed and direction of required migration do not point toward a climatic cul-de-sac by pointing beyond mountain tops. Here, we present an analytical approach that conforms to standard velocity algorithms if climate equivalents are nearby. Otherwise, the algorithm extends the search for climate refugia, which can be expanded to search for multivariate climate matches. With source and destination information available, forward and backward velocities can be calculated allowing useful inferences about conservation of species (present-to-future velocities) and management of species populations (future-to-present velocities).

The impact of reproduction on the stress axis of free-living male northern red backed voles (Myodes rutilus).

Activation of the hypothalamic-pituitary-adrenal (HPA) axis culminates in the release of glucocorticoids (henceforth CORT), which have wide-reaching physiological effects. Three hypotheses potentially explain seasonal variation in CORT. The enabling hypothesis predicts that reproductive season CORT exceeds post-reproductive season CORT because CORT enables reproductive investment. The inhibitory hypothesis predicts the opposite because CORT can negatively affect reproductive function. The costs of reproduction hypothesis predicts that HPA axis condition declines over and following the reproductive season. We tested these hypotheses in wild male red-backed voles (Myodes rutilus) during the reproductive and post-reproductive seasons. We quantified CORT levels in response to restraint stress tests consisting of three blood samples (initial, stress-induced, and recovery). Mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA levels in the brain were also quantified over the reproductive season. Total CORT (tCORT) in the initial and stress-induced samples were greater in the post-reproductive than in the reproductive season, which supported the inhibitory hypothesis. Conversely, free CORT (fCORT) did not differ between the reproductive and post-reproductive seasons, which was counter to both the enabling and inhibitory hypotheses. Evidence for HPA axis condition decline in CORT as well as GR and MR mRNA over the reproductive season (i.e. costs of reproduction hypothesis) was mixed. Moreover, all of the parameters that showed signs of declining condition over the reproductive season did not also show signs of declining condition over the post-reproductive season suggesting that the costs resulting from reproductive investment had subsided. In conclusion, our results suggest that different aspects of the HPA axis respond differently to seasonal changes and reproductive investment.