Birthdating studies reshape models for pituitary gland cell specification

AbstractThe intermediate and anterior lobes of the pituitary gland are derived from an invagination of oral ectoderm that forms Rathke's pouch. During gestation proliferating cells are enriched around the pouch lumen, and they appear to delaminate as they exit the cell cycle and differentiate. During late mouse gestation and the postnatal period, anterior lobe progenitors re-enter the cell cycle and expand the populations of specialized, hormone-producing cells. At birth, all cell types are present, and their localization appears stratified based on cell type. We conducted a birth dating study of Rathke's pouch derivatives to determine whether the location of specialized cells at birth is correlated with the timing of cell cycle exit. We find that all of the anterior lobe cell types initiate differentiation concurrently with a peak between e11.5 and e13.5. Differentiation of intermediate lobe melanotropes is delayed relative to anterior lobe cell types. We discovered that specialized cell types are not grouped together based on birth date and are dispersed throughout the anterior lobe. Thus, the apparent stratification of specialized cells at birth is not correlated with cell cycle exit. Thus, the currently popular model of cell specification, dependent upon timing of extrinsic, directional gradients of signaling molecules, needs revision. We propose that signals intrinsic to Rathke's pouch are necessary for cell specification between e11.5 and e13.5 and that cell–cell communication likely plays an important role in regulating this process

Predicting pharmacy naloxone stocking and dispensing following a statewide standing order, Indiana 2016

BACKGROUND: While naloxone, the overdose reversal medication, has been available for decades, factors associated with its availability through pharmacies remain unclear. Studies suggest that policy and pharmacist beliefs may impact availability. Indiana passed a standing order law for naloxone in 2015 to increase access to naloxone. OBJECTIVE: To identify factors associated with community pharmacy naloxone stocking and dispensing following the enactment of a statewide naloxone standing order. METHODS: A 2016 cross-sectional census of Indiana community pharmacists was conducted following a naloxone standing order. Community, pharmacy, and pharmacist characteristics, and pharmacist attitudes about naloxone dispensing, access, and perceptions of the standing order were measured. Modified Poisson and binary logistic regression models attempted to predict naloxone stocking and dispensing, respectively. RESULTS: Over half (58.1%) of pharmacies stocked naloxone, yet 23.6% of pharmacists dispensed it. Most (72.5%) pharmacists believed the standing order would increase naloxone stocking, and 66.5% believed it would increase dispensing. Chain pharmacies were 3.2 times as likely to stock naloxone. Naloxone stocking was 1.6 times as likely in pharmacies with more than one full-time pharmacist. Pharmacies where pharmacists received naloxone continuing education in the past two years were 1.3 times as likely to stock naloxone. The attempted dispensing model yielded no improvement over the constant-only model. CONCLUSIONS: Pharmacies with larger capacity took advantage of the naloxone standing order. Predictors of pharmacist naloxone dispensing should continue to be explored to maximize naloxone access

Elements of Success: Lessons from a Decade of Restoration Project Identification, Cultivation and Implementation

Coastal geologic processes create and maintain the nearshore habitats upon which forage fish and many other Puget Sound species of concern rely. Shoreline modifications, like bulkheads, disrupt and damage sediment supply and transport processes that form beaches and provide appropriate spawning substrate for surf smelt and Pacific sand lance (Penttila 2007, Carrasquero-Verde et al 2005, Johannessen and MacLennan 2007). Shoreline modifications have been identified as one of the greatest threats to our nearshore ecosystems (Thom et al. 1994) and are ranked as one of the top three threats to the marine ecosystem in the San Juan County Marine Stewardship Area Plan adopted by the San Juan County Council in 2007 and by the Puget Sound Partnership’s San Juan Local Integrating Organization (SJC Action Agenda 2011, SJC Marine Resources Committee 2007). Successful restoration requires an understanding of the strategic actions to target, as well as long-term focused communication and technical support at all project stages including identification, cultivation, funding, design, construction and monitoring. Investment of resources at the early phases of project development, including prioritization, landowner site visits, feasibility studies and conceptual designs, helps ensure that technically sound, ecologically important projects, with willing landowners, advance to final design and implementation. Friends of the San Juans will share lessons learned from multiple nearshore marine restoration projects implemented in San Juan County with public, private and tribal landowners. There will be an emphasis placed on the key relationships and project management elements required to foster efficient and effective projects from a restoration plan report to rehabilitation of habitat and habitat forming processes

All hormone-producing cell types of the pituitary intermediate and anterior lobes derive from prop1-expressing progenitors

Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone-secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations.Fil: Davis, Shannon W.. University of South Carolina; Estados UnidosFil: Keisler, Jessica L.. University of South Carolina; Estados UnidosFil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schade, Vanessa. University of Michigan; Estados UnidosFil: Camper, Sally A.. University of Michigan; Estados Unido

Accounting for predator species identity reveals variable relationships between nest predation rate and habitat in a temperate forest songbird.

