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Sher, D.

Publications and source records attributed to Sher, D..

14 recordsLinked to original sources

Organizing principles in the Nitrogen-Carbon Landscape of Marine Heterotrophic Bacteria

Marine microbes metabolize a wide range of carbon and nitrogen sources, shaping global biogeochemical cycles. Despite being crucial at the global scale, the coupling between carbon and nitrogen remains poorly understood at the level of individual metabolites and bacteria. By phenotyping a library of marine heterotrophic bacteria across increasingly complex carbon and nitrogen sources, we generated a snapshot of this coupling. Growth phenotypes were weakly explained by phylogeny, but could be organized around substrate properties, including C:N stoichiometry and degree of reduction. Beyond explainable average trends along these axes, different strains displayed significant variability. For some bacteria, nitrogen use efficiency was associated with ammonium secretion, consistent with their role in ecological interactions. Furthermore, nonlinearities emerged in how yields depend on combinations of resources, such as mixtures of amino acids and dipeptides. These organizing principles may help understand the ecological role of marine heterotrophic bacteria and parametrize models of biogeochemical cycles.

systems biology↗

Nanobubble based sonobiopsy reveals circulating protein signatures of BBB opening and glioblastoma

Focused ultrasound (FUS) and microbubbles can transiently increase blood brain barrier (BBB) permeability, yet verification of BBB opening (BBBO) relies mainly on contrast-enhanced MRI, offering limited insight into the molecular consequences of barrier modulation. Sonobiopsy, which uses FUS induced BBBO to release brain derived molecules into the bloodstream, provides a molecular readout from blood samples. Nanobubbles (NBs) are smaller agents that circulate more effectively in the brain microvasculature and have shown enhanced BBBO in capillaries. Here, NB-mediated proteomic sonobiopsy is used to improve biomarker efflux and increase molecular sensitivity, with the goal of defining the molecular signature produced by BBBO in healthy and glioblastoma (GBM) models, and distinguishing biomarkers associated with tumor pathology from BBBO biomarkers. Plasma collected before and after NB-mediated FUS underwent data-independent acquisition-based mass spectrometry, revealing post-BBBO changes in healthy and tumor bearing mice. In healthy cohorts, 77 proteins were reproducibly altered after BBBO. Six proteins (Dpysl3, Myl1, Mybpc1, Vsig4, Krt33a, Krtap6-5) were detectable only after BBBO in healthy mice. In 005 glioma bearing mice, the BBBO signature identified in healthy animals was preserved, and comparison with matched shams isolated tumor specific effects. Three proteins, Itih4, Lrg1, and Hp, rose significantly after BBBO only in GBM and reached higher post treatment levels than in shams, nominating candidate GBM-associated markers accessible via blood. These findings establish NB-mediated proteomic sonobiopsy as a promising method for BBBO verification and for detecting GBM associated protein signals, supporting the development of scalable BBBO confirmation and protein-based diagnostics in neuro oncology. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/692317v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@d0186aorg.highwire.dtl.DTLVardef@1f2fe8borg.highwire.dtl.DTLVardef@25921forg.highwire.dtl.DTLVardef@9c3566_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Low-frequency ultrasound-mediated blood-brain barrier opening enables non-invasive lipid nanoparticle RNA delivery to glioblastoma

Ionizable Lipid Nanoparticles (LNPs) are an FDA-approved non-viral RNA delivery system, though their use for brain therapy is restricted by the blood-brain barrier (BBB). Focused ultrasound combined with microbubbles can disrupt the BBB, but delivering large particles requires balancing increased peak negative pressures while maintaining microvascular integrity. Herein, we optimized low-frequency ultrasound parameters to induce high-amplitude microbubble oscillations, enabling the safe delivery of LNPs across the BBB. First, BBB opening was assessed at different frequencies (850, 250, and 80 kHz) and pressures by monitoring the extravasation of Evans blue (~1 kDa). Next, the delivery of 4, 70, and 150 kDa Dextrans, LNPs entrapping Cy5-siRNAs (~70 nm in diameter), and LNPs entrapping mRNA (~100 nm in diameter) was evaluated via microscopy and bioluminescence. In a glioblastoma syngeneic mouse model, siRNA-Cy5-LNP was successfully delivered. A frequency of 850 kHz and 125 kPa pressure induced safe BBB opening, enabling delivery of both small molecules and LNPs. In healthy brains, LNP entrapping siRNAs delivery increased 10-fold compared to controls, and LNPs with mRNAs showed a 12-fold increase in bioluminescence after 24 hours. In glioblastoma tumors, LNPs with siRNAs delivery resulted in a 6.7-fold increase in fluorescence. This study paves the way for non-invasive LNP delivery to the brain, offering a versatile platform for brain therapies. TOC graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=76 SRC="FIGDIR/small/634427v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@cad2bdorg.highwire.dtl.DTLVardef@1d1936corg.highwire.dtl.DTLVardef@259d83org.highwire.dtl.DTLVardef@1883aed_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Jellyfish blooms Through the Microbial Lens: Temporal Changes, Cross-Species and Jellyfish-Water Comparisons

In this study, we explore the dynamics of bacterial communities associated with Rhopilema nomadica blooms, the predominant jellyfish in the Eastern Mediterranean Sea. We collected over 120 samples from more than 30 individuals across five major bloom events, capturing both lesser-studied winter blooms and the peaks and declines of summer blooms. Our analysis revealed significant microbial shifts-increases in Endozoicomonas and unclassified Rickettsiales were significantly more abundance during late summer blooms, while Tenacibaculum dominated in winter. Additionally, we examined microbial patterns within specific tissues--bell, gonads, tentacles, and gastrovascular system--to assess variations across these different niches. This revealed high relative abundance of specific taxa tailored to different tissue-Bacteroides was predominantly found in the bell, Simkaniaceae in the gonads, and Endozoicomonas in the tentacles. Further expanding our research, we compared the top taxa of R. nomadica with those of nine other jellyfish species from different locations. Interestingly, while no universal core microbiome was found, several taxa, including Endozoicomonas, Mycoplasma, and Spiroplasma, were common across different species, suggesting their potential ecological roles across jellyfish. Lastly, our study of potential bacterial transmission modes revealed that key bacteria associated with R. nomadica are exclusively found near bloom areas, and are absent from remote seawater, highlighting potential localized transmission dynamics between jellyfish and their immediate marine environment. Our study marks the first exploration of microbial dynamics within R. nomadica, while also broadening the understanding of other jellyfish microbial communities and setting the stage for future studies to delve deeper into their complex interactions. IMPORTANCEJellyfish blooms, like those of Rhopilema nomadica in the Eastern Mediterranean, impact marine ecosystems and human industries. Understanding the complex relationships between jellyfish and their microbiomes is important, as these interactions may influence bloom formation and decline. Our study explores microbiome variations across different stages of R. nomadica blooms, identifies common bacteria among jellyfish from various locations, and examines potential transmission modes of the main jellyfish-associated bacteria. Microbial communities vary significantly between bloom stages and jellyfish tissues, becoming less diverse towards the end of the bloom. Although no universal core microbiome was discovered, taxa such as Endozoicomonas, Mycoplasma, and Spiroplasma are prevalent across various jellyfish, suggesting significant ecological roles. Finally, our findings indicate that key bacteria associated with R. nomadica predominantly reside near bloom areas and are absent from distant seawater, highlighting localized transmission mode. This study enhances our understanding of jellyfish-associated microbial communities and their role in bloom dynamics.

microbiology↗

Diversity in the Utilization of Different Molecular Classes of Dissolved Organic Matter by Heterotrophic Marine Bacteria

