A Wellness Needs Assessment of Persons with Disabilities in Northern Florida: Physical Activity and Nutrition

Engaging an individual with a disability in health promotion activities may be challenging. This challenge is demonstrated by the prevalence of obesity among people with disabilities (PWDs) being higher than those without, and PWD twice as likely to be physically inactive. The combination of physical inactivity and high prevalence of obesity supports a need for health promotion activities. To examine the need for wellness promotion activities for PWDs, we surveyed consumers at a Center for Independent Living in North Central Florida (CILNCF). A survey was developed with items from the Physical Activity Scale for Individuals with Physical Disability (PASIPD) and nutrition items from Florida’s Behavioral Risk Factor Surveillance System (BRFSS). Among 36 participants, 25% reported exercise was difficult due to their disability and only 6% reported their attendant assisted with exercise. Participants reported doing less than the national recommendation of medium-strength exercise (83%) and hard-strength training activities (80%). Participants reported not meeting daily guidelines for fruit (42%) and green vegetable consumption (41%). Results demonstrate a lack of physical activity and adequate nutrition among PWDs. Community service organizations such as the CILNCF represent an ideal location to administer physical activity and nutrition education and interventions

System for the measurement of ultra-low stray light levels

An apparatus is described for measuring the effectiveness of stray light suppression light shields and baffle arrangements used in optical space experiments and large space telescopes. The light shield and baffle arrangement and a telescope model are contained in a vacuum chamber. A source of short, high-powered light energy illuminates portions of the light shield and baffle arrangement and reflects a portion of same to a photomultiplier tube by virtue of multipath scattering. The resulting signal is transferred to time-channel electronics timed by the firing of the high energy light source allowing time discrimination of the signal thereby enabling the light scattered and suppressed by the model to be distinguished from the walls and holders around the apparatus

Structure-based inhibitors of amyloid beta core suggest a common interface with tau.

Alzheimer's disease (AD) pathology is characterized by plaques of amyloid beta (Aβ) and neurofibrillary tangles of tau. Aβ aggregation is thought to occur at early stages of the disease, and ultimately gives way to the formation of tau tangles which track with cognitive decline in humans. Here, we report the crystal structure of an Aβ core segment determined by MicroED and in it, note characteristics of both fibrillar and oligomeric structure. Using this structure, we designed peptide-based inhibitors that reduce Aβ aggregation and toxicity of already-aggregated species. Unexpectedly, we also found that these inhibitors reduce the efficiency of Aβ-mediated tau aggregation, and moreover reduce aggregation and self-seeding of tau fibrils. The ability of these inhibitors to interfere with both Aβ and tau seeds suggests these fibrils share a common epitope, and supports the hypothesis that cross-seeding is one mechanism by which amyloid is linked to tau aggregation and could promote cognitive decline

Who Should Decide? Decision-Making Preferences for Primary HPV Testing for Cervical Cancer Screening Among U.S. Women

Revised U.S. guidelines for cervical cancer screening provide the option of primary human papillomavirus (HPV) testing, Pap testing, or co-testing. Primary HPV testing has not yet been an option for American women, and women may be reluctant to change screening methods. The purpose of this study was to assess correlates of women’s preferences for primary HPV testing decision-making (self, provider, or shared) for cervical cancer screening. Women, aged 30-65, completed an online survey in June of 2018 (n = 812). The outcome variable was preference for decision-making for an HPV test instead of a Pap test on a scale of, healthcare provider, me, or shared. Predictor variables included testing attitudes, social norms, information seeking, previous screening, and socio-demographics. Women who disagreed that people important to them think that they should get the HPV test instead of a Pap test, who were not willing to receive an HPV test instead of a Pap test, and who did not receive HPV vaccinations were less likely to include a provider in their decision-making. In contrast, women who were not up-to-date with their cervical cancer screenings, who had some college or technical level education, or who were over 50 years of age were more likely to prefer to have a healthcare provider included in their decision-making process. While some variation was discovered, women mostly preferred a shared decision or personal decision for HPV testing. Resources to facilitate the decision-making process about this new option for cervical cancer screening are needed

Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity.

