ParticleStats: open source software for the analysis of particle motility and cytoskeletal polarity

The study of dynamic cellular processes in living cells is central to biology and is particularly powerful when the motility characteristics of individual objects within cells can be determined and analysed statistically. However, commercial programs only offer a limited range of inflexible analysis modules and there are currently no open source programs for extensive analysis of particle motility. Here, we describe ParticleStats (http://www.ParticleStats.com), a web server and open source programs, which input the X,Y coordinate positions of objects in time, and output novel analyses, graphical plots and statistics for motile objects. ParticleStats comprises three separate analysis programs. First, ParticleStats:Directionality for the global analysis of polarity, for example microtubule plus end growth in Drosophila oocytes. Second, ParticleStats:Compare for the analysis of saltatory movement in terms of runs and pauses. This can be applied to chromosome segregation and molecular motor-based movements. Thirdly ParticleStats:Kymographs for the analysis of kymograph images, for example as applied to separation of chromosomes in mitosis. These analyses have provided key insights into molecular mechanisms that are not possible from qualitative analysis alone and are widely applicable to many other cell biology problems

Work/ family demands and cardiometabolic risk and sleep duration in extended care employees: multilevel findings from the Work, family and Health Network

The study investigates the associations of work-family conflict and other work and family conditions with objectively-measured outcomes cardiometabolic risk and sleep duration in a study of employees in nursing homes. Multilevel analyses are used to assess cross-sectional associations between employee and job characteristics and health in analyses of 1,524 employees in 30 extended care facilities in a single company. We examine work and family conditions in relation to two major study health outcomes: 1) a validated, Framingham cardiometabolic risk score based on measured blood pressure, cholesterol, glycosylated hemoglobin (HbA1c), body mass index (BMI), and self-reported tobacco consumption, and 2) wrist actigraphy-based measures of sleep duration. In fully-adjusted multi-level models, Work-To-Family conflict, but not Family-to-Work conflict was positively associated with cardiometabolic risk. Having a lower-level occupation (nursing assistants vs. nurses) was also associated with increased cardiometabolic risk, while being married and having younger children at home was protective. A significant age by Work-To-Family conflict interaction revealed that higher Work-To-Family conflict was more strongly associated with increased cardiometabolic risk in younger employees. With regard to sleep duration, high Family-To-Work Conflict was significantly associated with shorter sleep duration. In addition, working long hours and having younger children at home were both independently associated with shorter sleep duration. High Work-To-Family Conflict was associated with longer sleep duration. These results indicate that different dimensions of work-family conflict (i.e., Work-To-Family Conflict and Family-To-Work Conflict) may both pose threats to cardiometabolic risk and sleep duration for employees. This study contributes to the research on work- family conflict suggesting that Work-To-Family and Family-To-Work conflict are associated with specific outcomes. Translating theory and our findings to preventive interventions entails recognition of the dimensionality of work and family dynamics and the need to target specific work and family conditions

Limited Alpine Climatic Warming and Modeled Phenology Advancement for Three Alpine Species in the Northeast United States

Premise of the study: Most alpine plants in the Northeast United States are perennial and flower early in the growing season, extending their limitedgrowing season. Concurrently, they risk the loss of reproductive efforts to late frosts. Quantifying long-term trends in northeastern alpine flower phenology and late-spring/early-summer frost risk is limited by a dearth of phenology and climate data, except for Mount Washington, New Hampshire (1916 m a.s.l.). Methods: Logistic phenology models for three northeastern US alpinespecies (Diapensia lapponica, Carex bigelowii and Vaccinium vitis-idaea) were developed from 4 yr (2008–2011) of phenology and air temperature measurements from 12 plots proximate to Mount Washington’s long-term summit meteorological station. Plot-level air temperature, the logistic phenology models, and Mount Washington’s climate data were used to hindcast model yearly (1935–2011) floral phenology and frost damage risk for the focal species. Key results: Day of year and air growing degree-days with threshold temperatures of −4°C (D. lapponica and C. bigelowii) and −2°C (V. vitis-idaea) best predicted flowering. Modeled historic flowering dates trended significantly earlier but the 77-yr change was small (1.2–2.1 d) and did not significantly increase early-flowering risk from late-spring/early-summer frost damage. Conclusions: Modeled trends in phenological advancement and sensitivity for three northeastern alpine species are less pronounced compared with lower elevations in the region, and this small shift in flower timing did not increase risk of frost damage. Potential reasons for limited earlier phenological advancement at higher elevations include a slower warming trend and increased cloud exposure with elevation and/or inadequate chilling requirements

Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth

Systemic delivery of siRNA to solid tumors remains challenging. In this study, we investigated the systemic delivery of a siRNA nanoparticle targeting ribonucleotide reductase subunit M2 (RRM2), and evaluated its intratumoral kinetics, efficacy and mechanism of action. Knockdown of RRM2 by an RNAi mechanism strongly inhibited cell growth in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines. In a mouse xenograft model of HNSCC, a single intravenous injection led to the accumulation of intact nanoparticles in the tumor that disassembled over a period of at least 3 days, leading to target gene knockdown lasting at least 10 days. A four-dose schedule of siRNA nanoparticle delivering RRM2 siRNA targeted to HNSCC tumors significantly reduced tumor progression by suppressing cell proliferation and inducing apoptosis. These results show promise for the use of RRM2 siRNA-based therapy for HNSCC and possibly NSCLC

Interventions associated with brown adipose tissue activation and the impact on energy expenditure and weight loss: A systematic review

BackgroundBrown adipose tissue (BAT) plays a role in modulating energy expenditure. People with obesity have been shown to have reduced activation of BAT. Agents such as β-agonists, capsinoids, thyroid hormone, sildenafil, caffeine, or cold exposure may lead to activation of BAT in humans, potentially modulating metabolism to promote weight loss.MethodsWe systematically searched electronic databases for clinical trials testing the effect of these agents and cold exposure on energy expenditure/thermogenesis and the extent to which they may impact weight loss in adults.ResultsA total of 695 studies from PubMed, Web of Science, and Medline electronic databases were identified. After the removal of duplicates and further evaluation, 47 clinical trials were analyzed. We observed significant heterogeneity in the duration of interventions and the metrics utilized to estimate thermogenesis/energy expenditure. Changes observed in energy expenditure do not correlate with major weight changes with different interventions commonly known to stimulate thermogenesis. Even though cold exposure appears to consistently activate BAT and induce thermogenesis, studies are small, and it appears to be an unlikely sustainable therapy to combat obesity. Most studies were small and potential risks associated with known side effects of some agents such as β-agonists (tachycardia), sibutramine (hypertension, tachycardia), thyroid hormone (arrhythmias) cannot be fully evaluated from these small trials.ConclusionThough the impact of BAT activation and associated increases in energy expenditure on clinically meaningful weight loss is a topic of great interest, further data is needed to determine long-term feasibility and efficacy

Deletion of SA β-Gal+ Cells Using Senolytics Improves Muscle Regeneration in Old Mice

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl2 or PBS 7- or 28 days prior to euthanization. Senescence-associated β-Galactosidase positive (SA β-Gal+) cell abundance was low in muscle from both young and old mice and increased similarly 7 days following injury in both age groups, with no effect of D+Q. Most SA β-Gal+ cells were also CD11b+ in young and old mice 7- and 14 days following injury, suggesting they are infiltrating immune cells. By 14 days, SA β-Gal+/CD11b+ cells from old mice expressed senescence genes, whereas those from young mice expressed higher levels of genes characteristic of anti-inflammatory macrophages. SA β-Gal+ cells remained elevated in old compared to young mice 28 days following injury, which were reduced by D+Q only in the old mice. In D+Q-treated old mice, muscle regenerated following injury to a greater extent compared to vehicle-treated old mice, having larger fiber cross-sectional area after 28 days. Conversely, D+Q blunted regeneration in young mice. In vitro experiments suggested D+Q directly improve myogenic progenitor cell proliferation. Enhanced physical function and improved muscle regeneration demonstrate that senolytics have beneficial effects only in old mice

Supporting patients with low health literacy: what role do radiation therapists play?

