Lineaments in the Grand Canyon area, northern Arizona - A radar analysis

Side-looking radar analysis of Grand Canyon Arizona geomorpholog

Cotinine-assessed second-hand smoke exposure and risk of cardiovascular disease in older adults

Objectives: To examine whether second-hand smoke (SHS) exposure measured by serum cotinine is associated with increased coronary heart disease (CHD) and stroke risk among contemporary older British adults. Design: Prospective population-based study with self-reported medical history and health behaviours. Fasting blood samples were analysed for serum cotinine and cardiovascular disease (CVD) risk markers. Setting: Primary care centres in 25 British towns in 1998–2001. Patients: 8512 60–79-year-old men and women selected from primary care registers. Main outcome measures: Fatal and non-fatal myocardial infarction (MI; n=445) and stroke (n=386) during median 7.8-year follow-up. Main exposure: Observational study of serum cotinine assayed from fasting blood sample using liquid chromatography tandem mass spectrometry method, and self-reported smoking history. Results: Among 5374 non-smokers without pre-existing CVD, geometric mean cotinine was 0.15 ng/ml (IQR 0.05–0.30). Compared with non-smokers with cotinine ≤0.05 ng/ml, higher cotinine levels (0.06–0.19, 0.2–0.7 and 0.71–15.0 ng/ml) showed little association with MI; adjusted HRs were 0.92 (95% CI 0.63 to 1.35), 1.07 (0.73 to 1.55) and 1.09 (0.69 to 1.72), p(trend)=0.69. Equivalent HRs for stroke were 0.82 (0.55 to 1.23), 0.74 (0.48 to 1.13) and 0.69 (0.41 to 1.17), p(trend)=0.065. The adjustment for sociodemographic, behavioural and CVD risk factors had little effect on the results. The HR of MI for smokers (1–9 cigarettes/day) compared with non-smokers with cotinine ≤0.05 ng/ml was 2.14 (1.39 to 3.52) and 1.03 (0.52 to 2.04) for stroke. Conclusions: In contemporary older men and women, SHS exposure (predominantly at low levels) was not related to CHD or stroke risks, but we cannot rule out the possibility of modest effects at higher exposure levels

Facilitating Neuron-Specific Genetic Manipulations in Drosophila melanogaster Using a Split GAL4 Repressor.

Efforts to map neural circuits have been galvanized by the development of genetic technologies that permit the manipulation of targeted sets of neurons in the brains of freely behaving animals. The success of these efforts relies on the experimenter's ability to target arbitrarily small subsets of neurons for manipulation, but such specificity of targeting cannot routinely be achieved using existing methods. In Drosophila melanogaster, a widely-used technique for refined cell type-specific manipulation is the Split GAL4 system, which augments the targeting specificity of the binary GAL4-UAS (Upstream Activating Sequence) system by making GAL4 transcriptional activity contingent upon two enhancers, rather than one. To permit more refined targeting, we introduce here the "Killer Zipper" (KZip+), a suppressor that makes Split GAL4 targeting contingent upon a third enhancer. KZip+ acts by disrupting both the formation and activity of Split GAL4 heterodimers, and we show how this added layer of control can be used to selectively remove unwanted cells from a Split GAL4 expression pattern or to subtract neurons of interest from a pattern to determine their requirement in generating a given phenotype. To facilitate application of the KZip+ technology, we have developed a versatile set of LexAop-KZip+ fly lines that can be used directly with the large number of LexA driver lines with known expression patterns. KZip+ significantly sharpens the precision of neuronal genetic control available in Drosophila and may be extended to other organisms where Split GAL4-like systems are used

Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering

How are falls and fear of falling associated with objectively measured physical activity in a cohort of community-dwelling older men?

BACKGROUND: Falls affect approximately one third of community-dwelling older adults each year and have serious health and social consequences. Fear of falling (FOF) (lack of confidence in maintaining balance during normal activities) affects many older adults, irrespective of whether they have actually experienced falls. Both falls and fear of falls may result in restrictions of physical activity, which in turn have health consequences. To date the relation between (i) falls and (ii) fear of falling with physical activity have not been investigated using objectively measured activity data which permits examination of different intensities of activity and sedentary behaviour. METHODS: Cross-sectional study of 1680 men aged 71-92 years recruited from primary care practices who were part of an on-going population-based cohort. Men reported falls history in previous 12 months, FOF, health status and demographic characteristics. Men wore a GT3x accelerometer over the hip for 7 days. RESULTS: Among the 12% of men who had recurrent falls, daily activity levels were lower than among non-fallers; 942 (95% CI 503, 1381) fewer steps/day, 12(95% CI 2, 22) minutes less in light activity, 10(95% CI 5, 15) minutes less in moderate to vigorous PA [MVPA] and 22(95% CI 9, 35) minutes more in sedentary behaviour. 16% (n = 254) of men reported FOF, of whom 52% (n = 133) had fallen in the past year. Physical activity deficits were even greater in the men who reported that they were fearful of falling than in men who had fallen. Men who were fearful of falling took 1766(95% CI 1391, 2142) fewer steps/day than men who were not fearful, and spent 27(95% CI 18, 36) minutes less in light PA, 18(95% CI 13, 22) minutes less in MVPA, and 45(95% CI 34, 56) minutes more in sedentary behaviour. The significant differences in activity levels between (i) fallers and non-fallers and (ii) men who were fearful of falling or not fearful, were mediated by similar variables; lower exercise self-efficacy, fewer excursions from home and more mobility difficulties. CONCLUSIONS: Falls and in particular fear of falling are important barriers to older people gaining health benefits of walking and MVPA. Future studies should assess the longitudinal associations between falls and physical activity