hIAPP fibrils are associated with Type-II Diabetes, but the link of hIAPP structure to islet cell death remains elusive. Here we observe that hIAPP fibrils are cytotoxic to cultured pancreatic β-cells, leading us to determine the structure and cytotoxicity of protein segments composing the amyloid spine of hIAPP. Using the cryoEM method MicroED, we discover that one segment, 19-29 S20G, forms pairs of β-sheets mated by a dry interface that share structural features with and are similarly cytotoxic to full-length hIAPP fibrils. In contrast, a second segment, 15-25 WT, forms non-toxic labile β-sheets. These segments possess different structures and cytotoxic effects, however, both can seed full-length hIAPP, and cause hIAPP to take on the cytotoxic and structural features of that segment. These results suggest that protein segment structures represent polymorphs of their parent protein and that segment 19-29 S20G may serve as a model for the toxic spine of hIAPP

Exact Thermodynamics of the Double sinh-Gordon Theory in 1+1-Dimensions

We study the classical thermodynamics of a 1+1-dimensional double-well sinh-Gordon theory. Remarkably, the Schrodinger-like equation resulting from the transfer integral method is quasi-exactly solvable at several temperatures. This allows exact calculation of the partition function and some correlation functions above and below the short-range order (``kink'') transition, in striking agreement with high resolution Langevin simulations. Interesting connections with the Landau-Ginzburg and double sine-Gordon models are also established.Comment: 4 pages, 3 figures (embedded using epsf), uses RevTeX plus macro (included). Minor revision to match journal version, Phys. Rev. Lett. (in press

The RacGAP β2-Chimaerin Selectively Mediates Axonal Pruning in the Hippocampus

SummaryAxon pruning and synapse elimination promote neural connectivity and synaptic plasticity. Stereotyped pruning of axons that originate in the hippocampal dentate gyrus (DG) and extend along the infrapyramidal tract (IPT) occurs during postnatal murine development by neurite retraction and resembles axon repulsion. The chemorepellent Sema3F is required for IPT axon pruning, dendritic spine remodeling, and repulsion of DG axons. The signaling events that regulate IPT axon pruning are not known. We find that inhibition of the small G protein Rac1 by the Rac GTPase-activating protein (GAP) β2-Chimaerin (β2Chn) mediates Sema3F-dependent pruning. The Sema3F receptor neuropilin-2 selectively binds β2Chn, and ligand engagement activates this GAP to ultimately restrain Rac1-dependent effects on cytoskeletal reorganization. β2Chn is necessary for axon pruning both in vitro and in vivo, but it is dispensable for axon repulsion and spine remodeling. Therefore, a Npn2/β2Chn/Rac1 signaling axis distinguishes DG axon pruning from the effects of Sema3F on repulsion and dendritic spine remodeling

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

Chaos and the continuum limit in the gravitational N-body problem II. Nonintegrable potentials

This paper continues a numerical investigation of orbits evolved in `frozen,' time-independent N-body realisations of smooth time-independent density distributions corresponding to both integrable and nonintegrable potentials, allowing for N as large as 300,000. The principal focus is on distinguishing between, and quantifying, the effects of graininess on initial conditions corresponding, in the continuum limit, to regular and chaotic orbits. Ordinary Lyapunov exponents X do not provide a useful diagnostic for distinguishing between regular and chaotic behaviour. Frozen-N orbits corresponding in the continuum limit to both regular and chaotic characteristics have large positive X even though, for large N, the `regular' frozen-N orbits closely resemble regular characteristics in the smooth potential. Viewed macroscopically both `regular' and `chaotic' frozen-N orbits diverge as a power law in time from smooth orbits with the same initial condition. There is, however, an important difference between `regular' and `chaotic' frozen-N orbits: For regular orbits, the time scale associated with this divergence t_G ~ N^{1/2}t_D, with t_D a characteristic dynamical time; for chaotic orbits t_G ~ (ln N) t_D. At least for N>1000 or so, clear distinctions exist between phase mixing of initially localised orbit ensembles which, in the continuum limit, exhibit regular versus chaotic behaviour. For both regular and chaotic ensembles, finite-N effects are well mimicked, both qualitatively and quantitatively, by energy-conserving white noise with amplitude ~ 1/N. This suggests strongly that earlier investigations of the effects of low amplitude noise on phase space transport in smooth potentials are directly relevant to real physical systems.Comment: 20 pages, including 21 FIGURES, uses RevTeX macro

Non-Small Cell Lung Carcinoma Cell Motility, Rac Activation and Metastatic Dissemination Are Mediated by Protein Kinase C Epsilon

Background: Protein kinase C (PKC) e, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCe in lung cancer metastasis has not yet been established. Principal Findings: Here we show that RNAi-mediated knockdown of PKCe in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCe depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCe with eV1-2, a specific PKCe inhibitor. PKCe was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCe-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis. Conclusions: Our results implicate PKCe as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target