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Ullah, H.

Publications and source records attributed to Ullah, H..

10 recordsLinked to original sources

Biosurfactant production under cold-saline stress is a strain specific trait independent from phylogeny and biosynthetic gene content

Abstract Microbial genomes code for far more biosynthetic potential than a single cell typically expresses, but the environmental and cellular controls that determine whether the latent capacity is realised remain poorly understood. Biosurfactants, surface-active metabolites proposed to aid survival in cold and saline habitats, exemplify this gap: capacity is often inferred from genomes or detected chemically, but is rarely linked to the specific conditions that stimulate its production in the same organisms. Here we combine whole-genome sequencing, untargeted LC-MS/MS metabolomics, and quantitative surface-tension assays across 25 bacterial isolates isolated from the cold, hypersaline Qaidam Basin (a terrestrial analogue for ancient Mars) and contrasting marine environments. We show that biosurfactant production is not a fixed lineage trait but a regulated, strain-specific response that emerges under combined cold and salt stress. This response is structured into three tiers: genomic capacity defines the accessible chemical space; the genomic complement of pathway-regulator genes tracks responsiveness; strain-level physiological state determines realised output. Regulatory-gene content, rather than biosynthetic-cluster count, predicted surfactant production across strains. Production was amplified by low temperature and high salinity and showed little phylogenetic signal, with near-clonal strains differing in their stress-response. These findings reshape biochemical adaptation in extreme environments as a problem of conditional activation, not only of genomic potential, but of cellular systems that permit its expression, which requires looking beyond biosynthetic-gene content to the cellular factors that determine whether that potential is expressed.

microbiology↗

Genome-resolved metagenomics reveals seasonally defined life strategies in hypersaline sediments

Abstract Background. Hypersaline sediments are long-standing models for microbial adaptation and are increasingly regarded as reservoirs of novel biosynthetic potential, including surface-active compounds. Inferences about biosurfactant production in such communities have rested largely on taxonomic affiliation, targeted single-gene surveys or metabolite detection, rather than on genome-resolved evidence that the pathways are encoded. The seasonal restructuring of these communities has also rarely been resolved at genome level. Results. We sequenced summer and winter sediments from the hyperarid Qaidam Basin on the northern Tibetan Plateau, recovering 44 metagenome-assembled genomes and 1,468 biosynthetic gene clusters from 2.98 Gbp of assembly. Evaporative and cryoconcentration processes raised winter porewater chloride by two to three orders of magnitude relative to summer. The community switched between osmoadaptation strategies. Summer sediments were dominated by salt-in haloarchaea with acidic proteomes and rhodopsin phototrophy, whereas winter sediments were dominated by salt-out bacteria with near-neutral proteomes and winter-enriched compatible-solute biosynthesis. The salt-in bacterium Salinibacter occupied the expected intermediate position, providing an internal control. The winter surface-active response was envelope-associated rather than secreted, comprising phospholipase-derived lysophospholipids, desaturase-mediated membrane remodelling, substitution of phospholipids by phosphorus-free ornithine and sulfoquinovosyl lipids, and capsular exopolysaccharide export. Dedicated secreted biosurfactant pathways were not detected. Of 69 NRPS clusters, only one carried the starter condensation domain diagnostic of lipopeptide assembly, and it matched no characterised reference. Profile-based, read-level and orthology-based searches independently recovered no complete lipopeptide, rhamnolipid or trehalolipid pathway. Apparent biosurfactant genes in 40 of 44 genomes resolved to housekeeping homologues upon domain verification, and an independent catalogue of 1,773 regional genomes reproduced the same absence. Conclusions. Surface activity in this hypersaline community is retained at the cell envelope rather than secreted, and dedicated biosurfactant biosynthesis is not a community-level trait. Because both taxonomic affiliation and gene-name annotation overestimate this capacity, genome-resolved verification is required before biosynthetic potential inferred from extreme environments is treated as real.

