Diversification of the VH3-53 immunoglobulin gene segment by somatic hypermutation results in neutralization of SARS-CoV-2 virus variants.

COVID-19 induces re-circulating long-lived memory B cells (MBC) that, upon re-encounter with the pathogen, are induced to mount immunoglobulin responses. During convalescence, antibodies are subjected to affinity maturation, which enhances the antibody binding strength and generates new specificities that neutralize virus variants. Here, we performed a single-cell RNA sequencing analysis of spike-specific B cells from a SARS-CoV-2 convalescent subject. After COVID-19 vaccination, matured infection-induced MBC underwent recall and differentiated into plasmablasts. Furthermore, the transcriptomic profiles of newly activated B cells transiently shifted toward the ones of atypical and CXCR3+ B cells and several B-cell clonotypes massively expanded. We expressed monoclonal antibodies (mAbs) from all B-cell clones from the largest clonotype that used the VH3-53 gene segment. The in vitro analysis revealed that some somatic hypermutations enhanced the neutralization breadth of mAbs in a putatively stochastic manner. Thus, somatic hypermutation of B-cell clonotypes generates an anticipatory memory that can neutralize new virus variants.

Structural Homology-Based Drug Repurposing Approach for Targeting NSP12 SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2, also known as SARS-CoV-2, is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 has a highly conserved non-structural protein 12 (NSP-12) involved in RNA-dependent RNA polymerase (RdRp) activity. For the identification of potential inhibitors for NSP-12, computational approaches such as the identification of homologous proteins that have been previously targeted by FDA-approved antivirals can be employed. Herein, homologous proteins of NSP-12 were retrieved from Protein DataBank (PDB) and the evolutionary conserved sequence and structure similarity of the active site of the RdRp domain of NSP-12 was characterized. The identified homologous structures of NSP-12 belonged to four viral families: Coronaviridae, Flaviviridae, Picornaviridae, and Caliciviridae, and shared evolutionary conserved relationships. The multiple sequences and structural alignment of homologous structures showed highly conserved amino acid residues that were located at the active site of the RdRp domain of NSP-12. The conserved active site of the RdRp domain of NSP-12 was evaluated for binding affinity with the FDA-approved antivirals, i.e., Sofosbuvir and Dasabuvir in a molecular docking study. The molecular docking of Sofosbuvir and Dasabuvir with the active site that contains conserved motifs (motif A-G) of the RdRp domain of NSP-12 revealed significant binding affinity. Furthermore, MD simulation also inferred the potency of Sofosbuvir and Dasabuvir. In conclusion, targeting the active site of the RdRp domain of NSP-12 with Dasabuvir and Sofosbuvir might reduce viral replication and pathogenicity and could be further studied for the treatment of SARS-CoV-2.

DDQ-Catalyzed Oxidative C(sp3)-H Functionalization of Aryltetralins and Subsequent Chemoselective Oxidative Demethylation to Access Dihydronaphthalenes and Dihydronaphthoquinones.

A highly controlled DDQ-catalyzed oxidative C(sp3)-H functionalization of three contiguous carbon atoms in aryltetralins is reported for efficient access to diverse oxygenated dihydronaphthalene scaffolds. The first total synthesis of pachypostaudin B is realized. Further, a CAN-mediated chemoselective oxidative demethylation on the dihydronaphthalene scaffolds is demonstrated to arrive at the rarely observed dihydronaphthoquinone core in moderate to good yields. The present methodology enables quick access to a library of magnoshinin and merrilliaquinone analogs.

Wintertime Air Quality in Megacity Dhaka, Bangladesh Strongly Affected by Influx of Black Carbon Aerosols from Regional Biomass Burning.

Clean air is a key parameter for a sustainable society, and currently, megacity Dhaka has among the worst air qualities in the world. This results from poorly constrained contributions of a variety of sources from both local emissions and regional influx from the highly polluted Indo-Gangetic Plain, impacting the respiratory health of the 21 million inhabitants in the Greater Dhaka region. An important component of the fine particulate matter (PM2.5) is black carbon (BC) aerosols. In this study, we investigated the combustion sources of BC using a dual carbon isotope (δ13C and Δ14C) in Dhaka during the high-loading winter period of 2013/14 (regular and lockdown/hartal period) in order to guide mitigation policies. On average, BC (13 ± 6 µg m-3) contributed about 9% of the PM2.5 (145 ± 79 µg m-3) loadings. The relative contribution from biomass combustion under regular conditions was 44 ± 1% (with the rest from fossil combustion), while during periods of politically motivated large-scale lockdown of business and traffic, the biomass burning contribution increased to 63 ± 1%. To reduce the severe health impact of BC and other aerosol pollution in Dhaka, mitigation should therefore target regional-scale biomass/agricultural burning in addition to local traffic.

Assessment of heavy metal pollution in the agricultural soils, plants, and in the atmospheric particulate matter of a suburban industrial region in Dhaka, Bangladesh.

Unplanned industrialization and improper management of wastes and gases into open surfaces are affecting the agricultural lands causing heavy metal pollution. This study monitored a suburban industrial zone located beside the Dhaka Export Processing Zone (DEPZ) at the Dhaka district in Bangladesh. We studied the heavy metal (Fe, Mn, Cr, Cu, Ni, Co, Zn, Pb, and Cd) concentration in the agricultural soils, plants, and in the atmospheric particulate matter (PM). The soils were found moderately contaminated with Fe, Cu, Ni, Co, and Zn and less contamination with Mn, Cr, Pb, and Cd. The enrichment factor (EF) and pollution load index (PLI) concluded a moderate level of soil pollution in this region. Besides, the plant samples showed an excess level of Cr and a similar level of Cu, Ni, Co, Zn, Pb, and Cd compared with the levels of industrial polluted sites of Bangladesh. The atmospheric PM analysis showed the presence of Fe, Mn, Cu, Ni, Zn, and Pb metals. The EF showed the anthropogenic origin of Mn and Ni in the atmospheric PM. The statistical correlation (r < 0.0001) of soil and plant heavy metals showed the possibility of transfer of metals from soil to plant which will cause the increase of pollution intensity. Overall, this agricultural region became an intermediate pollution zone. This study will help the decision-maker become conscious of heavy metal pollution in the suburban regions to monitor agricultural lands from anthropogenic pollution.

Source Quantification of South Asian Black Carbon Aerosols with Isotopes and Modeling.

Black carbon (BC) aerosols perturb climate and impoverish air quality/human health-affecting ∼1.5 billion people in South Asia. However, the lack of source-diagnostic observations of BC is hindering the evaluation of uncertain bottom-up emission inventories (EIs) and thereby also models/policies. Here, we present dual-isotope-based (Δ14C/δ13C) fingerprinting of wintertime BC at two receptor sites of the continental outflow. Our results show a remarkable similarity in contributions of biomass and fossil combustion, both from the site capturing the highly populated highly polluted Indo-Gangetic Plain footprint (IGP; Δ14C-fbiomass = 50 ± 3%) and the second site in the N. Indian Ocean representing a wider South Asian footprint (52 ± 6%). Yet, both sites reflect distinct δ13C-fingerprints, indicating a distinguishable contribution of C4-biomass burning from peninsular India (PI). Tailored-model-predicted season-averaged BC concentrations (700 ± 440 ng m-3) match observations (740 ± 250 ng m-3), however, unveiling a systematically increasing model-observation bias (+19% to -53%) through winter. Inclusion of BC from open burning alone does not reconcile predictions (fbiomass = 44 ± 8%) with observations. Direct source-segregated comparison reveals regional offsets in anthropogenic emission fluxes in EIs, overestimated fossil-BC in the IGP, and underestimated biomass-BC in PI, which contributes to the model-observation bias. This ground-truthing pinpoints uncertainties in BC emission sources, which benefit both climate/air-quality modeling and mitigation policies in South Asia.

Scalable Total Syntheses of Some Natural and Unnatural Lamellarins: Application of a One-Pot Domino Process for Regioselective Access to the Central 1,2,4-Trisubstituted Pyrrole Core.

Short and scalable total syntheses of lamellarin G trimethyl ether, lamellarin D trimethyl ether, lamellarin H, lamellarin η, dihydrolamellarin η, and lamellarin U have been realized in four to six linear steps with an overall yield of ≤22%. Highlights of the synthesis include single-step access to the central 1,2,4-trisubstituted pyrrole core in a highly regioselective manner via a one-pot [3+2] cycloaddition/elimination/aromatization sequence-based domino process. Subsequent, palladium-mediated double C-H oxidative coupling in a single-pot operation provides access to the pentacyclic coumarin-fused pyrrolo-dihydroisoquinoline core present in lamellarins.

Total syntheses of several iridolactones and the putative structure of noriridoid scholarein A: an intramolecular Pauson-Khand reaction based one-stop synthetic solution.

A simple and general approach towards the total syntheses of several iridolactones such as (±)-boschnialactone, (±)-7-epi-boschnialactone, (±)-teucriumlactone, (±)-iridomyrmecin, (±)-isoboonein, (±)-7-epi-argyol, (±)-scabrol A, (±)-7-epi-scabrol A, and (±)-patriscabrol as well as the putative structure of scholarein A is delineated. The synthetic strategy features a diastereoselective intramolecular Pauson-Khand reaction (IPKR) to construct the iridoid framework followed by some strategic synthetic manipulations to access the targeted monoterpenes including those having diverse oxy-functionalization patterns and with 3-5 contiguous stereogenic centres in a highly stereocontrolled manner. Also, the present endeavour includes the first total synthesis of scabrol A.

Comparative efficiency of wheat straw and sugarcane bagasse biochar reduces the cadmium bioavailability to spinach and enhances the microbial activity in contaminated soil.

Biochar is considered a novel soil amendment for cadmium (Cd) stabilization in contaminated soils. A pot experiment was conducted to examine the efficiency of wheat straw and sugarcane bagasse induced biochar on Cd mobility in soil and its bioavailability to spinach in contaminated soil. Soil pH, Cd contents in plant tissues and microbial biomass were examined. Results showed that Cd was significantly decreased by 30.95% and 20.83% with wheat straw and sugarcane bagasse biochar at 2% application rate respectively, relative to the control. Similarly, Cd contents were decreased in plants shoots by 15.41 and 14.33%, while in roots by 48.3 and 35.54%, when wheat straw and sugarcane biochar were added at 2% application rate respectively. Moreover, soil microbial biomass was significantly increased with the application of all biochar types and their applications rates. Finally, wheat straw biochar at 2% application rate can be considered as an effective approach for Cd stabilization in contaminated soils.

Rice straw- and rapeseed residue-derived biochars affect the geochemical fractions and phytoavailability of Cu and Pb to maize in a contaminated soil under different moisture content.

Management of toxic elements contaminated upland and wetland soils using biochar is of great concern from both agricultural and environmental points of view. The impact of rice straw- and rapeseed residue-derived biochars produced under 300 °C and 550 °C (added to the soil at 2% and 5%; w/w) on the geochemical fractions, phytoavailability, and uptake of Cu and Pb in a contaminated mining soil under different moisture contents (80%, 60%, and 40% of soil field capacity) was investigated in a greenhouse pot experiment using maize. The higher rate of rice straw-derived biochar pyrolyzed at 550 °C caused a significant reduction in the mobile (soluble + exchangeable) fraction of Cu (59.42%) and Pb (75.4%) and increased the residual fractions of Cu (37.8%) and Pb (54.7%) in the treated soil under the highest moisture content (80%) as compared to the untreated soil. Therefore, this biochar significantly decreased the phytoavailability (CaCl2-extractable form) of Cu by 59.5% and Pb by 67.6% under the highest moisture content. Also, at the same moisture level (80%), the higher rate of rapeseed residue-derived biochar pyrolyzed at 550 °C decreased significantly the phytoavailability of Cu by 46.5% and Pb by 60.52% as compared to the untreated soil. The 5% rate of the higher temperature pyrolyzed rice straw and rapeseed biochars decreased the uptake of Cu and Pb by the roots and shoots of maize up to 51% for Cu and 45% for Pb. Immobilization of Cu and Pb in the biochar-treated soil at 80% moisture content may possibly due to the associated increase of soil pH and poorly-crystalline Fe oxides content, and/or the metals precipitation with sulfides. These results indicated that application of high temperature pyrolyzed rice straw- and rapeseed residue-derived biochars at 5% could immobilize Cu and Pb and decrease their uptake by maize under high levels of moisture content; consequently, they can be used for phyto-management of Cu and Pb contaminated wetland soils.

Effective Role of Biochar, Zeolite and Steel Slag on Leaching Behavior of Cd and Its Fractionations in Soil Column Study.

Remediation of cadmium (Cd) from contaminated soils is considered a complicated task of environmental safety. A column leaching experiment was planned to estimate the influence of biochar (BC), zeolite (ZE) and steel slag (SL) at 1.5% and 3% application rate on Cd leaching behavior and chemical fractionation in contaminated soil. A sequential extraction procedure, the European Community Bureau of Reference (BCR), Toxicity Characteristic Leaching Procedure (TCLP) and NH4NO3 were performed after leaching was completed. The soluble portion of Cd was decreased by 36.3%, 18.4% and 28.7% and Cd contents in leachate were decreased by 44.8%, 30% and 31.3% after BC, ZE and SL addition at 3% rate, respectively over control soil. The greater reduction in TCLP extractable Cd was observed by 29.6% with BC and 22.4% with ZE and 25.7% with SL at 3% application rate. Overall, biochar can be considered an efficient soil amendment to reduce Cd leaching as well as increased its stabilization within soil profile.

Molecular characterization and multidisciplinary management of Gerbich hemolytic disease of the newborn.

Gerbich (Ge) antigens are high frequency red cell antigens expressed on glycophorin C (GYPC) and glycophorin D. Hemolytic disease of the fetus and newborn (HDFN) due to Gerbich antibody is rare and presents a clinical challenge, as Gerbich negative blood is scarce. We report a case of HDFN due to maternal Ge3 negative phenotype and anti-Ge3 alloimmunization, successfully managed by transfusion of maternal blood. Molecular testing revealed that the mother has homozygous deletion of exon 3 of GYPC, the father is homozygous wildtype for GYPC, and the infant is obligate heterozygote expressing Ge3.

Global Sources of Fine Particulate Matter: Interpretation of PM2.5 Chemical Composition Observed by SPARTAN using a Global Chemical Transport Model.

Exposure to ambient fine particulate matter (PM2.5) is a leading risk factor for the global burden of disease. However, uncertainty remains about PM2.5 sources. We use a global chemical transport model (GEOS-Chem) simulation for 2014, constrained by satellite-based estimates of PM2.5 to interpret globally dispersed PM2.5 mass and composition measurements from the ground-based surface particulate matter network (SPARTAN). Measured site mean PM2.5 composition varies substantially for secondary inorganic aerosols (2.4-19.7 µg/m3), mineral dust (1.9-14.7 µg/m3), residual/organic matter (2.1-40.2 µg/m3), and black carbon (1.0-7.3 µg/m3). Interpretation of these measurements with the GEOS-Chem model yields insight into sources affecting each site. Globally, combustion sectors such as residential energy use (7.9 µg/m3), industry (6.5 µg/m3), and power generation (5.6 µg/m3) are leading sources of outdoor global population-weighted PM2.5 concentrations. Global population-weighted organic mass is driven by the residential energy sector (64%) whereas population-weighted secondary inorganic concentrations arise primarily from industry (33%) and power generation (32%). Simulation-measurement biases for ammonium nitrate and dust identify uncertainty in agricultural and crustal sources. Interpretation of initial PM2.5 mass and composition measurements from SPARTAN with the GEOS-Chem model constrained by satellite-based PM2.5 provides insight into sources and processes that influence the global spatial variation in PM2.5 composition.

