ABSTRACT
BACKGROUND: Pegfilgrastim-cbqv/CHS-1701 (UDENYCA®) (hereafter referred to as pegfilgrastim-cbqv) was approved in 2018 by the US Food and Drug Administration as a biosimilar for pegfilgrastim (Neulasta®) (hereafter referred to as pegfilgrastim). Both pegfilgrastim-cbqv and pegfilgrastim are conjugates of recombinant human granulocyte colony stimulating factor (r-metHuG-CSF) with a 20 kDa polyethylene glycol (PEG) indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients receiving myelosuppressive anticancer drugs. The demonstration of analytical similarity for PEG-protein conjugates presents unique challenges since both the protein and PEG attributes must be characterized. OBJECTIVE: The current study demonstrates the analytical similarity of pegfilgrastim-cbqv and the reference product, pegfilgrastim. In addition to the physicochemical and functional characterization of the protein, the study assessed attributes specific to PEGylation including PEG size and polydispersity, site of attachment, linker composition, and PEGylation process-related variants. METHODS: The structural, functional, and stability attributes of pegfilgrastim-cbqv and pegfilgrastim were compared using state-of-the-art analytical methods. For the protein, the primary structure, disulfide structure, and secondary and tertiary structures were assessed using traditional protein characterization techniques such as mass spectrometry (MS), circular dichroism (CD), intrinsic fluorescence, and differential scanning calorimetry (DSC), as well as more advanced techniques such as two-dimensional (2D) nuclear magnetic resonance (NMR) and hydrogen deuterium exchange (HDX). For the PEG moiety, the site of attachment, occupancy, linker composition, size and polydispersity were compared using mass spectrometry (both intact and after endoprotease digestion), multiangle light scattering detection (MALS), and Edman degradation. Purity assessments included the assessment of both protein variants and PEGylation variants using chromatographic and electrophoretic analytical separation techniques. The functional similarity between pegfilgrastim-cbqv and pegfilgrastim was compared using both a cell-based bioassay and surface plasmon resonance (SPR). The degradation rates and stability profiles were compared under accelerated and stressed conditions. RESULTS: Biosimilarity was demonstrated by a thorough assessment of physiochemical and functional attributes, as well as comparative stability, of pegfilgrastim-cbqv relative to pegfilgrastim. These studies demonstrated identical primary structure and disulfide structure, highly similar secondary and tertiary structure, as well as functional similarity. The impurity profile of pegfilgrastim-cbqv was comparable to that of pegfilgrastim with only minor differences in PEGylation variants and a slight offset in the PEG molar mass. These differences were not clinically relevant. The degradation profiles were qualitatively and quantitatively similar under accelerated and stress conditions. CONCLUSION: The structural, functional, and stability data demonstrate that pegfilgrastim-cbqv is highly similar to the reference product, pegfilgrastim.
Subject(s)
Biosimilar Pharmaceuticals , Filgrastim , Polyethylene Glycols , Filgrastim/chemistry , Polyethylene Glycols/chemistry , Biosimilar Pharmaceuticals/chemistry , Humans , Recombinant Proteins/chemistryABSTRACT
INTRODUCTION: Adopting healthy lifestyle behaviors has the potential to slow cognitive decline in older adults by reducing risks associated with dementia. Curriculum-based group health coaching may aid in establishing behavior change centered for dementia risk factors. METHODS: In this pilot clinical care patient group study (n = 6), we examined the effects of a six-month online Cognitive Health Program combined with a weekly telehealth support group led by the course creator, and personalized health optimization by a collaborating physician, in older adults with subjective cognitive decline. Cognition was assessed at baseline and post-intervention using a computerized battery. RESULTS: Cognitive changes were estimated with nonparametric tests and effect sizes (Cohen's d). Results showed significant improvements in global cognition (p < 0.03, d = 1.6), spatial planning (p < 0.01, d = 2.3), and visuospatial processing (p < 0.05, d = 1.1) compared to baseline. Participants reported high levels of satisfaction with the virtual group format and online curriculum. CONCLUSIONS: This small pilot study suggests that a virtual six-month personalized health coaching group with self-paced online health education is feasible and potentially efficacious for improving cognition in participants with subjective cognitive complaints. This format may facilitate behavior change to slow cognitive decline. Future studies should include a control group, a larger, more diverse sample as well as assessing mood and other subjective measures.
