Kin Israel Notarte

Background: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. This study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting in silico key sites in the structures of SARS-CoV-2 nsps. One hundred four anti-HIV phytochemicals were subjected to molecular docking with nsp3, 5, 10, 12, 13, 15, and 16. Top compounds in complex with the nsps were investigated further through molecular dynamics. The drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top compounds were also predicted using SwissADME. Their toxicity was likewise determined using OSIRIS Property Explorer. Results: Among the top-scoring compounds, the polyphenolic functionalized natural products comprised of biflavones 1, 4, 11, 13, 14, 15; ellagitannin 9; and bisisoquinoline alkaloid 19 were multi-targeting and exhibited strongest binding affinities to at least two nsps (binding energy = − 7.7 to − 10.8 kcal/mol). The top ligands were stable in complex with their target nsps as determined by molecular dynamics. Several top-binding compounds were computationally druggable, showed good gastrointestinal absorptive property, and were also predicted to be non-toxic. Conclusions: Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 non-structural proteins 3, 5, 10, 12, 13, 15, and 16. Our results highlight the importance of polyhydroxylated aromatic substructures for effective attachment in the binding/catalytic sites of nsps involved in post-translational mechanism pathways. As such with the nsps playing vital roles in viral pathogenesis, our findings provide inspiration for the design and discovery of novel anti-COVID-19 drug prototypes.

Inhibition of the major cyclic adenosine monophosphate-metabolizing enzyme PDE4 has shown potential for the discovery of drugs for cancer, inflammation, and neurodegenerative disorders such as Alzheimer’s disease. As a springboard to explore new anti-cancer and anti-Alzheimer’s chemical prototypes from rare Annonaceae species, the present study evaluated anti-PDE4B along with antiproliferative and anti-cholinesterase activities of the extracts of the Philippine endemic species Uvaria alba using in vitro assays and framed the resulting biological significance through computational binding and reactivity-based experiments. Thus, the PDE4 B2B-inhibiting dichloromethane sub-extract (UaD) of U. alba elicited antiproliferative activity against chronic myelogenous leukemia (K-562) and cytostatic effects against human cervical cancer (HeLa). The extract also profoundly inhibited acetylcholinesterase (AChE), an enzyme involved in the progression of neurodegenerative diseases. Chemical profiling analysis of the bioactive extract identified 18 putative secondary metabolites. Molecular docking and molecular dynamics simulations showed strong free energy binding mechanisms and dynamic stability at 50-ns simulations in the catalytic domains of PDE4 B2B, ubiquitin-specific peptidase 14, and Kelch-like ECH-associated protein 1 (KEAP-1 Kelch domain) for the benzylated dihydroflavone dichamanetin (16), and of an AChE and KEAP-1 BTB domain for 3-(3,4-dihydroxybenzyl)-3′,4′,6-trihydroxy-2,4-dimethoxychalcone (8) and grandifloracin (15), respectively. Density functional theory calculations to demonstrate Michael addition reaction of the most electrophilic metabolite and kinetically stable grandifloracin (15) with Cys151 of the KEAP-1 BTB domain illustrated favorable formation of a β-addition adduct. The top-ranked compounds also conferred favorable in silico pharmacokinetic properties.

Purpose: Bacillus megaterium strain BHS1, isolated from an alkaline water sample taken from Mavi Gölü (Blue Lake, Turkey), can grow on minimal medium containing 2,2-dichloropropionic acid. We characterized this bacterium at the genomic level. Methods: The HiSeq platform was used to carry out genome sequencing, de novo assembly, and scaffolding with strain BHS1. Next, genome data were analyzed to demarcate DNA regions containing protein-coding genes and determine the function of certain BHS1 genes. Finally, results from a colorimetric chloride ion–release assay demonstrated that strain BHS1 produces dehalogenase. Results: De novo assembly of the BHS1 genomic sequence revealed a genome size of ~ 5.37 Mb with an average G+C content of 38%. The predicted nuclear genome harbors 5509 protein-coding genes, 1353 tRNA genes, 67 rRNA genes, and 6 non-coding (mRNA) genes. Genomic mapping of strain BHS1 revealed its amenability to synthesize two families of dehalogenases (Cof-type haloacid dehalogenase IIB family hydrolase and haloacid dehalogenase type II), suggesting that these enzymes can participate in the catabolism of halogenated organic acids. The mapping identified seven Na ⁺ /H ⁺ antiporter subunits that are vital for adaptation of the bacterium to an alkaline environment. Apart from a pairwise analysis to the well-established L-2-haloacid dehalogenases, whole-cell analysis strongly suggested that the haloacid dehalogenase type II might act stereospecifically on L-2-chloropropionic acid, D,L-2-chloropropionic acid, and 2,2-dichloropropionic acid. Whole-cell studies confirmed the utilization of these three substrates and the gene’s role in dehalogenation. Conclusions: To our knowledge, this is the first report of the full genome sequence for strain BHS1, which enabled the characterization of selected genes having specific metabolic activities and their roles in the biodegradation of halogenated compounds.

At the start of the pandemic, the Philippines had to send swab samples to the Victorian Infectious Diseases Reference Laboratory in Melbourne, Australia for COVID-19 confirmation. With the increasing number of suspected cases needing confirmatory diagnostic testing, there was a demand to rapidly expand the capacity for widescale testing. Remarkably, within 200 days from announcement of the first confirmed COVID-19 case in the Philippines in January 30, 2020, the country has been able to expand its testing capacity from one national reference laboratory, the Research Institute for Tropical Medicine (RITM), to more than 100 licensed reverse transcription-polymerase chain reaction (RT-PCR) and cartridge-based PCR laboratories across the country. Due to the shortage of a trained clinical laboratory workforce, diagnostic centers are forced to hire additional personnel who have limited experience and technical knowledge and skills of molecular assays, especially in processing specimens, interpreting the results, identifying errors, and troubleshooting, in order to meet the demand of increased testing. Thus, the vulnerability to diagnostic errors, including cross-contamination, is increased and with the tendency for generating false-positive results that can compromise the health of the patient and disrupt the efficacy of public health policies and public health response, surveillance programs, and restrictive measures for containing the outbreak. Hence, this review article aims to present the different sources of contamination in the laboratory setting where RT-PCR assays are conducted, as well as provide efficient, effective and feasible solutions to address these issues, most especially in low-and middle-income countries (LMICs) like the Philippines.

Coal is one of the most commonly utilized fossil fuel for energy production across the globe leading to higher amount of emission of sulfur dioxide (SO2) in the atmosphere. Combustion of coal containing higher contents of sulfur is a major factor responsible for acid rain and associated environmental degradation. The currently used physico-chemical approaches for removal of sulfur from coal are expensive, toxic in nature and inappropriate for different types of coal. The application of microbial resources for removal of sulfur from coal is an ecofriendly technique and could be successfully employed at industrial scale after laboratory scale process optimization. The process of sulfur removal by microbes is carried out by enzymes and is considerably influenced by different factors including pH, temperature, nutrient composition, shaking or standing condition, coal types and most importantly type of microorganisms used. Different bacteria and fungi isolated from coal contaminated site as well as non-contaminated site exhibiting sulfur removal potential can be used as next generation tool for development of clean coal technology. Furthermore, through the application of modern genetic manipulation techniques, enhanced expression of genes responsible for desulfurization can be performed in order to accelerate the process of sulfur removal from coal. The present chapter is prepared with an aim to discuss the diverse microbial population participating in desulfurization, their efficiency, mechanism of sulfur elimination, role of important environmental factors along with possible applications and challenges in industrial scale sulfur removal.

