Integrating sample similarities into latent class analysis: a tree-structured shrinkage approach

This paper is concerned with using multivariate binary observations to estimate the probabilities of unobserved classes with scientific meanings. We focus on the setting where additional information about sample similarities is available and represented by a rooted weighted tree. Every leaf in the given tree contains multiple samples. Shorter distances over the tree between the leaves indicate a priori higher similarity in class probability vectors. We propose a novel data integrative extension to classical latent class models with tree-structured shrinkage. The proposed approach enables (1) borrowing of information across leaves, (2) estimating data-driven leaf groups with distinct vectors of class probabilities, and (3) individual-level probabilistic class assignment given the observed multivariate binary measurements. We derive and implement a scalable posterior inference algorithm in a variational Bayes framework. Extensive simulations show more accurate estimation of class probabilities than alternatives that suboptimally use the additional sample similarity information. A zoonotic infectious disease application is used to illustrate the proposed approach. The paper concludes by a brief discussion on model limitations and extensions.     

Trade-offs and seasonal variation in territorial defence and predator evasion in the European Robin Erithacus rubecula

The low incidence of intraspecific combat in territorial systems has traditionally been accounted for by theories that emphasize the bio-energetic advantages or the diminished risk of injury of threat display posture when compared with combat. Recently, however, it has been suggested that territory-holding passerines engaging in highly aggressive defensive behaviour are likely to pay a cost in terms of reduced vigilance for avian predators. To examine this further, two defensive options (combat and threat display) were evoked and observed in territorial European Robins Erithacus rubecula , in both winter and summer. It was found that Robins that engaged in combat during simulated territorial intrusion were significantly slower to react to a stuffed Sparrowhawk Accipiter nisus , than those eliciting threat display. Therefore, the decreased vigilance in escalated fighting may result in higher vulnerability to predation, and this might help, in part, to explain why threat display is favoured over direct combat. Moreover, the mean time to evade the predator was significantly longer in summer than in winter in threat-displaying Robins. In addition to this finding, a clear difference in the type of behaviour adopted between the seasons was observed, with lower incidence of combatative response during the winter months. This difference in response to the appearance of a predator is discussed in relation to reduced levels of safe cover, a reduction in the availability of alternative prey during the winter months and to seasonal fluctuations in plasma androgen levels.     

Comparison of the Molecular Forms of the Kex2/Subtilisin-Like Serine Proteases SPC2, SPC3, and Furin in Neuroendocrine Secretory Vesicles Reveals Differences in Carboxyl-Terminus Truncation and Membrane Association

Abstract: The molecular forms and membrane association of SPC2, SPC3, and furin were investigated in neuroendocrine secretory vesicles from the anterior, intermediate, and neural lobes of bovine pituitary and bovine adrenal medulla. The major immunoreactive form of SPC2 was the full-length enzyme with a molecular mass of 64 kDa. The major immunoreactive form of SPC3 was truncated at the carboxyl terminus and had a molecular mass of 64 kDa. Full-length 86-kDa SPC3 with an intact carboxyl terminus was found only in bovine chromaffin granules. Immunoreactive furin was also detected in secretory vesicles. The molecular masses of 80 and 76 kDa were consistent with carboxyl-terminal truncation of furin to remove the transmembrane domain. All three enzymes were distributed between the soluble and membrane fractions of secretory vesicles although the degree of membrane association was tissue specific and, in the case of SPC3, dependent on the molecular form of the enzyme. Significant amounts of membrane-associated and soluble forms of SPC2, SPC3, and furin were found in pituitary secretory vesicles, whereas the majority of the immunoreactivity in chromaffin granules was membrane associated. More detailed analyses of chromaffin granule membranes revealed that 86-kDa SPC3 was more tightly associated with the membrane fraction than the carboxyl terminus-truncated 64-kDa form.     

The VirB4 ATPase of Agrobacterium tumefaciens is a cytoplasmic membrane protein exposed at the periplasmic surface.