ABSTRACT
BACKGROUND: Adalimumab-aqvh/CHS-1420 (YUSIMRYTM) (hereafter referred to as adalimumab-aqvh) was recently approved by the US Food and Drug Administration as a biosimilar for adalimumab. OBJECTIVE: The current study was conducted to investigate the analytical similarity of adalimumab-aqvh and the reference product, adalimumab. METHODS: The structural, functional, and stability attributes of adalimumab-aqvh and adalimumab were compared using state-of-the-art assays. The primary structure, disulfide structure, glycan profile, secondary and tertiary structures, molar mass, size variants, free thiol, charge variants, hydrophobic variants, post-translational modifications, subvisible particles, host cell proteins, and protein concentration were investigated. The functional similarity between adalimumab-aqvh and adalimumab was demonstrated by comparing fragment antigen-binding (Fab)-associated and fragment crystallizable (Fc)-associated biological activities. The stability of adalimumab-aqvh and of adalimumab was compared through forced degradation. RESULTS: The structural attributes of adalimumab-aqvh were identical to those of adalimumab or met the similarity criteria, with a few exceptions. Adalimumab-aqvh and adalimumab exhibited comparable stability profiles and functional activities. Any observed differences in the physiochemical attributes did not impact the conclusion of similarity because they did not influence any functional activities related to the adalimumab mechanism of action. CONCLUSION: The structural, functional, and stability data provide convincing evidence of biosimilarity between adalimumab-aqvh and the reference product, adalimumab.
Subject(s)
Biosimilar Pharmaceuticals , Humans , Adalimumab/chemistry , Adalimumab/pharmacology , Biosimilar Pharmaceuticals/chemistryABSTRACT
Key ecological features (KEFs) are elements of Australia's Commonwealth marine environment considered to be important for biodiversity or ecosystem function, yet many KEFs are poorly researched, which can impede effective decision-making about future development and conservation. This study investigates a KEF positioned over the Last Glacial Maximum (LGM) shoreline on the northwest shelf of Australia (known as the 'Ancient Coastline at ~125m depth contour'; AC125). Seafloor bathymetry, sedimentology and benthic habitats were characterised within five study areas using multibeam sonar, sediment samples and towed video imagery. Direct evidence for the existence of a palaeoshoreline formed during the LGM was not found, however candidate areas to find palaeoshoreline material at or just below the modern seabed were discovered. Approximately 98% of the seabed surveyed was comprised of unconsolidated soft sediment habitat (mud/sand/silt) supporting negligible epibenthic biota. The prevalence of soft sediment suggests that post-glacial sediments have infilled parts of the palaeoshoreline, with cross-shelf, probably tidal currents in the northern section of the study area responsible for some of the sediment mobilisation and southern study areas more influenced by oceanic conditions. Within study areas, total biotic cover ranged from 0.02% to 1.07%. Of the biota encountered, most comprised filter feeder organisms (including gorgonians, sponges, and whip corals) whose distribution was associated with pockets of consolidated hard substrate. Benthic community composition varied with both study area and position in relation to the predicted AC125. In general, consolidated substrate was proportionally higher in water shallower than the AC125 compared to on the AC125 or deeper than the AC125. Spatially continuous maps of predicted benthic habitat classes (pre-determined benthic communities) in each study area were developed to characterise biodiversity. Spatial modelling corroborated depth and large-scale structural complexity of the seafloor as surrogates for predicting likely habitat class. This study provides an important assessment of the AC125 and shows that if a distinct coastline exists in the areas we surveyed, it is now largely buried and as such does not provide a unique hard substrate habitat. However, much work remains to fully locate and map the ancient coastline within the vast region of the AC125 and additional surveys in shallow waters adjacent to the AC125 may identify whether some sections lie outside the currently defined KEF.
