Genetically-Directed, Cell Type-Specific Sparse Labeling for the Analysis of Neuronal Morphology

Background: In mammals, genetically-directed cell labeling technologies have not yet been applied to the morphologic analysis of neurons with very large and complex arbors, an application that requires extremely sparse labeling and that is only rendered practical by limiting the labeled population to one or a few predetermined neuronal subtypes. Methods and Findings: In the present study we have addressed this application by using CreER technology to noninvasively label very small numbers of neurons so that their morphologies can be fully visualized. Four lines of IRES-CreER knock-in mice were constructed to permit labeling selectively in cholinergic or catecholaminergic neurons [choline acetyltransferase (ChAT)-IRES-CreER or tyrosine hydroxylase (TH)-IRES-CreER], predominantly in projection neurons [neurofilament light chain (NFL)-IRES-CreER], or broadly in neurons and some glia [vesicle-associated membrane protein2 (VAMP2)-IRES-CreER]. When crossed to the Z/AP reporter and exposed to 4-hydroxytamoxifen in the early postnatal period, the number of neurons expressing the human placental alkaline phosphatase reporter can be reproducibly lowered to fewer than 50 per brain. Sparse Cre-mediated recombination in ChAT-IRES-CreER;Z/AP mice shows the full axonal and dendritic arbors of individual forebrain cholinergic neurons, the first time that the complete morphologies of these very large neurons have been revealed in any species. Conclusions: Sparse genetically-directed, cell type-specific neuronal labeling with IRES-creER lines should prove useful fo

PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass

Background: Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor - 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding.Methods: Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS.Results: Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = - 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively.Conclusions: Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.publishersversionPeer reviewe

History of Reading Struggles Linked to Enhanced Learning in Low Spatial Frequency Scenes

People with dyslexia, who face lifelong struggles with reading, exhibit numerous associated low-level sensory deficits including deficits in focal attention. Countering this, studies have shown that struggling readers outperform typical readers in some visual tasks that integrate distributed information across an expanse. Though such abilities would be expected to facilitate scene memory, prior investigations using the contextual cueing paradigm failed to find corresponding advantages in dyslexia. We suggest that these studies were confounded by task-dependent effects exaggerating known focal attention deficits in dyslexia, and that, if natural scenes were used as the context, advantages would emerge. Here, we investigate this hypothesis by comparing college students with histories of severe lifelong reading difficulties (SR) and typical readers (TR) in contexts that vary attention load. We find no differences in contextual-cueing when spatial contexts are letter-like objects, or when contexts are natural scenes. However, the SR group significantly outperforms the TR group when contexts are low-pass filtered natural scenes [F(3, 39) = 3.15, p<.05]. These findings suggest that perception or memory for low spatial frequency components in scenes is enhanced in dyslexia. These findings are important because they suggest strengths for spatial learning in a population otherwise impaired, carrying implications for the education and support of students who face challenges in school

Gender-related differences in physiologic color space: a functional transcranial Doppler (fTCD) study

Simultaneous color contrast and color constancy are memory processes associated with color vision, however, the gender-related differences of 'physiologic color space' remains unknown. Color processing was studied in 16 (8 men and 8 women) right-handed healthy subjects using functional transcranial Doppler (fTCD) technique. Mean flow velocity (MFV) was recorded in both right (RMCA) and left (LMCA) middle cerebral arteries in dark and white light conditions, and during color (blue and yellow) stimulations. The data was plotted in a 3D quadratic curve fit to derive a 'physiologic color space' showing the effects of luminance and chromatic contrasts. In men, wavelength-differencing of opponent pairs (yellow-blue) was adjudged by changes in the RMCA MFV for Yellow plotted on the Y-axis, and the RMCA MFV for Blue plotted on the X-axis. In women, frequency-differencing for opponent pairs (blue-yellow) was adjudged by changes in the LMCA MFV for Yellow plotted on the Y-axis, and the LMCA MFV for Blue plotted on the X-axis. The luminance effect on the LMCA MFV in response to white light with the highest luminous flux, was plotted on the (Z - axis), in both men and women. The 3D-color space for women was a mirror-image of that for men, and showed enhanced color constancy. The exponential function model was applied to the data in men, while the logarithmic function model was applied to the data in women. Color space determination may be useful in the study of color memory, adaptive neuroplasticity, cognitive impairment in stroke and neurodegenerative diseases

Bacteria are important dimethylsulfoniopropionate producers in coastal sediments

Dimethylsulfoniopropionate (DMSP) and its catabolite dimethyl sulfide (DMS) are key marine nutrients, with roles in global sulfur cycling, atmospheric chemistry, signalling and, potentially, climate regulation. DMSP production was previously thought to be an oxic and photic process, mainly confined to the surface oceans. However, here we show that DMSP concentrations and DMSP/DMS synthesis rates were higher in surface marine sediment from e.g., saltmarsh ponds, estuaries and the deep ocean than in the overlying seawater. A quarter of bacterial strains isolated from saltmarsh sediment produced DMSP (up to 73 mM), and previously unknown DMSP-producers were identified. Most DMSP-producing isolates contained dsyB, but some alphaproteobacteria, gammaproteobacteria and actinobacteria utilised a methionine methylation pathway independent of DsyB, previously only associated with higher plants. These bacteria contained a methionine methyltransferase ‘mmtN’ gene - a marker for bacterial DMSP synthesis via this pathway. DMSP-producing bacteria and their dsyB and/or mmtN transcripts were present in all tested seawater samples and Tara Oceans bacterioplankton datasets, but were far more abundant in marine surface sediment. Approximately 108 bacteria per gram of surface marine sediment are predicted to produce DMSP, and their contribution to this process should be included in future models of global DMSP production. We propose that coastal and marine sediments, which cover a large part of the Earth’s surface, are environments with high DMSP and DMS productivity, and that bacteria are important producers within them

Brain Responses to Violet, Blue, and Green Monochromatic Light Exposures in Humans: Prominent Role of Blue Light and the Brainstem

BACKGROUND: Relatively long duration retinal light exposure elicits nonvisual responses in humans, including modulation of alertness and cognition. These responses are thought to be mediated in part by melanopsin-expressing retinal ganglion cells which are more sensitive to blue light than violet or green light. The contribution of the melanopsin system and the brain mechanisms involved in the establishment of such responses to light remain to be established. METHODOLOGY/PRINCIPAL FINDINGS: We exposed 15 participants to short duration (50 s) monochromatic violet (430 nm), blue (473 nm), and green (527 nm) light exposures of equal photon flux (10(13)ph/cm(2)/s) while they were performing a working memory task in fMRI. At light onset, blue light, as compared to green light, increased activity in the left hippocampus, left thalamus, and right amygdala. During the task, blue light, as compared to violet light, increased activity in the left middle frontal gyrus, left thalamus and a bilateral area of the brainstem consistent with activation of the locus coeruleus. CONCLUSION/SIGNIFICANCE: These results support a prominent contribution of melanopsin-expressing retinal ganglion cells to brain responses to light within the very first seconds of an exposure. The results also demonstrate the implication of the brainstem in mediating these responses in humans and speak for a broad involvement of light in the regulation of brain function

Understanding the retinal basis of vision across species

The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision