Gonadal hormones, but not sex, affect the acquisition and maintenance of a Go/No-Go odor discrimination task in mice

In mice, olfaction is crucial for identifying social odors (pheromones) that signal the presence of suitable mates. We used a custom-built olfactometer and a thirst-motivated olfactory discrimination Go/No-Go (GNG) task to ask whether discrimination of volatile odors is sexually dimorphic and modulated in mice by adult sex hormones. Males and females gonadectomized prior to training failed to learn even the initial phase of the task, which involved nose poking at a port in one location obtaining water at an adjacent port. Gonadally intact males and females readily learned to seek water when male urine (S+) was present but not when female urine (S−) was present; they also learned the task when non-social odorants (amyl acetate, S+; peppermint, S−) were used. When mice were gonadectomized after training the ability of both sexes to discriminate urinary as well as non-social odors was reduced; however, after receiving testosterone propionate (castrated males) or estradiol benzoate (ovariectomized females), task performance was restored to pre-gonadectomy levels. There were no overall sex differences in performance across gonadal conditions in tests with either set of odors; however, ovariectomized females performed more poorly than castrated males in tests with non-social odors. Our results show that circulating sex hormones enable mice of both sexes to learn a GNG task and that gonadectomy reduces, while hormone replacement restores, their ability to discriminate between odors irrespective of the saliency of the odors used. Thus, gonadal hormones were essential for both learning and maintenance of task performance across sex and odor type.We thank David Giese for help in programming the apparatus used in GNG testing and Alberto Cruz-Martin for comments on an early version of the manuscript. This work was supported by NIDCD grant DC008962 to JAC. (DC008962 - NIDCD grant)Accepted manuscrip

Optogenetic activation of accessory olfactory bulb input to the forebrain differentially modulates investigation of opposite versus same-sex urinary chemosignals and stimulates mating in male mice

Surgical or genetic disruption of vomeronasal organ (VNO)-accessory olfactory bulb (AOB) function previously eliminated the ability of male mice to processes pheromones that elicit territorial behavior and aggression. By contrast, neither disruption significantly affected mating behaviors, although VNO lesions reduced males' investigation of nonvolatile female pheromones. We explored the contribution of VNO-AOB pheromonal processing to male courtship using optogenetic activation of AOB projections to the forebrain. Protocadherin-Cre male transgenic mice received bilateral AOB infections with channelrhodopsin2 (ChR2) viral vectors, and an optical fiber was implanted above the AOB. In olfactory choice tests, males preferred estrous female urine (EFU) over water; however, this preference was eliminated when diluted (5%) EFU was substituted for 100% EFU. Optogenetic AOB activation concurrent with nasal contact significantly augmented males' investigation compared to 5% EFU alone. Conversely, concurrent optogenetic AOB activation significantly reduced males' nasal investigation of diluted urine from gonadally intact males (5% IMU) compared to 5% IMU alone. These divergent effects of AOB optogenetic activation were lost when males were prevented from making direct nasal contact. Optogenetic AOB stimulation also failed to augment males' nasal investigation of deionized water or of food odors. Finally, during mating tests, optogenetic AOB stimulation delivered for 30 s when the male was in physical contact with an estrous female significantly facilitated the occurrence of penile intromission. Our results suggest that VNO-AOB signaling differentially modifies males' motivation to seek out female vs male urinary pheromones while augmenting males' sexual arousal leading to intromission and improved reproductive performance

A guide to best practices for Gene Ontology (GO) manual annotation.

The Gene Ontology Consortium (GOC) is a community-based bioinformatics project that classifies gene product function through the use of structured controlled vocabularies. A fundamental application of the Gene Ontology (GO) is in the creation of gene product annotations, evidence-based associations between GO definitions and experimental or sequence-based analysis. Currently, the GOC disseminates 126 million annotations covering >374,000 species including all the kingdoms of life. This number includes two classes of GO annotations: those created manually by experienced biocurators reviewing the literature or by examination of biological data (1.1 million annotations covering 2226 species) and those generated computationally via automated methods. As manual annotations are often used to propagate functional predictions between related proteins within and between genomes, it is critical to provide accurate consistent manual annotations. Toward this goal, we present here the conventions defined by the GOC for the creation of manual annotation. This guide represents the best practices for manual annotation as established by the GOC project over the past 12 years. We hope this guide will encourage research communities to annotate gene products of their interest to enhance the corpus of GO annotations available to all. DATABASE URL: http://www.geneontology.org