Subject(s)
Anthozoa , Ecosystem , Animals , Western Australia , Biodiversity , BiotaABSTRACT
BACKGROUND: Strength and mobility are essential for activities of daily living. With aging, weaker handgrip strength, mobility, and asymmetry predict poorer cognition. We therefore sought to quantify the relationship between handgrip metrics and volumes quantified on brain magnetic resonance imaging (MRI). OBJECTIVE: To model the relationships between handgrip strength, mobility, and MRI volumetry. METHODS: We selected 38 participants with Alzheimer's disease dementia: biomarker evidence of amyloidosis and impaired cognition. Handgrip strength on dominant and non-dominant hands was measured with a hand dynamometer. Handgrip asymmetry was calculated. Two-minute walk test (2MWT) mobility evaluation was combined with handgrip strength to identify non-frail versus frail persons. Brain MRI volumes were quantified with Neuroreader. Multiple regression adjusting for age, sex, education, handedness, body mass index, and head size modeled handgrip strength, asymmetry and 2MWT with brain volumes. We modeled non-frail versus frail status relationships with brain structures by analysis of covariance. RESULTS: Higher non-dominant handgrip strength was associated with larger volumes in the hippocampus (pâ=â0.02). Dominant handgrip strength was related to higher frontal lobe volumes (pâ=â0.02). Higher 2MWT scores were associated with larger hippocampal (pâ=â0.04), frontal (pâ=â0.01), temporal (pâ=â0.03), parietal (pâ=â0.009), and occipital lobe (pâ=â0.005) volumes. Frailty was associated with reduced frontal, temporal, and parietal lobe volumes. CONCLUSION: Greater handgrip strength and mobility were related to larger hippocampal and lobar brain volumes. Interventions focused on improving handgrip strength and mobility may seek to include quantified brain volumes on MR imaging as endpoints.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Aged , Activities of Daily Living , Hand Strength , Brain/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , HippocampusABSTRACT
BACKGROUND: Distinguishing between subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia in a scalable, accessible way is important to promote earlier detection and intervention. OBJECTIVE: We investigated diagnostic categorization using an FDA-cleared quantitative electroencephalographic/event-related potential (qEEG/ERP)-based cognitive testing system (eVox® by Evoke Neuroscience) combined with an automated volumetric magnetic resonance imaging (vMRI) tool (Neuroreader® by Brainreader). METHODS: Patients who self-presented with memory complaints were assigned to a diagnostic category by dementia specialists based on clinical history, neurologic exam, neuropsychological testing, and laboratory results. In addition, qEEG/ERP (nâ=â161) and quantitative vMRI (nâ=â111) data were obtained. A multinomial logistic regression model was used to determine significant predictors of cognitive diagnostic category (SCD, MCI, or dementia) using all available qEEG/ERP features and MRI volumes as the independent variables and controlling for demographic variables. Area under the Receiver Operating Characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the prediction models. RESULTS: The qEEG/ERP measures of Reaction Time, Commission Errors, and P300b Amplitude were significant predictors (AUCâ=â0.79) of cognitive category. Diagnostic accuracy increased when volumetric MRI measures, specifically left temporal lobe volume, were added to the model (AUCâ=â0.87). CONCLUSION: This study demonstrates the potential of a primarily physiological diagnostic model for differentiating SCD, MCI, and dementia using qEEG/ERP-based cognitive testing, especially when combined with volumetric brain MRI. The accessibility of qEEG/ERP and vMRI means that these tools can be used as adjuncts to clinical assessments to help increase the diagnostic certainty of SCD, MCI, and dementia.
Subject(s)
Cognitive Dysfunction , Dementia , Humans , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Neuropsychological Tests , Magnetic Resonance Imaging , Evoked Potentials , Dementia/diagnostic imaging , Dementia/psychologyABSTRACT
An understanding of stock recruitment dynamics in fisheries is fundamental to successful management. Pinctada maxima is a bivalve mollusc widely distributed throughout the Indo-Pacific and is the main species targeted for cultured pearl and pearl shell production in Australia. Pearl production in Australia relies heavily on wild-caught individuals, the majority of which come from the Eighty Mile Beach region near Broome in Western Australia. In this study, we used a genotyping by sequencing approach to explore fine-scale patterns of genetic connectivity among inshore shallow and offshore deep populations of P. maxima near Eighty Mile Beach. Our results revealed high-levels of gene flow among inshore and offshore sites and no differences in genetic diversity between depths. Global estimates of genetic differentiation were low (F ST = 0.006) but significantly different from zero, and pairwise estimates of genetic differentiation among sites were significant in only 3% of comparisons. Moreover, Bayesian clustering detected no separation of inshore and offshore sample sites, and instead showed all samples to be admixed among sites, locations and depths. Despite an absence of any clear spatial clustering among sites, we identified a significant pattern of isolation by distance. In a dynamic environment like Eighty Mile Beach, genetic structure can change from year-to-year and successive dispersal and recruitment events over generations likely act to homogenize the population. Although we cannot rule out the null hypothesis of panmixia, our data indicate high levels of dispersal and connectivity among inshore and offshore fishing grounds.
