Sequential and Coordinated Actions of c-Myc and N-Myc Control Appendicular Skeletal Development

BACKGROUND: During limb development, chondrocytes and osteoblasts emerge from condensations of limb bud mesenchyme. These cells then proliferate and differentiate in separate but adjacent compartments and function cooperatively to promote bone growth through the process of endochondral ossification. While many aspects of limb skeletal formation are understood, little is known about the mechanisms that link the development of undifferentiated limb bud mesenchyme with formation of the precartilaginous condensation and subsequent proliferative expansion of chondrocyte and osteoblast lineages. The aim of this study was to gain insight into these processes by examining the roles of c-Myc and N-Myc in morphogenesis of the limb skeleton. METHODOLOGY/PRINCIPAL FINDINGS: To investigate c-Myc function in skeletal development, we characterized mice in which floxed c-Myc alleles were deleted in undifferentiated limb bud mesenchyme with Prx1-Cre, in chondro-osteoprogenitors with Sox9-Cre and in osteoblasts with Osx1-Cre. We show that c-Myc promotes the proliferative expansion of both chondrocytes and osteoblasts and as a consequence controls the process of endochondral growth and ossification and determines bone size. The control of proliferation by c-Myc was related to its effects on global gene transcription, as phosphorylation of the C-Terminal Domain (pCTD) of RNA Polymerase II, a marker of general transcription initiation, was tightly coupled to cell proliferation of growth plate chondrocytes where c-Myc is expressed and severely downregulated in the absence of c-Myc. Finally, we show that combined deletion of N-Myc and c-Myc in early limb bud mesenchyme gives rise to a severely hypoplastic limb skeleton that exhibits features characteristic of individual c-Myc and N-Myc mutants. CONCLUSIONS/SIGNIFICANCE: Our results show that N-Myc and c-Myc act sequentially during limb development to coordinate the expansion of key progenitor populations responsible for forming the limb skeleton

Climate warming disrupts mast seeding and its fitness benefits in European beech

© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Many plants benefit from synchronous year-to-year variation in seed production, called masting. Masting benefits plants because it increases the efficiency of pollination and satiates predators, which reduces seed loss. Here, using a 39-year-long dataset, we show that climate warming over recent decades has increased seed production of European beech but decreased the year-to-year variability of seed production and the reproductive synchrony among individuals. Consequently, the benefit that the plants gained from masting has declined. While climate warming was associated with increased reproductive effort, we demonstrate that less effective pollination and greater losses of seeds to predators offset any benefits to the plants. This shows that an apparently simple benefit of climate warming unravels because of complex ecological interactions. Our results indicate that in masting systems, the main beneficiaries of climate-driven increases in seed production are seed predators, not plants

Subcellular distribution of terminal α-D- and β-D-galactosyl residues in Ehrlich tumour cells studied by lectin-gold techniques

We have studied by high resolution in situ light and electron microscopic lectin-gold techniques the subcellular distribution of α- d -Gal residues using the Griffonia simplicifolia I-B 4 isolectin and compared it with that of β- d -Gal residues as detected with the Datura stramonium lectin in Ehrlich tumour cells grown as ascites or monolayer. The microvillar but not the smooth plasma membrane regions were labelled with the Griffonia simplicifolia I-B 4 isolectin whereas both plasma membrane regions were equally well labelled with the Datura stramonium lectin. Elements of the endocytotic/lysosomal system such as coated membrane invaginations and vesicles, early and late endosomes and secondary lysosomes were positive for both α- d -Gal and β- d -Gal residues. A particular feature of Ehrlich tumour cells is an elaborate tubular membrane system located in the pericentriolar region which is labelled throughout by both lectins and represents part of the endosomal system. In the Golgi apparatus labelling with both lectins was observed to commence in trans cisternae which is indirect evidence for a joint distribution of the sequentially acting β1,4 and α1,3-galactosyl-transferases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45677/1/10719_2004_Article_BF00731358.pd

Seasonal assembly of arthropod communities on milkweeds experiencing simulated herbivory

The seasonal assembly of arthropod communities is shaped by biotic and abiotic aspects of the habitat that limit the appearance or activity phenology of potential community members. In addition, previous interactions within the community, such as herbivore-induced plant defensive responses, aggregation, and predator avoidance likely affect the assembly of arthropod communities on individual plants. We observed the phenology of arthropod communities and defensive plant traits on 100 milkweed (Asclepias eriocarpa) individuals at monthly intervals over a growing season. We experimentally wounded a subset of plants each month (April–August) to observe the effect of simulated added herbivore damage on the seasonal assembly of these arthropod communities. All plant traits and measures of arthropod communities changed over the season. The observed response to experimental leaf damage suggested a trend of induced susceptibility in early months, but not late months. Plants receiving early-season simulated herbivory experienced more subsequent leaf damage than unmanipulated plants. We observed several lagged correlations in our study indicating that blue milkweed beetle (Chrysochus cobaltinus) abundance was lower in months following high natural leaf damage, and that the abundance of a secondary omnivore (Lygaeus kalmii) and total predator abundance tended to follow months with high C. cobaltinus abundance. Ahistorical habitat factors determined much of the observed seasonality of arthropod communities, but induced responses to simulated herbivory also contributed historical effects that influenced arthropod community assembly

