A carbohydrate-binding protein, B-GRANULE CONTENT 1, influences starch granule size distribution in a dose-dependent manner in polyploid wheat

In Triticeae endosperm (e.g. wheat and barley), starch granules have a bimodal size distribution (with A- and B-type granules) whereas in other grasses the endosperm contains starch granules with a unimodal size distribution. Here, we identify the gene, BGC1 (B-GRANULE CONTENT 1), responsible for B-type starch granule content in Aegilops and wheat. Orthologues of this gene are known to influence starch synthesis in diploids such as rice, Arabidopsis, and barley. However, using polyploid Triticeae species, we uncovered a more complex biological role for BGC1 in starch granule initiation: BGC1 represses the initiation of A-granules in early grain development but promotes the initiation of B-granules in mid grain development. We provide evidence that the influence of BGC1 on starch synthesis is dose dependent and show that three very different starch phenotypes are conditioned by the gene dose of BGC1 in polyploid wheat: normal bimodal starch granule morphology; A-granules with few or no B-granules; or polymorphous starch with few normal A- or B-granules. We conclude from this work that BGC1 participates in controlling B-type starch granule initiation in Triticeae endosperm and that its precise effect on granule size and number varies with gene dose and stage of development

Ambitious subsidy reform by the WTO presents opportunities for ocean health restoration

This is the author accepted manuscript. The final version is available from Springer via the DOI in this recordThe World Trade Organization (WTO) is in a unique position to deliver on Sustainable Development Goal (SDG) 14.6 by reforming global fisheries subsidies in 2020. Yet, a number of unanswered questions threaten to inhibit WTO delegates from crafting a smart agreement that improves global fisheries health. We combine global data on industrial fishing activity, subsidies, and stock assessments to show that: (1) subsidies prop up fishing effort all across the world’s ocean and (2) larger subsidies tend to occur in fisheries that are poorly managed. When combined, this evidence suggests that subsidy reform could have geographically-extensive consequences for many of the world’s largest fisheries. While much work remains to establish causality and make quantitative predictions, this evidence informs the rapidly-evolving policy debate and we conclude with actionable policy suggestions.Pew Charitable Trust

Using Unoccupied Aerial Vehicles to Map and Monitor Changes in Emergent Kelp Canopy after an Ecological Regime Shift

Kelp forests are complex underwater habitats that form the foundation of many nearshore marine environments and provide valuable services for coastal communities. Despite their ecological and economic importance, increasingly severe stressors have resulted in declines in kelp abundance in many regions over the past few decades, including the North Coast of California, USA. Given the significant and sustained loss of kelp in this region, management intervention is likely a necessary tool to reset the ecosystem and geospatial data on kelp dynamics are needed to strategically implement restoration projects. Because canopy-forming kelp forests are distinguishable in aerial imagery, remote sensing is an important tool for documenting changes in canopy area and abundance to meet these data needs. We used small unoccupied aerial vehicles (UAVs) to survey emergent kelp canopy in priority sites along the North Coast in 2019 and 2020 to fill a key data gap for kelp restoration practitioners working at local scales. With over 4,300 hectares surveyed between 2019 and 2020, these surveys represent the two largest marine resource-focused UAV surveys conducted in California to our knowledge. We present remote sensing methods using UAVs and a repeatable workflow for conducting consistent surveys, creating orthomosaics, georeferencing data, classifying emergent kelp and creating kelp canopy maps that can be used to assess trends in kelp canopy dynamics over space and time. We illustrate the impacts of spatial resolution on emergent kelp canopy classification between different sensors to help practitioners decide which data stream to select when asking restoration and management questions at varying spatial scales. Our results suggest that high spatial resolution data of emergent kelp canopy from UAVs have the potential to advance strategic kelp restoration and adaptive management

Collagen scaffold and lipoaspirate fluid - Derived stem cells for the treatment of cartilage defects in a Rabbit Model

The purpose of the present study was to assess and compare the chondroregenerative properties of PLA (processed lipoaspirate) and LAF (lipoaspirate fluid) cells, in a preclinical rabbit model of knee cartilage defect. The defects were repaired by a collagen I/III scaffold and added LAF-cells, PLA-cells or no cells, upon the study group. The results showed that collagen scaffolds seeded with LAF-derived stem cells appear to have slightly better activity and outcomes when compared to PLA-cells, in terms of cartilage regeneration

A review of the opportunities and challenges for using remote sensing for management of surface-canopy forming kelps

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cavanaugh, K. C., Bell, T., Costa, M., Eddy, N. E., Gendall, L., Gleason, M. G., Hessing-Lewis, M., Martone, R., McPherson, M., Pontier, O., Reshitnyk, L., Beas-Luna, R., Carr, M., Caselle, J. E., Cavanaugh, K. C., Miller, R. F., Hamilton, S., Heady, W. N., Hirsh, H. K., Hohman R., Lee L. C., Lorda J., Ray J., Reed D. C., Saccomanno V. R., Schroeder, S. B. A review of the opportunities and challenges for using remote sensing for management of surface-canopy forming kelps. Frontiers in Marine Science, 8, (2021): 753531, https://doi.org/10.3389/fmars.2021.753531.Surface-canopy forming kelps provide the foundation for ecosystems that are ecologically, culturally, and economically important. However, these kelp forests are naturally dynamic systems that are also threatened by a range of global and local pressures. As a result, there is a need for tools that enable managers to reliably track changes in their distribution, abundance, and health in a timely manner. Remote sensing data availability has increased dramatically in recent years and this data represents a valuable tool for monitoring surface-canopy forming kelps. However, the choice of remote sensing data and analytic approach must be properly matched to management objectives and tailored to the physical and biological characteristics of the region of interest. This review identifies remote sensing datasets and analyses best suited to address different management needs and environmental settings using case studies from the west coast of North America. We highlight the importance of integrating different datasets and approaches to facilitate comparisons across regions and promote coordination of management strategies.Funding was provided by the Nature Conservancy (Grant No. 02042019-5719), the U.S. National Science Foundation (Grant No. OCE 1831937), and the U.S. Department of Energy ARPA-E (Grant No. DE-AR0000922)

MCM2 - a promising marker for premalignant lesions of the lung: a cohort study

BACKGROUND: Because cells progressing to cancer must proliferate, marker proteins specific to proliferating cells may permit detection of premalignant lesions. Here we compared the sensitivities of a classic proliferation marker, Ki-67, with a new proliferation marker, MCM2, in 41 bronchial biopsy specimens representing normal mucosa, metaplasia, dysplasia, and carcinoma in situ. METHODS: Parallel sections were stained with antibodies against MCM2 and Ki-67, and the frequencies of staining were independently measured by two investigators. Differences were evaluated statistically using the two-sided correlated samples t-test and Wilcoxon rank sum test. RESULTS: For each of the 41 specimens, the average frequency of staining by anti-MCM2 (39%) was significantly (p < 0.001) greater than by anti-Ki-67 (16%). In metaplastic lesions anti-MCM2 frequently detected cells near the epithelial surface, while anti-Ki-67 did not. CONCLUSIONS: We conclude that MCM2 is detectable in 2-3 times more proliferating premalignant lung cells than is Ki-67. The promise of MCM2 as a sensitive marker for premalignant lung cells is enhanced by the fact that it is present in cells at the surface of metaplastic lung lesions, which are more likely to be exfoliated into sputum. Future studies will determine if use of anti-MCM2 makes possible sufficiently early detection to significantly enhance lung cancer survival rates

Preneoplastic lesions of the lung

Lung cancer is the leading cause of cancer deaths worldwide. If we can define and detect preneoplastic lesions, we might have a chance of improving survival. The World Health Organization has defined three preneoplastic lesions of the bronchial epithelium: squamous dysplasia/carcinoma in situ; atypical adenomatous hyperplasia; and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. These lesions are believed to progress to squamous cell carcinoma, adenocarcinoma and carcinoid tumors, respectively. In this review we summarize the data supporting the preneoplastic nature of these lesions, and delve into some of the genetic changes found in atypical adenomatous hyperplasia and squamous dysplasia/carcinoma in situ

Transformation of human bronchial epithelial cells alters responsiveness to inflammatory cytokines

BACKGROUND: Inflammation is commonly associated with lung tumors. Since inflammatory mediators, including members of the interleukin-6 (IL-6) cytokine family, suppress proliferation of normal epithelial cells, we hypothesized that epithelial cells must develop mechanisms to evade this inhibition during the tumorigenesis. This study compared the cytokine responses of normal epithelial cells to that of premalignant cells. METHODS: Short-term primary cultures of epithelial cells were established from bronchial brushings. Paired sets of brushings were obtained from areas of normal bronchial epithelium and from areas of metaplastic or dysplastic epithelium, or areas of frank endobronchial carcinoma. In 43 paired cultures, the signalling through the signal transducer and activator of transcription (STAT) and extracellular regulated kinase (ERK) pathways and growth regulation by IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), interferon-γ (IFNγ) or epidermal growth factor (EGF) were determined. Inducible expression and function of the leukemia inhibitory factor receptor was assessed by treatment with the histone deacetylase inhibitor depsipeptide. RESULTS: Normal epithelial cells respond strongly to OSM, IFNγ and EGF, and respond moderately to IL-6, and do not exhibit a detectable response to LIF. In preneoplastic cells, the aberrant signaling that was detected most frequently was an elevated activation of ERK, a reduced or increased IL-6 and EGF response, and an increased LIF response. Some of these changes in preneoplastic cell signaling approach those observed in established lung cancer cell lines. Epigenetic control of LIF receptor expression by histone acetylation can account for the gain of LIF responsiveness. OSM and macrophage-derived cytokines suppressed proliferation of normal epithelial cells, but reduced inhibition or even stimulated proliferation was noted for preneoplastic cells. These alterations likely contribute to the supporting effects that inflammation has on lung tumor progression. CONCLUSION: This study indicates that during the earliest stage of premalignant transformation, a modified response to cytokines and EGF is evident. Some of the altered cytokine responses in primary premalignant cells are comparable to those seen in established lung cancer cell lines

Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum

The use of 5-methylcytosine demethylating agents in conjunction with inhibitors of histone deacetylation may offer a new therapeutic strategy for lung cancer. Monitoring the efficacy of gene demethylating treatment directly within the tumour may be difficult due to tumour location. This study determined the positive and negative predictive values of sputum and serum for detecting gene methylation in primary lung cancer. A panel of eight genes was evaluated by comparing methylation detected in the primary tumour biopsy to serum and sputum obtained from 72 patients with Stage III lung cancer. The prevalence for methylation of the eight genes in sputum (21–43%) approximated to that seen in tumours, but was 0.7–4.3-fold greater than detected in serum. Sputum was superior to serum in classifying the methylation status of genes in the tumour biopsy. The positive predictive value of the top four genes (p16, DAPK, PAX5 β, and GATA5) was 44–72% with a negative predictive value for these genes ⩾70%. The highest specificity was seen for the p16 gene, and this was associated with a odds ratio of six for methylation in the tumour when this gene was methylated in sputum. In contrast, for serum, the individual sensitivity for all genes was 6–27%. Evaluating the combined effect of methylation of at least one of the four most significant genes in sputum increased the positive predictive value to 86%. These studies demonstrate that sputum can be used effectively as a surrogate for tumour tissue to predict the methylation status of advanced lung cancer where biopsy is not feasible

Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc