Peak ADAMTS13 activity to assess ADAMTS13 conformation and risk of relapse in immune-mediated thrombotic thrombocytopenic purpura.

ABSTRACT: Previous studies have demonstrated that >38% of patients with immune-mediated thrombotic thrombocytopenic purpura in remission with activity >50% had an open ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) conformation. We assessed ADAMTS13 conformation in remission (ADAMTS13 activity >60%), focusing on peak ADAMTS13 activity levels and longitudinal assessment in 420 samples across 157 patients. Fewer cases had an open conformation at peak ADAMTS13 activity than unselected remission samples with ADAMTS13 activity >60% (23% vs 43%). Patients with a closed ADAMTS13 conformation at peak ADAMTS13 activity had an eightfold lower relapse rate in the subsequent year (9% vs 46%) and a fivefold lower relapse rate within 2 years (23% vs 62%) compared with cases with an open conformation. Patients with an open conformation at peak ADAMTS13 activity required preemptive anti-CD20 treatment earlier than those with a closed conformation (median, 10 vs 25 months). Longitudinally, an open conformation was evident at, and often preceded relapse. When the conformation was already open before relapse, an increase in the conformation index at relapse was seen despite the undetectable anti-ADAMTS13 immunoglobulin G (IgG) antibody. In cases with detectable anti-ADAMTS13 IgG antibody, these became undetectable before achieving a closed conformation, highlighting the relapse risk even with undetectable anti-ADAMTS13 IgG antibody and the clinical utility of open/closed during monitoring. To our knowledge, this is the first study to show an association between relapse risk and ADAMTS13 conformation when activity levels are at a peak. The open conformation identifies antibody-mediated subclinical disease that is not detectable by the current ADAMTS13 testing.

Delayed normalization of ADAMTS13 activity in acute thrombotic thrombocytopenic purpura in the caplacizumab era.

The benefits of caplacizumab in acute immune-mediated thrombotic thrombocytopenic purpura (iTTP) are well established. We identified a delayed normalization of a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) activity (>30%) in a subgroup treated with caplacizumab, not evident in the precaplacizumab era. Patients treated with caplacizumab (n = 64) achieved ADAMTS13 activity >30% at median 31 days after plasma exchange (PEX), compared with 11.5 days in the noncaplacizumab group (n = 50, P = .0004). Eighteen of 64 (28%) patients treated with caplacizumab had ADAMTS13 activity <10% at stopping caplacizumab with a longer time to ADAMTS13 activity >30% (median, 139 days after completing PEX). Eighteen of 64 (28%) patients receiving extended caplacizumab (31-58 days) failed to achieve ADAMTS13 activity >30% at the time of caplacizumab cessation, compared with 4 of 47 (8.5%) historical controls at a similar timepoint (30 + 28 days, P < .0001). Failure to achieve ADAMTS13 activity >30% within 30 + 28 days was 6 times more likely with caplacizumab (odds ratio, 6.3; P = .0006). ADAMTS13 antigen <30% at caplacizumab cessation was associated with increased iTTP recurrence (4/10 vs 0/9 in patients with ADAMTS13 antigen ≥30%). Admission anti-ADAMTS13 immunoglobulin G (IgG) antibody level did not predict recurrence. Anti-ADAMTS13 IgG antibody levels, immunosuppression, and ethnicity did not account for differences in ADAMTS13 activity response. ADAMTS13 antigen levels ≥30% may be useful to guide stopping caplacizumab therapy after extended use with ADAMTS13 activity <10%. The reason for delayed ADAMTS13 normalization is unclear and requires further investigation.

Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination.

BACKGROUND: The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a year, several vaccines have been developed and millions of doses delivered. Reporting of adverse events is a critical postmarketing activity. METHODS: We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications. RESULTS: In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype. All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation. No evidence of thrombophilia or causative precipitants was identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient. On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms. CONCLUSIONS: Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine. Rapid identification of this rare syndrome is important because of the therapeutic implications.

Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis.

The COVID-19 pandemic has resulted in the rapid development of a range of vaccines against SARS-CoV-2. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare but life-threatening complication of primarily adenoviral-based vaccines associated with the presence of antibodies to a PF4/polyanion neoepitope and measured by using enzyme-linked immunosorbent assays. Presented are serial anti-PF4/polyanion antibody, platelet, and D-dimer measurements in a large cohort of patients and their relation to relapse. Overall, 51% of patients using the Stago assay had persistently positive anti-PF4/polyanion levels 100 days' postdiagnosis, whereas 94% of patients monitored by using the Immucor assay remain positive. The median duration of positivity of the PF4 assay is 87 days, with 72% of patients remaining positive after a median follow-up of 105 days. The use of plasma exchange seemed to reduce anti-PF4/polyanion levels and increase platelet counts in the acute setting more rapidly than other therapies. The rate of relapse in this study was 12.6%, with all relapsed cases exhibiting persistently positive PF4 antibodies and falling platelet counts. Only one patient had extension of their thrombosis. Overall, despite the persistence of PF4 antibodies in 72% of patients, the rate of relapse was low and did not seem to result in recrudescence of the aggressive clinical picture seen at index presentation. Monitoring of these patients in the UK cohort is ongoing and will aid in definition of the natural history of this novel condition.

Sustainable pathways for solar desalination using nanofluids: A critical review.

Water is a fundamental requirement for the survival of human beings. Although water is abundantly available across the globe, access to freshwater still remains a major concern. Most of the water available is saline or brackish, which is not fit for human consumption. Desalination is the optimum solution for production of potable water from saline water. A major shortcoming of conventional desalination technologies is their dependence on fossil fuel that results in environmental degradation, global warming, etc. Therefore, sustainable desalination technology has evolved as a need of hour. Among all renewable energy resources, solar energy is abundantly available and can be potentially harvested. Therefore, solar energy can be used to drive sustainable desalination technologies. A solar still converts saline water into freshwater in a single step using solar energy. But the major drawbacks of solar still are relatively lower efficiency and lower yield. Nanofluids are widely used to overcome these limitations due to their extraordinary and unique properties. This paper critically reviews the recent research performed on the application of nanofluids in solar desalination systems. Methods of nanofluid preparation, their types and properties are also discussed in detail. Application of nanofluids in solar desalination systems is discussed with special attention on performance enhancement of solar stills. Combinations of nanofluids with various other performance enhancement techniques are also considered. The effectiveness of nanofluids in solar stills is found to be dependent majorly on the nature and concentration of the nanofluid used.

Anterior retropharyngeal approach (ARPA) for high cervical spine.

BACKGROUND: One of the major challenges in operating on the spine lies in taking an anterior approach for the high cervical spine. In patients with a short neck, Klippel-Fiel syndrome or when the C3 vertebra is high in relation to the hyoid bone, it will be difficult to access the C3 body. The transoral route is a highly contaminated zone, and therefore, no instrumentation or grafts can be placed through it. METHOD: The anterior retropharyngeal approach (ARPA) for the high cervical spine. CONCLUSION: The anterior retropharyngeal approach is an excellent approach for the high cervical spine where instrumentation is needed. This route provides wide exposure of the C1-C3 region, avoiding the contaminated of the oral cavity.

Multi-location evaluation of field pea in Indian climates: eco-phenological dynamics, crop-environment relationships, and identification of mega-environments.

Characterization of crop-growing environments in relation to crop's genotypic performance is crucial to harness positive genotype-by-environment interactions (GEI) in systematic breeding programs. Given that, the study aimed to delineate the impact of diverse environments on crop phenology and yield traits of dwarf-statured field pea, pinpointing location(s) favoring higher yield and distinctiveness within breeding lines. We tested twelve field pea breeding lines across twenty locations in India, covering Central Zone (CZ), North Western Plain Zone (NWPZ), North Eastern Plain Zone (NEPZ), and Northern Hill Zone (NHZ). Across these locations, maximum and minimum temperatures during flowering (TMAXF, TMINF) and reproductive period (TMAXRP, TMINRP) ranged 18.9-28.3, 3.3-18.0, 15.0-30.8, and 7.9-22.1oC, respectively. Meanwhile, notable variations in phenological and agronomic traits (coefficient of variation) were observed: flowering (31%), days to maturity (21%), reproductive period (18%), grain yield (48%), and 100-seed weight (18%). Combined ANOVA demonstrated an oversized impact of environment (81%) on yield, while genotype and GEI effects were 2% and 14%, respectively. The variables TMINF, TMINRP, and cumulative growing degree-day showed positive correlations with yield, while extended vegetative and maturity durations negatively influenced yield (p < 0.05). Additionally, linear mixed-models and PCA results explained that instability in crop phenology had significant influence on field pea yield. Seed weight was markedly varied within the locations (9.9-20.8 g) and both higher and lower seed weights were associated with lower yields (Optimal = 17.1 g). HA-GGE biplot-based on environment focus-scaling demonstrated three mega-environments and specific locations viz. Kota (CZ), SK Nagar (CZ), Raipur (CZ), Sehore (CZ), and Pantnagar (NWPZ) as the ideal testing-environments with high efficiency in selecting new genotypes with wider adaptability. The study findings highlight distinct impact of environments on crop phenology and agronomic traits of field pea (dwarf-type), hold substantial value in designing efficient field pea (dwarf-type) breeding program at mega-environment scale.

Reactivation of varicella zoster virus following trigeminal schwannoma resection.