Subject(s)
Pinctada , Humans , Animals , Pinctada/genetics , Gene Flow , Western Australia , Bayes Theorem , FisheriesABSTRACT
Offshore platforms, subsea pipelines, wells and related fixed structures supporting the oil and gas (O&G) industry are prevalent in oceans across the globe, with many approaching the end of their operational life and requiring decommissioning. Although structures can possess high ecological diversity and productivity, information on how they interact with broader ecological processes remains unclear. Here, we review the current state of knowledge on the role of O&G infrastructure in maintaining, altering or enhancing ecological connectivity with natural marine habitats. There is a paucity of studies on the subject with only 33 papers specifically targeting connectivity and O&G structures, although other studies provide important related information. Evidence for O&G structures facilitating vertical and horizontal seascape connectivity exists for larvae and mobile adult invertebrates, fish and megafauna; including threatened and commercially important species. The degree to which these structures represent a beneficial or detrimental net impact remains unclear, is complex and ultimately needs more research to determine the extent to which natural connectivity networks are conserved, enhanced or disrupted. We discuss the potential impacts of different decommissioning approaches on seascape connectivity and identify, through expert elicitation, critical knowledge gaps that, if addressed, may further inform decision making for the life cycle of O&G infrastructure, with relevance for other industries (e.g. renewables). The most highly ranked critical knowledge gap was a need to understand how O&G structures modify and influence the movement patterns of mobile species and dispersal stages of sessile marine species. Understanding how different decommissioning options affect species survival and movement was also highly ranked, as was understanding the extent to which O&G structures contribute to extending species distributions by providing rest stops, foraging habitat, and stepping stones. These questions could be addressed with further dedicated studies of animal movement in relation to structures using telemetry, molecular techniques and movement models. Our review and these priority questions provide a roadmap for advancing research needed to support evidence-based decision making for decommissioning O&G infrastructure.
Subject(s)
Ecosystem , Fishes , Animals , Invertebrates , Larva , Oceans and SeasABSTRACT
Marine diversity across the Australian continental shelf is shaped by characteristic benthic habitats which are determined by geomorphic features such as paleoshorelines. In north-western Australia there has been little attention on the fish communities that inhabit an ancient coastline at ~125 m depth (the designated AC125), which is specified as a key ecological feature (KEF) of the region and is thought to comprise hard substrate and support enhanced diversity. We investigated drivers of fish species richness and assemblage composition spanning six degrees of latitude along sections of the ancient coastline, categorised as 'on' and 'off' the AC125 based on depth, across a range of habitats and seafloor complexity (~60-180 m depth). While some surveyed sections of the AC125 had hard bottom substrate and supported enhanced fish diversity, including over half of the total species observed, species richness and abundance overall were not greater on the AC125 than immediately adjacent to the AC125. Instead, depth, seafloor complexity and habitat type explained patterns in richness and abundance, and structured fish assemblages at both local and broad spatial scales. Fewer fishes were associated with deep sites characterized by negligible complexity and soft-bottom habitats, in contrast to shallower depths that featured benthic biota and pockets of complex substrate. Drivers of abundance of common species were species-specific and primarily related to sampling Areas, depth and substrate. Fishes of the ancient coastline and adjacent habitats are representative of mesophotic fish communities of the region, included species important to fisheries and conservation, and several species were observed deeper than their currently known distribution. This study provides the first assessment of fish biodiversity associated with an ancient coastline feature, improving our understanding of the function it plays in regional spatial patterns in abundance of mesophotic fishes. Management decisions that incorporate the broader variety of depths and habitats surrounding the designated AC125 could enhance the ecological role of this KEF, contributing to effective conservation of fish biodiversity on Australia's north west shelf.