Heterotrophic marine bacteria utilize and recycle dissolved organic matter (DOM), impacting biogeochemical cycles. It is currently unclear to what extent distinct DOM components can be utilized by different heterotrophic clades. Here, we ask how a natural microbial community from the Eastern Mediterranean Sea responds to different molecular classes of DOM. These molecular classes - peptides, amino acids, amino sugars, disaccharides, monosaccharides and organic acids - together comprise much of the biomass of living organisms, released upon their death as DOM. Bulk bacterial activity increased after 24-hours for all treatments relative to the control, while glucose and ATP uptake decreased or remained unchanged. The relative abundance of several bacterial families, assessed using 16S rRNA amplicon sequencing, increased in some treatments: peptides promoted an increase in Pseudoalteromonadaceae, disaccharides promoted both Pseudoalteromonadaceae and Alteromonadaceae, and most other treatments were dominated by Vibrionaceae. While some results were consistent with recent laboratory-based studies, for example Pseudoalteromonadaceae favoring peptides, other clades behaved differently. Alteromonadaceae, for example, grew well in the lab on many substrates but dominated in seawater samples when disaccharides were added. These results highlight the diversity in DOM utilization among heterotrophic bacteria and complexities in the response of natural communities. ImportanceThe marine DOM pool contains numerous molecular classes, which change depending on the phytoplankton species, environmental conditions and interactions with other microbes, viruses and predators. In turn, the availability of these macromolecular pools affects the composition and function of the whole microbial community. Tracing the path between different carbon sources to specific microbes is another step towards revealing the dynamic interaction between bacteria and the DOM pool. This is especially important in warm and oligotrophic marine systems (e.g., Eastern Mediterranean Sea) where nutrients are scarce and may therefore affect microbial activity and growth.

microbiology↗

Collaborative metabolic curation of an emerging model marine bacterium, Alteromonas macleodii ATCC 27126

Inferring the metabolic capabilities of an organism from its genome is a challenging process, relying on computationally-derived or manually curated metabolic networks. Manual curation can correct mistakes in the draft network and add missing reactions based on the literature, but requires significant expertise and is often the bottleneck for high-quality metabolic reconstructions. Here, we present a synopsis of a community curation workshop for the emerging model marine bacterium Alteromonas macleodii ATCC 27126 and its genome database in BioCyc, focusing on pathways for utilizing organic carbon and nitrogen sources. Due to the scarcity of biochemical information or gene knock-outs, the curation process relied primarily on published growth phenotypes and bioinformatic analyses, including comparisons with related Alteromonas strains. We report full pathways for the utilization of the algal polysaccharides alginate and pectin in contrast to inconclusive evidence for one carbon metabolism and mixed acid fermentation, in accordance with the lack of growth on methanol and formate. Pathways for amino acid degradation are ubiquitous across Alteromonas macleodii strains, yet enzymes in the pathways for the degradation of threonine, tryptophan and tyrosine were not identified. Nucleotide degradation pathways are also partial in ATCC 27126. We postulate that demonstrated growth on nitrate as sole N source proceeds via a nitrate reductase pathway that is a hybrid of known pathways. Our evidence highlights the value of joint and interactive curation efforts, but also shows major knowledge gaps regarding Alteromonas metabolism. The manually-curated metabolic reconstruction is available as a "Tier-2" database on BioCyc. ImportanceMetabolic reconstructions are vital for the systemic understanding of an organisms ecology. Here, we report the outcome of a collaborative, interactive curation workshop to build a curated "metabolic encyclopedia" for Alteromonas macleodii ATCC 27126, a marine heterotrophic bacterium with widespread occurrence. Curating pathways for polysaccharide degradation, one-carbon metabolism, and others closed major knowledge gaps, and identified further avenues of research. Our study highlights how the combination of bioinformatic, genomic and physiological evidence can be harvested into a detailed metabolic model, but also identifies challenges if little experimental data is available for support. Overall, we show how an interactive get-together by a diverse group of scientists can advance the ecological understanding of emerging model bacteria, with relevance for the entire scientific community.

microbiology↗

An Interplay of Phytoplankton Donor Species and Transformation of Released Compounds over Time Defines Bacterial Communities Following Phytoplankton DOMp Pulses

Phytoplankton-bacteria interactions are stimulated by phytoplankton-released dissolved organic matter (DOMp). Two factors that shape the accompanying bacterial community are i) the "donor" phytoplankton species, defining the initial composition of released DOMp, and ii) the DOMp transformation over time. We added phytoplankton DOM from two globally abundant species - the diatom Skeletonema marinoi and the cyanobacterium Prochlorococcus MIT9312 - to natural bacterial communities in the Eastern Mediterranean and determined the bacterial responses over a time-course of 72 h in terms of cell numbers, bacterial production (BP), alkaline phosphatase activity (APA), and changes in active bacterial community compositions based on rRNA amplicon sequencing. Both DOMp types were demonstrated to serve the bacterial community as carbon and potentially phosphorus source. Diatom-derived DOM induced higher BP and lower APA compared to cyanobacterium DOM after 24 h, but not after 48 and 72 h of incubation, and also maintained higher Shannon diversities over the course of the experiment, indicating a better bacterial accessibility and broader disposability of diatom derived DOM. Bacterial communities significantly differed between DOMp types as well as different incubation times, pointing to a certain bacterial specificity for the DOMp donor as well as a successive utilization of phytoplankton DOM by different bacterial taxa. The highest differences in bacterial community composition with DOMp types occurred shortly after additions, suggesting a high specificity towards highly bioavailable DOMp compounds. We conclude that phytoplankton associated bacterial communities are strongly shaped by an interplay between phytoplankton donor and the transformation of its released DOMp over time. IMPORTANCEPhytoplankton-bacteria interactions maintain biogeochemical cycles of global importance. Phytoplankton photosynthetically fix carbon dioxide and subsequently release the synthesized compounds as dissolved organic matter (DOMp), which becomes processed and recycled by heterotrophic bacteria. Yet, the combined effect of the phytoplankton donor species and time-dependent transformation of DOMp compounds on the accessibility to the bacterial community has not been explored until now. The diatom Skeletonema marinoi and the cyanobacterium Prochlorococcus MIT9312 are globally important phytoplankton species, and our study revealed that DOMp of both species was selectively incorporated by the bacterial community. The donor species had the highest impact shortly after DOMp appropriation, and its effect diminished over time. Our results improve the understanding of biogeochemical cycles between phytoplankton and bacteria, and solve yet unresolved questions of phytoplankton-bacteria interactions.

microbiology↗

Selecting 16S rRNA primers for microbiome analysis in a host-microbe system: the case of the jellyfish Rhopilema nomadica

Amplicon sequencing of the 16S rRNA gene is extensively used to characterize bacterial communities, including those living in association with eukaryotic hosts. Deciding which region of the 16S rRNA gene to analyze and selecting the appropriate PCR primers remained a major decision when initiating any new microbiome study. Here, we compared three commonly used primers targeting different hypervariable regions of the 16S rRNA gene, V1V2, V3V4, and V4V5, using the jellyfish Rhopilema nomadica as a model. Although all primers exhibit a similar pattern in bacterial community composition, the performance of the V3V4 primer set was superior to V1V2 and V4V5. The V1V2 primers misclassified bacteria from the Bacilli class and exhibited low classification resolution for Rickettsiales, which represent the second most abundant 16S rRNA gene sequence in all the primers. The V4V5 primer set detected almost the same community composition as the V3V4, but the ability of these primers to also amplify eukaryotic 18S rRNA gene may hinder bacterial community observations. However, after overcoming the challenges possessed by each one of those primers, we found that all three of them show very similar bacterial community dynamics and composition. Nevertheless, based on our results, we propose that the V3V4 primer set is the most suitable for studying jellyfish-associated bacterial communities. Our results suggest that, at least for jellyfish samples, it may be feasible to directly compare microbial community estimates from different studies, each using different primers but otherwise similar experimental protocols. More generally, we recommend specifically testing different primers as a prelude to large-scale 16S rRNA gene amplicon analyses, especially of previously unstudied host-microbe associations.

microbiology↗

Phytoplankton exudates provide full nutrition to a subset of accompanying heterotrophic bacteria via carbon, nitrogen and phosphorus allocation

Marine bacteria rely on phytoplankton exudates as carbon sources (DOCp). Yet, it is unclear to what extent phytoplankton exudates also provide nutrients such as phytoplankton-derived N and P (DONp, DOPp). We address these questions by exudate addition experiments from the ubiquitous pico-cyanobacterium Prochlorococcus to contrasting ecosystems in the Eastern Mediterranean - a coastal and an open-ocean, oligotrophic station. Nutrient addition did not lower the incorporation of exudate DONp, nor did it reduce alkaline phosphatase activity, suggesting that bacterial communities are able to exclusively cover their nitrogen and phosphorus demands with organic forms provided by phytoplankton exudates. Approximately half of the cells in each ecosystem took up detectable amounts of Prochlorococcus-derived C and N, yet based on 16S rRNA sequencing different bacterial genera were responsible for the observed exudate utilization patterns. In the coastal community, several phylotypes of Aureimarina, Psychrosphaera and Glaciecola responded positively to the addition of phytoplankton exudates, whereas phylotypes of Pseudoalteromonas increased and dominated the open ocean communities. Together, our results strongly indicate that phytoplankton exudates provide coastal and open-ocean bacterial communities with organic carbon, nitrogen and phosphorus, and that phytoplankton exudate serve a full-fledged meal for specific members of the accompanying bacterial community in the nutrient-poor eastern Mediterranean.

ecology↗

Seasonal dynamics of phytoplankton and bacterioplankton at the ultra-oligotrophic southeastern Mediterranean Sea

The Eastern Mediterranean Sea (EMS) is a poorly studied ultra-oligotrophic marine environment, dominated by small-size phyto- and bacterioplankton. Here, we describe the dynamics of a single annual cycle (2018-19) of phyto- and bacterioplankton (abundances, pigments and productivity) in relation to the physical and chemical conditions in the photic water column at an offshore EMS site (Station THEMO-2, [~]1,500m depth, 50km offshore). We show that phytoplankton biomass (as chlorophyll a), primary and bacterial productivity differed between the mixed winter (January-April) and the thermally stratified (May-December) periods. Prochlorococcus and Synechococcus numerically dominated the picophytoplankton populations, with each clade revealing different temporal and depth changes indicative to them, while pico-eukaryotes (primarily haptophytes) were less abundant, yet likely contributed significant biomass. Estimated primary productivity ([~]32 gC m-2 y-1) was lower compared with other well-studied oligotrophic locations, including the north Atlantic and Pacific (BATS and HOT observatories), the western Mediterranean (DYFAMED observatory) and the Red Sea, and was on-par with the ultra-oligotrophic South Pacific Gyre. In contrast, integrated bacterial production ([~]11 gC m-2 y-1) was similar to other oligotrophic locations. Phytoplankton seasonal dynamics were similar to those at BATS and the Red Sea, suggesting an observable effect of winter mixing in this ultra-oligotrophic location. These results highlight the ultra-oligotrophic conditions in the EMS and provide, for the first time in this region, a full-year baseline and context to ocean observatories in the region. HighlightsO_LIBacterioplankton dynamics were assessed monthly in the Eastern Mediterranean Sea C_LIO_LISmall-sized picophytoplankton numerically dominated the phytoplankton community C_LIO_LISeasonal phytoplankton dynamics are similar to BATS and Red Sea, but not to HOT C_LIO_LIAnnual primary productivity is among the lowest in the worlds oceans C_LIO_LIBacterial to primary production ratio is higher than most oligotrophic seas C_LI

microbiology↗

Seasonal dynamics are the major driver of microbial diversity and composition in intensive freshwater aquaculture

Aquaculture facilities such as fishponds are one of the most anthropogenically impacted freshwater ecosystems. The high fish biomass reared in aquaculture is associated with an intensive input into the water of fish-feed and fish excrements. This nutrients load may affect the microbial community in the water, which in turn can impact the fish health. To determine to what extent aquaculture practices and natural seasonal cycles affect the microbial populations, we characterized the microbiome of an inter-connected aquaculture system at monthly resolution, over three years. The system comprised two fishponds, where fish are grown, and a "control" operational water reservoir in which fish are not actively stocked. Clear natural seasonal cycles of temperature and inorganic nutrients concentration, as well as recurring cyanobacterial blooms during summer, were observed in both the fishponds and the reservoir. The structure of the aquatic bacterial communities in the system, characterized using 16S rRNA sequencing, was explained primarily by the natural seasonality, whereas aquaculture-related parameters had only a minor explanatory power. However, the cyanobacterial blooms were characterized by different cyanobacterial clades dominating at each fishpond, possibly in response to distinct nitrogen and phosphate ratios. In turn, nutrient ratios may have been by the magnitude of fish feed input. Taken together, our results show that, even in strongly anthropogenically impacted aquatic ecosystems, the structure of bacterial communities is mainly driven by the natural seasonality, with more subtle effects if aquaculture-related factors. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/433039v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@154d693org.highwire.dtl.DTLVardef@d35ae9org.highwire.dtl.DTLVardef@1f5a7a2org.highwire.dtl.DTLVardef@d07fbc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe present three years of monthly microbiome data from an aquaculture facility. C_LIO_LIThe microbiome changes seasonally, likely driven by temperature and rainwater runoff. C_LIO_LISummer blooms of toxin-producing cyanobacteria are repeatedly observed. C_LIO_LIFish food may impact microbiome through changes in nutrient ratios. C_LI

