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Results for “Functional proteome”

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PubMed2005

GoldIII porphyrin 1a induced apoptosis by mitochondrial death pathways related to reactive oxygen species.

Apoptosis is a tightly controlled multistep mechanism of cell death, and mitochondria are considered to play a central role in this process. Mitochondria initiate two distinct apoptosis pathways, one caspase-dependent and the other caspase-independent. In addition, mitochondrial production of reactive oxygen species (ROS) seems to play a role in cell death. Most chemotherapeutic agents induce apoptosis through at least one of these pathways. The post-initiation mechanisms of gold(III) porphyrin 1a were investigated in this study. HONE1 cells exposed to gold(III) porphyrin 1a underwent apoptosis after 24 hours. Functional proteomic studies revealed the alteration of several cytoplasmic protein expressions in HONE1 cells after treatment with the drug. These proteins include enzymes participating in energy production and proteins involved in cellular redox balance. There was a quick attenuation of mitochondrial membrane potential (DeltaPsi(m)) with the alterations of Bcl-2 family proteins, the release of cytochrome c, and apoptosis-inducing factor (AIF) following gold(III) porphyrin 1a treatment. Cytochrome c in turn activated caspase-9 and caspase-3. Cotreatment with caspase inhibitor (zVAD-fmk) showed that the activated caspases worked in conjunction with AIF-initiated apoptosis pathways. Further study showed that ROS played a part in gold(III) porphyrin 1a-induced apoptosis by regulating DeltaPsi(m). In summary, gold(III) porphyrin 1a induced apoptosis through both caspase-dependent and caspase-independent mitochondrial pathways, and intracellular oxidation affected gold(III) porphyrin 1a-induced apoptosis. These results support a role for gold(III) porphyrin 1a as a promising anticancer drug lead and as a possible novel therapeutic agent directed toward the mitochondria.

Apoptosis↗

PubMed2003

Biomarkers in drug discovery and development: from target identification through drug marketing.

Biomarkers of disease play an important role in medicine and have begun to assume a greater role in drug discovery and development. The challenge for biomarkers is to allow earlier, more robust drug safety and efficacy measurements. Their role in drug development will continue to grow for the foreseeable future. For biomarkers to assume their rightful role, greater understanding of the mechanism of disease progression and therapeutic intervention is needed. In addition, greater understanding of the requirements for biomarker selection and validation, biomarker assay method validation and application, and clinical endpoint validation and application is needed. Biomarkers need to be taken into account while the therapeutic target is still being identified and the concept is being formulated. Biomarkers need to be incorporated into a continuous cycle that takes what is learned from the discovery and development of one series of biomarkers and translates it into the next series of biomarkers. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application, using such techniques as pharmacoepidemiology, pharmacogenetics, pharmacogenomics, and functional proteomics; bioanalytical method development and validation; disease process and therapeutic intervention assessments; and pharmacokinetic/pharmacodynamic modeling and simulation to improve and refine drug development. The potential for biomarkers in medicine and drug development will be limited by the least effective component of the processes. The team approach will minimize the potential for the least effective component to be fatal to the rest of the process. As scientific/regulatory foundations for biomarkers in medicine and drug development begin to be established, successes and applications will need to be effectively communicated with all of the stakeholders, including not only internal and external drug developers and regulators but also the medical community, to ensure that biomarkers are totally integrated into drug discovery and development as well as the practice of medicine.

Biomarkers↗

PubMed2004

CD155/PVR plays a key role in cell motility during tumor cell invasion and migration.

BACKGROUND: Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. METHODS: We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. RESULTS: Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and alphav-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. CONCLUSION: These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis.

Cell Line, Tumor↗

PubMed2004

Mapping phosphorylation sites: a new strategy based on the use of isotopically labelled DTT and mass spectrometry.

