Matrix Metalloproteinase 13 From Satellite Cells is Required for Efficient Muscle Growth and Regeneration

Background/Aims: Cell migration and extracellular matrix remodeling underlie normal mammalian development and growth as well as pathologic tumor invasion. Skeletal muscle is no exception, where satellite cell migration replenishes nuclear content in damaged tissue and extracellular matrix reforms during regeneration. A key set of enzymes that regulate these processes are matrix metalloproteinases (MMP)s. The collagenase MMP-13 is transiently upregulated during muscle regeneration, but its contribution to damage resolution is unknown. The purpose of this work was to examine the importance of MMP-13 in muscle regeneration and growth in vivo and to delineate a satellite cell specific role for this collagenase. Methods: Mice with total and satellite cell specific Mmp13 deletion were utilized to determine the importance of MMP-13 for postnatal growth, regeneration after acute injury, and in chronic injury from a genetic cross with dystrophic (mdx) mice. We also evaluated insulin-like growth factor 1 (IGF-1) mediated hypertrophy in the presence and absence of MMP-13. We employed live-cell imaging and 3D migration measurements on primary myoblasts obtained from these animals. Outcome measures included muscle morphology and function. Results: Under basal conditions, Mmp13-/- mice did not exhibit histological or functional deficits in muscle. However, following acute injury, regeneration was impaired at 11 and 14 days post injury. Muscle hypertrophy caused by increased IGF-1 was blunted with minimal satellite cell incorporation in the absence of MMP-13. Mmp13-/- primary myoblasts displayed reduced migratory capacity in 2D and 3D, while maintaining normal proliferation and differentiation. Satellite cell specific deletion of MMP-13 recapitulated the effects of global MMP-13 ablation on muscle regeneration, growth and myoblast movement. Conclusion: These results show that satellite cells provide an essential autocrine source of MMP-13, which not only regulates their migration, but also supports postnatal growth and resolution of acute damage. © 2020 The Author(s). Published by Cell Physiol Biochem Press GmbH&Co. K

National CO2 budgets (2015–2020) inferred from atmospheric CO2 observations in support of the Global Stocktake

Accurate accounting of emissions and removals of CO2 is critical for the planning and verification of emission reduction targets in support of the Paris Agreement. Here, we present a pilot dataset of country-specific net carbon exchange (NCE; fossil plus terrestrial ecosystem fluxes) and terrestrial carbon stock changes aimed at informing countries’ carbon budgets. These estimates are based on "top-down" NCE outputs from the v10 Orbiting Carbon Observatory (OCO-2) modeling intercomparison project (MIP), wherein an ensemble of inverse modeling groups conducted standardized experiments assimilating OCO-2 column-averaged dry-air mole fraction (XCO2) retrievals (ACOS v10), in situ CO2 measurements, or combinations of these data. The v10 OCO-2 MIP NCE estimates are combined with "bottom-up" estimates of fossil fuel emissions and lateral carbon fluxes to estimate changes in terrestrial carbon stocks, which are impacted by anthropogenic and natural drivers. These flux and stock change estimates are reported annually (2015–2020) as both a global 1° × 1° gridded dataset and as a country-level dataset. Across the v10 OCO-2 MIP experiments, we obtain increases in the ensemble median terrestrial carbon stocks of 3.29–4.58 PgCO2 yr-1 (0.90–1.25 PgC yr-1). This is a result of broad increases in terrestrial carbon stocks across the northern extratropics, while the tropics generally have stock losses but with considerable regional variability and differences between v10 OCO-2 MIP experiments. We discuss the state of the science for tracking emissions and removals using top-down methods, including current limitations and future developments towards top-down monitoring and verification systems

Global Carbon Budget 2023

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land-use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based f CO2 products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. Additional lines of evidence on land and ocean sinks are provided by atmospheric inversions, atmospheric oxygen measurements, and Earth system models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and incomplete understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2022, EFOS increased by 0.9 % relative to 2021, with fossil emissions at 9.9 ± 0.5 Gt C yr−1 (10.2 ± 0.5 Gt C yr−1 when the cement carbonation sink is not included), and ELUC was 1.2 ± 0.7 Gt C yr−1, for a total anthropogenic CO2 emission (including the cement carbonation sink) of 11.1 ± 0.8 Gt C yr−1 (40.7±3.2 Gt CO2 yr−1). Also, for 2022, GATM was 4.6±0.2 Gt C yr−1 (2.18±0.1 ppm yr−1; ppm denotes parts per million), SOCEAN was 2.8 ± 0.4 Gt C yr−1, and SLAND was 3.8 ± 0.8 Gt C yr−1, with a BIM of −0.1 Gt C yr−1 (i.e. total estimated sources marginally too low or sinks marginally too high). The global atmospheric CO2 concentration averaged over 2022 reached 417.1 ± 0.1 ppm. Preliminary data for 2023 suggest an increase in EFOS relative to 2022 of +1.1 % (0.0 % to 2.1 %) globally and atmospheric CO2 concentration reaching 419.3 ppm, 51 % above the pre-industrial level (around 278 ppm in 1750). Overall, the mean of and trend in the components of the global carbon budget are consistently estimated over the period 1959–2022, with a near-zero overall budget imbalance, although discrepancies of up to around 1 Gt C yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows the following: (1) a persistent large uncertainty in the estimate of land-use changes emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living-data update documents changes in methods and data sets applied to this most recent global carbon budget as well as evolving community understanding of the global carbon cycle. The data presented in this work are available at https://doi.org/10.18160/GCP-2023 (Friedlingstein et al., 2023)

