Developmental expression of claudins in the mammary gland

Claudins are a large family of membrane proteins whose classic function is to regulate the permeability of tight junctions in epithelia. They are tetraspanins, with four alpha-helices crossing the membrane, two extracellular loops, a short cytoplasmic N-terminus and a longer and more variable C-terminus. The extracellular ends of the helices are known to undergo side-to-side (cis) interactions that allow the formation of claudin polymers in the plane of the membrane. The extracellular loops also engage in head-to-head (trans) interactions thought to mediate the formation of tight junctions. However, claudins are also present in intracellular structures, thought to be vesicles, with less well-characterized functions. Here, we briefly review our current understanding of claudin structure and function followed by an examination of changes in claudin mRNA and protein expression and localization through mammary gland development. Claudins-1, 3, 4, 7, and 8 are the five most prominent members of the claudin family in the mouse mammary gland, with varied abundance and intracellular localization during the different stages of post-pubertal development. Claudin-1 is clearly localized to tight junctions in mammary ducts in non-pregnant non-lactating animals. Cytoplasmic puncta that stain for claudin-7 are present throughout development. During pregnancy claudin-3 is localized both to the tight junction and basolaterally while claudin-4 is found only in sparse puncta. In the lactating mouse both claudin-3 and claudin-8 are localized at the tight junction where they may be important in forming the paracellular barrier. At involution and under challenge by lipopolysaccharide claudins -1, -3, and -4 are significantly upregulated. Claudin-3 is still colocalized with tight junction molecules but is also distributed through the cytoplasm as is claudin-4. These largely descriptive data provide the essential framework for future mechanistic studies of the function and regulation of mammary epithelial cell claudins

Gene regulatory networks in lactation: identification of global principles using bioinformatics

<p>Abstract</p> <p>Background</p> <p>The molecular events underlying mammary development during pregnancy, lactation, and involution are incompletely understood.</p> <p>Results</p> <p>Mammary gland microarray data, cellular localization data, protein-protein interactions, and literature-mined genes were integrated and analyzed using statistics, principal component analysis, gene ontology analysis, pathway analysis, and network analysis to identify global biological principles that govern molecular events during pregnancy, lactation, and involution.</p> <p>Conclusion</p> <p>Several key principles were derived: (1) nearly a third of the transcriptome fluctuates to build, run, and disassemble the lactation apparatus; (2) genes encoding the secretory machinery are transcribed prior to lactation; (3) the diversity of the endogenous portion of the milk proteome is derived from fewer than 100 transcripts; (4) while some genes are differentially transcribed near the onset of lactation, the lactation switch is primarily post-transcriptionally mediated; (5) the secretion of materials during lactation occurs not by up-regulation of novel genomic functions, but by widespread transcriptional suppression of functions such as protein degradation and cell-environment communication; (6) the involution switch is primarily transcriptionally mediated; and (7) during early involution, the transcriptional state is partially reverted to the pre-lactation state. A new hypothesis for secretory diminution is suggested – milk production gradually declines because the secretory machinery is not transcriptionally replenished. A comprehensive network of protein interactions during lactation is assembled and new regulatory gene targets are identified. Less than one fifth of the transcriptionally regulated nodes in this lactation network have been previously explored in the context of lactation. Implications for future research in mammary and cancer biology are discussed.</p

Climate Change and Market-Based Insurance Feedbacks

Climatic events have accounted for 91% of $1.05 trillion in insured costs for global catastrophic events from 1980 to 2016. Costs are driven by socio-economic development and increased frequency and severity of climatic disasters driven by climate change. Government policies to reduce systemic risk (e.g., cap-and-trade, carbon tax) have been a predominant approach for mitigation and adaptation. Alternatively, market-based incentives for climate change adaptation and mitigation already operate via the insurance industry to lessen impacts on society. Insurance feedbacks include changes in 1) premiums and insurance policies, 2) non-coverage, and 3) policy making and litigation. Alongside government policies, insurance feedbacks could be used to facilitate climate change adaptation and mitigation to a significant degree. Ultimately, a negotiated distribution of climate-related costs between the public and private insurance is needed

Pauli Diagonal Channels Constant on Axes

We define and study the properties of channels which are analogous to unital qubit channels in several ways. A full treatment can be given only when the dimension d is a prime power, in which case each of the (d+1) mutually unbiased bases (MUB) defines an axis. Along each axis the channel looks like a depolarizing channel, but the degree of depolarization depends on the axis. When d is not a prime power, some of our results still hold, particularly in the case of channels with one symmetry axis. We describe the convex structure of this class of channels and the subclass of entanglement breaking channels. We find new bound entangled states for d = 3. For these channels, we show that the multiplicativity conjecture for maximal output p-norm holds for p=2. We also find channels with behavior not exhibited by unital qubit channels, including two pairs of orthogonal bases with equal output entropy in the absence of symmetry. This provides new numerical evidence for the additivity of minimal output entropy

A Distance-Limited Imaging Survey of Sub-Stellar Companions to Solar Neighborhood Stars

We report techniques and results of a Palomar 200-inch (5 m) adaptive optics imaging survey of sub-stellar companions to solar-type stars. The survey consists of Ks coronagraphic observations of 21 FGK dwarfs out to 20 pc (median distance about 17 pc). At 1-arcsec separation (17 projected AU) from a typical target system, the survey achieves median sensitivities 7 mag fainter than the parent star. In terms of companion mass, that corresponds to sensitivities of 50MJ (1 Gyr), 70MJ (solar age), and 75MJ (10 Gyr), using the evolutionary models of Baraffe and colleagues. Using common proper motion to distinguish companions from field stars, we find that no system shows positive evidence of a previously unknown substellar companion (searchable separation about 20-250 projected AU at the median target distance).Comment: 29 pages, 5 figures. Carson et al. 2008, AJ, in pres