Trees on networks: resolving statistical patterns of phylogenetic similarities among interacting proteins

Background  

Phylogenies capture the evolutionary ancestry linking extant species. Correlations and similarities among a set of species are mediated by and need to be understood in terms of the phylogenic tree. In a similar way it has been argued that biological networks also induce correlations among sets of interacting genes or their protein products.     

Sex steroids and 5-en-3 beta-hydroxysteroids in specific regions of the human brain and cranial nerves

Sex steroids and 5-en-3 beta-hydroxysteroids were determined by radioimmunoassay in specific regions of the human brain, in the anterior and posterior pituitary, in one sensory organ, the retina and in the cranial nerves. Progesterone, androstenedione, testosterone and estrone were found in all areas of the brain and in all the cranial nerves but not in all cases. There was no sex difference except in the case of androstenedione where values were higher in women in some brain areas. Estrone values were always higher than those of estradiol in both men and women. No 5 alpha-dihydrotestosterone was detected in any of the samples studied. The values for pregnenolone, dehydroepiandrosterone and their sulfates were much higher than those of the sex steroids in all areas of the brain and in all the cranial nerves. Values for pregnenolone were greater than those of its sulfate while those of dehydroepiandrosterone were in general equal to or higher than those of its sulfate. The values for pregnenolone were greater than those of dehydroepiandrosterone. There were no obvious regional differences in the concentrations of the 5-en-3 beta-hydroxysteroids either in specific areas of the brain or in the cranial nerves. But there was a definite trend for the free dehydroepiandrosterone values to be higher in women. The possible significance of these observations is discussed.     

Acute watery diarrhea as the initial presenting feature of a pheochromocytoma in an 84-year-old female patient

We report the case of an 84-year-old woman who was initially admitted to the emergency room of our institution for frank dehydration caused by acute and severe secretory diarrheas along with acidosis and hypokalemia. After extensive gastrointestinal investigations, the etiology of the diarrhea remained unclear. Because clinical symptoms and ionogram parameters worsened, despite intravenous fluids and electrolyte replacement, an abdominal CT scan was performed and unexpectedly revealed a 4.5-cm mass in the right adrenal gland. Several separate 24-hour urine catecholamines were shown to be highly elevated. The diagnosis of pheochromocytoma was confirmed by MIBG scintigraphy and MRI. Before the admission, the patient never experienced symptoms suggestive of pheochromocytoma, except dry mouth and fear of impending death on several occasions. After 2 weeks, the diarrhea stopped abruptly and spontaneously without specific medication but after adequate rehydration. The patient subsequently underwent surgical removal of the adrenal medullary mass. Postoperatively, urinary catecholamines returned to normal values. Immunohistochemical study of the tumor confirmed the diagnosis of pheochromocytoma and revealed the presence of VIP-positive cells organized as islets in scattered areas of the tissue. This case illustrates the protean mode of presentation of pheochromocytoma, as well as the ability of medullary neural crest-derived cells to produce various neuropeptides potentially responsible for a large variety of symptoms.     

Scaling the amplitudes of the circadian pattern of resting oxygen consumption, body temperature and heart rate in mammals

We questioned whether the amplitudes of the circadian pattern of body temperature (T(b)), oxygen consumption (V (O(2))) and heart rate (HR) changed systematically among species of different body weight (W). Because bodies of large mass have a greater heat capacitance than those of smaller mass, if the relative amplitude (i.e., amplitude/mean value) of metabolic rate was constant, one would expect the T(b) oscillation to decrease with the increase in the species W. We compiled data of T(b), V (O(2)) and HR from a literature survey of over 200 studies that investigated the circadian pattern of these parameters. Monotremata, Marsupials and Chiroptera, were excluded because of their characteristically low metabolic rate and T(b). The peak-trough ratios of V (O(2)) (42 species) and HR (35 species) averaged, respectively, 1.57+/-0.08, and 1.35+/-0.07, and were independent of W. The daily high values of T(b) did not change, while the daily low T(b) values slightly increased, with the species W; hence, the high-low T(b) difference (57 species) decreased with W (3.3 degrees C.W(-0.13)). However, the decrease in T(b) amplitude with W was much less than expected from physical principles, and the high-low T(b) ratio remained significantly above unity even in the largest mammals. Thus, it appears that in mammals, despite the huge differences in physical characteristics, the amplitude of the circadian pattern is a fixed (for V (O(2)) and HR), or almost fixed (for T(b)), fraction of the 24-h mean value. Presumably, the amplitudes of the oscillations are controlled parameters of physiological significance.     

A systematic review of the literature examining the diagnostic efficacy of measurement of fractionated plasma free metanephrines in the biochemical diagnosis of pheochromocytoma

BACKGROUND: Fractionated plasma metanephrine measurements are commonly used in biochemical testing in search of pheochromocytoma. METHODS: We aimed to critically appraise the diagnostic efficacy of fractionated plasma free metanephrine measurements in detecting pheochromocytoma. Nine electronic databases, meeting abstracts, and the Science Citation Index were searched and supplemented with previously unpublished data. Methodologic and reporting quality was independently assessed by two endocrinologists using a checklist developed by the Standards for Reporting of Diagnostic Studies Accuracy Group and data were independently abstracted. RESULTS: Limitations in methodologic quality were noted in all studies. In all subjects (including those with genetic predisposition): the sensitivities for detection of pheochromocytoma were 96%-100% (95% CI ranged from 82% to 100%), whereas the specificities were 85%-100% (95% CI ranged from 78% to 100%). Statistical heterogeneity was noted upon pooling positive likelihood ratios when those with predisposition to disease were included (p < 0.001). However, upon pooling the positive or negative likelihood ratios for patients with sporadic pheochromocytoma (n = 191) or those at risk for sporadic pheochromocytoma (n = 718), no statistical heterogeneity was noted (p = 0.4). For sporadic subjects, the pooled positive likelihood ratio was 5.77 (95% CI = 4.90, 6.81) and the pooled negative likelihood ratio was 0.02 (95% CI = 0.01, 0.07). CONCLUSION: Negative plasma fractionated free metanephrine measurements are effective in ruling out pheochromocytoma. However, a positive test result only moderately increases suspicion of disease, particularly when screening for sporadic pheochromocytoma.     

Microstructure of anaerobic granules bioaugmented with Desulfitobacterium frappieri PCP-1

Oligonucleotide probes were used to study the structure of anaerobic granular biofilm originating from a pentachlorophenol-fed upflow anaerobic sludge bed reactor augmented with Desulfitobacterium frappieri PCP-1. Fluorescence in situ hybridization demonstrated successful colonization of anaerobic granules by strain PCP-1. Scattered microcolonies of strain PCP-1 were detected on the biofilm surface after 3 weeks of reactor operation, and a dense outer layer of strain PCP-1 was observed after 9 weeks. Hybridization with probes specific for Eubacteria and Archaea probes showed that Eubacteria predominantly colonized the outer layer, while Archaea were observed in the granule interior. Mathematical simulations showed a distribution similar to that observed experimentally when using a specific growth rate of 2.2 day(-1) and a low bacterial diffusion of 10(-7) dm(2) day(-1). Also, the simulations showed that strain PCP-1 proliferation in the outer biofilm layer provided excellent protection of the biofilm from pentachlorophenol toxicity.