ecology↗

Physiological and transcriptomic variability indicative of differences in key functions within a single coral colony

Polyps in different locations on individual stony coral colonies experience variation in numerous environmental conditions including flow and light, potentially leading to transcriptional and physiological differences across the colony. Here, we describe high-resolution physiological measurements and differential gene expression from multiple locations within a single colony of Stylophora pistillata, aiming to relate these to environmental gradients across the coral colony. We observed broad transcriptional responses in both the host and photosymbiont in response to height above the substrate, cardinal direction, and, most strongly, location along the branch axis. Specifically, several key physiological processes in the host appear more active toward branch tips including several metabolic pathways, toxin production for prey capture or defense, and biomolecular mechanisms of biomineralization. Further, the increase in gene expression related to these processes toward branch tips is conserved between S. pistillata and Acropora spp. The photosymbiont appears to respond transcriptionally to relative light intensity along the branch and due to cardinal direction. These differential responses were observed across the colony despite its genetic homogeneity and likely inter-polyp communication. While not a classical division of labor, each part of the colony appears to have distinct functional roles related to polyps differential exposure to environmental conditions.

genomics↗

Microbial communities in an ultra-oligotrophic sea are more affected by season than by distancefrom shore

Marine microbial communities vary seasonally and spatially, but these two factors are rarely addressed together. We studied temporal and spatial patterns of the microbial community structure and activity along a coast to offshore transect from the Israeli coast of the Eastern Mediterranean Sea (EMS) over six cruises, in three seasons of two consecutive years. The ultra-oligotrophic status of the South Eastern Mediterranean Sea was reflected in the microbial community composition that was dominated by oligotrophic microbial groups such as SAR11 throughout the year, even at the most coastal station sampled. Seasons affected microbial communities much more than distance from shore explaining about half of the observed variability in the microbial community, compared to only about 6% that was explained by station. However, the most coastal site differed significantly in community structure and activity from the three further offshore stations in early winter and summer, but not in spring. Our data on the microbial community composition and its seasonality from a transect into the South Eastern Levantine basin support the notion that the EMS behaves similar to open gyres rather than an inland sea.

ecology↗

The role of land use types and water chemical properties in structuring the microbiome of a connected lakes system

Lakes and other freshwater bodies are intimately connected to the surrounding land, yet to what extent land-use affects the quality of freshwater and the microbial communities living in various freshwater environments is largely unknown. We address this question through an analysis of the land use surrounding 46 inter-connected lakes located within 7 different drainage basins in northern Germany, and the microbiomes of these lakes during early summer. Lake microbiome structure was not determined by the specific drainage basin or by basin size, and bacterial distribution did not seem to be limited by distance. Instead, land use within the drainage basin could predict, to some extent, NO2+NO3 concentrations in the water, which (together with temperature, chlorophyll a and total phosphorus) affected water microbiome structure. Land use directly surrounding the water bodies, however, had little observable effects on water quality or the microbiome. Several microbial lineages, including environmentally important Cyanobacteria and Verrucomicrobia, were differentially partitioned between the lakes. As the amount of available data on land use (e.g. from remote sensing) increases, identifying relationships between land use, aquatic microbial communities and their effect on water quality will be important to better manage freshwater resources worldwide, e.g. by systemically identifying water bodies prone to ecological changes or the presence of harmful organisms.

microbiology↗