Genetic and epigenetic analyses of IFN-γ gene proximal promoter region underlying positive correlation between persistently high anti-SARS-CoV-2 IgG and IFN-γ among COVID-19 vaccinated Bangladeshi adults.

IFN-γ is an immunological modulator influencing IgG isotype and concentration, which present a correlate of protection to evaluate vaccine efficacy. As transiently expressed, stable genetic and epigenetic signatures of the cytokine's expression may exist. This study investigates correlation between plasma IFN-γ and anti-SARS-CoV-2 IgG levels, seeking genetic polymorphisms and epigenetic variations within the IFN-γ gene proximal promoter. 200 COVID-19-vaccinated adults were classified into seropositive and seronegative groups based on plasma anti-SARS-CoV-2 IgG. Upon correlation analysis between anti-SARS-CoV-2 IgG and IFN-γ levels, IFN-γ gene proximal promoter region was subjected to nucleotide sequencing for two subsets: seronegative (21 < Days post-vaccination ≤180, n = 11) and seropositive (IgG > Q3 and Days post-vaccination >180, n = 24). Relative unmethylation of IFN-γ proximal promoter was assessed for the latter subset and its correlation with plasma IFN-γ and IgG levels was evaluated. A statistically significant positive correlation (r = 0.492, p = 0.018) was observed between IFN-γ and anti-SARS-CoV-2 IgG in the seropositive group with persistently high IgG titre (IgG > Q3, Days elapsed post-vaccination >180). A heterozygous 5'-UTR variant (rs776667149:C>T) identified in one seronegative individual revealed a potential impact on PKR-mediated translational attenuation of IFN-γ mRNA. No significant correlation was found between IFN-γ proximal promoter unmethylation and its plasma levels among HAR individuals with Days post-vaccination of either >180 (r = 0.14, p = 0.679) or < 180 (r = -0.062, p = 0.693). This study demonstrates an extent of humoral immunity against SARS-CoV-2 among COVID-19 vaccinated Bangladeshi population. This study suggests plasma IFN-γ may play a role in maintaining persistent anti-SARS-CoV-2 IgG levels, which warrants further investigation along with genetic and/or epigenetic basis to fully establish its protective nature in COVID-19 vaccination.

Coding-complete genomes of 18 SARS-CoV-2 Omicron JN.1, JN.1.4, and JN.1.11 sub-lineages in Bangladesh.

We report 18 coding-complete genome sequences of emerging SARS-CoV-2 Omicron sub-lineages JN.1, JN.1.4, and JN.1.11 from Bangladesh. Nasopharyngeal swab samples were obtained from individuals with COVID-19 symptoms between December 2023 and January 2024. Whole genome sequencing was performed following the ARTIC Network-based protocol using Oxford Nanopore Technology.

Coding-complete genomes of XBB.1.16, XBB.2.3, FL.4 (alias of XBB.1.9.1.4), and XBB.3 of SARS-CoV-2 Omicron isolated from Bangladesh.

We announce the coding-complete genomes of four different strains of SARS-CoV-2 Omicron lineages, XBB.1.16, XBB.2.3, FL.4 (alias of XBB.1.9.1.4), and XBB.3. These strains were obtained between October 2022 and May 2023 from nasopharyngeal swabs of four Bangladeshi individuals, while one of them had a travel history. Genomic data were produced by implementing ARTIC Network-based amplicon sequencing using the Oxford Nanopore Technology.

Most frequently harboured missense variants of hACE2 across different populations exhibit varying patterns of binding interaction with spike glycoproteins of emerging SARS-CoV-2 of different lineages.

Since the emergence of SARS-CoV-2 at Wuhan in the Hubei province of China in 2019, the virus has accumulated various mutations, giving rise to many variants. According to the combinations of mutations acquired, these variants are classified into lineages and greatly differ in infectivity and transmissibility. In 2021 alone, a variant of interest (VoI) Mu (B.1.621), as well as, variants of concern (VoC) Delta (B.1.617.2) and Omicron (BA.1, BA.2) and later in 2022, BA.4, BA.5, and BA.2.12.1 have emerged. Since then, the world has seen prominent surges in the rate of infection during short periods of time. However, not all populations have suffered equally, which suggests a possible role of host genetic factors. Here, we investigated the strength of binding of the spike glycoprotein receptor-binding domain (RBD) of the SARS-CoV-2 variants: Mu, Delta, Delta Plus (AY.1), Omicron sub-variants BA.1, BA.2, BA.4, BA.5, and BA.2.12.1 with the human angiotensin-converting enzyme 2 (hACE2) missense variants prevalent in major populations. In this purpose, molecular docking analysis, as well as, molecular dynamics simulation was performed of the above-mentioned SARS-CoV-2 RBD variants with the hACE2 containing the single amino acid substitutions prevalent in African (E37K), Latin American (F40L), non-Finnish European (D355 N), and South Asian (P84T) populations, in order to predict the effects of the lineage-defining mutations of the viral variants on receptor binding. The effects of these mutations on protein stability were also explored. The protein-protein docking and molecular dynamics simulation analyses have revealed variable strength of attachment and exhibited altered interactions in the case of different hACE2-RBD complexes. In vitro studies are warranted to confirm these findings which may enable early prediction regarding the risk of transmissibility of newly emerging variants across different populations in the future.

Sustainability of the coastal zone of the Ganges-Brahmaputra-Meghna delta under climatic and anthropogenic stresses.

The Ganges-Brahmaputra-Meghna (GBM) delta is one of the world's largest deltas. It is currently experiencing high rates of relative sea-level rise of about 5 mm/year, reflecting anthropogenic climate change and land subsidence. This is expected to accelerate further through the 21st Century, so there are concerns that the GBM delta will be progressively submerged. In this context, a core question is: can sedimentation on the delta surface maintain its elevation relative to sea level? This research seeks to answer this question by applying a two-dimensional flow and morphological model which is capable of handling dynamic interactions between the river and floodplain systems and simulating floodplain sedimentation under different flow-sediment regimes and anthropogenic interventions. We find that across a range of flood frequencies and adaptation scenarios (including the natural polder-free state), the retained volume of sediment varies between 22% and 50% of the corresponding sediment input. This translates to average rates of sedimentation on the delta surface of 5.5 mm/yr to 7.5 mm/yr. Hence, under present conditions, sedimentation associated with quasi-natural conditions can exceed current rates of relative sea-level rise and potentially create new land mass. These findings highlight that encouraging quasi-natural conditions through the widespread application of active sediment management measures has the potential to promote more sustainable outcomes for the GBM delta. Practical measures to promote include tidal river management, and appropriate combinations of cross-dams, bandal-like structures, and dredging.

Host-derived fecal microRNAs can indicate gut microbiota healthiness and ability to induce inflammation.

Disruption of intestine-microbiota symbiosis can result in chronic gut inflammation. We hypothesize that assessing the initial inflammatory potential of the microbiota in patients is essential and that host-derived miRNAs, which can be found in feces, could fulfill this function. We investigated whether the gut microbiota composition impacts the fecal miRNA profile and thereby indicates its ability to influence intestinal inflammation. Methods: We used high-throughput qPCR to compare fecal miRNA profile between germ-free and conventional mice. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas (IL10-/- and TLR5-/- associated microbiota) was performed. Results: We identified 12 fecal miRNAs impacted by the presence of a microbiota. Conventionalization of germfree mice by various colitogenic and non-colitogenic microbiotas associated with the development of intestinal inflammation (IL10-/- and TLR5-/- associated microbiota) yielded distinctively altered fecal miRNA profiles compared to that of mice receiving a "healthy" microbiota. Correlation analysis revealed the existence of interactions between the 12 abovementioned miRNAs and specific microbiota members. Conclusion: These results showed that fecal miRNA profile can be differentially and specifically impacted by microbiota composition, and that miRNA could importantly serve as markers of the colitogenic potential of the microbiota. This is particularly relevant to assess individual state of the microbiota in patients with dysbiosis-related disorders, such as IBD and potentially determine their ability to respond to therapeutics.

Purification of Total RNA from DSS-treated Murine Tissue via Lithium Chloride Precipitation.

We have developed a protocol to purify RNA from DSS (Dextran Sulfate Sodium)-treated mouse tissues. This method, which prevents downstream inhibition of q-RT-PCR observed in DSS-treated tissues, relies on successive precipitations with lithium chloride.