FindFoci: a focus detection algorithm with automated parameter training that closely matches human assignments, reduces human inconsistencies and increases speed of analysis

Accurate and reproducible quantification of the accumulation of proteins into foci in cells is essential for data interpretation and for biological inferences. To improve reproducibility, much emphasis has been placed on the preparation of samples, but less attention has been given to reporting and standardizing the quantification of foci. The current standard to quantitate foci in open-source software is to manually determine a range of parameters based on the outcome of one or a few representative images and then apply the parameter combination to the analysis of a larger dataset. Here, we demonstrate the power and utility of using machine learning to train a new algorithm (FindFoci) to determine optimal parameters. FindFoci closely matches human assignments and allows rapid automated exploration of parameter space. Thus, individuals can train the algorithm to mirror their own assignments and then automate focus counting using the same parameters across a large number of images. Using the training algorithm to match human assignments of foci, we demonstrate that applying an optimal parameter combination from a single image is not broadly applicable to analysis of other images scored by the same experimenter or by other experimenters. Our analysis thus reveals wide variation in human assignment of foci and their quantification. To overcome this, we developed training on multiple images, which reduces the inconsistency of using a single or a few images to set parameters for focus detection. FindFoci is provided as an open-source plugin for ImageJ

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

Differential processing of the direction and focus of expansion of optic flow stimuli in areas MST and V3A of the human visual cortex

Human neuropsychological and neuroimaging studies have raised the possibility that different attributes of optic flow stimuli, namely radial direction and the position of the focus of expansion (FOE), are processed within separate cortical areas. In the human brain, visual areas V5/MT+ and V3A have been proposed as integral to the analysis of these different attributes of optic flow stimuli. To establish direct causal relationships between neural activity in human (h)V5/MT+ and V3A and the perception of radial motion direction and FOE position, we used transcranial magnetic stimulation (TMS) to disrupt cortical activity in these areas while participants performed behavioral tasks dependent on these different aspects of optic flow stimuli. The cortical regions of interest were identified in seven human participants using standard functional MRI retinotopic mapping techniques and functional localizers. TMS to area V3A was found to disrupt FOE positional judgments but not radial direction discrimination, whereas the application of TMS to an anterior subdivision of hV5/MT+, MST/TO-2 produced the reverse effects, disrupting radial direction discrimination but eliciting no effect on the FOE positional judgment task. This double dissociation demonstrates that FOE position and radial direction of optic flow stimuli are signaled independently by neural activity in areas hV5/MT+ and V3A.NEW & NOTEWORTHY Optic flow constitutes a biologically relevant visual cue as we move through any environment. With the use of neuroimaging and brain-stimulation techniques, this study demonstrates that separate human brain areas are involved in the analysis of the direction of radial motion and the focus of expansion in optic flow. This dissociation reveals the existence of separate processing pathways for the analysis of different attributes of optic flow that are important for the guidance of self-locomotion and object avoidance

Paradigms in multiple sclerosis: time for a change, time for a unifying concept

It has recently been suggested that, rather than being an autoimmune disease, multiple sclerosis (MS) is an example of a neurocristopathy, a pathological process resulting from a faulty development of the neural crest. Whilst several characteristics of the disease suggest a neurocristopathy, other aetiological factors require consideration, including hygiene-related factors that alter the immune responses to common pathogens resulting in an eclipse of immune reactivity that could protect against MS, the possible role of human endogenous retroviruses (HERVs) in pathogenesis and autoimmune phenomena, HLA polymorphism, vitamin D levels before and after birth and immune repair mechanisms. A postulated aetiological factor in MS, associated with altered vitamin D metabolism and abnormal HERV expression, is a long-lasting disturbed redox regulation in the biosynthesis of a melanoma-like melanin pigment. Although intensive further studies on melanin pigments in nerve tissue in MS are required, the known properties of a pathological form of such pigments in melanoma could explain a number of observations in MS, including the impact of light, UV-light, and vitamin D, and could explain the clinical manifestations of MS on the basis of an oscillating process of oxidative charge and discharge of the pigments and a threshold phenomenon with a change of the quasi-catalytic function of the pigment from destroying reactive oxygen radicals or species to transforming them to more harmful long-persisting highly reactive species. Taken together with the consequences of an adaptive process in partly demyelinated neurons, resulting in an increase in number of mitochondria, and the impact of stressful life events, these conditions are necessary and sufficient to explain the disease process of MS with its spatial (plaques) and temporal (attacks and remissions) characteristics. This suggested unifying concept of the pathogenesis of MS may open perspectives for prevention, diagnosis and therapy. In particular, prevention may be achieved by vaccinating against Epstein-Barr virus in early childhood

Physical, Psychological and Emotional Benefits of Green Physical Activity: An Ecological Dynamics Perspective