Determination of Serum Antibody to Bordetella pertussis Adenylate Cyclase Toxin in Vaccinated and Unvaccinated Children and in Children and Adults with Pertussis

Presence of antibody to adenylate cyclase toxin (ACT) has been noted following Bordetella pertussis infection. Because ACT is not presently in any acellular pertussis vaccines, it has been considered as a possible antigen to use in B. pertussis diagnostic enzyme-linked immunosorbent assay (ELISA) studies. We determined antibody to B. pertussis ACT by ELISA and Western blot tests in serum samples obtained from unvaccinated children, from children vaccinated with several diphtheria and tetanus toxoid vaccines (DTP vaccines), from children vaccinated with vaccines containing acellular pertussis components in combination with diphtheria and tetanus toxoids (DTaP vaccines), and from children and adults with pertussis. Primary infections with either B. pertussis or Bordetella parapertussis stimulated a vigorous antibody response to ACT. In contrast, patients in whom DTP and DTaP vaccines failed had minimal ACT antibody responses. The lack of a significant ACT antibody response in children in whom the vaccine failed is of interest but would seem to preclude the use of ACT in diagnostic test

Thunderstorms Producing Sferic-Geolocated Gamma-Ray Flashes Detected by TETRA-II

The terrestrial gamma-ray flash (TGF) and Energetic Thunderstorm Rooftop Array (TETRA-II) detected 22 X-ray/gamma-ray flash events associated with lightning between October 2015 and March 2019 across three ground-based detector locations in subtropical and tropical climates in Louisiana, Puerto Rico, and Panama. Each detector array consists of a set of bismuth germanate scintillators that record X-ray and gamma-ray bursts over the energy range 50 keV–6 MeV (million electron volts). TETRA-II events have characteristics similar to both X-ray bursts associated with lightning leaders and TGFs: sub-millisecond duration, photons up to MeV energies, and association with nearby lightning (typically within 3 km). About 20 of the 22 events are geolocated to individual lightning strokes via spatiotemporally coincident sferics. An examination of radar reflectivity and derived products related to events located within the Next Generation Weather Radar (NEXRAD) monitoring region indicates that events occur within mature cells of severe and non-severe multicellular and squall line thunderstorms, with core echo tops which are at or nearing peak altitude. Events occur in both high lightning frequency thunderstorm cells and low lightning frequency cells. Events associated with high frequency cells occur within 5 min of significant lightning jumps. Among NEXRAD-monitored events, hail is present within 8 km and 5 min of all except a single low-altitude cold weather thunderstorm. An association is seen with maximum thunderstorm development, lightning jumps, and hail cells, indicating that the TETRA-II X-ray/gamma-ray events are associated with the peak storm electrification and development of electric fields necessary for the acceleration of electrons to high energies

Chromatin environment and cellular context specify compensatory activity of paralogous MEF2 transcription factors

Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes, but how TFs dynamically respond to paralog depletion on a genome-wide scale in vivo remains incompletely understood. Using single and double conditional knockout of myocyte enhancer factor 2 (MEF2) family TFs in granule neurons of the mouse cerebellum, we find that MEF2A and MEF2D play functionally redundant roles in cerebellar-dependent motor learning. Although both TFs are highly expressed in granule neurons, transcriptomic analyses show MEF2D is the predominant genomic regulator of gene expression in vivo. Strikingly, genome-wide occupancy analyses reveal upon depletion of MEF2D, MEF2A occupancy robustly increases at a subset of sites normally bound to MEF2D. Importantly, sites experiencing compensatory MEF2A occupancy are concentrated within open chromatin and undergo functional compensation for genomic activation and gene expression. Finally, motor activity induces a switch from non-compensatory to compensatory MEF2-dependent gene regulation. These studies uncover genome-wide functional interdependency between paralogous TFs in the brain

Tetrahymena Genome Database (TGD): a new genomic resource for Tetrahymena thermophila research

We have developed a web-based resource (available at ) for researchers studying the model ciliate organism Tetrahymena thermophila. Employing the underlying database structure and programming of the Saccharomyces Genome Database, the Tetrahymena Genome Database (TGD) integrates the wealth of knowledge generated by the Tetrahymena research community about genome structure, genes and gene products with the newly sequenced macronuclear genome determined by The Institute for Genomic Research (TIGR). TGD provides information curated from the literature about each published gene, including a standardized gene name, a link to the genomic locus in our graphical genome browser, gene product annotations utilizing the Gene Ontology, links to published literature about the gene and more. TGD also displays automatic annotations generated for the gene models predicted by TIGR. A variety of tools are available at TGD for searching the Tetrahymena genome, its literature and information about members of the research community

CASTER - a concept for a Black Hole Finder Probe based on the use of new scintillator technologies

The primary scientific mission of the Black Hole Finder Probe (BHFP), part of the NASA Beyond Einstein program, is to survey the local Universe for black holes over a wide range of mass and accretion rate. One approach to such a survey is a hard X-ray coded-aperture imaging mission operating in the 10--600 keV energy band, a spectral range that is considered to be especially useful in the detection of black hole sources. The development of new inorganic scintillator materials provides improved performance (for example, with regards to energy resolution and timing) that is well suited to the BHFP science requirements. Detection planes formed with these materials coupled with a new generation of readout devices represent a major advancement in the performance capabilities of scintillator-based gamma cameras. Here, we discuss the Coded Aperture Survey Telescope for Energetic Radiation (CASTER), a concept that represents a BHFP based on the use of the latest scintillator technology.Comment: 12 pages; conference paper presented at the SPIE conference "UV, X-Ray, and Gamma-Ray Space Instrumentation for Astronomy XIV." To be published in SPIE Conference Proceedings, vol. 589

CASTER: a scintillator-based black hole finder probe

The primary scientific mission of the Black Hole Finder Probe (BHFP), part of the NASA Beyond Einstein program, is to survey the local Universe for black holes over a wide range of mass and accretion rate. One approach to such a survey is a hard X-ray coded-aperture imaging mission operating in the 10-600 keV energy band, a spectral range that is considered to be especially useful in the detection of black hole sources. The development of new inorganic scintillator materials provides improved performance (for example, with regards to energy resolution and timing) that is well suited to the BHFP science requirements. Detection planes formed with these materials coupled with a new generation of readout devices represent a major advancement in the performance capabilities of scintillator-based gamma cameras. Here, we discuss the Coded Aperture Survey Telescope for Energetic Radiation (CASTER), a concept that represents a BHFP based on the use of the latest scintillator technology

Approaching the knee -- balloon-borne observations of cosmic ray composition

Below the knee in the cosmic ray spectrum, balloon and spacecraft experiments offer the capability of direct composition and energy measurements on the primary particles. A major difficulty is obtaining enough exposure to extend the range of direct measurements sufficiently high in energy to permit overlap with ground-based observations. Presently, balloon and space measurements extend only up to ~100 TeV, well below the range of ground-based experiments. The prospect of Ultra-Long Duration Balloon missions offers the promise of multiple long flights that can build up exposure. The status of balloon measurements to measure the high energy proton and nuclear composition and spectrum is reviewed, and the statistical considerations involved in searching for a steepening in the spectrum are discussed. Given the very steeply falling spectrum, it appears unlikely that balloon experiments will be able to extend the range of direct measurements beyond 1000 TeV any time in the near future. Especially given the recent suggestions from KASCADE that the proton spectrum steepens only at 4000-5000 TeV, the chance of detecting the knee with direct measurements of protons to iron on balloons is not likely to occur without significant increases in the payload and flight duration capabilities of high altitude balloons.Comment: 10 pages, to be published, J. Phys. Conf. Ser. (Proc. Workshop on Physics at the End of the Galactic Cosmic Ray Spectrum, Aspen, April 2005