Purpose: Health literacy plays a key role in a patient’s ability to use health information and services, and can affect health outcomes. This study aimed to explore radiation therapists’ perspectives on how they support people with lower health literacy who are undergoing radiotherapy. Methods: Semi-structured interviews were conducted with 25 radiation therapists working in radiation oncology departments in New South Wales, Australia. Results: The four key themes were (1) the process of identifying a patient with low health literacy, (2) the perceived consequences of low health literacy, (3) managing and responding to the needs of different health literacy groups and (4) recommendations to address low health literacy in radiotherapy. Radiation therapists appeared to make an informal, intuitive judgment about a patient’s health literacy, using a variety of verbal and non-verbal cues as well as impromptu conversations with the multi-disciplinary team. Patients perceived to have lower health literacy were described as having greater difficulties assimilating knowledge and engaging in self-care. Although participants reported communicating to patients at a basic level initially, they subsequently tailored their communication to match a patient’s health literacy. Strategies reported to communicate to low health literacy groups ranged from using lay language with minimal medical terminology, using visual aids (photos), using analogies, reiterating information and asking family members with higher literacy to attend consultations. Conclusion: A more structured approach to supporting patients with low health literacy and integrating health literacy training in radiation oncology departments may help to minimise the adverse outcomes typically experienced by this population

Cardiovascular risk factors among Chamorros

BACKGROUND: Little is known regarding the cardiovascular disease risk factors among Chamorros residing in the United States. METHODS: The Chamorro Directory International and the CDC's Behavioral Risk Factor Surveillance System Questionnaire (BRFSS) were used to assess the health related practices and needs of a random sample of 228 Chamorros. RESULTS: Inactivity, hypertension, elevated cholesterol and diabetes mellitus were more prevalent in this Chamorro sample compared to the US average. Participants who were 50-and-older or unemployed were more likely to report hypertension, diabetes and inactivity, but they were also more likely to consume more fruits and vegetables than their younger and employed counterparts. Women were more likely to report hypertension and diabetes, whereas men were more likely to have elevated BMI and to have never had their blood cholesterol checked. CONCLUSION: The study provides data that will help healthcare providers, public health workers and community leaders identify where to focus their health improvement efforts for Chamorros and create culturally competent programs to promote health in this community

A BAC pooling strategy combined with PCR-based screenings in a large, highly repetitive genome enables integration of the maize genetic and physical maps

BACKGROUND: Molecular markers serve three important functions in physical map assembly. First, they provide anchor points to genetic maps facilitating functional genomic studies. Second, they reduce the overlap required for BAC contig assembly from 80 to 50 percent. Finally, they validate assemblies based solely on BAC fingerprints. We employed a six-dimensional BAC pooling strategy in combination with a high-throughput PCR-based screening method to anchor the maize genetic and physical maps. RESULTS: A total of 110,592 maize BAC clones (~ 6x haploid genome equivalents) were pooled into six different matrices, each containing 48 pools of BAC DNA. The quality of the BAC DNA pools and their utility for identifying BACs containing target genomic sequences was tested using 254 PCR-based STS markers. Five types of PCR-based STS markers were screened to assess potential uses for the BAC pools. An average of 4.68 BAC clones were identified per marker analyzed. These results were integrated with BAC fingerprint data generated by the Arizona Genomics Institute (AGI) and the Arizona Genomics Computational Laboratory (AGCoL) to assemble the BAC contigs using the FingerPrinted Contigs (FPC) software and contribute to the construction and anchoring of the physical map. A total of 234 markers (92.5%) anchored BAC contigs to their genetic map positions. The results can be viewed on the integrated map of maize [1,2]. CONCLUSION: This BAC pooling strategy is a rapid, cost effective method for genome assembly and anchoring. The requirement for six replicate positive amplifications makes this a robust method for use in large genomes with high amounts of repetitive DNA such as maize. This strategy can be used to physically map duplicate loci, provide order information for loci in a small genetic interval or with no genetic recombination, and loci with conflicting hybridization-based information