Subject(s)
Biota , Conservation of Natural Resources , Fishes , Animals , Western AustraliaABSTRACT
Objective: To study whether memory control beliefs predict response to memory training, or change as a result of participating in memory training. Methods: Eighty community based participants with subjective memory complaints Community-based study at UCLA were randomized to one of three conditions: Memory Training, the program consisted of weekly 120-minute classes featuring instruction in three specific strategies: Method of Loci; Chunking Technique; and Face-Name Association, Health Education or Wait-List over seven weeks. All participants underwent pre- and 1-week post-intervention follow-up memory testing for recalling word lists (in serial order and any order) and face-name pairs. Memory control beliefs were assessed at baseline and follow-up using the Memory Controllability Inventory, which consists of four subscales; Present Ability; Potential Improvement; Effort Utility; and Inevitable Decrement. Results: Sixty-three participants (mean age [SD] 68.3 [6.7] years) were included in the analysis. ANCOVA revealed significant group differences in the Present Ability subscale, F2,58 = 4.93, p =.01. Participants in the Memory Training group significantly improved on the Present Ability subscale compared to the Health Education group (mean difference =.96, SE =.31, p =.003, effect size = 0.93). From regression analyses, baseline Memory Controllability Inventory subscales did not significantly predict memory performance after memory training. Conclusions: Baseline memory control beliefs did not predict memory performance following the intervention, but participating in memory training enhanced memory control beliefs about current memory function. These results suggest that participating in memory training can enhance confidence in one's memory ability.
Subject(s)
Aging , Memory , Aged , Cognition , Humans , Learning , Memory Disorders/therapyABSTRACT
BACKGROUND: Antioxidant nutrients such as the polyphenols in pomegranate juice may prevent neuronal damage from the free radicals produced during normal metabolism. Previous research in animals and a short-term clinical trial in middle-aged and older adults support the potential memory benefits of pomegranate juice; however, the long-term effects of pomegranate juice consumption on cognition have not been studied. OBJECTIVE: In this study, we investigated the long-term effect of pomegranate juice on memory in nondemented middle-aged and older adults. METHODS: We performed a 12-month, randomized, double-blind, placebo-controlled trial of pomegranate juice in middle-aged and older adults. Two hundred and sixty-one subjects (aged 50-75 y) were randomly assigned to consume pomegranate juice [8 oz (236.5 mL) per day] or a placebo drink (8 oz, matched constituents of pomegranate juice except for pomegranate polyphenols). Memory measures [Brief Visuospatial Memory Test-Revised (BVMT-R) and Buschke Selective Reminding Test (SRT)] were assessed at 6 and 12 mo and analyzed using a mixed-effects general linear model. RESULTS: Twenty-eight subjects in the pomegranate juice group and 33 subjects in the placebo group dropped out before completing the study. Baseline variables in the 98 pomegranate juice and 102 placebo group subjects who completed the study did not differ significantly. Group by time interaction was statistically significant for BVMT-R Learning (F[2, 257]= 5.90, P = 0.003; between-group effect size [ES] = 0.45): the change within the pomegranate group was not significant (ES = 0.15), whereas the placebo group showed a significant decline (ES = -0.35). Changes in the other BVMT-R scores as well as the SRT measures were not significantly different between groups. CONCLUSIONS: Daily consumption of pomegranate juice may stabilize the ability to learn visual information over a 12-mo period. This trial was registered at clinicaltrials.gov as NCT02093130.
Subject(s)
Aging/metabolism , Fruit and Vegetable Juices/analysis , Memory , Pomegranate/metabolism , Aged , Aging/psychology , Cognition , Double-Blind Method , Female , Fruit/chemistry , Fruit/metabolism , Humans , Male , Middle Aged , Pomegranate/chemistryABSTRACT
BACKGROUND: Early identification and treatment of individuals with autism spectrum disorder (ASD) improves outcomes, but specific evidence needed to individualize treatment recommendations is lacking. Biomarkers that could be routinely measured within the clinical setting could potentially transform clinical care for patients with ASD. This demonstration project employed collection of biomarker data during regular autism specialty clinical visits and explored the relationship of biomarkers with clinical ASD symptoms. METHODS: Eighty-three children with ASD, aged 5-10 years, completed a multi-site feasibility study integrating the collection of biochemical (blood serotonin, urine melatonin sulfate excretion) and clinical (head circumference, dysmorphology exam, digit ratio, cognitive and behavioral function) biomarkers during routine ASD clinic visits. Parents completed a demographic survey and the Aberrant Behavior Checklist-Community. Cognitive function was determined by record review. Data analysis utilized Wilcoxon two-sample tests and Spearman correlations. RESULTS: Participants were 82% male, 63% White, 19% Hispanic, with a broad range of functioning. Group means indicated hyperserotonemia. In a single regression analysis adjusting for race and median household income, higher income was associated with higher levels of blood serotonin and urine melatonin sulfate excretion levels (p = 0.004 and p = 0.04, respectively). Melatonin correlated negatively with age (p = 0.048) and reported neurologic problems (p = 0.02). Dysmorphic status correlated with higher reported stereotyped behavior (p = 0.02) and inappropriate speech (p = 0.04). CONCLUSION: This demonstration project employed collection of multiple biomarkers, allowed for examination of associations between biochemical and clinical measures, and identified several findings that suggest direction for future studies. This clinical research model has promise for integrative biomarker research in individuals with complex, heterogeneous neurodevelopmental disorders such as ASD.