© 2015 Springer International Publishing Switzerland Increasing evidence supports the multiple benefits to physical, psychological and emotional wellbeing of green physical activity, a topic of increasing interest in the past decade. Research has revealed a synergistic benefit of green physical activity, which includes all aspects of exercise and physical activity in the presence of nature. Our theoretical analysis suggests there are three distinct levels of engagement in green physical activity, with each level reported to have a positive effect on human behaviours. However, the extent to which each level of green physical activity benefits health and wellbeing is assumed to differ, requiring confirmation in future research. This elucidation of understanding is needed because previous literature has tended to focus on recording empirical evidence rather than developing a sound theoretical framework to understand green physical activity effects. Here we propose an ecological dynamics rationale to explain how and why green physical activity might influence health and wellbeing of different population groups. This framework suggests a number of unexplored, interacting constraints related to types of environment and population groups, which shape reported levels of benefit of green physical activity. Further analysis is needed to clarify the explicit relationship between green physical activity and health and wellbeing, including levels of engagement, types of environmental constraints, levels of physical activity, adventure effects, skill effects and sampling of different populations

Ultraviolet Laser Action in Ferromagnetic Zn1−xFexO Nanoneedles

Fe-doped ZnO nanoneedles (NDs) were fabricated by an Ar+ ion sputtering technique operated at room temperature. The as-grown samples show both ferromagnetic and lasing properties. The saturated magnetization moment was measured from 0.307 to 0.659 emu cm−3 at the field of 10 kOe with various Fe concentrations. Intense ultraviolet random lasing emission was observed from Zn1 − xFexO NDs at room temperature. The X-ray photoelectron spectroscopy result reveals that the doped Fe atoms occupy the Zn sites and lead to a decrease in oxygen deficiency

Marine Dynamics and Productivity in the Bay of Bengal

The Bay of Bengal provides important ecosystem services to the Bangladesh delta. It is also subject to the consequences of climate change as monsoon atmospheric circulation and fresh water input from the major rivers are the dominating influences. Changes in marine circulation will affect patterns of biological production through alterations in the supply of nutrients to photosynthesising plankton. Productivity in the northern Bay will also be sensitive to changes in riverborne nutrients. In turn, these changes could influence potential fish catch. The Bay also affects the physical environment of Bangladesh: relative sea-level rise is expected to be in the range of 0.5–1.7 m by 2100, and changing climate could affect the development of tropical cyclones over the Bay

Plasma and Muscle Myostatin in Relation to Type 2 Diabetes

OBJECTIVE: Myostatin is a secreted growth factor expressed in skeletal muscle tissue, which negatively regulates skeletal muscle mass. Recent animal studies suggest a role for myostatin in insulin resistance. We evaluated the possible metabolic role of myostatin in patients with type 2 diabetes and healthy controls. DESIGN: 76 patients with type 2 diabetes and 92 control subjects were included in the study. They were matched for age, gender and BMI. Plasma samples and biopsies from the vastus lateralis muscle were obtained to assess plasma myostatin and expression of myostatin in skeletal muscle. RESULTS: Patients with type 2 diabetes had higher fasting glucose (8.9 versus 5.1 mmol/L, P<0.001), plasma insulin (68.2 versus 47.2 pmol/L, P<0.002) and HOMA2-IR (1.6 versus 0.9, P<0.0001) when compared to controls. Patients with type 2 diabetes had 1.4 (P<0.01) higher levels of muscle myostatin mRNA content than the control subjects. Plasma myostatin concentrations did not differ between patients with type 2 diabetes and controls. In healthy controls, muscle myostatin mRNA correlated with HOMA2-IR (r = 0.30, P<0.01), plasma IL-6 (r = 0.34, P<0.05) and VO2 max (r = -0.26, P<0.05), however, no correlations were observed in patients with type 2 diabetes. CONCLUSIONS: This study supports the idea that myostatin may have a negative effect on metabolism. However, the metabolic effect of myostatin appears to be overruled by other factors in patients with type 2 diabetes

Spatiotemporal processing of somatosensory stimuli in schizotypy

Unusual interaction behaviors and perceptual aberrations, like those occurring in schizotypy and schizophrenia, may in part originate from impaired remapping of environmental stimuli in the body space. Such remapping is contributed by the integration of tactile and proprioceptive information about current body posture with other exteroceptive spatial information. Surprisingly, no study has investigated whether alterations in such remapping occur in psychosis-prone individuals. Four hundred eleven students were screened with respect to schizotypal traits using the Schizotypal Personality Questionnaire. A subgroup of them, classified as low, moderate, and high schizotypes were to perform a temporal order judgment task of tactile stimuli delivered on their hands, with both uncrossed and crossed arms. Results revealed marked differences in touch remapping in the high schizotypes as compared to low and moderate schizotypes. For the first time here we reveal that the remapping of environmental stimuli in the body space, an essential function to demarcate the boundaries between self and external world, is altered in schizotypy. Results are discussed in relation to recent models of 'self-disorders' as due to perceptual incoherence