High Resolution Maps of the Vasculature of An Entire Organ

The structure of vascular networks represents a great, unsolved problem in anatomy. Network geometry and topology differ dramatically from left to right and person to person as evidenced by the superficial venation of the hands and the vasculature of the retinae. Mathematically, we may state that there is no conserved topology in vascular networks. Efficiency demands that these networks be regular on a statistical level and perhaps optimal. We have taken the first steps towards elucidating the principles underlying vascular organization, creating the rst map of the hierarchical vasculature (above the capillaries) of an entire organ. Using serial blockface microscopy and fluorescence imaging, we are able to identify vasculature at 5 μm resolution. We have designed image analysis software to segment, align, and skeletonize the resulting data, yielding a map of the individual vessels. We transformed these data into a mathematical graph, allowing computationally efficient storage and the calculation of geometric and topological statistics for the network. Our data revealed a complexity of structure unexpected by theory. We observe loops at all scales that complicate the assignment of hierarchy within the network and the existence of set length scales, implying a distinctly non-fractal structure of components within

Human Time-Frequency Acuity Beats the Fourier Uncertainty Principle

The time-frequency uncertainty principle states that the product of the temporal and frequency extents of a signal cannot be smaller than $1/(4\pi)$. We study human ability to simultaneously judge the frequency and the timing of a sound. Our subjects often exceeded the uncertainty limit, sometimes by more than tenfold, mostly through remarkable timing acuity. Our results establish a lower bound for the nonlinearity and complexity of the algorithms employed by our brains in parsing transient sounds, rule out simple "linear filter" models of early auditory processing, and highlight timing acuity as a central feature in auditory object processing.Comment: 4 pages, 2 figures; Accepted at PR

Increased origin activity in transformed versus normal cells: identification of novel protein players involved in DNA replication and cellular transformation

Using libraries of replication origins generated previously, we identified three clones that supported the autonomous replication of their respective plasmids in transformed, but not in normal cells. Assessment of their in vivo replication activity by in situ chromosomal DNA replication assays revealed that the chromosomal loci corresponding to these clones coincided with chromosomal replication origins in all cell lines, which were more active by 2–3-fold in the transformed by comparison to the normal cells. Evaluation of pre-replication complex (pre-RC) protein abundance at these origins in transformed and normal cells by chromatin immunoprecipitation assays, using anti-ORC2, -cdc6 and -cdt1 antibodies, showed that they were bound by these pre-RC proteins in all cell lines, but a 2–3-fold higher abundance was observed in the transformed by comparison to the normal cells. Electrophoretic mobility shift assays (EMSAs) performed on the most efficiently replicating clone, using nuclear extracts from the transformed and normal cells, revealed the presence of a DNA replication complex in transformed cells, which was barely detectable in normal cells. Subsequent supershift EMSAs suggested the presence of transformation-specific complexes. Mass spectrometric analysis of these complexes revealed potential new protein players involved in DNA replication that appear to correlate with cellular transformation

Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases

Degraded time-frequency acuity to time-reversed notes.

Time-reversal symmetry breaking is a key feature of many classes of natural sounds, originating in the physics of sound production. While attention has been paid to the response of the auditory system to "natural stimuli," very few psychophysical tests have been performed. We conduct psychophysical measurements of time-frequency acuity for stylized representations of "natural"-like notes (sharp attack, long decay) and the time-reversed versions of these notes (long attack, sharp decay). Our results demonstrate significantly greater precision, arising from enhanced temporal acuity, for such sounds over their time-reversed versions, without a corresponding decrease in frequency acuity. These data inveigh against models of auditory processing that include tradeoffs between temporal and frequency acuity, at least in the range of notes tested and suggest the existence of statistical priors for notes with a sharp-attack and a long-decay. We are additionally able to calculate a minimal theoretical bound on the sophistication of the nonlinearities in auditory processing. We find that among the best studied classes of nonlinear time-frequency representations, only matching pursuit, spectral derivatives, and reassigned spectrograms are able to satisfy this criterion

Difference in performance on different shaped notes.

<p>On the left is performance on the “time-reversed” pulse divided by performance on the “time-forward” notelike pulse. On the right is performance on the “notelike” pulse divided by performance on the gaussian pulse. The dotted red line indicates a perfect tradeoff in performance, i.e. . On both figures, axes are logarithmic.</p

Results of Psychophysical Testing.

<p>We plot our data on a standard time-frequency plane with on the x axis and on the y axis. The red circles are the results from the “time-forward” notelike pulse, the green crosses are from the “time-reversed” version. The uncertainty bound is the black diagonal; the axes are logarithmic. The data from the “time-reversed” pulse are shifted notably to the right () from the original “time-forward” notelike one.</p