ABSTRACT
The mechanisms that determine patterns of species dispersal are important factors in the production and maintenance of biodiversity. Understanding these mechanisms helps to forecast the responses of species to environmental change. Here, we used a comparative framework and genomewide data obtained through RAD-Seq to compare the patterns of connectivity among breeding colonies for five penguin species with shared ancestry, overlapping distributions and differing ecological niches, allowing an examination of the intrinsic and extrinsic barriers governing dispersal patterns. Our findings show that at-sea range and oceanography underlie patterns of dispersal in these penguins. The pelagic niche of emperor (Aptenodytes forsteri), king (A. patagonicus), Adélie (Pygoscelis adeliae) and chinstrap (P. antarctica) penguins facilitates gene flow over thousands of kilometres. In contrast, the coastal niche of gentoo penguins (P. papua) limits dispersal, resulting in population divergences. Oceanographic fronts also act as dispersal barriers to some extent. We recommend that forecasts of extinction risk incorporate dispersal and that management units are defined by at-sea range and oceanography in species lacking genetic data.
Subject(s)
Animal Distribution , Genetics, Population , Genomics , Spheniscidae/genetics , Animals , Antarctic Regions , Ecosystem , Gene Flow , Genetic Variation , Genotyping Techniques , Phylogeny , Polymorphism, Single Nucleotide , Spheniscidae/classificationABSTRACT
The predominance of self-recruitment in many reef-building corals has fundamental and complex consequences for their genetic diversity, population persistence and responses to climate change. Knowledge of genetic structure over local scales needs to be placed within a broad spatial context, and also integrated with genetic monitoring through time to disentangle these consequences. Here, we examined patterns of genetic diversity over multiple spatio-temporal scales across tropical Australia in the ubiquitous brooding coral, Seriatopora hystrix. We also analysed complimentary environmental and demographic data to elucidate the seascape drivers of these patterns. Large genetic differences were detected between the east vs. west coasts of Australia. In northwest Australia, geographic differentiation dominated genetic structure over multiple scales. However, three sympatric lineages were detected at the largest offshore reef system (Scott Reef). Similar to the differences observed among putative species in eastern Australia, these lineages were associated with different levels of wave exposure. Local genetic structure within the Scott Reef system was relatively stable over 10 years, but temporal differences were observed that reflected small but important genetic changes over a few generations during recovery after severe bleaching. These results highlight the importance of self-recruitment together with occasional longer distance connectivity for the persistence of a metapopulation across spatially and temporally variable environments. Our multidimensional research provides a foundation for further long-term genetic monitoring to inform conservation strategies and highlights that sampling scales, ecological effects and cryptic diversity are important considerations to develop realistic understanding of the evolutionary resilience of corals.
Subject(s)
Anthozoa/genetics , Gene Expression Profiling , Animals , Australia , Cluster Analysis , Coral Reefs , Genotype , Microsatellite Repeats/genetics , Phylogeography , Principal Component Analysis , Time FactorsABSTRACT
BACKGROUND: Physical activity (PA) plays a major role in maintaining cognition in older adults. PA has been shown to be correlated with total hippocampal volume, a memory-critical region within the medial temporal lobe (MTL). However, research on associations between PA and MTL sub-region integrity is limited. OBJECTIVE: To examine the relationship between PA, MTL thickness, and its sub-regions, and cognitive function in non-demented older adults with memory complaints. METHODS: Twenty-nine subjects aged ≥60 years, with memory complaints were recruited for this cross-sectional study. PA was tracked for 7 days using accelerometers, and average number of steps/day determined. Subjects were categorized into two groups: those who walked ≤4000 steps/day (lower PA) and those with >4000 steps/day (higher PA). Subjects received neuropsychological testing and 3T MRI scans. Nonparametric ANCOVAs controlling for age examined differences between the two groups. RESULTS: Twenty-six subjects aged 72.7(8.1) years completed the study. The higher PA group (nâ=â13) had thicker fusiform gyrus (median differenceâ=â0.11âmm, effect size (ES)â=â1.43, pâ=â0.001) and parahippocampal cortex (median differenceâ=â0.12âmm, ESâ=â0.93, pâ=â0.04) compared to the lower PA group. The higher PA group also exhibited superior performance in attention and information-processing speed (median differenceâ=â0.90, ESâ=â1.61, pâ=â0.003) and executive functioning (median differenceâ=â0.97, ESâ=â1.24, pâ=â0.05). Memory recall was not significantly different between the two groups. CONCLUSION: Older non-demented individuals complaining of memory loss who walked >4000 steps each day had thicker MTL sub-regions and better cognitive functioning than those who walked ≤4000 steps. Future studies should include longitudinal analyses and explore mechanisms mediating hippocampal related atrophy.
Subject(s)
Exercise , Hippocampus/pathology , Memory Disorders/physiopathology , Aged , Aged, 80 and over , Cognition , Cross-Sectional Studies , Executive Function , Female , Geriatric Assessment/methods , Humans , Magnetic Resonance Imaging , Male , Memory , Middle Aged , Neuropsychological TestsABSTRACT
OBJECTIVE: Because curcumin's anti-inflammatory properties may protect the brain from neurodegeneration, we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography (FDDNP-PET). METHODS: Forty subjects (age 51-84 years) were randomized to a bioavailable form of curcumin (Theracurmin® containing 90 mg of curcumin twice daily [N = 21]) or placebo (N = 19) for 18 months. Primary outcomes were verbal (Buschke Selective Reminding Test [SRT]) and visual (Brief Visual Memory Test-Revised [BVMT-R]) memory, and attention (Trail Making A) was a secondary outcome. FDDNP-PET signals (15 curcumin, 15 placebo) were determined in amygdala, hypothalamus, medial and lateral temporal, posterior cingulate, parietal, frontal, and motor (reference) regions. Mixed effects general linear models controlling for age and education, and effect sizes (ES; Cohen's d) were estimated. RESULTS: SRT Consistent Long-Term Retrieval improved with curcumin (ES = 0.63, p = 0.002) but not with placebo (ES = 0.06, p = 0.8; between-group: ES = 0.68, p = 0.05). Curcumin also improved SRT Total (ES = 0.53, p = 0.002), visual memory (BVMT-R Recall: ES = 0.50, p = 0.01; BVMT-R Delay: ES = 0.51, p = 0.006), and attention (ES = 0.96, p < 0.0001) compared with placebo (ES = 0.28, p = 0.1; between-group: ES = 0.67, p = 0.04). FDDNP binding decreased significantly in the amygdala with curcumin (ES = -0.41, p = 0.04) compared with placebo (ES = 0.08, p = 0.6; between-group: ES = 0.48, p = 0.07). In the hypothalamus, FDDNP binding did not change with curcumin (ES = -0.30, p = 0.2), but increased with placebo (ES = 0.26, p = 0.05; between-group: ES = 0.55, p = 0.02). CONCLUSIONS: Daily oral Theracurmin may lead to improved memory and attention in non-demented adults. The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory.
Subject(s)
Aging/drug effects , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Attention/drug effects , Brain/drug effects , Curcumin/pharmacology , Memory/drug effects , Plaque, Amyloid/drug therapy , tau Proteins/drug effects , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Brain/diagnostic imaging , Curcumin/administration & dosage , Double-Blind Method , Female , Humans , Male , Middle Aged , Placebos , Positron-Emission Tomography , Treatment OutcomeABSTRACT
The evolutionary history of Antarctic organisms is becoming increasingly important to understand and manage population trajectories under rapid environmental change. The Antarctic sea spider Nymphon australe, with an apparently large population size compared with other sea spider species, is an ideal target to look for molecular signatures of past climatic events. We analysed mitochondrial DNA of specimens collected from the Antarctic continent and two Antarctic islands (AI) to infer past population processes and understand current genetic structure. Demographic history analyses suggest populations survived in refugia during the Last Glacial Maximum. The high genetic diversity found in the Antarctic Peninsula and East Antarctic (EA) seems related to multiple demographic contraction-expansion events associated with deep-sea refugia, while the low genetic diversity in the Weddell Sea points to a more recent expansion from a shelf refugium. We suggest the genetic structure of N. australe from AI reflects recent colonization from the continent. At a local level, EA populations reveal generally low genetic differentiation, geographically and bathymetrically, suggesting limited restrictions to dispersal. Results highlight regional differences in demographic histories and how these relate to the variation in intensity of glaciation-deglaciation events around Antarctica, critical for the study of local evolutionary processes. These are valuable data for understanding the remarkable success of Antarctic pycnogonids, and how environmental changes have shaped the evolution and diversification of Southern Ocean benthic biodiversity.
ABSTRACT
Understanding the boundaries of breeding populations is of great importance for conservation efforts and estimates of extinction risk for threatened species. However, determining these boundaries can be difficult when population structure is subtle. Emperor penguins are highly reliant on sea ice, and some populations may be in jeopardy as climate change alters sea-ice extent and quality. An understanding of emperor penguin population structure is therefore urgently needed. Two previous studies have differed in their conclusions, particularly whether the Ross Sea, a major stronghold for the species, is isolated or not. We assessed emperor penguin population structure using 4,596 genome-wide single nucleotide polymorphisms (SNPs), characterized in 110 individuals (10-16 per colony) from eight colonies around Antarctica. In contrast to a previous conclusion that emperor penguins are panmictic around the entire continent, we find that emperor penguins comprise at least four metapopulations, and that the Ross Sea is clearly a distinct metapopulation. Using larger sample sizes and a thorough assessment of the limitations of different analytical methods, we have shown that population structure within emperor penguins does exist and argue that its recognition is vital for the effective conservation of the species. We discuss the many difficulties that molecular ecologists and managers face in the detection and interpretation of subtle population structure using large SNP data sets, and argue that subtle structure should be taken into account when determining management strategies for threatened species, until accurate estimates of demographic connectivity among populations can be made.
Subject(s)
Conservation of Natural Resources , Genetics, Population , Spheniscidae/genetics , Animals , Antarctic Regions , Climate Change , Ice Cover , Polymorphism, Single Nucleotide , Population DensityABSTRACT
Ecological processes in the deep sea are poorly understood due to the logistical constraints of sampling thousands of metres below the ocean's surface and remote from most land masses. Under such circumstances, genetic data provides unparalleled insight into biological and ecological relationships. We use microsatellite DNA to compare the population structure, reproductive mode and dispersal capacity in two deep sea corals from seamounts in the Southern Ocean. The solitary coral Desmophyllum dianthus has widespread dispersal consistent with its global distribution and resilience to disturbance. In contrast, for the matrix-forming colonial coral Solenosmilia variabilis asexual reproduction is important and the dispersal of sexually produced larvae is negligible, resulting in isolated populations. Interestingly, despite the recognised impacts of fishing on seamount communities, genetic diversity on fished and unfished seamounts was similar for both species, suggesting that evolutionary resilience remains despite reductions in biomass. Our results provide empirical evidence that a group of seamounts can function either as isolated islands or stepping stones for dispersal for different taxa. Furthermore different strategies will be required to protect the two sympatric corals and consequently the recently declared marine reserves in this region may function as a network for D. dianthus, but not for S. variabilis.
Subject(s)
Animal Distribution/physiology , Anthozoa/genetics , Islands , Oceans and Seas , Alleles , Analysis of Variance , Animals , Biodiversity , Gene Flow , Genetic Variation , Heterozygote , Principal Component Analysis , Species Specificity , TasmaniaABSTRACT
INTRODUCTION: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with apolipoprotein E (APOE), has received attention more recently as a promising gene in Alzheimer's disease (AD) risk. TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. METHODS: In this study, we examined the effects of TOMM40 using high-resolution magnetic resonance imaging in 65 healthy, older subjects with and without the APOE ε4 AD-risk variant. RESULTS: Examining individual subregions within the MTL, we found a significant relationship between increasing poly-T lengths of the TOMM40 variant and thickness of the entorhinal cortex only in subjects who did not carry the APOE ε4 allele. DISCUSSION: Our data provide support for TOMM40 variant repeat length as an important contributor to AD-like MTL pathology in the absence of APOE ε4.