Acute Clearance of Human Metapneumovirus Occurs Independently of Natural Killer Cells

Human metapneumovirus (HMPV) is a major cause of respiratory disease. The role of NK cells in protection against HMPV is unclear. We show that while HMPV-infected C57BL/6 mice had higher numbers of functional lung NK cells than mock-treated mice, comparing NK cell-depleted and control mice did not reveal differences in lung viral titers, histopathology, cytokine levels, or T cell numbers or function. These data indicate that NK cells are not required for host control of HMPV.     

The Erwin equation of biodiversity: From little steps to quantum leaps in the discovery of tropical insect diversity

Almost 40 years ago, Terry L. Erwin published a seemingly audacious proposition: There may be as many as 30 million species of insects in the world. Here, we translate Erwin's verbal argument into a diversity-ratio model—the Erwin Equation of Biodiversity—and discuss how it has inspired other biodiversity estimates. We categorize, describe the assumptions for, and summarize the most commonly used methods for calculating estimates of global biodiversity. Subsequent diversity-ratio extrapolations have incorporated parameters representing empirical insect specialization ratios, and how insect specialization changes at different spatial scales. Other approaches include macroecological diversity models and diversity curves. For many insect groups with poorly known taxonomies, diversity estimates are based on the opinions of taxonomic experts. We illustrate our current understanding of insect diversity by focusing on the six most speciose insect orders worldwide. For each order, we compiled estimates of the (a) maximum estimated number of species, (b) minimum estimated number of species, and (c) number of currently described species. By integrating these approaches and considering new information, we believe an estimate of 5.5 million species of insects in the world is much too low. New molecular methodologies (e.g., metabarcoding and NGS studies) are revealing daunting numbers of cryptic and previously undescribed species, at the same time increasing our precision but also uncertainty about present estimates. Not until technologies advance and sampling become more comprehensive, especially of tropical biotas, will we be able to make robust estimates of the total number of insect species on Earth.     

Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.     

RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain

Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis.     

Neurotrophins,but not depolarization,regulate substance P expression in the developing optic tectum

Neurotransmitter expression can be regulated by both activity and neurotrophins in a number of in vitro systems. We examined whether either of these factors was likely to play a role in the in vivo optic nerve‐dependent regulation of a substance P‐like immunoreactive (SP‐ir) population of cells in the developing optic tectum of the frog. In contrast to our previous results with the adult system, blocking tectal cell responses to glutamate release by retinal ganglion cells with 6‐cyano‐7‐nitroquinoxaline‐2,3 dione (CNQX) did not affect the percent of SP‐ir cells in the developing tectum. Treatment with d‐(‐)‐2‐amino‐5‐phosphonovaleric acid (d‐AP‐5) was also ineffective in this regard, although both it and CNQX treatment disrupted visual map topography. Chronic treatment with brain‐derived neurotrophic factor (BDNF) and neurotrophin‐4/5 (NT‐4/5) produced increases in SP‐ir cells in the treated lobes of normal animals, which were significant in the case of NT‐4/5. Both substances also prevented the decrease of SP cells that would otherwise occur in the deafferented lobe of unilaterally optic nerve‐transected tadpoles. These changes in the percent of SP‐ir cells occurred without any detectable changes in the overall number of tectal cells. NGF had no effect on SP expression. Nor did it affect topographic map formation, which was disrupted by treatment with either BDNF or NT‐4/5. Our results demonstrate that different mechanisms regulate SP expression in the developing and adult tectum. They indicate that neurotrophin levels in the developing optic tectum may selectively regulate a specific neuropeptide‐expressing population of cells. © 2001 John Wiley & Sons, Inc. J Neurobiol 48: 131–149, 2001     

Circadian dysfunction in response to in?vivo treatment with the mitochondrial toxin 3-nitropropionic acid

