Hensen's node is the “organizer” of the avian and mammalian early embryo. It has many functions, including neural induction and patterning of the ectoderm and mesoderm. Some of the signals responsible for these activities are known but these do not explain the full complexity of organizer activity. Here we undertake a functional screen to discover new secreted factors expressed by the node at this time of development. Using a Signal Sequence Trap in yeast, we identify several candidates. Here we focus on Calreticulin. We show that in addition to its known functions in intracellular Calcium regulation and protein folding, Calreticulin is secreted, it can bind to BMP4 and act as a BMP antagonist in vivo and in vitro. Calreticulin is not sufficient to account for all organizer functions but may contribute to the complexity of its activity.
Breast-fed infant microbiota is typically rich in bifidobacteria. Herein, major human milk oligosaccharides (HMOS) are assessed for their ability to promote the growth of bifidobacteria and to acidify their environment, key features of prebiotics. During in vitro anaerobic fermentation of infant microbiota, supplementation by HMOS significantly decreased the pH even greater than supplementation by fructooligosaccharide (FOS), a prebiotic positive control. HMOS elevated lactate concentrations, increased the proportion of Bifidobacterium spp. in culture, and through their fermentation into organic acids, decreased the proportion of Escherichia and Clostridium perfringens. Three principal components of HMOS, 2'-fucosyllactose, lactodifucotetraose and 3-fucosyllactose, were consumed in these cultures. These three principal oligosaccharides of human milk were then individually tested as supplements for in vitro growth of four individual representative strains of infant gut microbes. Bifidobacterium longum JCM7007 and B. longum ATCC15697 efficiently consumed oligosaccharides and produced abundant lactate and short-chain fatty acids, resulting in significant pH reduction. The specificity of fermentation differed by microbe species and strain and by oligosaccharide structure. Escherichia coli K12 and C. perfringens did not utilize appreciable fucosylated oligosaccharides, and a typical mixture of organic acid fermentation products inhibited their growth. In summary, 2'-fucosyllactose, lactodifucotetraose, and 3-fucosyllactose, when cultured with B. longum JCM7007 and B. longum ATCC15697, exhibit key characteristics of a prebiotic in vitro. If these bifidobacteria are representative of pioneering or keystone species for human microbiota, fucosylated HMOS could strongly promote colonization and maintenance of a mutualist symbiotic microbiome. Thus, these simple glycans could mediate beneficial effects of human milk on infant health.
A bi-static E-band (80GHz) electronically scanned imaging radar system has been fabricated and tested. This radar system combines a stare-mode array within a frequency-scanned antenna to extract azimuth and elevation information, while utilizing a frequency modulated CW (FMCW) transceiver to extract range. This unique architecture provides state of the art instantaneous field of view and voxel refresh rates for electronically scanned systems while requiring less RF components than conventional phased array systems, enabling a cost-effective means for volume production of electronically scanned high resolution imaging radar.
A 16-channel receiver module operating at E-band frequencies (80 GHz) is presented. This receiver module is a key component in our 3D FMCW imaging radar. The receiver, with an RF band of 78 to 81 GHz, employs a dual-conversion architecture with an IF band of 4.5 to 7.5 GHz. With a conversion gain of 48 dB, it has demonstrated a noise figure of typically 8 dB. This receiver, employing 115 MMICs and 8 alumina MICs, has established a new level of integration for mm-wave multi-chip modules (MCMs). The size of this module is only 2.375 times 1.355 times 0.63 inch with 16 waveguide inputs spaced 85 mils center-to-center.