Prenatal Exposure of the Ovine Fetus to Androgens Sexually Differentiates the Steroid Feedback Mechanisms That Control Gonadotropin Releasing Hormone Secretion and Disrupts Ovarian Cycles

Exposure of the female sheep fetus to exogenous testosterone in early pregnancy permanently masculinizes the reproductive neuroendocrine axis. Specifically, in utero androgens given to female lambs from day 30 to 90 of a 147 day pregnancy dramatically altered the response of the gonadotropin releasing hormone (GnRH) neuronal network in the hypothalamus to both estrogen (E) and progesterone (P) feedback. Elevated concentrations of estrogen stimulated a massive release of GnRH in gonadectomized female sheep; however, male and androgenized female lambs were unable to respond to high E concentrations by producing this preovulatory-like “surge” of GnRH. Further, the inhibitory actions of progesterone (P) were also sexually differentiated and adult males and androgenized females were much less responsive to P-negative feedback than normal ewes. The consequences of these abnormal steroid feedback mechanisms were reflected in the fact that only 72% of ovary-intact androgenized ewes exhibited normal estrous cycles in their first breeding season whereas none had a single estrous cycle during the second breeding season. In contrast, 100% of the control animals exhibited repeated reproductive cycles in both seasons. These data indicate that a relatively short exposure to male hormones during in utero life permanently alters the neural mechanisms that control reproduction and leads progressively to a state of infertility.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44102/1/10508_2004_Article_365183.pd

Targeted Nasal Vaccination Provides Antibody-Independent Protection Against Staphylococcus aureus

Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S. aureus infection in the absence of any antigen-specific antibodies. These findings can help inform future developments in staphylococcal vaccine development and studies into the requirements for protective immunity against S. aureu

Accounting for variability when resurrecting dormant propagules substantiates their use in eco-evolutionary studies

There has been a steady rise in the use of dormant propagules to study biotic responses to environmental change over time. This is particularly important for organisms that strongly mediate ecosystem processes, as changes in their traits over time can provide a unique snapshot into the structure and function of ecosystems from decades to millennia in the past. Understanding sources of bias and variation is a challenge in the field of resurrection ecology, including those that arise because often-used measurements like seed germination success are imperfect indicators of propagule viability. Using a Bayesian statistical framework, we evaluated sources of variability and tested for zero-inflation and overdispersion in data from 13 germination trials of soil-stored seeds of Schoenoplectus americanus, an ecosystem engineer in coastal salt marshes in the Chesapeake Bay. We hypothesized that these two model structures align with an ecological understanding of dormancy and revival: zero-inflation could arise due to failed germinations resulting from inviability or failed attempts to break dormancy, and overdispersion could arise by failing to measure important seed traits. A model that accounted for overdispersion, but not zero-inflation, was the best fit to our data. Tetrazolium viability tests corroborated this result: most seeds that failed to germinate did so because they were inviable, not because experimental methods failed to break their dormancy. Seed viability declined exponentially with seed age and was mediated by seed provenance and experimental conditions. Our results provide a framework for accounting for and explaining variability when estimating propagule viability from soil-stored natural archives which is a key aspect of using dormant propagules in eco-evolutionary studies

Txikispora philomaios n. sp., n. g., a micro-eukaryotic pathogen of amphipods, reveals parasitism and hidden diversity in Class Filasterea

This study provides a morphological, ultrastructural, and phylogenetic characterization of a novel micro-eukaryotic parasite (2.3–2.6 µm) infecting amphipod genera Echinogammarus and Orchestia. Longitudinal studies across two years revealed that infection prevalence peaked in late April and May, reaching 64% in Echinogammarus sp. and 15% in Orchestia sp., but was seldom detected during the rest of the year. The parasite infected predominantly hemolymph, connective tissue, tegument, and gonad, although hepatopancreas and nervous tissue were affected in heavier infections, eliciting melanization and granuloma formation. Cell division occurred inside walled parasitic cysts, often within host hemocytes, resulting in hemolymph congestion. Small subunit (18S) rRNA gene phylogenies including related environmental sequences placed the novel parasite as a highly divergent lineage within Class Filasterea, which together with Choanoflagellatea represent the closest protistan relatives of Metazoa. We describe the new parasite as Txikispora philomaios n. sp. n. g., the first confirmed parasitic filasterean lineage, which otherwise comprises four free-living flagellates and a rarely observed endosymbiont of snails. Lineage-specific PCR probing of other hosts and surrounding environments only detected T. philomaios in the platyhelminth Procerodes sp. We expand the known diversity of Filasterea by targeted searches of metagenomic datasets, resulting in 13 previously unknown lineages from environmental samples.Ministerio de Economía y Competitividad, Grant/Award Number: BFU2017- 90114- P; Horizon 2020 Framework Programme, Grant/Award Number: 747789; Department for Environment, Food and Rural Affairs, UK Government, Grant/Award Number: FB002A and FC1214; Hezkuntza, Hizkuntza Politika Eta Kultura Saila, Eusko Jaurlaritza, Grant/Award Number: PRE_2016_2_0124; Agencia Estatal de Investigación (AEI); Fondo Europeo de Desarrollo Regional (FEDER); Ayuda Juan de la Cierva—Incorporación, Grant/Award Number: IJC2018- 036657-