Phosphoproteomics, nowadays, represents a front line in functional proteomics as testified by the number of papers recently appearing in the literature. In an attempt to improve and simplify the methods so far suggested we have set up a simple isotope-coded approach to label and quantitate phospho-Ser/-Thr residues in protein mixtures. First of all, after appropriate oxidation of cysteine/cystine residues followed by tryptic hydrolysis, we have optimised and simplified the beta-elimination reaction to get the corresponding alkene moiety from the phosphate esters. This was achieved by (a) separating the elimination reaction from the addition reaction, (b) the use of Ba(OH)(2) as alkali reagent and (c) its further elimination by the simple addition of solid CO(2) to the peptide mixture. The Michael reaction was then performed, after the removal of BaCO(3) by centrifugation, by adding dithiothreitol (DTT) to the peptide mixture. Finally, the direct purification of the modified phosphopeptides was performed on a thiol-sepharose column. The availability of fully deuterated DTT, introducing a 6 Da difference with respect to the non-deuterated species, allows quantitation of the differential extent of signalling modification when analysed by matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) and liquid chromatography/mass spectrometry. The entire procedure has been set up by using bovine alpha-casein, and resulted in the identification of all the phosphorylated tryptic peptides, including the tetraphosphorylated peptides, which escaped all previously reported procedures

Amino Acid Sequence↗

PubMed2004

Separation and identification of photosynthetic antenna membrane proteins by high- performance liquid chromatography electrospray ionization mass spectrometry.

Functional proteomics of membrane proteins is an important tool for the understanding of protein networks in biological membranes. Nevertheless, structural studies on this part of the proteome are limited. The present review attempts to cover the vast array of methods that have appeared in the last few years for separation and identification of photosynthetic proteins of thylakoid membranes present in chloroplasts, a good model for setting up analytical methods suitable for membrane proteins. The two major methods for the separation of thylakoid membrane proteins are gel electrophoresis and liquid chromatography. Isoelectric focusing in a first dimension followed by denaturing sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) in a second dimension is an effective way to resolve large numbers of soluble and peripheral membrane proteins. However, it is not applicable for isolation of native protein complexes or for the separation of highly hydrophobic membrane proteins. High-performance liquid chromatography (HPLC), on the other hand, is highly suitable for any type of membrane protein separation due to its compatibility with detergents that are necessary to keep the hydrophobic proteins in solution. With regard to the identification of the separated proteins, several methods are available, including immunological and mass spectrometric methods. Besides immunological identification, peptide mass fingerprinting, peptide fragment fingerprinting or intact molecular mass determination by electrospray ionization mass spectrometry (ESI-MS) or matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) have been shown to be very sensitive and effective. In particular, identification of proteins by their intact molecular mass is advantageous for the investigation of numerous biological problems, because it is rapid and reflects the full sequence of the protein and all its posttranslational modifications. However, intact molecular mass determinations of gel-separated membrane proteins are hampered due to the difficulties in extracting the hydrophobic proteins from the gel, whereas HPLC on-line interfaced with ESI-MS enables the rapid and accurate determination of intact molecular masses and consequently an unequivocal protein identification. This strategy can be viewed as a multidimensional separation technique distinguishing between hydrophobicity in the first dimension and between different mass-to-charge ratios in the second dimension, allowing the separation and identification even of isomeric forms.

Chromatography, High Pressure Liquid↗

PubMed2005

Rrp15p, a novel component of pre-ribosomal particles required for 60S ribosome subunit maturation.

In eukaryotes ribosome biogenesis required that rRNAs primary transcripts are assembled in pre-ribosomal particles and processed. Protein factors and pre-ribosomal complexes involved in this complex pathway are not completely depicted. The essential ORF YPR143W encodes in yeast for an uncharacterized protein product, named here Rrp15p. Cellular function of Rrp15p has not so far defined even if nucleolar location was referred. With the aim to define the possible role of this orphan gene, we performed TAP-tagging of Rrp15p and investigated its molecular association with known pre-ribosomal complexes. Comparative sucrose gradient sedimentation analyses of yeast lysates expressing the TAP-tagged Rrp15p, strongly indicated that this protein is a component of the pre-60S particles. Northern hybridization, primer extension and functional proteomics on TAP-affinity isolated complexes proved that Rrp15p predominately associated with pre-rRNAs and proteins previously characterized as components of early pre-60S ribosomal particles. Finally, depletion of Rrp15p inhibited the accumulation of 27S and 7S pre-rRNAs and 5.8S and 25S mature rRNA. These results provide the first indication that Rrp15p is a novel factor involved in the early maturation steps of the 60S subunits. Moreover, the identification of the protein kinase CK2 in the Rrp15p-containing pre-ribosomal particles here reported, sustains the link between ribosome synthesis and cell cycle progression.