Sleep disorders are common in neurodegenerative diseases including Huntington''s disease (HD) and develop early in the disease process. Mitochondrial alterations are believed to play a critical role in the pathophysiology of neurodegenerative diseases. In the present study, we evaluated the circadian system of mice after inhibiting mitochondrial complex II of the respiratory chain with the toxin 3-nitropropionic acid (3-NP). We found that a subset of mice treated with low doses of 3-NP exhibited severe circadian deficit in behavior. The temporal patterning of sleep behavior is also disrupted in some mice with evidence of difficulty in the initiation of sleep behavior. Using the open field test during the normal sleep phase, we found that the 3-NP-treated mice were hyperactive. The molecular clockwork responsible for the generation of circadian rhythms as measured by PER2::LUCIFERASE was disrupted in a subset of mice. Within the SCN, the 3-NP treatment resulted in a reduction in daytime firing rate in the subset of mice which had a behavioral deficit. Anatomically, we confirmed that all of the treated mice showed evidence for cell loss within the striatum but we did not see evidence for gross SCN pathology. Together, the data demonstrates that chronic treatment with low doses of the mitochondrial toxin 3-NP produced circadian deficits in a subset of treated mice. This work does raise the possibility that the neural damage produced by mitochondrial dysfunction can contribute to the sleep/circadian dysfunction seen so commonly in neurodegenerative diseases.     

Anthropogenic nitrogen sources and relationships to riverine nitrogen export in the northeastern U.S.A.

Human activities have greatly altered the nitrogen (N) cycle, accelerating the rate of N fixation in landscapes and delivery of N to water bodies. To examine relationships between anthropogenic N inputs and riverine N export, we constructed budgets describing N inputs and losses for 16 catchments, which encompass a range of climatic variability and are major drainages to the coast of the North Atlantic Ocean along a latitudinal profile from Maine to Virginia. Using data from the early 1990's, we quantified inputs of N to each catchment from atmospheric deposition, application of nitrogenous fertilizers, biological nitrogen fixation, and import of N in agricultural products (food and feed). We compared these inputs with N losses from the system in riverine export.The importance of the relative sources varies widely by catchment and is related to land use. Net atmospheric deposition was the largest N source (>60%) to the forested basins of northern New England (e.g. Penobscot and Kennebec); net import of N in food was the largest source of N to the more populated regions of southern New England (e.g. Charles & Blackstone); and agricultural inputs were the dominant N sources in the Mid-Atlantic region (e.g. Schuylkill & Potomac). Over the combined area of the catchments, net atmospheric deposition was the largest single source input (31%), followed by net imports of N in food and feed (25%), fixation in agricultural lands (24%), fertilizer use (15%), and fixation in forests (5%). The combined effect of fertilizer use, fixation in crop lands, and animal feed imports makes agriculture the largest overall source of N. Riverine export of N is well correlated with N inputs, but it accounts for only a fraction (25%) of the total N inputs. This work provides an understanding of the sources of N in landscapes, and highlights how human activities impact N cycling in the northeast region.     

Kin recognition by paternal half-siblings in captive Papio cynocephalus

Our objective in this study was to evaluate whether a group of paternally related, subadult baboons (Papio cynocephalus) would preferentially interact with kin or nonkin when they had been raised apart from kin other than their mothers. Subjects and their mothers were removed from the breeding group and placed in alternate housing within 24 h after birth to ensure that the subjects would not have a social history with either their sire or their half-siblings. At 90 days of age, the 23 subjects were separated from their mothers and assigned to a peer–peer social group. Behavioral performance was measured using focal animal sampling techniques and 12 molecular behavioral criteria. Analyses of the data indicate that in dyadic interactions kin did not interact more frequently than nonkin in performance of affiliative, sociosexual, and agonistic behaviors. The hypothesis that baboons recognize kin in the absence of maternal associations was not supported by the data; moreover, we suggest that social learning and social history are the most likely mechanisms for kin recognition. Am. J. Primatol. 43:147–157, 1997. © 1997 Wiley-Liss, Inc.