microbiology↗

Rapid Detection of Active Coronavirus Infection by Lateral Flow Test Strips: A New Approach to Distinguish Replicating Viruses from Non-Replicating Viruses

This manuscript describes the development of an alternative method to detect active coronavirus infection, which targets negative-sense RNA, a product of active viral replication. Few diagnostic methods are capable of discriminating between replicating and non-replicating viruses, complicating decisions related to quarantine and therapeutic interventions. We propose strand-specific nucleic acid diagnostics as a means of distinguishing between active and inactive RNA virus infections and prototype a CRISPR-based lateral flow assay that specifically detects replicating coronaviruses. Such a paradigm in diagnostics could guide more effective public health measures to curb the spread of SARS-CoV-2 and other single-stranded viruses.

microbiology↗

A New Approach for Active Coronavirus Infection Identification by Targeting the Negative RNA Strand- A Replacement for the Current Positive RNA-based qPCR Detection Method

This manuscript describes the development of an alternative method to detect active coronavirus infection, in light of the current COVID-19 pandemic caused by the SARS-CoV-2 virus. The pandemic, which was first identified in Wuhan, China in December 2019, has had a significant impact on global health as well as on the economy and daily life in the world. The current positive RNA-based detection systems are unable to discriminate between replicating and non-replicating viruses, complicating decisions related to quarantine and therapeutic interventions. The proposed method targets the negative strand of the virus and has the potential to effectively distinguish between active and inactive infections, which could provide a more accurate means of determining the spread of the virus and guide more effective public health measures during the current pandemic.

microbiology↗

Genotypic variation in tolerance to salinity in Pakistani okra (Abelmoschus esculentus L.) varieties as assessed at seed germination, seedling growth and biochemical characters

Salt stress is one of the major abiotic stresses that causes reduction in crops yield. Okra (Abelmoschus esculentus L.) is a high-value nutraceutical vegetable because its various parts are used for different purposes. This study was conducted to calculate the salt tolerance among thirteen okra varieties. Different salt (NaCl) levels: 0, 50, 75 and 100 mM were selected to measure the response of the okra varieties to stress. The experimental data showed that all varieties were affected by salt level with a differential variation in their stress response, demonstrating the presence of genetic variability. Five varieties: "NAYAB-F1", "Arka anamika", "MALAV-27", "Sarhad Green" and 051-F1 showed germination at all stress levels (0, 50, 75 and 100 mM), six varieties: "Feveeri Green", "Punjab Selection", "Local Multani", "Shehzadi", "Green Star" and "Hunza" showed germination at (0, 50 and 75 mM) and two: "Anmol" and "Sabz Pari" showed germination at (0 and 50 mM). As a result of salt stress, germination percentage (PG), leaf fresh and dry weight (LFW and LDW), shoot fresh and dry weight (SFW and SDW), root fresh and dry weight (RFW and RDW) were significantly reduced with increasing stress level. Based on the performance of variety to salt stress, five varieties were selected for biochemical analysis, concentrating on the determination of osmolytes. The values of sugar and proline were affected both by the varieties and salt levels. Variety "NAYAB-F1" showed higher sugar and proline content at all stress levels compared to varieties "Arka anamika", "MALAV-27", "051-F1" and Sarhad Green. Correspondingly, in the stressed seedling a decreasing trend in chlorophyll "a" and "b" were noted depending on the varieties and stress concentrations. After a series of experiment, it has been concluded that varieties "NAYAB-F1", "Arka anamika", "MALAV-27", "Sarhad Green" and "051-F1" were recommended as salt tolerant varieties and could be utilized in the breeding program of salt tolerant okra.

developmental biology↗

Meta-analysis of fecal metagenomes reveals global viral signatures and its diagnostic potential for colorectal cancer and adenoma

IntroductionGut microbiome plays an important role in maintaining human health. Although mounting evidence has revealed the critical function of the gut bacteriome in the progression of CRC, the contribution of gut viral community to CRC is rarely studied. ObjectivesThe present study aimed to reveal the gut virome signatures of colorectal adenoma patients and CRC patients and decipher the potential viral markers to build clinical predictive models for diagnosis. Methods1,282 available fecal metagenomes data from 9 published CRC studies were collected. A new virus database was constructed based on a reference-independent virome approach for further analysis. Viral markers were filtered by statistical methods and used to build machine learning models such as Random Forest and Least Absolute Shrinkage and Selection Operator (LASSO) to distinguish patients from controls. New fecal samples were collected to validate the generalization of predictive model. ResultsThe gut viral composition of CRC patients was drastically altered compared with healthy, as evidenced by changes in several Siphoviridae viruses and a reduction of Microviridae, whereas the virome variation in adenoma patients was relatively low. The viral markers contained the phages of Porphyromonas, Fusobacterium, Hungatella, and Ruminococcaceae. In 9 cohorts and independent validation cohorts, a random forest (RF) classifier and LASSO model got the optimal AUC 0.830 and 0.906, respectively. While the gut virome analysis of adenoma patients identified 88 differential viruses and achieved an optimal AUC of 0.772 for discriminating patients from controls. ConclusionOur findings demonstrate the distinctly different composition of gut virome between healthy controls and CRC patients, and highlight the potential of viral markers for clinical diagnosis.

microbiology↗

Crippled Coronavirus: 5'-PolyU targeted Oligo prevents development of infectious Virions

Current RNA viral pandemic of COVID-19 has been worsened by rapidly spreading viral variants. To inhibit mutation-based development of new escape variants, elements that are indispensable for the virus may be targeted. The 5-polyU tract of the antigenome offers one such target. Host cells do not harbor 5-polyU tracts on any of their transcripts, making the tract an attractive virus-specific target. We hypothesize that inhibiting the 5-polyU by complementary oligonucleotide can limit the use of the tract as template for virus to generate 3 polyA tails of RNA viruses. Here, we used a frameshift-inducing DNA oligonucleotide with 3 polyAs to target the 5-polyU tract of mouse coronavirus (MHV-A59). Results from assays for double stranded RNA (dsRNA) synthesis, infectivity of released virions, and syncytium formation indicate that the oligonucleotide treatment prevented generation of infectious virions. Our results show a unique mode of action of the designed 3-polyA oligonucleotide against mouse coronavirus which leaves host cells unaffected. This strategy can be adopted for the development of novel classes of oligonucleotide-based drugs that inhibit the production of infectious RNA viruses, including the coronaviruses. Since the 5-polyU tract is conserved and is essential for variants of coronaviruses, this strategy can potentially address coronavirus variant emergence as well.

microbiology↗

The Achilles' heel of coronaviruses: targeting the 5' Polyuridines tract of the antigenome to inhibit Mouse coronavirus virus-induced cell death

The current coronavirus pandemic situation is worsened by the rapidly-spreading SARS-CoV-2 virus variants. Identification of viral targets that are indispensable for the virus can be targeted to inhibit mutation-based new escape variant development. The 5-polyU tract of the antigenome offers such a target. Host cells do not harbor 5-polyU tracts on any of their transcripts, making the tract an attractive, virus-specific target. Inhibiting the 5-polyU can limit the use of the tract as template to generate 3 polyA tails of +RNAs of coronaviruses. Here, a modified DNA oligo with 3 polyAs is used to target the 5-polyU tract in mouse coronavirus (MHV-A59). The oligo treatment in mouse 17CL-1 cells infected with MHV-A59 significantly prevented virus-induced cell deaths. This proof-of-concept result shows a unique mode of action against mouse coronavirus without affecting host cells, and can be used for the development of novel classes of drugs that inhibit coronavirus infection in host cells, specifically by the COVID-19-causing virus SARS-CoV-2. In addition, as the 5-polyU tract is immediately generated upon infection, the tag can also be targeted for reliable early detection of viral infection.

microbiology↗

Scaffold Protein RACK1 inhibitor compounds prevent the Focal Adhesion Kinase mediated breast cancer cell migration and invasion potential

Scaffold protein RACK1 mediates cancer cell migration mostly through regulation of focal adhesion (FA) assembly by promoting a focal adhesion kinase (FAK) activation downstream of the integrin clustering and adhesion at the extracellular matrix (ECM). Here we demonstrated the efficacy of our recently developed RACK1 Y246 phosphorylation inhibitor compounds (SD29 and SD29-14) to inhibit the migration and invasion of MCF7 and MDA-MB-231 breast cancer cell lines. Using multiple assays, our results confirmed that inhibitor compounds effectively prevent the filopodia/lamellipodia development and inhibits the migration of breast cancer cells. A mechanistic model of the inhibitor compounds has been developed. Migration and invasion capabilities of the cancer cells define the metastasis of cancer. Thus, our results suggest a potential therapeutic mechanism of the inhibitors to prevent metastasis in diverse cancers.

cancer biology↗

Bioaccumulation of heavy metals in commercially important fish species from the tropical river estuary suggests higher potential child health risk than adults

The Karnaphuli, a major river of Bangladesh, located off the coast of Chittagong in the Bay of Bengal is largely exposed to the heavy metal pollutants, which may be toxic to humans and aquatic fauna. The estuary is a striking example of a site where human pressure and ecological values collide with each other. In spite of being a major supplier of fish food for local community, there has been no study carried out to date to assess the potential human health risk due to heavy metal contamination in the fish species from this estuary. Therefore, the aim of present study was to assess bioaccumulation status and the potential human health risk evaluation for local consumers. Six commercially important fish species, Apocryptes bato, Pampus chinensis, Hyporhamphus limbatus, Liza parsia, Mugil cephalus, and Tenualosa toil from the Karnaphuli River estuary were collected to analyze heavy metals concentration level. Heavy metals As, Pb, Cd, Cr and Cu were detected from the samples using inductively coupled plasma mass spectrometry (Model: ELAN9000, Perkin-Elmer, Germany). The hierarchy of the measured concentration level of the metals was as follows: Pb (mean: 13.88, range: 3.19 - 6.19) > Cu (mean: 12.10, range: 10.27 - 16.41) > As (mean: 4.89, range: 3.19 - 6.19) > Cr (mean: 3.36, range: 2.46 - 4.17) > Cd (mean: 0.39, range: 0.21 - 0.74). The Fultons condition factor denoted that organisms were particularly in better condition and most of the species were in positive allometric growth. The Bioaccumulation factors (BAFs) observed in the species of the contaminants were organized in the following ranks: Cu (1971.42) > As (1042.93) > Pb (913.66) > Cr (864.99) > Cd (252.03), and among all the specimens, demersal fish, A. bato corresponded to the maximum bio-accumulative organism. Estimated daily intake (EDI), target hazard quotient (THQ) and carcinogenic risk (CR) assessed for human health risk implications suggest that the values are within the acceptable threshold for all sorts of consumers. Hence none of them would experience non-carcinogenic and carcinogenic health effect for the ingestion of the fishes. However, children are shown to be largely susceptible than adults to non-carcinogenic and carcinogenic health effect due to the consumption of fish. Therefore, an appropriate guidlines and robust management measures needed to be taken to restore the estuarine health condition for greater benefit of the quality of fish products for local consumption.\n\nGraphical abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC=\"FIGDIR/small/681478v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (28K):\norg.highwire.dtl.DTLVardef@802d07org.highwire.dtl.DTLVardef@10c300eorg.highwire.dtl.DTLVardef@126f608org.highwire.dtl.DTLVardef@e28cf0_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