Amino Acid Sequence↗

PubMed2003

Virtual screening on natural products for discovering active compounds and target information.

Natural products, containing inherently large-scale structural diversity than synthetic compounds, have been the major resources of bioactive agents and will continually play as protagonists for discovering new drugs. However, how to access this diverse chemical space efficiently and effectively is an exciting challenge for medicinal chemists and pharmacologists. While virtual screening, which has shown a great promise in drug discovery, will play an important role in digging out lead (active) compounds from natural products. This review focuses on the strategy of virtual screening based on molecular docking and, with successful examples from our laboratory, illustrates the efficiency of virtual screening in discovering active compounds from natural products. On the other hand, the sequencing of the human genome and numerous pathogen genomes has resulted in an unprecedented opportunity for discovering potential new drug targets. Chemogenomics has appeared as a new technology to initiate target discovery by using active compounds as probes to characterize proteome functions. Natural products are the ideal probes for such research. Binding affinity fingerprint is a powerful chemogenomic descriptor to characterize both small molecules and pharmacologically relevant proteins. Therefore, this review also discusses binding affinity fingerprint strategy for identifying target information from the genomic data by using natural products as the probes.

Biological Products↗

PubMed2006

A method for rapid protease substrate evaluation and optimization.

We have developed a high throughput assay for the measurement of protease activity in solution. This technology will accelerate research in functional proteomics and enable biologists to streamline protease substrate evaluation and optimization. The peptide sequences that serve as protease substrates in this assay are labeled on the carboxy terminus with a biotin moiety and a fluorescent tag is attached to the amino terminus. Protease cleavage causes the biotin containing fragment to be detached from the labeled peptide fragment. Following the protease treatment, all biotin containing species (uncleaved substrates and the cleaved carboxy terminal fragment of the substrate) are removed by incubation with streptavidin beads. The cleaved fluorescently labeled amino terminal part of the substrate remains in solution. The measured fluorescence intensity of the solution is directly proportional to the activity of the protease. This assay was validated using trypsin, chymotrypsin, caspase-3, subtilisin-A, enterokinase and tobacco etch virus protease.

Biological Assay↗

PubMed2001

Conquering antibacterial resistance.

Application and combination of proteomics, functional genomics, bioinformatics, combinatorial chemistry and high-throughput screening enable scientists to identify new molecular targets and novel chemical structures for fighting bacterial infections. At the same time, it is doubtful that these new approaches will ablate the problem of resistance, because the unique and inherent properties of bacteria ensure that the emergence of resistance is inevitable. At the Society for Medicines Research meeting Conquering Antibacterial Resistance held September 28, 2000, members discussed the causes of and potential solutions to this increasing and accumulating threat.

Journal Article↗

PubMed2002

APBioNet: the Asia-Pacific regional consortium for bioinformatics.

Bioinformatics and computational biology, along with the related fields of genomics, proteomics, functional genomics and systems biology are new wave scientific disciplines that harness composite computational power across networks to advance biological knowledge at the most basic level and to direct traditional laboratory-based research efforts in the biomedical sciences. 'Fostering the growth of bioinformatics and allied disciplines in the Asia-Pacific region' is the motto of the first regional bioinformatics society, the Asia-Pacific Bioinformatics Network (APBioNet). APBioNet addresses the issues of hardware, software, databases and networks pertaining to bioinformatics, with the additional layer of pertinent education, training and research. Recent milestones achieved include hosting an international bioinformatics symposium in Asia and setting up large-scale regional grid-computing projects.

Asia↗

PubMed2004

[A new approach to protein phosphorylation modification analysis for neuron].

OBJECTIVE: To develop a new method for analysis of protein phosphorylation modification in cultured neuron. METHODS: Cultured neurons were pre-incubated in DMEM without sodium phosphate for 15 min to deplete the metabolic pools. Neurons were then labeled with [32P] orthophosphate (2.78 x 10(6) Bq/ml) for 1.5 h and stimulated by either insulin (100 nmol/L), EGF (20 nm/L) or saline for 0, 5, 20, 60, 120 min. Reactions were terminated by freezing neurons in liquid nitrogen prior to the solubilizing of them in a lysis buffer containing 8 mol/L urea, 4% CHAPS, 2% Bio-lyte, pH 3-10, 2 mmol/L TBP. Protein concentrations were determined with Bio-Rad DC Protein Assay kit. The 32P-labled lysates isoelectrically focused on IPG Drystrip pH 3-10 or pH 4-7 Linear gels were subsequently separated in second-dimensional SDS-PAGE. The dried gel was autoradiographed for 5 days at -70 degrees C with an intensifying screen. Alternatively, the separated proteins were visualized by Coomassie Brilliant Blue (CBB) R250 straining. RESULTS: Autoradiography of the 2-DE-separated 32P-laebled neuron lysates revealed around 100 phosphoproteins. This phosphoprotein pattern was stable at 1.5 h after radiolabelling and did not vary significantly for up to 4 h further incubation in the absence of hormone. Most of the major proteins which are phosphorylated in response to insulin or EGF migrated with pH 4.6-6.5 and MW 20000-130000. Insulin and EGF induced similar but not identical patterns of protein phosphoryltion in neurons. Only a few phosphoproteins were abundant enough to be visualized by CBB straining, suggesting that abundance of these phosphoproteins is extremely low. Responses to both isulin and EGF are marked by more increased labeling of the constitutive phosphoproteins, compared with the appearance of new phosphoproteins. CONCLUSION: This approach co-application of 32P-labeled with 2-DE separation and autoradiography has proven to be specific and sensitive in phosphoprotein analysis for neuron. It was valuable in functional proteomic analysis for protein phosphorylation modification during cellular signal transduction.

Animals↗

PubMed2004

Bacterial degradation of aromatic pollutants: a paradigm of metabolic versatility.

Although most organisms have detoxification abilities (i.e mineralization, transformation and/or immobilization of pollutants), microorganisms, particularly bacteria, play a crucial role in biogeochemical cycles and in sustainable development of the biosphere. Next to glucosyl residues, the benzene ring is the most widely distributed unit of chemical structure in nature, and many of the aromatic compounds are major environmental pollutants. Bacteria have developed strategies for obtaining energy from virtually every compound under oxic or anoxic conditions (using alternative final electron acceptors such as nitrate, sulfate, and ferric ions). Clusters of genes coding for the catabolism of aromatic compounds are usually found in mobile genetic elements, such as transposons and plasmids, which facilitate their horizontal gene transfer and, therefore, the rapid adaptation of microorganisms to new pollutants. A successful strategy for in situ bioremediation has been the combination, in a single bacterial strain or in a syntrophic bacterial consortium, of different degrading abilities with genetic traits that provide selective advantages in a given environment. The advent of high-throughput methods for DNA sequencing and analysis of gene expression (genomics) and function (proteomics), as well as advances in modelling microbial metabolism in silico, provide a global, rational approach to unravel the largely unexplored potentials of microorganisms in biotechnological processes thereby facilitating sustainable development.

Bacteria↗

PubMed2005

Breast cancer cell lines grown in vivo: what goes in isn't always the same as what comes out.

