Maternal Behavior is Impaired in Female Mice Lacking Type 3 Adenylyl Cyclase

Although chemosensory signals generated by mouse pups may trigger maternal behavior of females, the mechanism for detection of these signals has not been fully defined. As some odorant receptors are coupled to the type 3 adenylyl cyclase (AC3), we evaluated the role of AC3 for maternal behavior using AC3−/− female mice. Here, we report that maternal behavior is impaired in virgin and postpartum AC3−/− mice. Female AC3−/− mice failed the pup retrieval assay, did not construct well-defined nests, and did not exhibit maternal aggression. Furthermore, AC3−/− females could not detect odorants or pup urine in the odorant habituation test and were unable to detect pups by chemoreception. In contrast to wild-type mice, AC activity in main olfactory epithelium (MOE) preparations from AC3−/− female mice was not stimulated by odorants or pheromones. Moreover, odorants and pheromones did not evoke electro-olfactogram (EOG) responses in the MOE of AC3−/− female mice. We hypothesize that the detection of chemical signals that trigger maternal behavior in female mice depends upon AC3 in the MOE

The sense of smell, its signalling pathways, and the dichotomy of cilia and microvilli in olfactory sensory cells

Smell is often regarded as an ancillary perception in primates, who seem so dominated by their sense of vision. In this paper, we will portray some aspects of the significance of olfaction to human life and speculate on what evolutionary factors contribute to keeping it alive. We then outline the functional architecture of olfactory sensory neurons and their signal transduction pathways, which are the primary detectors that render olfactory perception possible. Throughout the phylogenetic tree, olfactory neurons, at their apical tip, are either decorated with cilia or with microvilli. The significance of this dichotomy is unknown. It is generally assumed that mammalian olfactory neurons are of the ciliary type only. The existance of so-called olfactory microvillar cells in mammals, however, is well documented, but their nature remains unclear and their function orphaned. This paper discusses the possibility, that in the main olfactory epithelium of mammals ciliated and microvillar sensory cells exist concurrently. We review evidence related to this hypothesis and ask, what function olfactory microvillar cells might have and what signalling mechanisms they use

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

The Arequipa Massif of Peru : new SHRIMP and isotope constraints on a Paleoproterozoic inlier in the Grenvillian orogen

The enigmatic Arequipa Massif of southwestern Peru is an outcrop of Andean basement that underwent Grenville-age metamorphism, and as such it is important for the better constraint of Laurentia–Amazonia ties in Rodinia reconstruction models. U–Pb SHRIMP zircon dating has yielded new evidence on the evolution of the Massif between Middle Paleoproterozoic and Early Paleozoic. The oldest rock-forming events occurred in major orogenic events between ca. 1.79 and 2.1 Ga (Orosirian to Rhyacian), involving early magmatism (1.89–2.1 Ga, presumably emplaced through partly Archaean continental crust), sedimentation of a thick sequence of terrigenous sediments, UHT metamorphism at ca. 1.87 Ga, and late felsic magmatism at ca. 1.79 Ga. The Atico sedimentary basin developed in the Late-Mesoproterozoic and detrital zircons were fed from a source area similar to the high-grade Paleoproterozoic basement, but also from an unknown source that provided Mesoproterozoic zircons of 1200–1600 Ma. The Grenville-age metamorphism was of low-P type; it both reworked the Paleoproterozoic rocks and also affected the Atico sedimentary rocks. Metamorphism was diachronous: ca. 1040 Ma in the Quilca and Camaná areas and in the San Juán Marcona domain, 940 ± 6 Ma in the Mollendo area, and between 1000 and 850 Ma in the Atico domain. These metamorphic domains are probably tectonically juxtaposed. Comparison with coeval Grenvillian processes in Laurentia and in southern Amazonia raises the possibility that Grenvillian metamorphism in the Arequipa Massif resulted from extension and not from collision. The Arequipa Massif experienced Ordovician–Silurian magmatism at ca. 465 Ma, including anorthosites formerly considered to be Grenvillian, and high-T metamorphism deep within the magmatic arc. Focused retrogression along shear zones or unconformities took place between 430 and 440 Ma