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Air pollution is associated with cardiopulmonary disease and death in the general population. Fine particulate matter (PM2.5) is particularly harmful due to its ability to penetrate into areas of gas exchange within the lungs. Persons with advanced lung disease are believed to be particularly susceptible to PM2.5 exposure, but only a few studies have examined the effect of exposure on this population. Here we investigate the association between PM2.5 exposure and adverse waitlist events among lung transplant (LT) candidates.US registry data were used to identify LT candidates listed between January 1, 2010 and December 31, 2016. Annual PM2.5 concentration at year of listing was estimated for each candidate's ZIP Code using National Aeronautics and Space Administration's (NASA) Socioeconomic Data and Applications Center Global Annual PM2.5 Grids. We estimated crude and adjusted hazard ratios for adverse waitlist events, defined as death or removal, using Cox proportional hazards regression.Of the 15 075 included candidates, median age at listing was 60, 43.8% were female individuals, and 81.7% were non-Hispanic White. Median ZIP Code PM2.5 concentration was 9.06 µg/m3. When compared with those living in ZIP Codes with lower PM2.5 exposure (PM2.510.53 µg/m3), candidates in ZIP Codes in the highest quartile of PM2.5 exposure (≥10.53 µg/m3) had 1.14-fold (95% confidence interval, 1.04-1.25) risk of adverse waitlist events. The result remained significant after adjusting for demographics, education, insurance, smoking, lung allocation score, body mass index, and blood type (hazard ratio, 1.17; 95% confidence interval, 1.07-1.29).Elevated ambient PM2.5 concentration was associated with adverse waitlist events among LT candidates. These findings highlight the impact of air pollution on clinical outcomes in this critically ill population.

Supplementary Table 1: Description of TCGA derived mRNA expression cohorts used to examine LIF expression and associated transcript signaturesSupplementary Table 2: Transcription signatures used to identify biological processes and cell types correlated with LIF expression.Supplementary Table 3: GSEA results of REACTOME pathway gene sets for enriched gene sets in LIF treated macrophages. Supplementary Table 4: Leading edge genes selected from GSEA analysis of LIF treated macrophages with REACTOME pathway gene sets Supplementary Table 5: Summary of data collection statistics for crystal structures of MSC-1:LIF co-complex Supplementary Table 6: Summary of interactions between MSC-1 and LIF

Supplementary Figure 1. Transcriptomic analysis demonstrates an enrichment of immunological pathways in high LIF tumors. Supplementary Figure 2. LIF transcripts are associated with a panel of immunosuppressive macrophage/myeloid signatures across human tumor indications. Supplementary Figure 3. LIF transcripts are specifically associated with suppressive macrophage signatures across human tumor indications. Supplementary Figure 4. LIF transcripts tend to be highly expressed in aggressive tumors. Supplementary Figure 5. LIF drives polarization of immunosuppressive human macrophages. Supplementary Figure 6. RNAseq of LIF induced gene sets in human macrophages predict poor patient outcome and correlate with LIF across human tumor indications. Supplementary Figure 7. Structural analysis of MSC-1 reveals an overlapping epitope with the gp130 binding site and a free cysteine in HCDR3. Supplementary Figure 8. CT26 and MC38 tumors expression LIF protein and monotherapy MSC-1 is well tolerated. Supplementary Figure 9. MSC-1 and anti-PD1 combination is well tolerated and promotes tumor memory in responsive mice.

Purpose:Leukemia inhibitory factor (LIF) is a multifunctional cytokine with numerous reported roles in cancer and is thought to drive tumor development and progression. Characterization of LIF and clinical-stage LIF inhibitors would increase our understanding of LIF as a therapeutic target.Experimental Design:We first tested the association of LIF expression with transcript signatures representing multiple processes regulating tumor development and progression. Next, we developed MSC-1, a high-affinity therapeutic antibody that potently inhibits LIF signaling and tested it in immune competent animal models of cancer.Results:LIF was associated with signatures of tumor-associated macrophages (TAM) across 7,769 tumor samples spanning 22 solid tumor indications. In human tumors, LIF receptor was highly expressed within the macrophage compartment and LIF treatment drove macrophages to acquire immunosuppressive capacity. MSC-1 potently inhibited LIF signaling by binding an epitope that overlaps with the gp130 receptor binding site on LIF. MSC-1 showed monotherapy efficacy in vivo and drove TAMs to acquire antitumor and proinflammatory function in syngeneic colon cancer mouse models. Combining MSC-1 with anti-PD1 leads to strong antitumor response and a long-term tumor-free survival in a significant proportion of treated mice.Conclusions:Overall, our findings highlight LIF as a therapeutic target for cancer immunotherapy.

BACKGROUND: While several studies have observed that solid organ transplant recipients experience diminished antibody responses to SARS-CoV-2 mRNA vaccination, data specific to heart and lung transplant (HT/LT) recipients remains sparse. METHODS: US adult HT and LT recipients completed their vaccine series between January 7 and April 10, 2021. Reactogencity and SARS-CoV-2 anti-spike antibody were assessed after a priming dose (D1) and booster dose (D2). Modified Poisson regression with robust variance estimator was used to evaluate associations between participant characteristics and antibody development. RESULTS: Of 134 heart recipients, there were 38% non-responders (D1-/D2-), 48% booster responders (D1-/D2+), and 14% priming dose responders (D1+/D2+). Of 103 lung recipients, 64% were non-responders, 27% were booster responders, and 9% were priming dose responders. Lung recipients were less likely to develop antibodies (p < .001). Priming dose antibody response was associated with younger recipient age (p = .04), transplant-to-vaccination time ≥6 years (p < .01), and lack of anti-metabolite maintenance immunosuppression (p < .001). Pain at injection site was the most commonly reported reaction (85% after D1, 76% after D2). Serious reactions were rare, the most common being fatigue (2% after D1 and 3% after D2). No serious adverse events were reported. CONCLUSIONS: HT and LT recipients experienced diminished antibody response following vaccination; reactogenicity was comparable to that of the general population. LT recipients may exhibit a more impaired antibody response than HT recipients. While current recommendations are to vaccinate eligible candidates and recipients, further studies characterizing the cell-mediated immune response and clinical efficacy of these vaccines in this population are needed.

Purpose:Leukemia inhibitory factor (LIF) is a multifunctional cytokine with numerous reported roles in cancer and is thought to drive tumor development and progression. Characterization of LIF and clinical-stage LIF inhibitors would increase our understanding of LIF as a therapeutic target.Experimental Design:We first tested the association of LIF expression with transcript signatures representing multiple processes regulating tumor development and progression. Next, we developed MSC-1, a high-affinity therapeutic antibody that potently inhibits LIF signaling and tested it in immune competent animal models of cancer.Results:LIF was associated with signatures of tumor-associated macrophages (TAM) across 7,769 tumor samples spanning 22 solid tumor indications. In human tumors, LIF receptor was highly expressed within the macrophage compartment and LIF treatment drove macrophages to acquire immunosuppressive capacity. MSC-1 potently inhibited LIF signaling by binding an epitope that overlaps with the gp130 receptor binding site on LIF. MSC-1 showed monotherapy efficacy in vivo and drove TAMs to acquire antitumor and proinflammatory function in syngeneic colon cancer mouse models. Combining MSC-1 with anti-PD1 leads to strong antitumor response and a long-term tumor-free survival in a significant proportion of treated mice.Conclusions:Overall, our findings highlight LIF as a therapeutic target for cancer immunotherapy.

Prior studies have demonstrated a decreased humoral response in solid organ transplant recipients (SOTRs) to SARS-CoV-2 mRNA vaccination (17% antibody response after dose 1, 54% after dose 2) as compared to the general population (100%). However, these studies were dominated by kidney transplant recipients, and included only a small percentage of liver transplant (LT) recipients (19.6%).(1-4) Since LT recipients often receive milder induction and maintenance immunosuppression, they may have a more robust humoral response. To investigate this, we studied SARS-CoV-2 antibody development in a cohort of LT recipients who completed a two-dose mRNA vaccine series of either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech).

Pest spillover from wildlands to farms can create conflict between habitat conservation and agricultural production. For example, the key economic pest of hazelnuts in Oregon’s Willamette Valley is the filbertworm (Cydia latiferreana), a moth hosted by the native Oregon white oak (Quercus garryana). Oak habitat near hazelnut orchards can sustain source populations that compound pest load in hazelnuts throughout the growing season. This dynamic is of conservational concern as historical oak habitat has been greatly reduced and what remains is almost entirely on private land, often in proximity to hazelnut orchards. Here, we present a novel strategy to reconcile this regional conflict by using hogs (Sus domesticus) to reduce pest populations through prescribed foraging. From 2018 to 2020 we prescribed hog-foraging in early fall to glean filbertworm-infested acorns from an oak woodland understory. Hogs were both highly successful at reducing the total number of infested acorns and the ratio of infested acorns the following year. Despite an oak-masting year in 2019, foraging reduced both the emerging and adult mating population of filbertworm the following year. We did not measure significant changes in the woodland understory, suggesting intermittent hog-foraging may not entail tradeoffs for understory vegetation. Our results demonstrate that prescribed foraging in oak patches can be an effective strategy to reduce filbertworm source populations. By benefiting both conservation and farmers, this adaptive pest management approach provides a model for similar challenges and conflicts across the agricultural-wildland matrix.

The effects of altered nutrient supplies and herbivore density on species diversity vary with spatial scale, because coexistence mechanisms are scale dependent. This scale dependence may alter the shape of the species–area relationship (SAR), which can be described by changes in species richness (S) as a power function of the sample area (A): S = cAz, where c and z are constants. We analysed the effects of experimental manipulations of nutrient supply and herbivore density on species richness across a range of scales (0.01–75 m²) at 30 grasslands in 10 countries. We found that nutrient addition reduced the number of species that could co-occur locally, indicated by the SAR intercepts (log c), but did not affect the SAR slopes (z). As a result, proportional species loss due to nutrient enrichment was largely unchanged across sampling scales, whereas total species loss increased over threefold across our range of sampling scales.

BACKGROUND AND AIMS: Liver graft quality is evaluated by visual inspection prior to transplantation, a process highly dependent on surgeon's experience. We present an objective, non-invasive, quantitative way of assessing liver quality in real time using Raman spectroscopy, a laser-based tool for analysing biomolecular composition.APPROACH AND RESULTS: A novel porcine model of donation after circulatory death (DCD) with normothermic regional perfusion (NRP) allowed assessment of liver quality pre-mortem, during warm ischemia (WI) and post-NRP. 10% of circulating blood volume was removed in half of experiments to simulate blood recovery for DCD heart removal. Left median lobe biopsies were obtained before circulatory arrest, after 45 min of WI and after two hours of NRP, and analysed using spontaneous Raman spectroscopy, stimulated Raman spectroscopy (SRS) and staining. Measurements were also taken in situ from the porcine liver using a handheld Raman spectrometer at these time points from left median and right lateral lobes. Raman microspectroscopy detected congestion during WI by measurement of the intrinsic Raman signal of haemoglobin in red blood cells (RBCs), eliminating the need for exogenous labels. Critically, this microvascular damage was not observed during WI when 10% of circulating blood was removed before cardiac arrest. Two hours of NRP effectively cleared RBCs from congested livers. Intact RBCs were visualised rapidly at high resolution using SRS. Optical properties of ischemic livers were significantly different to pre-ischemic and post-NRP livers as measured using a handheld Raman spectrometer.CONCLUSIONS: Raman spectroscopy is an effective tool for detecting microvascular damage which could assist the decision to use marginal livers for transplantation. Reducing the volume of circulating blood before circulatory arrest in DCD may help reduce microvascular damage.

The identification of individuals, particularly at international border crossings, coupled with the evolving sophistication of identity documents are issues that authorities must contend with.\ud Particularly, the ability to distinguish legitimate from counterfeit documents, with high throughput, sensitivity, and selectivity is an ever-evolving challenge.\ud \ud Over the last decade, an increasing number of security features have been introduced by authorities in identification documents. The latest generation of travel documents (such as\ud passports and national ID cards) forego paper substrates for several layers of polycarbonate, allowing security features to be embedded within the documents. These security features may\ud contain information at either the superficial and sub-surface levels, thus increasing the document’s resilience to counterfeiting.\ud \ud As the documents become harder to forge, so does the sophistication of forgery detection. There appears to be an unmet and evolving need to identify such sophisticated forgeries, in a\ud non-destructive, high throughput manner.\ud \ud In this publication, we report on the application of optical coherence tomography (OCT) imaging on assessing security features in specimen passports and national ID cards. OCT\ud allows sub-surface imaging of translucent structures, non-destructively enabling quantitative visualisation of embedded security features.

Synchronous dynamics (fluctuations that occur in unison) are universal phenomena with widespread implications for ecological stability. Synchronous dynamics can amplify the destabilizing effect of environmental variability on ecosystem functions such as productivity, whereas the inverse, compensatory dynamics, can stabilize function. Here we combine simulation and empirical analyses to elucidate mechanisms that underlie patterns of synchronous versus compensatory dynamics. In both simulated and empirical communities, we show that synchronous and compensatory dynamics are not mutually exclusive but instead can vary by timescale. Our simulations identify multiple mechanisms that can generate timescale-specific patterns, including different environmental drivers, diverse life histories, dispersal, and non-stationary dynamics. We find that traditional metrics for quantifying synchronous dynamics are often biased toward long-term drivers and may miss the importance of short-term drivers. Our findings indicate key mechanisms to consider when assessing synchronous versus compensatory dynamics and our approach provides a pathway for disentangling these dynamics in natural systems.

Fluctuations in population abundances are often correlated through time across multiple locations, a phenomenon known as spatial synchrony. Spatial synchrony can exhibit complex spatial structures, termed ‘geographies of synchrony’, that can reveal mechanisms underlying population fluctuations. However, most studies have focused on spatial extents of 10s to 100s of kilometres, making it unclear how synchrony concepts and approaches should apply to dynamics at finer spatial scales. We used network analyses, multiple regression on similarity matrices, and wavelet coherence analyses to examine micro‐scale synchrony and geographies of synchrony, over distances up to 30 m, in a serpentine grassland plant community. We found that species' populations exhibited a geography of synchrony even over such short distances. Often, well‐synchronized populations were geographically separate, a spatial structure that was shaped mainly by gopher disturbance and dispersal limitation, and to a lesser extent by relationships with other plant species. Precipitation was a significant driver of site‐ and community‐wide temporal dynamics. Gopher disturbance appeared to drive synchrony on 2‐ to 6‐year timescales, and we detected coherent fluctuations among pairs of focal plant taxa. Synthesis. Micro‐geographies of synchrony are an intriguing phenomenon that may also help us better understand community dynamics. Additionally, the related geographies of synchrony and coherent temporal dynamics among some species pairs indicate that incorporating interspecific interactions can improve understanding of population spatial synchrony.

Medulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, Group 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated the antitumorigenic role of Wnt activation in Shh MB, we aimed to assess the effects of activated canonical Wnt signaling in Group 3 and 4 MBs. By using primary patient-derived MB brain tumor-initiating cell (BTIC) lines, we characterize differences in the tumor-initiating capacity of Wnt, Group 3, and Group 4 MB. With single cell RNA-seq technology, we demonstrate the presence of rare Wnt-active cells in non-Wnt MBs, which functionally retain the impaired tumorigenic potential of Wnt MB. In treating MB xenografts with a Wnt agonist, we provide a rational therapeutic option in which the protective effects of Wnt-driven MBs may be augmented in Group 3 and 4 MB and thereby support emerging data for a context-dependent tumor suppressive role for Wnt/β-catenin signaling., The Wnt molecular subgroup of medulloblastoma is associated with better prognosis than the other molecular subgroups. Here, the authors show that activating Wnt signaling impairs tumor development and improves survival in Group 3 and Group 4 medulloblastoma preclinical models.

On the Ground • We examined whether diversity metrics could be incorporated into the Ecological Site Descriptions and State and Transition Models (ESD-STM) framework to manage multiple goals including biodiversity on heterogeneous landscapes. • We evaluated plant diversity in two vegetation states (i.e., grassland and shrubland) across three ecological sites in Southern California and found that alpha diversity differed by ecological site and vegetation state. • Functional diversity remained similar across our three ecological sites. • Beta diversity between vegetation states was higher than that within each state—in other words, two states support more dissimilar vegetation communities than one state alone. • Describing both biodiversity metrics and forage values in ESD-STM may help guide conservation planning on working ranches, such as the Tejon Ranch in Southern California.

Professor Richard Hobbs has had a profound influence on the development of the discipline of restoration ecology. With more than 300 publications spanning a broad scope of applied ecological sciences, he has collaborated with hundreds of researchers. His sometimes‐provocative insights, balanced by extensive empirical research, will have a lasting impact by encouraging people to think more broadly about the science and practice of ecological restoration. Here, on the eve of his retirement, some of his staff and students, past and present, take a retrospective look at his contributions to restoration ecology both as a scientist and as a mentor.

Restoration ecology commonly seeks to re-establish species of interest in degraded habitats. Despite a rich understanding of how succession influences re-establishment, there are several outstanding questions that remain unaddressed: are short-term abundances sufficient to determine long-term re-establishment success, and what factors contribute to unpredictable restorations outcomes? In other words, when restoration fails, is it because the restored habitat is substandard, because of strong competition with invasive species, or alternatively due to changing environmental conditions that would equally impact established populations? Here, we re-purpose tools developed from modern coexistence theory to address these questions, and apply them to an effort to restore the endangered Contra Costa goldfields (Lasthenia conjugens) in constructed ("restored") California vernal pools. Using 16 years of data, we construct a population model of L. conjugens, a species of conservation concern due primarily to habitat loss and invasion of exotic grasses. We show that initial, short-term appearances of restoration success from population abundances is misleading, as year-to-year fluctuations cause long-term population growth rates to fall below zero. The failure of constructed pools is driven by lower maximum growth rates compared with reference ("natural") pools, coupled with a stronger negative sensitivity to annual fluctuations in abiotic conditions that yield decreased maximum growth rates. Nonetheless, our modeling shows that fluctuations in competition (mainly with exotic grasses) benefit L. conjugens through periods of competitive release, especially in constructed pools of intermediate pool depth. We therefore show how reductions in invasives and seed addition in pools of particular depths could change the outcome of restoration for L. conjugens. By applying a largely theoretical framework to the urgent goal of ecological restoration, our study provides a blueprint for predicting restoration success, and identifies future actions to reverse species loss. Funding Agencies|Air Force Center for Environmental Excellence; US Fish and Wildlife Service; CH2M Hill; NSF LTREB grants [DEB-0744520, DEB-1257385]; USDA NIFA Predoctoral Fellowship [2021-67034-35111]; Swedish Research Council (Vetenskapsradet) [2017-05245]; Spanish Ministry of Economy and Competitiveness (MINECO); European Social Fund through the Ramon y Cajal Program [RYC2017-23666]

Modelling species interactions in diverse communities traditionally requires a prohibitively large number of species-interaction coefficients, especially when considering environmental dependence of parameters. We implemented Bayesian variable selection via sparsity-inducing priors on non-linear species abundance models to determine which species interactions should be retained and which can be represented as an average heterospecific interaction term, reducing the number of model parameters. We evaluated model performance using simulated communities, computing out-of-sample predictive accuracy and parameter recovery across different input sample sizes. We applied our method to a diverse empirical community, allowing us to disentangle the direct role of environmental gradients on species intrinsic growth rates from indirect effects via competitive interactions. We also identified a few neighbouring species from the diverse community that had non-generic interactions with our focal species. This sparse modelling approach facilitates exploration of species interactions in diverse communities while maintaining a manageable number of parameters. Funding Agencies|NSF EPSCoRNational Science Foundation (NSF)NSF - Office of the Director (OD) [EPS-2019528]; Australian Research CouncilAustralian Research Council [DP140100574]; VetenskapsradetSwedish Research Council [2017-05245]; European Social FundEuropean Social Fund (ESF) [RYC-2017-23666]; Ministerio de Economia y CompetitividadSpanish Government; Deutsches Zentrum fur integrative Biodiversitatsforschung Halle-Jena-Leipzig [FZT 118, 02548816]

Declines in grassland diversity in response to nutrient addition are a general consequence of global change. This decline in species richness may be driven by multiple underlying processes operating at different time-scales. Nutrient addition can reduce diversity by enhancing the rate of local extinction via competitive exclusion, or by reducing the rate of colonization by constraining the pool of species able to colonize under new conditions. Partitioning net change into extinction and colonization rates will better delineate the long-term effect of global change in grasslands. We synthesized changes in richness in response to experimental fertilization with nitrogen, phosphorus and potassium with micronutrients across 30 grasslands. We quantified changes in local richness, colonization, and extinction over 8–10 years of nutrient addition, and compared these rates against control conditions to isolate the effect of nutrient addition from background dynamics. Total richness at steady state in the control plots was the sum of equal, relatively high rates of local colonization and extinction. On aggregate, 30%–35% of initial species were lost and the same proportion of new species were gained at least once over a decade. Absolute turnover increased with site-level richness but was proportionately greater at lower-richness sites relative to starting richness. Loss of total richness with nutrient addition, especially N in combination with P or K, was driven by enhanced rates of extinction with a smaller contribution from reduced colonization. Enhanced extinction and reduced colonization were disproportionately among native species, perennials, and forbs. Reduced colonization plateaued after the first few (

Analysing temporal patterns in plant communities is extremely important to quantify the extent and the consequences of ecological changes, especially considering the current biodiversity crisis. Long-term data collected through the regular sampling of permanent plots represent the most accurate resource to study ecological succession, analyse the stability of a community over time and understand the mechanisms driving vegetation change. We hereby present the LOng-Term Vegetation Sampling (LOTVS) initiative, a global collection of vegetation time-series derived from the regular monitoring of vascular plants in permanent plots. With 79 datasets from five continents and 7789 vegetation time-series monitored for at least six years and mostly on an annual basis, LOTVS possibly represents the largest collection of temporally fine-grained vegetation time-series derived from permanent plots and made accessible to the research community. As such, it has an outstanding potential to support innovative research in the fields of vegetation science, plant ecology and temporal ecology.

Background. The coronavirus disease 2019 (COVID-19) pandemic has had a variable course across the United States. Understanding its evolving impact on heart and lung transplantation (HT and LT) will help with planning for next phases of this pandemic as well as future ones. Methods. We used Scientific Registry of Transplant Recipients data from before the pandemic to predict the number of waitlist registrations and transplants expected to occur between March 15, 2020, and December 31, 2020 (if no pandemic had occurred), and compared these expectations to observed rates. The observed era was divided into wave 1 (March 15–May 31), wave 2 (June 1–September 30), and wave 3 (October 1–December 31). We used multilevel Poisson regression to account for center- and state-level COVID-19 incidence. Results. During wave 1, rates of heart registrations and transplants were 28% (incidence rate ratio [IRR]: 0.72 [95% confidence interval (CI), 0.67-0.77]) and 13% (IRR: 0.87 [95% CI, 0.80-0.93]) lower than expected; lung registrations and transplants were 40% (IRR: 0.60 [95% CI, 0.54-0.66]) and 28% (IRR: 0.72 [95% CI, 0.66-0.79]) lower. Decreases were greatest in states with the highest incidence where registrations were 53% (IRR: 0.47 [95% CI, 0.36-0.62]) and 59% (IRR: 0.41 [95% CI, 0.29-0.58]) and transplants were 57% (IRR: 0.43 [95% CI, 0.31-0.60]) and 58% (IRR: 0.42 [95% CI, 0.29-0.62]) lower than expected. Whereas HT largely recovered during waves 2 and 3, LT continued to fall short of expectations through the end of the year. Conclusions. The COVID-19 pandemic in the US substantially reduced thoracic transplant access. Ongoing evaluation of the risks and benefits of this dramatic practice change is critical to inform clinical decision-making moving forward.

Tissue engineering of a transplantable liver could provide an alternative to donor livers for transplant, solving the problem of escalating donor shortages. One of the challenges for tissue engineers is the extracellular matrix (ECM); a finely controlled in vivo niche which supports hepatocytes. Polymers and decellularized tissue scaffolds each provide some of the necessary biological cues for hepatocytes, however, neither alone has proved sufficient. Enhancing microenvironments using bioactive molecules allows researchers to create more appropriate niches for hepatocytes. We combined decellularized human liver tissue with electrospun polymers to produce a niche for hepatocytes and compared the human liver ECM to its individual components; Collagen I, Laminin-521 and Fibronectin. The resulting scaffolds were validated using THLE-3 hepatocytes. Immunohistochemistry confirmed retention of proteins in the scaffolds. Mechanical testing demonstrated significant increases in the Young’s Modulus of the decellularized ECM scaffold; providing significantly stiffer environments for hepatocytes. Each scaffold maintained hepatocyte growth, albumin production and influenced expression of key hepatic genes, with the decellularized ECM scaffolds exerting an influence which is not recapitulated by individual ECM components. Blended protein:polymer scaffolds provide a viable, translatable niche for hepatocytes and offers a solution to current obstacles in disease modelling and liver tissue engineering.

Synchrony is broadly important to population and community dynamics due to its ubiquity and implications for extinction dynamics, system stability, and species diversity. Investigations of synchrony in community ecology have tended to focus on covariance in the abundances of multiple species in a single location. Yet, the importance of regional environmental variation and spatial processes in community dynamics suggests that community properties, such as species richness, could fluctuate synchronously across patches in a metacommunity, in an analog of population spatial synchrony. Here, we test the prevalence of this phenomenon and the conditions under which it may occur using theoretical simulations and empirical data from 20 marine and terrestrial metacommunities. Additionally, given the importance of biodiversity for stability of ecosystem function, we posit that spatial synchrony in species richness is strongly related to stability. Our findings show that metacommunities often exhibit spatial synchrony in species richness. We also found that richness synchrony can be driven by environmental stochasticity and dispersal, two mechanisms of population spatial synchrony. Richness synchrony also depended on community structure, including species evenness and beta diversity. Strikingly, ecosystem stability was more strongly related to richness synchrony than to species richness itself, likely because richness synchrony integrates information about community processes and environmental forcing. Our study highlights a new approach for studying spatiotemporal community dynamics and emphasizes the spatial dimensions of community dynamics and stability.

Biliary diseases can cause inflammation, fibrosis, bile duct destruction, and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have therefore purified human biliary epithelial cells (hBECs) from human livers that were not used for liver transplantation. hBECs were tested as a cell therapy in a mouse model of biliary disease in which the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures, and fibrosis. hBECs are expandable and phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.