The revolution in metal industries worldwide and anthropogenic activities has added significantly large amount of metals into the natural environment leading to hazardous impact on diverse organisms. Remediation of metal contaminants using physicochemical techniques is expensive, ecologically unsafe, and secondary product generating calling for the judicious application of biological agents. The microbes inhabiting in metal-polluted soil and water, during the long course of evolution, have evolved the intricate mechanism of metal oxidation by employing cellular processes. The potential ability of microorganisms in oxidizing metals also possesses advantageous application in extraction of heavy metals, thereby serving as a foundation for contaminant treatment. Sometimes, the metals used by these microbes are utilized as electron donor to derive energy during the respiratory processes. For instance, under natural environmental conditions ferrous form of iron is rapidly oxidized to ferric iron and offers a strong substrate for its oxidation. Since the electrode potential of ferrous/ferric under acidic condition is high enough, only oxygen molecule with the sufficient availability of protons can be preferred as electron acceptor and subsequent formation of water molecule. Therefore ferrous iron can serve as electron donor only under aerobic environment. The process of iron oxidation occurs spontaneously if the pH is not very acidic. However, under strong acidic conditions, acidophilic microbes, especially bacteria, catalyze the oxidation of ferrous iron eventually resulting into formation of biogenic iron oxides. The oxidation of manganese [Mn(II)] to produce insoluble manganese oxides [Mn(III) and Mn(IV)] is also evident in different bacterial and fungal species directing their utilization for toxic substance remediation. Microbially facilitated Mn(II) oxidation under circumneutral environment has been recorded multifold greater as compared to abiotically catalyzed processes and thereby indicates the promising potential in generation of various oxides and hydroxides under aqueous and terrestrial environment. The formation of insoluble manganese oxides has environmentally important contribution in regulating the biogeochemical cycling of multiple elements occurring in the natural ecosystem. Moreover, biogenic manganese oxides can sequester organic as well as inorganic metal contaminants of hazardous nature. The arsenite [As(III)]-oxidizing bacteria are mostly documented in arsenic-enriched water and soil samples. The conversion of arsenite to arsenate [As(V)] facilitated by aio genes is considered as a mechanism of detoxification. Oxidative transformation of As(III) to more adsorptive As(V) by microbiological activities is quite helpful in treatment of arsenic-laden water and wastewater. The process of As(III) oxidation linked with reduction of nitrate causing reduced bioavailability of metalloid has also been demonstrated as a mechanism of alleviation of arsenic toxicity. The presence of arsenite-oxidizing microorganism in aqueous and terrestrial environment is intimately linked with immobilization.

Background: Undergraduate researches in universities are potential sources of useful data in medicinal plant research. In higher education institutions, many of these manuscripts remain untapped and inaccessible to researchers and scientists. If widely utilized, these can contribute in the growth of knowledge on medicinal plants. Objectives: This article aimed to catalogue the medicinal plant researches of the Bicol University –Department of Biology from 1991 to 2019, highlight significant developments, trends, and responsiveness of the research, and recommend policies to improve medicinal plant research in the next decade. Methodology: A complete list of undergraduate research titles was obtained and analyzed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) process. Categorization of researches included the medicinal plants studied, year of study, and the biological assays conducted. The final list included two things: researches that utilized medicinal plants and those researches which tested the biological and medicinal properties of plants. Results were presented in percentages. Results: To date, 18.72% of the 865 thesis titles archived in the department are medicinal plant researches and majority of which focused on antimicrobial and toxicity studies. There were 52 plant families, 99 genera, and 114 plant species investigated. Leguminosae and Asteraceae were the most studied plant families. The years 2011-2019 were the most fruitful in terms of research completed. Conclusion: Undergraduate researches can provide vital information on medicinal plants studies, especially on an institutional and regional level. It is recommended that medicinal plants research be included as a thematic area among higher education institutions, and that policies be implemented to support publication of researches.

The RAD51 gene encodes the protein that plays a central role in the repair of DNA double-strand breaks through the homologous recombination pathway. Association of RAD51 single nucleotide genetic polymorphism (SNP) with the development of cancer has been observed to be tumor site- and race-specific. Thus, this study aimed to determine the potential association between RAD51 135G>C SNP and breast cancer among selected Filipinos. Patients with histologically confirmed breast cancer (n=60) seen at the University of Santo Tomas Hospital (Manila) were age- and sex-matched with clinically healthy controls (n=60). Genomic DNA was extracted from the blood of participants and analyzed for RAD51 genotype by polymerase chain reaction-restriction enzyme fragment length polymorphism (PCR-RFLP). A significantly higher incidence of RAD51 C/C genotype was seen among the cases than the controls (p<0.05). The more common G/C genotype was not associated with breast cancer development, while the recessive less common C/C genotype was observed to potentially increase the risk. However, passive smokers carrying the RAD51 G/C genotype had significantly increased chance of developing breast cancer. RAD51 G/C genotype even when combined with other established risk factors like alcohol use, active smoking, and family history were not associated with breast cancer.

Fungal endophytes reside within tissues or between cells of living plants. These fungal endophytes protect their hosts through the production of secondary metabolites that can deter pathogens and herbivores. The continuous search for new drugs brought about by the reemergence of infectious diseases and the rise of antimicrobial resistance and cancer cases has led natural product researchers to tap these fungal endophytes as potential sources of biologically active compounds. This is best exemplified by the discovery of the anticancer drug, taxol, from fungal endophytes associated with the Pacific yew Taxus. In this paper, we highlighted studies that documented the diversity and biological activities of fungal endophytes associated with terrestrial plants, mangroves, macroalgae, and seagrasses collected from Indonesia, the Philippines, and other countries. It is estimated that Indonesia is home to 10% of the world’s known plant species, while the Philippines has 5% of the world’s flora and about 820 species of macroalgae. These represent vast hosts for the isolation of many potentially novel fungal endophytes. This chapter therefore serves as a springboard for further exploration of plant- and seaweed-associated fungi in the Southeast Asian region for drug discovery programs.

Fungi associated with mangroves are untapped sources of bioactive secondary metabolites. In this study, 628 mangrove leaf endophytic fungi (MLEF) were recorded from 19 mangrove hosts collected from the provinces of Zambales, Batangas, Cavite, and Quezon in Luzon Island, Philippines. The MLEF morphospecies were identified as belonging to the genera Aspergillus, Cladosporium, Colletotrichum, Fusarium, Nigrospora, Penicillium, Pestalotiopsis, Phialophora, and Trichoderma. Screening revealed that the MLEF crude culture extracts were promisingly potent against the gram-positive bacteria Staphylococcus aureus and Micrococcus luteus (ZOI > 19 mm) with no or partial activity against the gram-negative bacteria Klebsiella oxytoca and Pseudomonas aeruginosa. Our findings showed that mangrove leaf endophytic fungi are potential sources of bioactive compounds.

Endophytic fungi are less explored in terms of their pharmacological applications, thus screening their phytochemical constituents and biological activities is of interest. In this study, the endophytic fungi Nigrospora and Colletotrichum spp. were isolated from the leaves of Uvaria grandiflora. The identity of the endophytes was established by molecular analysis of their fungal intergenic spacer. Biological screening showed that the fungal endophytes were most active against methicillin-resistant Staphylococcus aureus (MRSA), with the ethyl acetate broth extract of Colletotrichum sp. showing the biggest zone of inhibition (ZOI) for MRSA at 19 mm. For antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, the ethyl acetate broth extract of Nigrospora sp. elicited better antibacterial activity (ZOI > 11 mm). Antioxidant assessment using 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and superoxide scavenging assays showed that Nigrospora broth extract had the best free radical scavenging activity with an IC 50 of 3.92 mg/mL. Meanwhile, the broth extract from Colletotrichum sp. showed the best reducing power (RP 50 = 4.41 mg/mL) and superoxide scavenging activity (SC 50 = 0.78 mg/mL). Using Artermia salina for toxicity screening, both fungi were toxic having an LD 50 < 0.40 mg/mL. The culture broth extracts showed greater antibacterial, antioxidant, and cytotoxic activities compared to the mycelial extracts. Phytochemical screening of the broth extract revealed the presence of flavonoids, sterols, phenols, and terpenoids in both fungal extracts. Tannins and coumarins were specifically detected in Colletotrichum sp., while alkaloids and indole derivatives were detected only in the Nigrospora endophyte.

The occurrence and bioactivities of marine-derived fungi are evaluated in this paper. A total of 16 morphospecies of marine-derived fungi (MDF) were isolated from four host macroalgae and two seagrasses and identified as belonging to the genera Aspergillus, Fusarium, Paecilomyces, Penicillium, Sclerotinia, Thamnidium and Trichoderma, including five mycelia sterilia. Among these host organisms, the rhodophyte Laurencia intermedia harboured the highest number of isolated MDF. Selected MDF were then assayed and showed to inhibit Pseudomonas aeruginosa (8-19 mm zone of inhibition) and Staphylococcus aureus (6-19 mm zone of inhibition), and were cytotoxic against the brine shrimp Artemia salina nauplii (LD 50 : 201.56-948.37 µg mL-1). The screening led to the selection of five of the most bioactive morphospecies, all belonging to the genus Aspergillus. These marine aspergilli were subjected to β-tubulin gene sequence analysis for species identification, and to mass production in different culture media with or without marine salts, and screening of the crude culture extracts for their cytotoxic and trypanocidal activities. Aspergillus tubingensis cultivated in potato dextrose broth with marine salt proved to be the most cytotoxic against P388 (IC 50 : 1028 ng mL-1) and HeLa (IC 50 : 1301 ng mL-1) cancer cells. On the other hand, A. fumigatus cultivated in malt extract broth without marine salt was shown to be the most potent against Trypanosoma congolense (IC 50 : 298.18 ng mL-1). Our study therefore showed that salinity may influence the bioactivities of some species of MDF.

Taal Lake in the Philippines is a hotspot of diverse organisms but also faces a great threat from toxic agrochemical contaminants. Specifically, fungi are promising bioremediation agents to degrade harmful pollutants in the environment; hence the documentation and identification of these isolates are crucial. This study aims to determine the occurrence of fungi from submerged woods and surface waters in Taal Lake and assess their biodegradation potential against butachlor, a widely used pesticide in the Philippines. The isolated fungi were identified by using morphological and/or molecular methods, and the occurrence of each species was recorded. The ability of selected fungal isolates to degrade butachlor was also determined. A total of 28 morphospecies belonging to 20 fungal genera were recorded. Of these, eight fungal isolates grew on a chemically defined medium with up to 100 ppm butachlor. Two fungal isolates identified by molecular methods as Neodeightonia subglobosa IFM 63572 and Sclerotium hydrophilum IFM 63573 effectively utilized and potentially degraded butachlor as their sole carbon source as evident in the increased mycelial biomass (up to 0.449 g/L increase for N. subglobosa IFM 63572 and 0.214 g/L for S. hydrophilum IFM 63573) and decreased butachlor concentration (up to 94.68% reduction for N. subglobosa IFM 63572 and 89.64% for S. hydrophilum IFM 63573) after five days of incubation. Mycelial mat was more effective in degrading butachlor than mycelial balls. This study showed the presence of fungi from submerged woods and surface waters in Taal Lake and their potential application in the biodegradation of butachlor.

Malformin A1, a cyclic pentapeptide, was isolated from the marine-derived fungus Aspergillus tubingensis IFM 63452. The identity of the compound was established based on TOF-MS and 1 H NMR data. Malformin A1 exhibited trypanocidal activity against Trypanosoma congolense (IC50: 15.08 ng/mL). Interestingly, the compound was selective for T. congolense rendering a selectivity index value that ranged from 3.33 to 4.67. It also demonstrated cytotoxicity against HeLa (IC50: 50.15 ng/mL) and P388 (IC50: 70.38 ng/mL) cell lines. To further identify the possible mechanism of its cytotoxic effect, immunofluorescence staining was conducted to follow the epigenetic changes induced by the compound in the amino acid lysine of histone H3 and H4 in HeLa. The compound induced repressive levels of H3K27me3, H3K27ac and H4K5ac, and enhanced levels of H3K9me2, H3K9me3 and H4K16ac supporting the compound's chemotherapeutic potential.

Lichens are remarkable sources of bioactive secondary metabolites with potential chemotherapeutic properties. In this study, we evaluated the bioactivities of three corticolous lichens collected from Mount Banahaw in Quezon Province, Philippines. The lichens Parmotrema gardneri, Pannaria sp., and Canoparmelia aptata were extracted with acetone and assayed for cytotoxicity, and antibacterial and antioxidant activities. Results showed that the lichen extracts of P. gardneri, Pannaria sp. and C. aptata were either active (13-19 mm, zone of inhibition, ZOI) or partially active (10-12 mm ZOI) against Pseudomonas aeruginosa and Staphylococcus aureus. For the cytotoxicity assay, P. gardneri had the lowest inhibition concentration (IC 50) values of 12.29 and 20.24 µg/mL for the human gastric adenocarcinoma (AGS) and human lung carcinoma (A549), respectively. The same lichen extract rendered selectivity with IC 50 of 66.35 µg/mL against the normal Madin Darby Canine Kidney (MDCK) cell lines. The extracts yielded low radical scavenging activity of less than 40% and generated low amounts of FeSO 4 per milligram sample. Metabolic profiling detected the presence of protocetraric acid, usnic acid, zeorin, atranorin, chloroatranorin, and galbinic acid.

The ethanolic extract of the green alga Bornetella oligospora was sequentially fractionated
with hexane, chloroform, ethyl acetate, and water, and concentrated in vacuo. Different
concentrations of the fractions, ranging from 1 to 150 ppm, were prepared in 80% DMSO, and
tested on sea urchin embryos at cleavage and free-swimming hatching. The chloroform
concentrate at 150 ppm was the most potent in altering sea urchin embryonic development
among fractions. The rate of cleavage in embryos exposed to this fraction was significantly
inhibited. Moreover, anomalous morphological features were observed among treated embryos
with less apoptosis during cleavage and no cell arrest during blastulation and the free-swimming
larval stage. The motility of treated larvae was also slowed. All embryos exposed to 80%
DMSO control remained unaffected. Preliminary phytochemical analysis detected the presence
of terpenoids in the hexane, chloroform, and aqueous fractions. The ethyl acetate fraction
tested positive for saponins. The chloroform fraction clearly altered embryonic development,
which could be indicative of its potential chemotherapeutic activity since sea urchin embryos
are used as a pre-screen model for determining potential anticancer property.

: The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has been proven to be more severe than the previous coronavirus outbreaks due to the virus’ high transmissibility. With the emergence of new variants, this global phenomenon took on a more dramatic turn with many countries recently experiencing higher surges of confirmed cases and deaths. On top of this, the inadequacy of effective treatment options for COVID-19 aggravated the problem. As a way to address the unavailability of target-specific viral therapeutics, computational strategies have been employed to hasten and systematize the search. The objective of this review is to provide initial data highlighting the utility of polyphenols as potential prophylaxis or treatment for COVID-19. In particular, presented here are virtually screened polyphenolic compounds which showed potential as either antagonists to viral entry and host cell recognition through binding with various receptor-binding regions of SARS-CoV-2 spike protein or as inhibitors of viral replication and post-translational modifications through binding with essential SARS-CoV-2 non-structural proteins.

The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) Lambda variant rapidly diffused across Peru following its identification in December 2020, and had now spread worldwide. In this study, we investigated infodemiologic trends in symptomatology associated with the Coronavirus Disease 2019 (COVID-19) following the spread of SARS-CoV-2 Lambda variant in Peru, enabling infodemiologic surveillance of SARS-CoV-2 in regions with high circulation of this new variant. Weekly Google Trends scores were obtained for key symptom keywords between March 1st, 2020 and July 4th, 2021, whilst case count data were obtained from Peruvian Ministry of Health. Multiple time series linear regression was used to assess trends in each score series, using the week of December 27th as cutoff for emergence of the Lambda variant. The significance of such trends was tested for each time period, before and after the cutoff date. A total 2,075,484 confirmed SARS-CoV-2 infections in Peru in relation to ...

EBV is a direct causative agent in around 1.5% of all cancers. The oncogenic properties of EBV are related to its ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. The EBV latency program is required for the immortalization of infected B cells and involves the expression of non-coding RNAs (ncRNAs), including viral microRNAs. These ncRNAs have different functions that contribute to virus persistence in the asymptomatic host and to the development of EBV-associated cancers. In this review, we discuss the function and potential clinical utility of EBV microRNAs and other ncRNAs in EBV-associated malignancies. This review is not intended to be comprehensive, but rather to provide examples of the importance of ncRNAs.