Tracking of sport and exercise types from midlife to old age: a 20-year cohort study of British men.

Background: Previous physical activity (PA) tracking studies have examined the stability of overall PA and/or PA types, but few have investigated how specific types of sport/exercise track over the life course. The aim of this study was to determine how specific sports/exercises in midlife track and predict future sport/exercise and PA in men transitioning to old age. Methods: Seven thousand seven hundred thirty-five men (aged 40-59 years) recruited in 1978-80 were followed up after 12, 16 and 20 years. At each wave men self-reported participation in sport/exercise. Frequent sport/exercise participants (> 1/month) reported the types of sport/exercise they engaged in. Men also reported total PA, health status, lifestyle behaviours and socio-demographic characteristics. Stability of each sport/exercise was assessed using kappa statistics and intraclass correlation coefficients. Logistic regression estimated the odds of participating in sport/exercise and being active at 20-year follow up according to specific types of sport/exercise in midlife. Results: Three thousand three hundred eighty-four men with complete data at all waves were included in analyses. Tracking of specific sports/exercises ranged from fair to substantial, with golf being the most common and most stable. Bowls was the most frequently adopted. Odds of participating in sport/exercise and being active in old age varied according to sport/exercise types in midlife. Golf and bowls in midlife were the strongest predictors of sport/exercise participation in old age. Golf, cricket and running/jogging in midlife were among the strongest predictors of being active in old age. Compared to participating in just one sport/exercise in midlife, sampling multiple sports/exercises was more strongly associated with sport/exercise participation and being active in old age. Conclusion: The stability of sport/exercise participation from midlife to old age varies by type. Specific sports/exercises in midlife may be more likely to predict future PA than others. However, participating in a range of sports/exercises may be optimal for preserving PA into old age

Sedentary time in older men and women: an international consensus statement and research priorities

Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies

Visualization and Analysis of 3D Microscopic Images

In a wide range of biological studies, it is highly desirable to visualize and analyze three-dimensional (3D) microscopic images. In this primer, we first introduce several major methods for visualizing typical 3D images and related multi-scale, multi-time-point, multi-color data sets. Then, we discuss three key categories of image analysis tasks, namely segmentation, registration, and annotation. We demonstrate how to pipeline these visualization and analysis modules using examples of profiling the single-cell gene-expression of C. elegans and constructing a map of stereotyped neurite tracts in a fruit fly brain

Asymmetric neurotransmitter release enables rapid odor lateralization in Drosophila

In Drosophila, most individual olfactory receptor neurons (ORNs) project bilaterally to both sides of the brain1,2. Having bilateral rather than unilateral projections may represent a useful redundancy. However, bilateral ORN projections to the brain should also compromise the ability to lateralize odors. Nevertheless, walking or flying Drosophila reportedly turn toward their more strongly stimulated antenna3-5. Here we show that each ORN spike releases ~40% more neurotransmitter from the axon branch ipsilateral to the soma, as compared to the contralateral branch. As a result, when an odor activates the antennae asymmetrically, ipsilateral central neurons begin to spike a few milliseconds before contralateral neurons, and ipsilateral central neurons also fire at a 30-50% higher rate. We show that a walking fly can detect a 5% asymmetry in total ORN input to its left and right antennal lobes, and can turn toward the odor in less time than it requires the fly to complete a stride. These results demonstrate that neurotransmitter release properties can be tuned independently at output synapses formed by a single axon onto two target cells with identical functions and morphologies. Our data also show that small differences in spike timing and spike rate can produce reliable differences in olfactory behavior

A Complete Developmental Sequence of a Drosophila Neuronal Lineage as Revealed by Twin-Spot MARCM

Labeling every neuron in a lineage in the fruit fly olfactory system reveals that every cell is born with a pre-determined cell fate that is invariant and dependent upon neuron birth orde