The VirB4 ATPase of Agrobacterium tumefaciens, a putative component of the T-complex transport apparatus, associates with the cytoplasmic membrane independently of other products of the Ti plasmid. VirB4 was resistant to extraction from membranes of wild-type strain A348 or a Ti-plasmidless strain expressing virB4 from an IncP replicon. To evaluate the membrane topology of VirB4, a nested deletion method was used to generate a high frequency of random fusions between virB4 and 'phoA, which encodes a periplasmically active alkaline phosphatase (AP) deleted of its signal sequence. VirB4::PhoA hybrid proteins exhibiting AP activity in Escherichia coli and A. tumefaciens had junction sites that mapped to two regions, between residues 58 and 84 (region 1) and between residues 450 and 514 (region 2). Conversely, VirB4::beta-galactosidase hybrid proteins with junction sites mapping to regions 1 and 2 exhibited low beta-galactosidase activities and hybrid proteins with junction sites elsewhere exhibited high beta-galactosidase activities. Enzymatically active VirB5::PhoA hybrid proteins had junction sites that were distributed throughout the length of the protein. Proteinase K treatment of A. tumefaciens spheroplasts resulted in the disappearance of the 87-kDa VirB4 protein and the concomitant appearance of two immunoreactive species of approximately 35 and approximately 45 kDa. Taken together, our data support a model in which VirB4 is topologically configured as an integral cytoplasmic membrane protein with two periplasmic domains.     

Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin

Terada, Lance S., John E. Repine, Dale Piermattei, andBrooks M. Hybertson. Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin.J. Appl. Physiol. 82(3): 913-917, 1997.The oxygen radical-producing enzyme xanthine oxidase (XO) canpromote neutrophil adherence to endothelium. Recognizing that a balanceoften exists in inflammatory processes, we sought to determine whetherXO initiates antiadherent pathways. We found that bovine pulmonaryarterial endothelial cells (EC) exposed to XO released increasedamounts of nitrite into the media, reflecting an increased productionof nitric oxide (NO). When EC were subjected to shear stress, treatmentwith XO and/or the NO synthase inhibitorN-nitro-L-arginine(L-NNA) increased neutrophilrolling behavior and firm neutrophil adherence to EC in an additivefashion. Both rolling and adherent interactions were abolished bymonoclonal antibodies directed against P-selectin. In addition,treatment of EC with XO and/orL-NNA increased both surfaceexpression of P-selectin and release of von Willebrand factor intomedia. Finally, treatment of EC with the NO donor sodium nitroprussidedecreased XO-mediated neutrophil rolling and adherence. We concludethat XO stimulates EC to produce NO and that NO decreases theP-selectin-dependent neutrophil adhesion initiated by XO. Suchincreases in endogenous NO may constitute an importantnegative-feedback response to the acute proadhesive effects of XO.

     

Tolerance and cross tolerance with morphine resulting from physiological release of endogenous opiates

Mice which had been exposed to a chronic schedule of warm water swimming showed the development of a significant tolerance to the antinociceptive response (tail-flick latency) and a significant, two-fold increase in the ED50 of morphine (tail-flick latency and abdominal constriction response). These results suggest the involvement of endogenous opiates during swim stress in mice and are consistent with the hypothesis that during chronic stress the opiate receptors are activated in a manner analogous to the repeated application of exogenous opiates producing tolerance, morphine cross tolerance and (as previously reported) withdrawal-like behaviour.     

Physical dependence on physiologically released endogenous opiates

Mice which had been submitted to a chronic schedule of warm water swimming exhibited a naloxone precipiated withdrawal behaviour which was remarkably similar to that produced in mice following chronic morphine treatment. These results are consistent with the activation of endogenous opiates during swim stress in mice and present the possibility that opiate receptors are activated in a manner analogous to the repeated application of exogenous opiates, producing both tolerance and withdrawal-like behaviour.     

Movement of Endotoxin Through Soil Columns

Land treatment of wastewater is an attractive alternative to conventional sewage treatment systems and is gaining widespread acceptance. Although land application systems prevent surface water pollution and augment the available water supplies, the potential dangers to human health should be evaluated. Since sewage may contain high amounts of bacterial endotoxin, the removal of endotoxin from sewage by percolation through soil was investigated. It was found that 90 to 99% of the endotoxin was removed after travel of sewage through 100 to 250 cm of loamy sand soil. When distilled water was allowed to infiltrate into the soil to simulate rainfall, the endotoxin was mobilized and moved in a concentrated band through the soil column. On testing samples from actual land treatment sites, as much as 480 ng of endotoxin per milliliter was found in some groundwater samples. The presence of endotoxin in potable water is known to be a potential problem under some circumstances, but the importance of endotoxin in water supplies has not been fully assessed. Therefore, the design, operation, and management of land application systems should take into account the fate of endotoxin in groundwater beneath the sites.