Seasonal assembly of arthropod communities on milkweeds experiencing simulated herbivory

The seasonal assembly of arthropod communities is shaped by biotic and abiotic aspects of the habitat that limit the appearance or activity phenology of potential community members. In addition, previous interactions within the community, such as herbivore-induced plant defensive responses, aggregation, and predator avoidance likely affect the assembly of arthropod communities on individual plants. We observed the phenology of arthropod communities and defensive plant traits on 100 milkweed (Asclepias eriocarpa) individuals at monthly intervals over a growing season. We experimentally wounded a subset of plants each month (April–August) to observe the effect of simulated added herbivore damage on the seasonal assembly of these arthropod communities. All plant traits and measures of arthropod communities changed over the season. The observed response to experimental leaf damage suggested a trend of induced susceptibility in early months, but not late months. Plants receiving early-season simulated herbivory experienced more subsequent leaf damage than unmanipulated plants. We observed several lagged correlations in our study indicating that blue milkweed beetle (Chrysochus cobaltinus) abundance was lower in months following high natural leaf damage, and that the abundance of a secondary omnivore (Lygaeus kalmii) and total predator abundance tended to follow months with high C. cobaltinus abundance. Ahistorical habitat factors determined much of the observed seasonality of arthropod communities, but induced responses to simulated herbivory also contributed historical effects that influenced arthropod community assembly

Climate teleconnections synchronize Picea glauca masting and fire disturbance: Evidence for a fire‐related form of environmental prediction

1.Synchronous pulses of seed masting and natural disturbance have positive feedbacks on the reproduction of masting species in disturbance‐prone ecosystems. We test the hypotheses that disturbances and proximate causes of masting are correlated, and that their large‐scale synchrony is driven by similar climate teleconnection patterns at both inter‐annual and decadal time scales. 2.Hypotheses were tested on white spruce (Picea glauca), a masting species which surprisingly persists in fire‐prone boreal forests while lacking clear fire adaptations. We built masting, drought and fire indices at regional (Alaska, Yukon, Alberta, Quebec) and subcontinental scales (western North America) spanning the second half of the 20th century. Superposed Epoch Analysis tested the temporal associations between masting events, drought and burnt area at the regional scale. At the sub‐continental scale, Superposed Epoch Analysis tested whether El Niño‐Southern Oscillation (ENSO) and its coupled effects with the Atlantic Multidecadal Oscillation (AMO) in the positive phase (AMO+/ENSO+) synchronize drought, burnt area and masting. We additionally tested the consistency of our synchronization hypotheses on a decadal temporal scale to verify whether long‐term oscillations in AMO+/ENSO + are coherent to decadal variation in drought, burnt area and masting. 3.Analyses demonstrated synchronicity between drought, fire and masting. In all regions the year before a mast event was drier and more fire‐prone than usual. During AMO+/ENSO + events sub‐continental indices of drought and burnt area experienced significant departures from mean values. The same was observed for large‐scale masting in the subsequent year, confirming 1 year lag between fire and masting. Sub‐continental indices of burnt area and masting showed in‐phase decadal fluctuations led by the AMO+/ENSO+. Results support the “Environmental prediction hypothesis” for mast seeding. 4.Synthesis. We provide evidence of large‐scale synchronicity between seed masting in Picea glauca and fire regimes in boreal forests of western North America at both inter‐annual and decadal time scales. We conclude that seed production in white spruce predicts changes in disturbance regimes by sharing the same large‐scale climate drivers with drought and fire. This gives new insides in a mechanism providing a fire‐sensitive species with higher than expected adaptability to changes in climate

Mortality after surgery with SARS-CoV-2 infection in England: A population-wide epidemiological study

Objectives: To confirm the incidence of perioperative SARS-CoV-2 infection and associated mortality after surgery. Design and setting: Analysis of routine electronic health record data from National Health Service (NHS) hospitals in England. Methods: We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between 1st January 2020 and 31st October 2020. The exposure was SARS-CoV-2 infection defined by ICD-10 codes. The primary outcome measure was 90-day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson co-morbidity index, index of multiple deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals. Results: We identified 1,972,153 patients undergoing surgery of whom 11,940 (0.6%) had SARS-CoV-2. In total, 19,100 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 2,618/11,940 [21.9%] vs No SARS-CoV-2: 16,482/1,960,213 [0.8%]; OR: 5.8 [5.5 – 6.1]; p<0.001). Amongst patients undergoing elective surgery 1,030/1,374,985 (0.1%) had SARS-CoV-2 of whom 83/1,030 (8.1%) died, compared with 1,092/1,373,955 (0.1%) patients without SARS-CoV-2 (OR: 29.0 [22.5 - 37.3]; p<0.001). Amongst patients undergoing emergency surgery 9,742/437,891 (2.2%) patients had SARS-CoV-2, of whom 2,466/9,742 (25.3%) died compared with 14,817/428,149 (3.5%) patients without SARS-CoV-2 (OR: 5.7 [5.4 – 6.0]; p<0.001). Conclusions: The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed