Antibody responses to a Cryptosporidium parvum rCP15/60 vaccine

Cryptosporidium parvum is a zoonotic apicomplexa-protozoan pathogen that causes gastroenteritis and diarrhoea in mammals worldwide. The organism is transmitted by ingestion of oocysts, which are shed in faeces, and completes its lifecycle in a single host.^1^ C. parvum is ubiquitous on dairy operations worldwide and is one of the leading causes of diarrhoea in calves on these farms.^2,3^ Here, for the first time, we describe the antibody response in a large group of cows to a recombinant C. parvum oocyst surface protein (rCP15/60) vaccine and the antibody response in calves fed rCP15/60-immune colostrum produced by these vaccinated cows. Results of recent genotype surveys indicate that calves are the only major reservoir for C. parvum infections in humans.^4^ Human C. parvum infections are particularly prevalent and often fatal in neonates in developing countries and to immunocompromised people, such as AIDs patients.^4^ Drug therapy against cryptosporidiosis is limited and not wholly efficacious in either humans or calves^5^, making development of an effective vaccine of paramount importance. To date, there is no commercially available effective vaccine against C. parvum, although passive immunization utilizing different zoite surface (glyco)proteins has showed promise.^6-9^ All cows we vaccinated produced an antibody response to the rCP15/60 vaccine and the magnitude of response correlated strongly with the subsequent level of antibody in their colostrum. All calves fed rCP15/60-immune colostrum showed a dose-dependent absorption of antibody. Our results demonstrate that vaccination of cows with rCP15/60 successfully induces antibodies against CP15/60 in their serum and colostrum and that these antibodies are then well absorbed when fed to neonatal calves. With further research, this C. parvum vaccine may well be a practical method of conferring passive protection to calves against cryptosporidiosis. Furthermore, a specifically targeted immune-colostrum may be valuable in protection and treatment of immunocompromised human patients with cryptosporidiosis

Mapping odorant sensitivities reveals a sparse but structured representation of olfactory chemical space by sensory input to the mouse olfactory bulb

© 2022, Burton et al. This article is distributed under the terms of the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive. Using high-throughput odorant delivery and ultrasensitive imaging of sensory inputs, we imaged responses to 185 odorants presented at concentrations determined to activate only one or a few glomeruli across the dorsal olfactory bulb. The resulting datasets defined the tuning properties of glomeruli - and, by inference, their cognate odorant receptors - in a low-concentration regime, and yielded consensus maps of glomerular sensitivity across a wide range of chemical space. Glomeruli were extremely narrowly tuned, with ~25% responding to only one odorant, and extremely sensitive, responding to their effective odorants at sub-picomolar to nanomolar concentrations. Such narrow tuning in this concentration regime allowed for reliable functional identification of many glomeruli based on a single diagnostic odorant. At the same time, the response spectra of glomeruli responding to multiple odorants was best predicted by straightforward odorant structural features, and glomeruli sensitive to distinct odorants with common structural features were spatially clustered. These results define an underlying structure to the primary representation of sensory space by the mouse olfactory system.Peer reviewe

The effects of job embeddedness on organizational citizenship, job performance, volitional absences, and voluntary turnover

This study extends theory and research on job embeddedness, which was disaggregated into its two major subdimensions, on-the-job and off-the-job embeddedness. As hypothesized, regression analyses revealed that off-the-job embeddedness was significantly predictive of subsequent voluntary turnover and volitional absences, whereas on-the-job embeddedness was not. Also as hypothesized, on-the-job embeddedness was significantly predictive of organizational citizenship and job performance, whereas off-the-job embeddedness was not. In addition, embeddedness moderated the effects of absences, citizenship, and performance on turnover. Implications are discussed

Molecular line mapping of the giant molecular cloud associated with RCW 106 - II. Column density and dynamical state of the clumps

We present a fully sampled C^{18}O (1-0) map towards the southern giant molecular cloud (GMC) associated with the HII region RCW 106, and use it in combination with previous ^{13}CO (1-0) mapping to estimate the gas column density as a function of position and velocity. We find localized regions of significant ^{13}CO optical depth in the northern part of the cloud, with several of the high-opacity clouds in this region likely associated with a limb-brightened shell around the HII region G333.6-0.2. Optical depth corrections broaden the distribution of column densities in the cloud, yielding a log-normal distribution as predicted by simulations of turbulence. Decomposing the ^{13}CO and C^{18}O data cubes into clumps, we find relatively weak correlations between size and linewidth, and a more sensitive dependence of luminosity on size than would be predicted by a constant average column density. The clump mass spectrum has a slope near -1.7, consistent with previous studies. The most massive clumps appear to have gravitational binding energies well in excess of virial equilibrium; we discuss possible explanations, which include magnetic support and neglect of time-varying surface terms in the virial theorem. Unlike molecular clouds as a whole, the clumps within the RCW 106 GMC, while elongated, appear to show random orientations with respect to the Galactic plane.Comment: 17 pages, to appear in MNRA

Effect of insulin on glucose metabolism in the dog after portacaval transposition

The effect of insulin on hepatic glucose metabolism was studied by a multiple-catheter technique in unanesthetized dogs with Eck fistula and with portacaval transposition. With the latter preparation, blood entering and leaving the liver was sampled from peripherally inserted catheters. In the unanesthetized Eck-fistula animals, insulin infusion produced a decrease in the hepatic glucose output. In the dogs with portacaval transposition, a constant infusion of insulin was given alternately by systemic and by intraportal routes. There was no significant difference between the effects of insulin administered by the two routes. During insulin infusion, glucose concentration differences across the liver were reduced, hepatic plasma flow was transiently elevated, and hepatic glucose output was decreased. After discontinuance of insulin, there was a transient rise of hepatic glucose output to above control values. </jats:p

An Analysis of Private School Closings

We add to the small literature on private school supply by exploring exits of K-12 private schools. We find that the closure of private schools is not an infrequent event, and use national survey data from the National Center for Education Statistics to study closures of private schools. We assume that the probability of an exit is a function of excess supply of private schools over the demand, as well as the school's characteristics such as age, size, and religious affiliation. Our empirical results generally support the implications of the model. Working Paper 07-0

Synaptotagmin-2 Is Essential for Survival and Contributes to Ca²⁺ Triggering of Neurotransmitter Release in Central and Neuromuscular Synapses

Biochemical and genetic data suggest that synaptotagmin-2 functions as a Ca²⁺ sensor for fast neurotransmitter release in caudal brain regions, but animals and/or synapses lacking synaptotagmin-2 have not been examined. We have now generated mice in which the 5’ end of the synaptotagmin-2 gene was replaced by lacZ. Using β-galactosidase as a marker, we show that, consistent with previous studies, synaptotagmin-2 is widely expressed in spinal cord, brainstem, and cerebellum, but is additionally present in selected forebrain neurons, including most striatal neurons and some hypothalamic, cortical, and hippocampal neurons. Synaptotagmin-2-deficient mice were indistinguishable from wild-type littermates at birth, but subsequently developed severe motor dysfunction, and perished at ~3 weeks of age. Electrophysiological studies in cultured striatal neurons revealed that the synaptotagmin-2 deletion slowed the kinetics of evoked neurotransmitter release without altering the total amount of release. In contrast, synaptotagmin-2-deficient neuromuscular junctions (NMJs) suffered from a large reduction in evoked release and changes in short-term synaptic plasticity. Furthermore, in mutant NMJs, the frequency of spontaneous miniature release events was increased both at rest and during stimulus trains. Viewed together, our results demonstrate that the synaptotagmin-2 deficiency causes a lethal impairment in synaptic transmission in selected synapses. This impairment, however, is less severe than that produced in forebrain neurons by deletion of synaptotagmin-1, presumably because at least in NMJs, synaptotagmin-1 is coexpressed with synaptotagmin-2, and both together mediate fast Ca²⁺-triggered release. Thus, synaptotagmin-2 is an essential synaptotagmin isoform that functions in concert with other synaptotagmins in the Ca²⁺ triggering of neurotransmitter release

Number of Years of Annual Mass Treatment With Azithromycin Needed to Control Trachoma in Hyper-endemic Communities in Tanzania

Background. The World Health Organization recommends mass treatment as part of a trachoma control strategy. However, scant empirical data from hyperendemic communities exist on the number of rounds of treatment needed to reach a goal of <5% prevalence in children. We determined the prevalence of trachoma and infection with Chlamydia trachomatis in communities after 3–7 years of annual mass treatment in Tanzania