Nest predation is the primary cause of nest failure in most ground-nesting bird species. Investigations of relationships between nest predation rate and habitat usually pool different predator species. However, such relationships likely depend on the specific predator involved, partly because habitat requirements vary among predator species. Pooling may therefore impair our ability to identify conservation-relevant relationships between nest predation rate and habitat. We investigated predator-specific nest predation rates in the forest-dependent, ground-nesting wood warbler Phylloscopus sibilatrix in relation to forest area and forest edge complexity at two spatial scales and to the composition of the adjacent habitat matrix. We used camera traps at 559 nests to identify nest predators in five study regions across Europe. When analyzing predation data pooled across predator species, nest predation rate was positively related to forest area at the local scale (1000 m around nest), and higher where proportion of grassland in the adjacent habitat matrix was high but arable land low. Analyses by each predator species revealed variable relationships between nest predation rates and habitat. At the local scale, nest predation by most predators was higher where forest area was large. At the landscape scale (10,000 m around nest), nest predation by buzzards Buteo buteo was high where forest area was small. Predation by pine martens Martes martes was high where edge complexity at the landscape scale was high. Predation by badgers Meles meles was high where the matrix had much grassland but little arable land. Our results suggest that relationships between nest predation rates and habitat can depend on the predator species involved and may differ from analyses disregarding predator identity. Predator-specific nest predation rates, and their relationships to habitat at different spatial scales, should be considered when assessing the impact of habitat change on avian nesting success

The increase of the functional entropy of the human brain with age

We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

Reproductive success of the wood warbler Phylloscopus sibilatrix varies across Europe

Differences in population trends across a species’ breeding range are ultimately linked to variation in demographic rates. In small songbirds, demographic rates related to fecundity typically have strong effects on population trends. Populations of a forest songbird, the wood warbler Phylloscopus sibilatrix, have been declining in many but not all regions of the European breeding range. We investigated if clutch size, hatching rate, nest survival and number of fledglings vary across Europe, and if nest survival is related to differences in the regionally dominant nest predator class (birds versus mammals). From 2009 to 2020, we monitored 1896 nests and used cameras at a subsample of 645 nests in six study regions: the United Kingdom (mid-Wales, Dartmoor, the New Forest), Germany (Hessen), Switzerland (Jura mountains) and Poland (Białowieża National Park). Number of fledglings was lowest in the New Forest (1.43 ± CI 0.23), intermediate in Jura (2.41 ± 0.31) and Białowieża (2.26 ± 0.24) and highest in mid-Wales (3.02 ± 0.48) and Dartmoor (2.92 ± 0.32). The reason for low reproductive success in the New Forest, Jura and Białowieża was low nest survival, and large clutch sizes in Białowieża did not compensate for high nest losses. High reproductive success in mid-Wales and Dartmoor was due to high nest survival and large clutch sizes. Overall predation rates were similar everywhere despite variation between the regions in the dominant nest predator class. Unsuccessful nests in mid-Wales were mainly predated by birds; in Dartmoor, the New Forest, Hessen and Jura similarly by birds and mammals; and in Białowieża exclusively by mammals. Regional reproductive success does not match the population trends recently reported for the wood warbler in the six study regions (i.e. high reproduction ≠ positive trend). Annual survival may be a decisive factor, but it is difficult to quantify for a nomadic species such as the wood warbler that rarely returns to the same breeding locations

High signal-to-noise ratio observations and the ultimate limits of precision pulsar timing

We demonstrate that the sensitivity of high-precision pulsar timing experiments will be ultimately limited by the broadband intensity modulation that is intrinsic to the pulsar's stochastic radio signal. That is, as the peak flux of the pulsar approaches that of the system equivalent flux density, neither greater antenna gain nor increased instrumental bandwidth will improve timing precision. These conclusions proceed from an analysis of the covariance matrix used to characterise residual pulse profile fluctuations following the template matching procedure for arrival time estimation. We perform such an analysis on 25 hours of high-precision timing observations of the closest and brightest millisecond pulsar, PSR J0437-4715. In these data, the standard deviation of the post-fit arrival time residuals is approximately four times greater than that predicted by considering the system equivalent flux density, mean pulsar flux and the effective width of the pulsed emission. We develop a technique based on principal component analysis to mitigate the effects of shape variations on arrival time estimation and demonstrate its validity using a number of illustrative simulations. When applied to our observations, the method reduces arrival time residual noise by approximately 20%. We conclude that, owing primarily to the intrinsic variability of the radio emission from PSR J0437-4715 at 20 cm, timing precision in this observing band better than 30 - 40 ns in one hour is highly unlikely, regardless of future improvements in antenna gain or instrumental bandwidth. We describe the intrinsic variability of the pulsar signal as stochastic wideband impulse modulated self-noise (SWIMS) and argue that SWIMS will likely limit the timing precision of every millisecond pulsar currently observed by Pulsar Timing Array projects as larger and more sensitive antennae are built in the coming decades.Comment: 16 pages, 9 figures, accepted for publication in MNRAS. Updated version: added DOI and changed manuscript to reflect changes in the final published versio