G-quadruplex structure and stability illuminated by 2-aminopurine phasor plots

The use of time-resolved fluorescence measurements in studies of telomeric G-quadruplex folding and stability has been hampered by the complexity of fluorescence lifetime distributions in solution. The application of phasor diagrams to the analysis of time-resolved fluorescence measurements, collected from either frequency-domain or time-domain instrumentation, allows for rapid characterization of complex lifetime distributions. Phasor diagrams are model-free graphical representations of transformed time-resolved fluorescence results. Simplification of complex fluorescent decays by phasor diagrams is demonstrated here using a 2-aminopurine substituted telomeric G-quadruplex sequence. The application of phasor diagrams to complex systems is discussed with comparisons to traditional non-linear regression model fitting. Phasor diagrams allow for the folding and stability of the telomeric G-quadruplex to be monitored in the presence of either sodium or potassium. Fluorescence lifetime measurements revealed multiple transitions upon folding of the telomeric G-quadruplex through the addition of potassium. Enzymatic digestion of the telomeric G-quadruplex structure, fluorescence quenching and Förster resonance energy transfer were also monitored through phasor diagrams. This work demonstrates the sensitivity of time-resolved methods for monitoring changes to the telomeric G-quadruplex and outlines the phasor diagram approach for analysis of complex time-resolved results that can be extended to other G-quadruplex and nucleic acid systems

Somatosensory Information Processing in the Aging Population

While it is well known that skin physiology – and consequently sensitivity to peripheral stimuli – degrades with age, what is less appreciated is that centrally mediated mechanisms allow for maintenance of the same degree of functionality in processing these peripheral inputs and interacting with the external environment. In order to demonstrate this concept, we obtained observations of processing speed, sensitivity (thresholds), discriminative capacity, and adaptation metrics on subjects ranging in age from 18 to 70. The results indicate that although reaction speed and sensory thresholds change with age, discriminative capacity, and adaptation metrics do not. The significance of these findings is that similar metrics of adaptation have been demonstrated to change significantly when the central nervous system (CNS) is compromised. Such compromise has been demonstrated in subject populations with autism, chronic pain, acute NMDA receptor block, concussion, and with tactile–thermal interactions. If the metric of adaptation parallels cortical plasticity, the results of the current study suggest that the CNS in the aging population is still capable of plastic changes, and this cortical plasticity could be the mechanism that compensates for the degradations that are known to naturally occur with age. Thus, these quantitative measures – since they can be obtained efficiently and objectively, and appear to deviate from normative values significantly with systemic cortical alterations – could be useful indicators of cerebral cortical health

ANNUAL REPORT 2022 - Data collection and analysis in support of single and multispecies stock assessments in Chesapeake Bay: The Chesapeake Bay Multispecies Monitoring and Assessment Program

The threats affecting living marine resources are diverse, including overfishing, climate change, and pollution. In response to long-term challenges in fisheries management, a more holistic evaluation of the natural and anthropogenic drivers of populations sizes is needed. Ecosystem management (EM), a suite of strategies that incorporate ecosystem considerations into fisheries and ecosystem management, can be difficult to implement in practice. In the Mid-Atlantic, efforts to implement EM are ongoing; one output has been the annual ‘State of the Ecosystem Report’ for the region, synthesizes available data on a variety of environmental, ecological, and socioeconomic factors. Historically, the data needed for EM in Chesapeake Bay were either incomplete or nonexistent. In 2002, the Chesapeake Bay Multispecies Monitoring and Assessment Program (ChesMMAP) was developed to assist in filling these data gaps, and ultimately to support Bay-specific species and ecosystem assessment modeling. ChesMMAP is a fishery-independent monitoring survey that uses a bottom trawl designed to sample late juvenile-to-adult fishes in the mainstem of Chesapeake Bay. Since 2002, this program has provided data on relative abundance, length, weight, sex ratio, maturity, age, and trophic interactions for several important fish species that inhabit the Bay seasonally. In this annual progress report, we synthesize available biological data on 12 bony fishes that support local recreational fisheries, including abundance (biomass and number), length- and age-structure, sex ratio, maturity stage, and diet composition. However, in 2019, the survey underwent a major redesign: VIMS took possession of a new research vessel, the R/V Virginia, and the survey bottom trawl gear was replaced with a net consistent with the gear used by other regional bottom trawl surveys (i.e., the Northeast Area Monitoring and Assessment Program and Northeast Fisheries Science Center trawl surveys). At this time, the survey stratification was revised and changes were made to the cruise schedule. During 15 calibration cruises (2019-2022), 516 paired-tows were completed, which was deemed sufficient for robust statistical analysis. Species-specific intercalibrations have been conducted by applying log-Gaussian Cox processes to the paired-tow data and modeling the size distribution of the population at each sampling site and the size-structured clustering of fish at small temporal and spatial scales. The manuscript describing the application to the ChesMMAP calibration data is currently in review. The ChesMMAP data inform Bay- and coast-wide fisheries management decisions and the broader use of these data in theses, dissertations, and the peer-reviewed literature contributes to a better understanding of the Bay ecosystem

Trait Hope and Preparation for Future Care Needs among Older Adult Primary Care Patients

We examined associations between trait hope and preparation for future care needs (PFCN) among 66 older adult primary care patients in western New York. Participants completed a questionnaire assessing PFCN (awareness, information gathering, decision-making, concrete planning, and avoidance), and the Adult Trait Hope Scale. In multivariate regressions, lower hope, particularly less agency, was associated with more awareness of needing care, whereas higher hopefulness, particularly pathways thinking, was associated with increased decision-making and concrete planning. Greater hopefulness appears to be linked to goal-directed planning behaviors, although those with lower hope may actually be more aware of the need for planning. Evidence-based programming that encourages learned hopefulness may contribute to enhanced health planning and decision-making among older adult primary care patients

Neurosensory Assessments of Concussion

ABSTRACT The purpose of this research was to determine if cortical metrics—a unique set of sensory-based assessment tools—could be used to characterize and differentiate concussed individuals from nonconcussed individuals. Cortical metrics take advantage of the somatotopic relationship between skin and cortex, and the protocols are designed to evoke interactions between adjacent cortical regions to investigate fundamental mechanisms that mediate cortical–cortical interactions. Student athletes, aged 18 to 22 years, were recruited into the study through an athletic training center that made determinations of postconcussion return-to-play status. Sensory-based performance tasks utilizing vibrotactile stimuli applied to tips of the index and middle fingers were administered to test an individual's amplitude discrimination, temporal order judgment, and duration discrimination capacity in the presence and absence of illusion-inducing conditioning stimuli. Comparison of the performances in the presence and abse..

Folding and Hydrodynamics of a DNA i-Motif from the c-MYC Promoter Determined by Fluorescent Cytidine Analogs

AbstractThe four-stranded i-motif (iM) conformation of cytosine-rich DNA has importance to a wide variety of biochemical systems that range from their use in nanomaterials to potential roles in oncogene regulation. The iM structure is formed at slightly acidic pH, where hemiprotonation of cytosine results in a stable C-C+ basepair. Here, we performed fundamental studies to examine iM formation from a C-rich strand from the promoter of the human c-MYC gene. We used a number of biophysical techniques to characterize both the hydrodynamic properties and folding kinetics of a folded iM. Our hydrodynamic studies using fluorescence anisotropy decay and analytical ultracentrifugation show that the iM structure has a compact size in solution and displays the rigidity of a double strand. By studying the rates of circular dichroism spectral changes and quenching of fluorescent cytidine analogs, we also established a mechanism for the folding of a random coil oligo into the iM. In the course of determining this folding pathway, we established that the fluorescent dC analogs tC° and PdC can be used to monitor individual residues of an iM structure and to determine the pKa of an iM. We established that the C-C+ hydrogen bonding of certain bases initiates the folding of the iM structure. We also showed that substitutions in the loop regions of iMs give a distinctly different kinetic signature during folding compared with bases that are intercalated. Our data reveal that the iM passes through a distinct intermediate form between the unfolded and folded forms. Taken together, our results lay the foundation for using fluorescent dC analogs to follow structural changes during iM formation. Our technique may also be useful for examining folding and structural changes in more complex iMs

Neptunism and transformism:Robert Jameson and other evolutionary theorists in early nineteenth-century Scotland

This paper sheds new light on the prevalence of evolutionary ideas in Scotland in the early nineteenth century and establish what connections existed between the espousal of evolutionary theories and adherence to the directional history of the earth proposed by Abraham Gottlob Werner and his Scottish disciples. A possible connection between Wernerian geology and theories of the transmutation of species in Edinburgh in the period when Charles Darwin was a medical student in the city was suggested in an important 1991 paper by James Secord. This study aims to deepen our knowledge of this important episode in the history of evolutionary ideas and explore the relationship between these geological and evolutionary discourses. To do this it focuses on the circle of natural historians around Robert Jameson, Wernerian geologist and professor of natural history at the University of Edinburgh from 1804 to 1854. From the evidence gathered here there emerges a clear confirmation that the Wernerian model of geohistory facilitated the acceptance of evolutionary explanations of the history of life in early nineteenth-century Scotland. As Edinburgh was at this time the most important center of medical education in the English-speaking world, this almost certainly influenced the reception and development of evolutionary ideas in the decades that followed.</p

Prevalence of Antibodies against Hantaviruses in Serum and Saliva of Adults Living or Working on Farms in Yorkshire, United Kingdom

We acknowledge Clement and colleagues for their comments [1] on our paper [2]. We agree that many controversies are being discussed by the hantavirus community, particularly surrounding the interpretation of serological results and the designation of new species and strains. Within this setting, we are grateful for the opportunity to respond to the key factual and methodological points raised by Clements et al. [...