A series of six 2,5-disubstituted adjacent bis(tetrahydrofuran) stereoisomers with trans/erythro/cis, trans/threo/trans, or cis/threo/cis relative stereochemistry have been synthesized from known dihydroxycyclooctenes via ring opening/cross metathesis and Pd(0)-mediated asymmetric double cycloetherification. The stereochemistry of four of these isomers has been found in the biologically active annonaceous acetogenin natural products. [reaction: see text].

The emerging picture of taste coding at the periphery is one of elegant simplicity. Contrary to what was generally believed, it is now clear that distinct cell types expressing unique receptors are tuned to detect each of the five basic tastes: sweet, sour, bitter, salty and umami. Importantly, receptor cells for each taste quality function as dedicated sensors wired to elicit stereotypic responses.

Visual, auditory, somatosensory, and olfactory stimuli generate temporally precise patterns of action potentials (spikes). It is unclear, however, how the precision of spike generation relates to the pattern and variability of synaptic input elicited by physiological stimuli. We determined how synaptic conductances evoked by light stimuli that activate the rod bipolar pathway control spike generation in three identified types of mouse retinal ganglion cells (RGCs). The relative amplitude, timing, and impact of excitatory and inhibitory input differed dramatically between On and Off RGCs. Spikes evoked by repeated somatic injection of identical light-evoked synaptic conductances were more temporally precise than those evoked by light. However, the precision of spikes evoked by conductances that varied from trial to trial was similar to that of light-evoked spikes. Thus, the rod bipolar pathway modulates different RGCs via unique combinations of synaptic input, and RGC temporal variability reflects variability in the input this circuit provides.

Experimental investigations have revealed that synapses possess interesting and, in some cases, unexpected properties. We propose a theoretical framework that accounts for three of these properties: typical central synapses are noisy, the distribution of synaptic weights among central synapses is wide, and synaptic connectivity between neurons is sparse. We also comment on the possibility that synaptic weights may vary in discrete steps. Our approach is based on maximizing information storage capacity of neural tissue under resource constraints. Based on previous experimental and theoretical work, we use volume as a limited resource and utilize the empirical relationship between volume and synaptic weight. Solutions of our constrained optimization problems are not only consistent with existing experimental measurements but also make nontrivial predictions.

In this paper, we present an approach for medical ultrasound (US) image enhancement. It is based on a novel perceptual saliency measure which favors smooth, long curves with constant curvature. The perceptual salient boundaries of tissues in US images are enhanced by computing the saliency of directional vectors in the image space, via a local searching algorithm. Our measure is generally determined by curvature changes, intensity gradient and the interaction of neighboring vectors. To restrain speckle noise during the enhancement process, an adaptive speckle suspension term is also combined into the proposed saliency measure. The results obtained on both simulated images and medical US data reveal superior performance of the novel approach over a number of commonly used speckle filters. Applications of US image segmentation show that although the proposed algorithm cannot remove the speckle noise completely and may discard weak anatomical structures in some case, it still provides a considerable gain to US image processing for computer-aided diagnosis.

Multipath propagation in shallow water can lead to mismatch losses when single-path replicas are usedfor horizontal array beamforming.Matched field processing(MFP) seeks to remedy this by using full-fieldacoustic propagationmodels to predict the multipath arrival structure. Ideally MFP can give source localization in range and depth as well as detection gains but robustly estimating range and depth is difficult in practice. The approach described here seeks to collapse full-field replica outputs to bearing which is robustly estimated while retaining any signal gains provided by the full-field model.Clusteranalysis is used to group together full-field replicas with similar responses. This yields a less redundant “sampled field” describing a set of representative multipath structures for each bearing. A detection algorithm is introduced that uses clustering to collapse beamformer outputs to bearing such that signal gains are retained while increases in the noise floor are minimized. Horizontal array data from SWELLEX-96 are used to demonstrate the detection benefits of sampled field as compared to single-pathbeamforming.

The early planarian embryo presents a complete ciliated epidermis and a pharynx and feeds on maternal yolk cells. In this paper, we report on all the elements involved in the formation of such an autonomous embryo, which we name cryptic larva. First, we provide a description of the spherical and fusiform yolk cells and their relationship with the blastomeres, from the laying of the egg capsule up to their final fate in mid embryonic stages. Then, we describe the early cleavage and the subsequent development of the tissues of the cryptic larva, namely, the primary epidermis, the embryonic pharynx, and a new cell type, the star cells. Finally, we discuss the possibility that the cryptic larva either constitutes a vestigial larva or, more likely, is the evolutionary result of the competition between multiple embryos for the limited and shared maternal resources in the egg capsule.

The neurotransmitter dopamine plays important roles in motor control, learning, and motivation in mammals and probably other animals as well. The strong dopaminergic projection to striatal regions and more moderate dopaminergic projections to other regions of the telencephalon predominantly arise from midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Homologous dopaminergic cell groups in songbirds project anatomically in a manner that may allow dopamine to influence song learning or song production. The electrophysiological properties of SNc and VTA neurons have not previously been studied in birds. Here we used whole cell recordings in brain slices in combination with tyrosine-hydroxylase immunolabeling as a marker of dopaminergic neurons to determine electrophysiological and pharmacological properties of dopaminergic and nondopaminergic neurons in the zebra finch SNc and VTA. Our results show that zebra finch dopaminergic neurons possess physiological properties very similar to those of mammalian dopaminergic neurons, including broad action potentials, calcium- and apamin-sensitive membrane-potential oscillations underlying pacemaker firing, powerful spike-frequency adaptation, and autoinhibition via D2 dopamine receptors. Moreover, the zebra finch SNc and VTA also contain nondopaminergic neurons with similarities (fast-firing, inhibition by the mu-opioid receptor agonist [d-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin (DAMGO)) and differences (strong h-current that contributes to spontaneous firing) compared with GABAergic neurons in the mammalian SNc and VTA. Our results provide insight into the intrinsic membrane properties that regulate the activity of dopaminergic neurons in songbirds and add to strong evidence for anatomical, physiological, and functional similarities between the dopaminergic systems of mammals and birds.

The thioredoxin system helps maintain a reducing environment in cells, but thioredoxin functions as more than simply an antioxidant. Thioredoxin functions depend on the protein's redox state, as determined by two conserved cysteines. Key biologic activities of thioredoxin include antioxidant, growth control, and antiapoptotic properties, resulting from interaction with target molecules including transcription factors. Mechanisms by which thioredoxin regulates cell growth include binding to signaling molecules such as apoptosis signal-regulating kinase-1 (ASK-1) and thioredoxin-interacting protein (Txnip). The molecular interplay between thioredoxin, ASK-1, and Txnip potentially influences cell growth and survival in diverse human diseases such as cancer, diabetes, and heart disease. In this review, we focus on the structure of thioredoxin and its functional regulation of cell growth through the interactions with signaling molecules.

The ubiquitous members of the aquaporin (AQP) family form transmembrane pores that are either exclusive for water (aquaporins) or are also permeable for other small neutral solutes such as glycerol (aquaglyceroporins). The purpose of this review is to provide an overview of our current knowledge of AQP structures and to describe the structural features that define the function of these membrane pores. The review will discuss the mechanisms governing water conduction, proton exclusion and substrate specificity, and how the pore permeability is regulated in different members of the AQP family.