Understanding Visitors’ Cognitive Appraisals at Meteorological Destination

While the uncertainty is increasingly becoming a challenge in the supply of meteorological landscape for destinations, little is known about the emotional experiences and behavioural tendencies of visitors triggered by this uncertainty under landscape viewing. Grounded upon cognitive appraisal theory, this study conducted in-depth interviews with 31 visitors who had experience of seeing the meteorological landscape to solicit their perceptions and appraisals of uncertainty. Results revealed that the uncertainty influenced visitors’ cognitive appraisal process, including cognitive appraisal, emotional experiences, coping strategies, and behavioural tendency in the future. Specifically, five positive and four negative emotions, and two coping strategies were identified. In addition, four types of revisit intention were also discussed and summarised. Interestingly, this study found that positive emotions didn’t always trigger positive behavioural tendencies, while negative emotions may also contribute positively to behavioural tendencies. Theoretical and practical implications for destination management are also offered

SUPPLY CHAIN COORDINATION WITH CVaR CRITERION

We study the coordination of supply chains with a risk-neutral supplier and a risk-averse retailer. Different from the downside risk setting, in a conditional value-at-risk (CVaR) framework, we show that the supply chain can be coordinated with the revenue-sharing, buy-back, two-part tariff and quantity flexibility contracts. Furthermore the revenue-sharing contracts are still equivalent to the buy-back contracts when the retail price is fixed. At the same time, it is shown that the risk-averse retailer of the coordinated supply chain can increase its profit by raising its risk-averse degree under mild conditions.Supply chain coordination, newsvendor model, risk-aversion, supply contract, conditional value-at-risk

Near-optimal (r,Q) policies for a two-stage serial inventory system with Poisson demand

We consider a two-stage serial inventory system whose cost structure exhibits economies of scale in both stages. In the system, stage 1 faces Poisson demand and replenishes its inventory from stage 2, and the latter stage in turn orders from an outside supplier with unlimited stock. Each shipment, either to stage 2 or to stage 1, incurs a fixed setup cost. We derive important properties for a given echelon-stock (r, Q) policy for an approximation of the problem where all states are continuous. Based on these properties, we design a simple heuristic algorithm that can be used to find a near-optimal (r, Q) policy for the original problem. Numerical examples are given to demonstrate the effectiveness of the algorithm.Multi-echelon inventory (r,Q) policy Stochastic demand Algorithm

Chloroplast transformation for bioencapsulation and oral delivery using the immunoglobulin G fragment crystallizable (Fc) domain

Abstract Proinsulin Like Growth Factor I (prolGF-I) and myostatin (Mstn) regulate muscle regeneration and mass when intravenously delivered. We tested if chloroplast bioencapsulated forms of these proteins may serve as a non-invasive means of drug delivery through the digestive system. We created tobacco (Nicotiana tabacum) plants carrying GFP-Fc1, proIGF-I-Fc1, and Mstn-Fc1 fusion genes, in which fusion with the immunoglobulin G Fc domain improved both protein stability and absorption in the small intestine. No transplastomic plants were obtained with the Mstn-Fc1 gene, suggesting that the protein is toxic to plant cells. proIGF-I-Fc1 protein levels were too low to enable in vivo testing. However, GFP-Fc1 accumulated at a high level, enabling evaluation of chloroplast-made Fc fusion proteins for oral delivery. Tobacco leaves were lyophilized for testing in a mouse system. We report that the orally administered GFP-Fc1 fusion protein (5.45 µg/g GFP-Fc1) has been taken up by the intestinal epithelium cells, evidenced by confocal microscopy. GFP-Fc1 subsequently entered the circulation where it was detected by ELISA. Data reported here confirm that chloroplast expression and oral administration of lyophilized leaves is a potential delivery system of therapeutic proteins fused with Fc1, with the advantage that the proteins may be stored at room temperature

Methane emissions from livestock in East Asia during 1961−2019

East Asia is a crucial region in the global methane (CH4) budget, with significant contributions from the livestock sector. However, the long-term trend and spatial pattern of CH4 emissions from livestock in this region have not been fully assessed. Here, we estimate CH4 emissions from 10 categories of livestock in East Asia during 1961−2019 following the Tier 2 approaches suggested by IPCC (2019). Our results show that livestock-sourced CH4 emission in 2019 was 13.22 [11.42−15.01] (mean [minimum−maximum of 95% confidence interval] Tg CH4 yr-1, accounting for an increase of 231% since 1961. From 1961 to 2019, the emissions increased first and then stabilized after 2000. The contribution of slaughtered livestock to total emissions increased from 3% in 1961 to 24% in 2019 as a result of a significant increase in the slaughtered population. Spatially, the emission hotspots were mostly distributed in eastern China, South Korea, and parts of Japan, but they tend to shift northward after 2000. This latest long-term inventory can help to understand CH4 budget and to assess CH4 mitigation potential at national and regional levels