Reconsidering Prenatal Hormonal Influences on Human Sexual Orientation: Lessons from Animal Research.

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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 high throughput screen for next-generation leads targeting malaria parasite transmission.

Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2–1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male–female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4- yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population.post-print3903 K

UAS Pilots Code – Annotated Version 1.0

The UAS PILOTS CODE (UASPC) offers recommendations to advance flight safety, ground safety, airmanship, and professionalism.6 It presents a vision of excellence for UAS pilots and operators, and includes general guidance for all types of UAS. The UASPC offers broad guidance—a set of values—to help a pilot interpret and apply standards and regulations, and to confront real world challenges to avoid incidents and accidents. It is designed to help UAS pilots develop standard operating procedures (SOPs), effective risk management,7 safety management systems (SMS), and to encourage UAS pilots to consider themselves aviators and participants in the broader aviation community

Single-dose intraoperative radiotherapy during lumpectomy for breast cancer:an innovative patient-centred treatment

In the randomised TARGIT-A trial, risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy was non-inferior to whole-breast external beam radiotherapy, for local recurrence. In the long-term, no difference was found in any breast cancer outcome, whereas there were fewer deaths from non-breast-cancer causes. TARGIT-IORT should be included in pre-operative consultations with eligible patients

Robustness Generalizations of the Shortest Feasible Path Problem for Electric Vehicles

Electric Vehicle routing is often modeled as a Shortest Feasible Path Problem (SFPP), which minimizes total travel time while maintaining a non-zero State of Charge (SoC) along the route. However, the problem assumes perfect information about energy consumption and charging stations, which are difficult to even estimate in practice. Further, drivers might have varying risk tolerances for different trips. To overcome these limitations, we propose two generalizations to the SFPP; they compute the shortest feasible path for any initial SoC and, respectively, for every possible minimum SoC threshold. We present algorithmic solutions for each problem, and provide two constructs: Starting Charge Maps and Buffer Maps, which represent the tradeoffs between robustness of feasible routes and their travel times. The two constructs are useful in many ways, including presenting alternate routes or providing charging prompts to users. We evaluate the performance of our algorithms on realistic input instances

Redox and pH gradients drive amino acid synthesis in iron oxyhydroxide mineral systems

Iron oxyhydroxide minerals, known to be chemically reactive and significant for elemental cycling, are thought to have been abundant in early-Earth seawater, sediments, and hydrothermal systems. In the anoxic Fe^(2+)-rich early oceans, these minerals would have been only partially oxidized and thus redox-active, perhaps able to promote prebiotic chemical reactions. We show that pyruvate, a simple organic molecule that can form in hydrothermal systems, can undergo reductive amination in the presence of mixed-valence iron oxyhydroxides to form the amino acid alanine, as well as the reduced product lactate. Furthermore, geochemical gradients of pH, redox, and temperature in iron oxyhydroxide systems affect product selectivity. The maximum yield of alanine was observed when the iron oxyhydroxide mineral contained 1:1 Fe(II):Fe(III), under alkaline conditions, and at moderately warm temperatures. These represent conditions that may be found, for example, in iron-containing sediments near an alkaline hydrothermal vent system. The partially oxidized state of the precipitate was significant in promoting amino acid formation: Purely ferrous hydroxides did not drive reductive amination but instead promoted pyruvate reduction to lactate, and ferric hydroxides did not result in any reaction. Prebiotic chemistry driven by redox-active iron hydroxide minerals on the early Earth would therefore be strongly affected by geochemical gradients of E_h, pH, and temperature, and liquid-phase products would be able to diffuse to other conditions within the sediment column to participate in further reactions

Constraints on UV Absorption in the Intracluster Medium of Abell 1030

We present results from an extensive HST spectroscopic search for UV absorption lines in the spectrum of the quasar B2~1028+313, which is associated with the central dominant galaxy in the cluster Abell~1030 ($z=0.178$). This is one of the brightest known UV continuum sources located in a cluster, and therefore provides an ideal opportunity to obtain stringent constraints on the column densities of any cool absorbing gas that may be associated with the intracluster medium (ICM). Our HST spectra were obtained with the FOS and GHRS, and provide continuous coverage at rest-frame wavelengths from $\sim 975$ to 4060~\AA, thereby allowing the investigation of many different elements and ionization levels. We utilize a new technique that involves simultaneous fitting of large numbers of different transitions for each species, thereby yielding more robust constraints on column densities than can be obtained from a single transition. This method yields upper limits of $\lesssim 10^{11} - 10^{13}$ cm$^{-2}$ on the column densities of a wide range of molecular, atomic and ionized species that may be associated with the ICM. We also discuss a possible \Lya and C IV absorption system associated with the quasar. We discuss the implications of the upper limits on cool intracluster gas in the context of the physical properties of the ICM and its relationship to the quasar.Comment: Astrophysical Journal, in press, 19 pages, includes 5 PostScript figures. Latex format, uses aas2pp4.sty and epsfig.sty file

Search for a Solution of the Pioneer Anomaly

In 1972 and 1973 the Pioneer 10 and 11 missions were launched. They were the first to explore the outer solar system and achieved stunning breakthroughs in deep-space exploration. But beginning in about 1980 an unmodeled force of \sim 8 \times 10^{-8} cm/s^2, directed approximately towards the Sun, appeared in the tracking data. It later was unambiguously verified as being in the data and not an artifact. The cause remains unknown (although radiant heat remains a likely origin). With time more and more effort has gone into understanding this anomaly (and also possibly related effects). We review the situation and describe ongoing programs to resolve the issue.Comment: 24 pages 8 figure