First observations of Weddell seals foraging in sponges in Erebus Bay, Antarctica

Attaching cameras to marine mammals allows for first-hand observation of underwater behaviours that may otherwise go unseen. While studying the foraging behaviour of 26 lactating Weddell seals (Leptonychotes weddellii) in Erebus Bay during the austral spring of 2018 and 2019, we witnessed three adults and one pup investigating the cavities of Rossellidae glass sponges, with one seal visibly chewing when she removed her head from the sponge. To our knowledge, this is the first report of such behaviour. While the prey item was not identifiable, some Trematomus fish (a known Weddell seal prey) use glass sponges for shelter and in which to lay their eggs. Three of the four sponge foraging observations occurred around 13:00 (NZDT). Two of the three sponge foraging adults had higher-than-average reproductive rates, and the greatest number of previous pups of any seal in our study population, each having ten pups in 12 years. This is far higher than the study population average of three previous pups (± 2.6 SD). This novel foraging strategy may have evolved in response to changes in prey availability, and could offer an evolutionary advantage to some individuals that exploit prey resources that others may not. Our observations offer new insight into the foraging behaviours of one of the world’s most studied marine mammals. Further research on the social aspects of Weddell seal behaviour may increase our understanding of the extent and mechanisms of behavioural transfer between conspecifics. Research into the specific foraging behaviour of especially successful or experienced breeders is also warranted

ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points

The stereocilia rootlet is a key structure in vertebrate hair cells, anchoring stereocilia firmly into the cell’s cuticular plate and protecting them from overstimulation. Using superresolution microscopy, we show that the ankyrin-repeat protein ANKRD24 concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets. Annular ANKRD24 continues into the lower rootlet, where it surrounds and binds TRIOBP-5, which itself bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed–TRIOBP-5 restores endogenous ANKRD24 to rootlets in these mice. Ankrd24KO/KO mice show progressive hearing loss and diminished recovery of auditory function after noise damage, as well as increased susceptibility to overstimulation of the hair bundle. We propose that ANKRD24 bridges the apical plasma membrane with the lower rootlet, maintaining a normal distribution of TRIOBP-5. Together with TRIOBP-5, ANKRD24 organizes rootlets to enable hearing with long-term resilience

Combining SIMS and mechanistic modelling to reveal nutrient kinetics in an algal-bacterial mutualism

Funder: Raymond and Beverly Sackler ScholarshipFunder: Mines ParisTechFunder: Swedish Museum of Natural HistoryFunder: University of IcelandFunder: Consortium of Danish geoscience institutionsMicrobial communities are of considerable significance for biogeochemical processes, for the health of both animals and plants, and for biotechnological purposes. A key feature of microbial interactions is the exchange of nutrients between cells. Isotope labelling followed by analysis with secondary ion mass spectrometry (SIMS) can identify nutrient fluxes and heterogeneity of substrate utilisation on a single cell level. Here we present a novel approach that combines SIMS experiments with mechanistic modelling to reveal otherwise inaccessible nutrient kinetics. The method is applied to study the onset of a synthetic mutualistic partnership between a vitamin B12-dependent mutant of the alga Chlamydomonas reinhardtii and the B12-producing, heterotrophic bacterium Mesorhizobium japonicum, which is supported by algal photosynthesis. Results suggest that an initial pool of fixed carbon delays the onset of mutualistic cross-feeding; significantly, our approach allows the first quantification of this expected delay. Our method is widely applicable to other microbial systems, and will contribute to furthering a mechanistic understanding of microbial interactions

Accrual of Older Patients With Breast Cancer to Alliance Systemic Therapy Trials Over Time: Protocol A151527

Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving