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Schrader, J.

Publications and source records attributed to Schrader, J..

16 recordsLinked to original sources

Global Patterns and Drivers of Bee Diversity and Endemism on Islands

Islands harbor a disproportionate share of global biodiversity1, yet insects, even invaluable pollinators such as bees2, remain underrepresented in island biogeography research3. Here, we present the first global checklist of island bees, recording 4,140 species across 306 islands. Although islands comprise only [~]5% of Earths land area, they support [~]20% of global bee diversity, and 43% of insular species are endemic, making up [~]8% of all known bee species. Island bee species richness, mirroring continental trends4, peaks at mid-latitudes. Native richness increases with island area and declines with isolation, consistent with patterns in other taxa5. The strength of species-area relationships varies among biomes and is steepest in mediterranean-type systems, which also support disproportionately high bee richness relative to flowering plant diversity. Endemism is highest on large tropical islands, reflecting extensive in situ diversification. Major centers of bee endemism include Madagascar, Malesia (e.g. the Greater Sundas and New Guinea), and Hawaii, where a single large radiation of Hylaeus (Nesoprosopis) dominates6. Among islands capable of supporting endemic species, endemism scales strongly with total richness. These findings highlight the need to integrate island bee diversity into global conservation planning and position bees as a model for understanding insect evolution and conservation on islands.

ecology↗

The most abundant plant species of Eastern Australia and our knowledge of their traits

O_LIThe rule that most species are relatively rare and few are common has been of central importance to many branches of ecology. This rule also implies that just a few species make up the majority of plant biomass in ecosystems. Focussing plant trait research on the most common species in a region could be useful for many applications, including understanding macroscale patterns of species assemblages at the continental scale, identifying strategies of abundant species or estimating landscape-scale fluxes of carbon and water. C_LIO_LIHere, we rank species based on their total cover across an entire continental region-- Eastern and Central Australia--and report the extent of trait coverage in terms of vegetation cover. To calculate species abundance and trait coverage, we used [~]100,000 vegetation plots from the Harmonised Australian Vegetation plot database overlaid across Australias vegetation classification scheme (the National Vegetation Information System), and we extracted traits from AusTraits, the most comprehensive regional trait database. C_LIO_LIJust 113 plant species (<1% of species found in the region) or the combined species of 16 genera make up 50% of the entire vegetation; approximately 10% of species or the combined species from 10% of the genera (1132 species and 140 genera) make up 90% of vegetation cover. Plant trait coverage tended to be higher when expressed as a proportion of vegetation cover than as a proportion of species in the most common woody genera Acacia and Eucalyptus. Gaps in the trait coverage of very common species were obvious, particularly among the grasses of central Australia. Expressing trait coverage weighted by abundance revealed that only a few additional trait measurements of the most common species and genera would be needed to characterise the traits of most of the vegetation in this part of the continent. C_LIO_LISynthesis: Our results show that a small fraction of species dominates most of the continent. This means that strategic sampling of a few common yet unsampled species could dramatically boost trait coverage and help address the Raunkiaeran shortfall of traits. Targeting these species would substantially improve ecosystem flux estimates and understanding of successful plant strategies at continental scales, with major benefits for vegetation modelling. C_LI

ecology↗

Nutrient niche differentiation among European herbaceous species reflects an extinction to invasion continuum

Threatened and invasive plant species may appear worlds apart; however, we propose that mechanisms underlying invasive success and extinction risk among European herbaceous species constitute a continuum from successful, well-dispersing, fast-growing species to threatened, slow-growing species. We provide empirical evidence for such an extinction-invasion continuum and show that threatened and naturalized invasive plant species occur at opposite ends. Threatened species persist in phosphorus-limited nutrient-poor habitats, while naturalized and invasive species more often occur in nitrogen-limited nutrient-rich habitats. These opposing niches suggest invasive species do not directly displace threatened species; instead, species replacement and extinction result from nutrient regime shifts. Mitigating and preventing nutrient enrichment, especially phosphorus, for nature conservation protects existing nutrient niches for threatened species and limits plant invasion.

ecology↗

Dual inhibition of lactate transporters MCT1 and MCT4 in pancreatic neuroendocrine tumors targets metabolic heterogeneity and functional redundancy

Our current understanding of the metabolic landscape of pancreatic neuroendocrine tumors (PanNETs) is very limited. Such knowledge could lead the development of novel therapeutic strategies for subgroups of PanNET patients based on the metabolic profile of their tumor. Here, we investigated the expression of lactate transporters MCT1 and MCT4 in two independent PanNET cohorts (n=93; n=70) and analyzed their association with tumor aggressiveness and therapeutic vulnerability in cell lines, spheroids and patient-derived tumoroids of PanNET. Immunohistochemistry revealed four expressor types: MCT1/4-negative, MCT1-positive, MCT4-positive, and MCT1/4-double positive with frequent regional co-expression. Both homogenous and heterogenous expression patterns were observed, indicating metabolic heterogeneity within the latter subset of PanNETs. MCT4 expression correlated with the hypoxia marker CA9, suggesting a hypoxic and acidic tumor microenvironment. Mechanistic studies revealed that MCT1 and MCT4 operate both as lactate efflux systems in PanNET cell lines, providing functional redundancy to their glycolytic roles. Inhibition of lactate efflux in normoxia and hypoxia using the dual MCT1/4 inhibitor syrosingopine significantly impaired lactate secretion, glycolysis, and proliferation across PanNET cell lines and 3D spheroid and patient-derived tumoroid models. In contrast, selective MCT1 or MCT4 inhibitors showed limited efficacy, underscoring the therapeutic need for co-targeting MCT1 and MCT4 due to functional redundancy and heterogenous expression. This work demonstrates MCT1 and MCT4 as metabolic markers and promising therapeutic targets of a subset of PanNETs with clinical features of aggressiveness.

cancer biology↗

A-Islands: A plant dataset for biodiversity research and species monitoring on Australian islands

Australias coastline is fringed by more than 8,000 continental islands. These islands feature a diverse array of landforms, rock and soil types and geological origins. Some of these islands are among the least invaded, most pristine habitats in Australia and support high plant diversity. Here, we present a new Australia-wide curated dataset for plant species occurrences on islands. Combining information from 1,349 species lists and floras, A-Islands includes data on >6,500 plant species from 844 islands ranging in size from 18 m2 to 4,400 km2, exhibiting different degrees of isolation from the mainland, and spanning all major Australian climate zones. Of these, 251 islands have been repeatedly sampled up to 11 times making it possible to investigate temporal compositional change. A-Islands is open access and will be continuously updated. Its simple data structure consisting of three comma separated files allows easy integration with other Australian and global plant-occurrence databases and can serve as a repository for island research in Australia. Knowing which species occur on Australia's islands will provide opportunities for future research, including studying changes in biodiversity and species-turnover within and among archipelagos, tests of classical island biogeography theory and as a baseline for ecological monitoring and conservation.

ecology↗

Defining the cardiac fibroblast secretome in the healthy and infarcted mouse heart

Cardiac fibroblasts (CF) are key players after myocardial infarction (MI), but their signaling is only incompletely understood. Here we report a first secretome atlas of CF in control (cCF) and post-MI hearts (miCF), combining a rapid cell isolation technique with SILAC and click chemistry. In CF, numerous paracrine factors involved in immune homeostasis were identified. Comparing secretome, transcriptome (SLAMseq), and cellular proteome disclosed protein turnover. In miCF at day 5 post-MI, significantly upregulated proteins included SLIT2, FN1, and CRLF1 in mouse and human samples. Comparing the miCF secretome at day 3 and 5 post-MI showed the dynamic nature of protein secretion. Specific in-vivo labeling of miCF proteins via biotin ligase TurboID using the POSTN promotor mirrored the in-vitro data. In summary, we have identified numerous paracrine factors specifically secreted from CF in mice and humans. This secretome atlas may lead to new biomarkers and/or therapeutic targets for the activated CF.

physiology↗

A neural alternative splicing program controls cellular function and growth in Pancreatic Neuroendocrine tumours

Pancreatic neuroendocrine tumours (PanNETs) are a rare heterogeneous group of neoplasms that arise from pancreatic islet cells. The hormone secreting function of pancreatic neuroendocrine cells is altered in PanNETs, rendering these tumours functional or non-- functional (secreting excessive or lower levels of hormones, respectively). Genome wide approaches have revealed the genomic landscape of PanNETs but have not shed light on this problematic hormone secretion. In the present work, we show that alternative splicing (AS) deregulation is responsible for changes in the secretory ability of PanNET cells. We reveal a group of alternative microexons that are regulated by the RNA binding protein SRRM3 and are preferentially included in mRNAs in PanNET cells, where SRRM3 is also upregulated. These microexons are part of a larger neural program regulated by SRRM3. We show that their inclusion gives rise to protein isoforms that change stimulus-induced secretory vesicles and their trafficking in PanNET cells. Moreover, the increased inclusion of these microexons results in an enhanced neuronal component in PanNET tumours. Using knock-down and splicing switching oligonucleotides in cellular and animal PanNET models, we show that decrease of the SRRM3 levels or even of the inclusion levels of the three most deregulated microexons can significantly alter the PanNET cell characteristics. Collectively, our study links secretory impairment and nerve dependency to alternative splicing deregulation in PanNETs, providing promising therapeutic targets for PanNET treatment.

cancer biology↗

Phylogenetic endemism of the world's seed plants

Assessing phylogenetic endemism, i.e., the distribution of geographically restricted and evolutionarily unique species, is key to understanding biogeographic patterns and processes and critical for global conservation planning. Here, we quantified the geographic distribution and drivers of phylogenetic endemism for ~320,000 seed plants worldwide and identified centers and drivers of evolutionarily young (neoendemism) and evolutionarily old endemism (paleoendemism). Tropical and subtropical islands of the Southern Hemisphere as well as tropical mountainous regions displayed the worlds highest phylogenetic endemism. Tropical moist forests (e.g. Amazonia) and continental islands in south-east Asia emerged as centers of paleoendemism, while both high neo- and paleoendemism were found on ancient continental fragment islands (e.g. Madagascar) and in Mediterranean-climate regions. Global variation in phylogenetic endemism was best explained by a combination of past and present environmental factors (80.3% - 88.1% of variance explained). Geographic isolation and environmental heterogeneity emerged as primary drivers promoting high phylogenetic endemism. Also, warm and wet climates with long-term climatic stability showed a significant positive effect. However, environmental effects on phylogenetic endemism varied with geographic isolation, reflecting the unique evolutionary and biogeographic dynamics on oceanic islands. Long-term climatic stability promoted the persistence of paleoendemics, while isolation promoted higher neoendemism leading to oceanic islands and tropical mountainous regions being centers of both neo- and paleoendemism. Our study provides new insights into the evolutionary underpinnings of biogeographic patterns in seed plants, and by identifying areas of high evolutionary and biogeographic uniqueness, it may serve as a key resource for setting global conservation priorities.

ecology↗

Patient-derived tumoroids of advanced high-grade neuroendocrine neoplasms mimic patient chemotherapy responses and guide the design of personalized combination therapies

There are no therapeutic predictive biomarkers or representative preclinical models for high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), a highly aggressive, fatal, and heterogeneous epithelial malignancy. We established patient-derived (PD) tumoroids from biobanked tissue samples of advanced high-grade GEP-NEN patients and applied this model for targeted rapid ex vivo pharmacotyping, next-generation sequencing, and perturbational profiling. We used tissue-matched PD tumoroids to profile individual patients, compared ex vivo drug response to patients clinical response to chemotherapy, and investigated treatment-induced adaptive stress responses. PD tumoroids recapitulated biological key features of high-grade GEP-NEN and mimicked clinical response to cisplatin and temozolomide ex vivo. When we investigated treatment-induced adaptive stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5A and interferon-beta, which act synergistically in combination with cisplatin. Since ex vivo drug response in PD tumoroids matched clinical patient responses to standard-of-care chemotherapeutics for GEP-NEN, our rapid and functional precision oncology approach could expand personalized therapeutic options for patients with advanced high-grade GEP-NEN.

cancer biology↗

Machine learning improves global models of plant diversity

Despite the paramount role of plant diversity for ecosystem functioning, biogeochemical cycles, and human welfare, knowledge of its global distribution is incomplete, hampering basic research and biodiversity conservation. Here, we used machine learning (random forests, extreme gradient boosting, neural networks) and conventional statistical methods (generalised linear models, generalised additive models) to model species richness and phylogenetic richness of vascular plants worldwide based on 830 regional plant inventories including c. 300,000 species and predictors of past and present environmental conditions. Machine learning showed an outstanding performance, explaining up to 80.9% of species richness and 83.3% of phylogenetic richness. Current climate and environmental heterogeneity emerged as the primary drivers, while past environmental conditions left only small but detectable imprints on plant diversity. Finally, we combined predictions from multiple modelling techniques (ensemble predictions) to reveal global patterns and centres of plant diversity at multiple resolutions down to 7,774 km2. Our predictive maps provide the most accurate estimates of global plant diversity available to date at grain sizes relevant for conservation and macroecology.

ecology↗

Cdk5 drives formation of heterogeneous pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bitransgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in {beta}-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. The utility of this model is enhanced by ability to form tumor-derived allografts. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

cancer biology↗

Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted heart

In the adult heart, the epicardium becomes activated after injury, contributing to cardiac healing by secretion of paracrine factors. Here we analyzed by single-cell RNA sequencing combined with RNA in situ hybridization and lineage tracing of WT1+ cells the cellular composition, location, and hierarchy of epicardial stromal cells (EpiSC) in comparison to activated myocardial fibroblasts/stromal cells in infarcted mouse hearts. We identified 11 transcriptionally distinct EpiSC populations, that can be classified in three groups each containing a cluster of proliferating cells. Two groups expressed cardiac specification makers and sarcomeric proteins suggestive of cardiomyogenic potential. Transcripts of HIF-1 and HIF-responsive genes were enriched in EpiSC consistent with an epicardial hypoxic niche. Expression of paracrine factors was not limited to WT1+ cells but was a general feature of activated cardiac stromal cells. Our findings provide the cellular framework by which myocardial ischemia may trigger in EpiSC the formation of cardioprotective/regenerative responses.

cell biology↗

Identification of fungal limonene-3-hydroxylases for biotechnological menthol production

More than 30,000 tons of menthol are produced every year as a flavor and fragrance compound or as medical component. So far, only extraction from plant material or chemical synthesis is possible. A sustainable alternative approach for menthol production could be a biotechnological-chemical two-step conversion, starting from (+)-limonene, which is a side product of the citrus processing industry. The first step requires a limonene-3-hydroxylase (L3H) activity that specifically catalyzes hydroxylation of limonene at carbon atom 3. Several protein engineering strategies already attempted to create limonene-3-hydroxylases from bacterial cytochrome P450 monooxygenases (CYPs or P450s), which can be efficiently expressed in bacterial hosts. However, their regiospecificity is rather low, if compared to the highly selective L3H enzymes from the biosynthetic pathway towards menthol in Mentha species. The only naturally occurring limonene-3-hydroxylase activity identified in microorganisms so far, was reported for a strain of the black yeast-like fungus Hormonema sp. in South Africa. We have discovered further fungi that can catalyze the intended reaction and identified potential CYP-encoding genes within the genome sequence of one of the strains. Using heterologous gene expression and biotransformation experiments in yeasts, we were able to identify limonene-3-hydroxylases from Aureobasidium pullulans and Hormonema carpetanum. Further characterization of the A. pullulans enzyme demonstrated its high stereospecificity and regioselectivity, its potential for limonene-based menthol production and its additional ability to convert -and {beta}-pinene to verbenol and pinocarveol, respectively. Importance(-)-Menthol is an important flavor and fragrance compound and furthermore has medicinal uses. To realize a two-step synthesis starting from renewable (+)-limonene, a regioselective limonene-3-hydroxylase enzyme is necessary. We identified enzymes from two different fungi, which catalyze this hydroxylation reaction and represent an important module for the development of a biotechnological process for (-)-menthol production from renewable (+)-limonene.

microbiology↗

Genetic analysis identifies the Ostrea stentina/aupouria/equestris oyster species complex in Hawai'i, and resolves its lineage as the western Pacific O. equestris

BackgroundExtensive phenotypic plasticity in oysters makes them difficult to identify based on morphology alone, but their identities can be resolved by applying genetic and genomic technologies. In this study, we collected unknown oyster specimens from Hawaiian waters for genetic identification. MethodsWe sequenced two partial gene fragments, mitochondrial 16S ribosomal RNA (16S) and cytochrome c oxidase subunit I (COI), in 48 samples: 27 unidentified oyster specimens collected from two locations on O ahu, 13 known specimens from a hatchery in Hilo, Hawai i Island, and 8 known specimens from Hilo Bay, Hawai i Island. ResultsMolecular data identified approximately 85% of unknown samples as belonging to the Ostrea stentina/aupouria/equestris species complex, a globally distributed group with a history of uncertain and controversial taxonomic status. The remaining unknown samples were the native Dendostrea sandvichensis (G. B. Sowerby II, 1871), and nonnative Crassostrea gigas (Thunberg, 1793), the latter of which is a commercial species that was introduced to Hawai I from multiple sources during the 20th century. Phylogenetic analysis placed Hawai i Ostrea alongside samples from China, Japan, and New Zealand, grouping them within the recently classified western Pacific O. equestris. Until now, four extant species of true oyster have been documented in Hawai i. This study expands the known range of O. equestris by providing the first verification of its occurrence in Hawai i.

genetics↗

Extracellular Adenine Nucleotide and Adenosine Metabolism in Calcific Aortic Valve Disease

Extracellular nucleotide catabolism contributes to immunomodulation, cell differentiation and tissue mineralization by controlling nucleotide and adenosine concentrations and its purinergic effects. Disturbances of purinergic signaling in valves may lead to its calcification. This study aimed to investigate the side-specific changes in extracellular nucleotide and adenosine metabolism in the aortic valve during calcific aortic valve disease (CAVD) and to identify the individual enzymes that are involved in these pathways as well as their cellular origin.\n\nStenotic aortic valves were characterized by reduced levels of extracellular ATP removal and impaired production of adenosine. Respectively, already reduced levels of extracellular adenosine were immediately degraded further due to the elevated rate of adenosine deamination. For the first time, we revealed that this metabolic pattern was observed only on the fibrosa surface of stenotic valve that is consistent with the mineral deposition on the aortic side of the valve. Furthermore, we demonstrated that non-stenotic valves expressed mostly ecto-nucleoside triphosphate diphosphohydrolase 1 (eNTPD1) and ecto-5nucleotidase (e5NT), while stenotic valves ecto-nucleotide pyrophosphatase/ phosphodiesterase 1, alkaline phosphatase and ecto-adenosine deaminase (eADA). On the surface of endothelial cells, isolated from non-stenotic valves, high activities of eNTPD1 and e5NT were found. Whereas, in valvular interstitial cells, eNPP1 activity was also detected. Stenotic valve immune infiltrate was an additional source of eADA. We demonstrated the presence of A1, A2a and A2b adenosine receptors in both, non-stenotic and stenotic valves with diminished expression of A2a and A2b in the former.\n\nExtracellular nucleotide and adenosine metabolism that involves complex ecto-enzyme pathways and adenosine receptor signaling were adversely modified in CAVD. In particular, diminished activities of eNTPD1 and e5NT with the increase in eADA that originated from valvular endothelial and interstitial cells as well as from immune inflitrate may affect aortic valve extracellular nucleotide concentrations to favor a proinflammatory milieu, highlighting a potential mechanism and target for CAVD therapy.

biochemistry↗

α-proteobacterial RNA degradosomes assemble liquid-liquid phase separated RNP bodies

Ribonucleoprotein (RNP) granules play an important role in organizing eukaryotic mRNA metabolism via liquid-liquid phase separation (LLPS) of mRNA decay factors into membrane-less \"droplet\" organelles in the cytoplasm. Here we show that the bacterium Caulobacter crescentus Ribonuclease (RNase) E assembles RNP LLPS droplets that we term bacterial RNP-bodies (BR-bodies) similar to eukaryotic P-bodies and stress granules. RNase E requires RNA to assemble a BR-body, and disassembly requires RNA cleavage, suggesting BR-bodies provide localized sites of RNA degradation. The unstructured C-terminal domain of RNase E is both necessary and sufficient to assemble the core of the BR-body, is functionally conserved in related -proteobacteria, and influences mRNA degradation. BR-bodies are rapidly induced under cellular stresses and provide enhanced cell growth under stress. To our knowledge, Caulobacter RNase E is the first bacterial protein identified that forms LLPS droplets, providing an effective strategy for subcellular organization in cells lacking membrane bound compartments.

molecular biology↗