Human cell lines constitute powerful model systems for the in vitro and in vivo analysis of cancer. Cancer lines that are invasive in culture often form tumors and metastases in immune deficient mice. It is generally assumed that, in such cases, the principal population of cancer cells in culture corresponds to the tumor-forming cells in vivo. Here, we high-light a recent functional proteomics investigation that suggests the contrary. In this study, cells derived from orthotopic xenograft tumors formed by the invasive breast cancer line MDA-MB-231 were found to exhibit profound differences in their enzyme activity profiles and increased tumor growth rates and metastasis when compared to the parental line. These findings suggest that the in vivo microenvironment of the mouse mammary fat pad cultivates the growth of human breast cancer cells with elevated tumorigenic properties. Characterization of the unique molecular properties of these tumor-forming cells may reveal new strategies for the diagnosis and treatment of breast cancer.

Animals↗

PubMed2006

VP-16 (etoposide) and calphostin C trigger different nuclear but akin cytoplasmic patterns of changes in the distribution and activity of protein kinase C-betaI in polyomavirus-transformed pyF111 rat fibroblasts.

Protein kinase C (PKC) isoforms regulate cell proliferation and apoptosis. Since the PKC isoenzyme complement varies considerably from cell type to cell type, a PKC's responsiveness to an apoptogenic challenge must be defined for both the type of apoptogen and the type of cell. We have already reported that the changes in the distribution and activity of PKC-delta in apoptosing polyomavirus-infected/transformed Fischer rat embryo pyF111 fibroblasts depend on the type of apoptogen. Here, we show that this is also true for PKC-betaI in pyF111 cells treated with the slow DNA-damaging VP-16 (etoposide) or the fast-acting (in the cytoplasm) calphostin C. These apoptogens caused quite different shifts of the PKC-betaI level and activity in the nuclear membrane (NM) and nucleoplasm (NP), but corresponding changes in the cytosol (CS) and cytoplasmic particulate (CP) fractions. The hefty translocation of PKC-betaI onto the CP fraction and its increased activity there suggest the possible triggering of a cytochrome c/caspase-mediated apoptosis-inducing mechanism common to both agents. The present results are a necessary lead-up to functional proteomic analyses aimed at identifying the molecules forming the local PKC-betaI signalling modules under different conditions.

Animals↗

PubMed2006

Down-regulation of 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A protein expression in oral squamous cell carcinoma.

Functional proteomics is a useful method to explore changes in protein expression in human diseases, including carcinomas. To identify tumor-associated proteins as biomarkers or molecular targets of human oral squamous cell carcinomas (OSCCs), we performed two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Comparison of the protein expression profiles of OSCC cell lines and normal oral keratinocytes identified six proteins with markedly different expression levels. Of the six proteins, we found a 1D-myo-inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) protein that was down-regulated in OSCC cell lines. ITPKA phosphorylates inositol 1,4,5-trisphosphate, which regulates the calcium (Ca2+) level within the cell by releasing Ca2+ from intracellular stores, and is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling. Western blots revealed dramatically down-regulated ITPKA expression in all OSCC cell lines examined. Real-time quantitative reverse transcriptase-polymerase chain reaction showed down-regulated ITPKA mRNA expression in nine of 12 (75%) OSCC cell lines. Immunohistochemistry analysis showed that 40 of 100 OSCC clinical samples had a significant decrease in ITPKA. Poorly differentiated tumors showed significantly lower immunoreactivity of the protein compared to well- and moderately-differentiated tumors. These data suggest that ITPKA may be related to carcinogenesis by the modulation of inositol polyphosphates and Ca2+ homeostasis and that ITPKA may be a potential novel molecular target, biomarker, parameter, or all of these of cellular differentiation and of intracellular Ca2+ homeostatic characteristics in clinical medicine.

Aged↗

PubMed2007

Triplet repeat instability correlates with dinucleotide instability in primary breast cancer.

The expansion of triplet repeat microsatellite sequences is the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders. This finding prompted us to study these sequences in primary breast cancer in which there is evidence of genetic anticipation. We used a PCR/silver stain method to determine whether triplet-repeat instability (TRI) was present in DNA from malignant breast tumors, and analyzed microsatellite instability (MSI) in triplets SCA1, SCA2, SCA3, SCA6, HD, DRPLA and X25-GAA. We studied 54 consecutive primary breast cancers previously analyzed for dinucleotide instability (DI) at 9 loci. Microsatellite instability (TRI and/or DI) was found in 28/54 (52%) cases, ranging from 0 to 56% in each patient. Dinucleotide instability occurred at > or =2 loci in 19/54 (35%) cases and TRI in 6/54 (11%). Considering single locus instability, we found DI in 26/54 (48%) tumors and TRI in 13/54 (24%). Triplets DRPLA and X25-GAA were most frequently unstable (14% of cases); SCA2 instability was not detected. Interestingly, most tumors with TRI had DI (11/13, 85%). There was a correlation between TRI and DI in the same tumor (42 vs 7% in DI+ and DI- tumors respectively, p=0.0028). Furthermore, TRI appears more frequently associated with lymph node metastases and more advanced clinical stages and more frequent in patients <50 years old, with positive steroidal hormone receptor status, positive p185 and negative p53. These findings are of interest because they demonstrate a relationship between TRI and the clinicopathological characteristics of cancer aggressiveness. Triplet repeat alterations can interfere with gene expression and proteomic functions, which suggests they can play a role in the neoplastic progression of mammary cells. Furthermore, the association of TRI and DI in the same tumor suggests that alterations in the DNA repair gene could culminate in selective phenotypes and breast cancer progression in a considerable number of patients.

Adult↗

PubMed2006

[Preparation of a concanavalin A immobilized affinity column and its application in the structural analysis of ribonuclease B].

The research on glycoproteomes represents an interesting field in the functional proteomics research. Affinity chromatography and mass spectrometry are powerful techniques that are used for gaining valuable information on glycoproteomes because glycoproteins and their unusual forms resulting from protein glycosylation can be important indicators of several diseases. In this study, the concanavalin A (Con A) immobilized silica packing was prepared and used for the separation of glycoprotein and glycopeptides. A very low, non-specific adsorption on the Con A affinity column was demonstrated by mass recovery of bovine serum albumin at more than 98.5%. The effect of concentration of methyl-alpha-D-mannopyranoside (alpha-Me-D-Man) in the mobile phase and the effect of flow rate on the retention behavior of ribonuclease B (RNase B) were also investigated. The standard glycoprotein RNase B was separated under optimized conditions using 0.2 mol/L alpha-Me-D-Man in the mobile phase at a flow rate of 0.5 mL/min. Meanwhile, the oligosaccharides and glycopeptides were enriched using a Con A column after digestion of the purified RNase B with peptide-N-glycosidase F (PNGase F) and trypsin. The structure of N-linked glycan and the rate and the site of glycosylation of RNase B were determined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). Glycoproteins and glycopeptides in human serum and digest solution could be separated by this method. The results showed that this method is rapid and sensitive for the purification and characterization of glycoproteins and glycopeptides.

Animals↗

PubMed2002

High-density synthetic peptide microarrays: emerging tools for functional genomics and proteomics.

New approaches for manufacturing and application of peptide arrays on planar surfaces are emerging, thereby opening advanced opportunities to probe the expression and function of the proteome. In complementing DNA and protein array analyses, peptide fragment screening directly addresses functional protein interaction sites, leading to a detailed insight into the discovered molecular recognition events, placing them in the context of the whole genome, and even allowing rapid determination of the chemical nature of these interactions. This information can then be transferred into powerful small peptide tools that interfere with these interactions in vivo and help to link targets with phenotypes. With the spreading of new peptide array tools, peptide screening will extend its impact on modern genome-driven molecular biology. This will advance the systematic discovery and validation of new pharmaceutical targets as well as the development of potent molecular diagnostics for medical and ecological monitoring.

Animals↗