Identifying the functional groups and the influence of synthetic chelators on Cd availability and microbial biomass carbon in Cd-contaminated soil.

Synthetic chelators play an important role in boosting the microbial biomass carbon (MBC), dissolved organic carbon (DOC), and heavy metal solubility in a contaminated soil toward a sustainability of environment for agricultural crops. Castor plant was grown under different levels of Cd contaminated soil (-Cd and +Cd) following adding three chelating agents, ethylenediaminetetraacetic acid (H4EDTA), nitriloacetic acid (H3 NTA), and NH4 citrate (ammonium citrate) to the soil at rates of 10, 15, and 25 mmol in 5 kg of soil per pot. The highest bioavailable Cd concentrations in soil and castor plant were obtained from NH4 citrate and H4EDTA treatments in the contaminated soil. Fourier transform infrared (FTIR) analysis showed that NH4 citrate was the most effective chelator in Cd-contaminated soil. MBC and DOC contents were significantly increased and reached at 81.98-80.37 and 1.96-1.90 mg kg-1 respectively, in the (H3 NTA) and NH4 citrate treatments in Cd-contaminated soil. Further research is needed to investigate the use of chelators in the phytoextraction of Cd-contaminated soils under field conditions and whether it may be beneficial in accelerating the phytoextraction of Cd through hyperaccumulating plants.

Comparative efficiency of rice husk-derived biochar (RHB) and steel slag (SS) on cadmium (Cd) mobility and its uptake by Chinese cabbage in highly contaminated soil.

Cadmium (Cd) contamination in red soil has been considered as a severe threat due to its toxic effects on plants and food security. This study aims to evaluate the comparative efficiency of rice husk-derived biochar (RHB) and steel slag (SS) metal stabilizer on decreasing Cd mobility and bioavailability to Chinese cabbage grown on acidic contaminated red soil. Several extraction techniques: a sequential extraction procedure, the European Community Bureau of Reference, toxicity characteristics leaching procedure, ammonium nitrate, and simple bioaccessibility extraction test were used to measure Cd mobility after amelioration of the investigated soil. The results indicated that application of stabilizer significantly increased soil chemical properties including soil pH, cation exchange capacity, nutrients, and organic matter. The soluble portion of Cd in soil was significantly decreased by 17.6-31.2% and 7.8-11.7% for RHB and SS at 1.5% and 3% application rate, respectively. Moreover, Cd bioaccessibility was significantly declined by 37.08% with RHB and 11.3% with SS at 3% rate. Inlcorporation of RHB at 3% can effectively immobilize Cd and thereby, reduce its phytoavailability to cabbage in Cd-contaminated soil to mitigate food security risks.

Cadmium Immobilization Potential of Rice Straw-Derived Biochar, Zeolite and Rock Phosphate: Extraction Techniques and Adsorption Mechanism.

Heavy metal contamination in agricultural soils has become a serious environmental concern due to their generally high mobility and toxic effects on plants and food security. An incubation study was conducted to assess the effectiveness of biochar (BC), zeolite (ZE) and rock phosphate (RP) stabilizers on the immobilization of cadmium (Cd) in contaminated soils. Various extraction techniques were carried out: a sequential extraction procedure, the European Community Bureau of Reference (BCR), the toxicity characteristics leaching procedure (TCLP) and extraction with ammonium nitrate. In addition, Cd adsorption by these materials was observed using Langmuir and Freundlich isotherms. The results showed that with an increase in soil pH the exchangeable fraction of Cd in soil was significantly reduced by 28%-29.4%, 9%-13% and 4%-14% for BC, ZE, and RP, respectively. According to the Langmuir adsorption isotherm, BC-amended soil showed a higher adsorption capacity (Qm) of Cd from 8.38 to 19.85 mg g-1. Overall, BC offered better results when compared to other amendments.

Levels of Organotin Compounds in Selected Fish Species from the Arabian Gulf.

In the present work, data on the levels of hazardous Organotin compounds in eight commercially important fish species, caught from Arabian Gulf, has been reported. Highest levels of tributyltin (TBT) (98.5 ng/g dry weight) were detected in Epinephelus Tauvina whereas minimum (43.7 ng/g) were found in Acanthoparagus Bifasciatus. Highest levels of triphenyltin (TPT) were detected in Lethrinus Miniatus (107.5 ng/g) whereas lowest were encountered in Acanthoparagus Bifasciatus (64.9 ng/g). Highest value of total butyltin compounds (∑BT) were found in emperors (Lethrinus Miniatus) (228.4 ng/g) whereas minimum was found in Acanthoparagus Bifasciatus (126.4 ng/g). Similarly highest value of total phenyltin compounds (∑PT) was encountered in Epinephelus Tauvina (281.9 ng/g) followed closely by Acanthoparagus Bifasciatus (281.7 ng/g). In addition, the estimated daily intake (EDI) of the local population from consumption of these fish was also evaluated. Highest EDI was found to be 10.8 ng/kg bw/day for epinephelus microdan. The data are also compared internationally.

Diabetic ketoacidosis characteristics and differences In type 1 versus type 2 diabetes patients.

BACKGROUND: Diabetes is undoubtedly one of the most challenging health problems of the 21st century. It is well known that diabetes once develop can lead to several complications. Diabetic ketoacidosis (DKA) is one of the life-threatening complications of diabetes. This study was designed to determine the frequency of DKA in diabetes patients and find out the clinical and biochemical determinants of DKA. METHODS: This descriptive study was conducted at Aga Khan University Hospital (AKUH) Karachi, Pakistan from January 2010 to February 2016. All known or newly diagnosed diabetic patients of >16 years of age irrespective of gender and type of diabetes were included. Information regarding patient's demographics, presenting symptoms, precipitating causes of DKA, biochemical profiles and outcome at the time of discharge was collected. RESULTS: Majority (54.7%) had moderate and 12.4% had severe DKA at presentation. Previous history of DKA was found higher in type 1 diabetes patients (T1DM) (14%) as compare to (4%) type 2 diabetes patients (T2DM) (p<0.05). DKA severity was observed more (12%) in newly diagnosed (T1DM) (p<0.05). Comorbidities were found more (81%) in (T2DM) (p<0.05) Mortality was also observed higher in Type 2 diabetes patients (p<0.05). CONCLUSIONS: Majority of the diabetics had moderate to severe DKA at presentation. Mortality and morbidity related with DKA was found considerably higher among patients with T2DM while infection, myocardial infarction and stroke found as triggering factors in these patients.

PBL triggers in relation to students' generated learning issues and predetermined faculty objectives: Study in a Malaysian public university.

OBJECTIVES: Foundational elements of problem based learning (PBL) are triggers, tutors and students. Ineffective triggers are important issues for students' inability to generate appropriate learning issues. The objective of this study was to evaluate PBL triggers and to determine similarities of students' generated learning issues with predetermined faculty objectives. METHODS: It was a retrospective study conducted in 2014 analyzing all 24 PBL-triggers used at Centre for Foundation Studies, International Islamic University Malaysia, in four semesters during two consecutive years 2011 and 2012. Triggers were used as textual and illustration format equally in each semester. Total 16 PBL-triggers with highest and lowest achieving similarities of learning issues with predetermined faculty objectives were selected equally from each semester and format. The trigger quality and learning issues related to predetermine faculty objectives were analyzed and presented as mean and percent distribution. RESULTS: Mean similarities score of students' generated learning issues were 3.4 over 5 predetermined faculty objectives which was 68%, varied from 58% to 79%. More than 70% similarities were generated from five textual and four illustrated triggers, while <70% similarities observed from four illustrated and three textual triggers. CONCLUSION: Whatever the trigger formats in PBL, it is the designing considering influential variables that influence higher outcomes. Triggers should have planned clues that lead students to generate issues correlate with faculty objectives. Educational institution should emphasize on training needs of faculty at regular interval to develop and re-in force teachers' skills in trigger design, thereby to promote a sustainable educational and organizational development.