Varicella zoster is found exclusively in humans. Infected people with this virus result in chickenpox followed by dormant virus within neural ganglia. This dormant virus, once activated, may affect any ganglia or nerves of the body but most commonly involves the thoracic, cervical and trigeminal nerves in decreasing order of frequency. We review three such cases in which manipulation of the trigeminal ganglion resulted in reactivation of varicella at homologous operative sites. Each patient underwent surgeries in which the trigeminal ganglion was manipulated for the resection of trigeminal schwannoma under a microscope through various approaches. All three patients developed reactivation of varicella at homologous operative sites. A thorough history of chickenpox infection should be taken in patients who are undergoing surgeries for trigeminal pathology. Early diagnosis should be made once any vesicular lesions are seen with prompt treatment. Reassurance and counselling are necessary in these patients. If possible, prophylaxis may be started in all such patients. Further studies are warranted to determine the exact cause of reactivation.

A Proton-Coupled Electron Transfer Strategy to the Redox-Neutral Photocatalytic CO2 Fixation.

Herein, we report our study on the design and development of a novel photocarboxylation method. We have used an organic photoredox catalyst (PC, 4CzIPN) and differently substituted dihydropyridines (DHPs) in combination with an organic base (1,5,7-triazabicyclodec-5-ene, TBD) to access a proton-coupled electron transfer (PCET) based manifold. In depth mechanistic investigations merging experimental analysis (NMR, IR, cyclic voltammetry) and density-functional theory (DFT) calculations reveal the key activity of a H-bonding complex between the DHP and the base. The thermodynamic and kinetic benefits of the PCET mechanism allowed the implementation of a redox-neutral fixation process leading to synthetically relevant carboxylic acids (18 examples with isolated yields up to 75%) under very mild reaction conditions. Finally, diverse product manipulations were performed to demonstrate the synthetic versatility of the obtained products.

C1-C2 coronal and sagittal joint angle based treatment algorithm for the need of transoral odointectomy in complex craniovertebral junction anomalies with Clinico-Radiological outcome analysis.

OBJECTIVE: Craniovertebral junction (CVJ) pathology by virtue of its complexity is a surgical challenge in the realm of neurosurgery. We analyzed the need for transoral odointectomy in view of their C1-C2 joint coronal and sagittal angle of 58 patients with complex CVJ anomalies treated surgically. The clinical and radiological outcome of the patients was assessed and a treatment algorithm is proposed. METHODS: A total of 58 cases were included in the Prospective study over the period of 2 years. Patients were evaluated clinically, investigated, and operated with reduction and rigid internal fixation with screws and rod. The clinical outcome was measured by Modified Japanese orthopedic association score(mJOA) and radiologically by conventional craniometrics indices. Paired 't' test used for statistical analysis. RESULTS: Mean age of patients: 30 years, with mean, follow up: 20.5 months. 46(80%) patients were operated by posterior and 12(20%) by combined approach (anterior transoral with posterior). Occipitocervial fixation was done in 15(25.8%) cases and C1-C2 fixation in 43(74.2%) cases. As compared to patients with low coronal angle, the patient with coronal angle >65° needed anterior decompression (87.5%) and all (100%) had Occipitocervical fixation. Clinical outcome analysis showed significant improvement in mean mJOA score (preop 11.9 Vs postop 14.6) after surgery. All craniometrics indices were significantly improved after surgery. The overall complication rate was 10% with a mortality of 1.7%. 6 months follow up completed in all patients with a 100% fusion rate. CONCLUSION: Occipitocervical fixation and anterior decompression is required in increased C1-C2 joint CA (>65°) for bony realignment and adequate decompression. Measurement of C1-C2 joint coronal and sagittal angle in complex CVJ anomalies will easily anticipate the surgeon regarding the need for anterior decompression inform of transoral odointectomy.

Fluorescein sodium fluorescence: role in stereotactic brain biopsy.

BACKGROUND: Stereotactic brain biopsy for eloquent area brain tumours is associated with complications like hemorrhage due to multiple sampling and increased operative time due to dependence on neuropathologist for frozen section assessment. In order to curb these limitations, we investigated the use of Fluorescein sodium fluorescence in confirming pathological tissue samples in stereotactic brain biopsy of gadolinium-enhancing tumours. METHODS: This prospective observational study included 23 consecutive patients who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. 93 specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Later the nature of the samples was confirmed on histopathology. The sensitivity and specificity of flourescein sodium fluorescence were calculated based on histopathological confirmation. RESULTS: 58 (62.3%) fluorescent and 35 (37.6%) nonfluorescent samples were obtained. All fluorescent specimens contained diagnostic tissue appropriate for tumor grading. Of 35 nonfluorescent specimens, 12 (34.3%) did not contain tumor, 11 (31.4%) contained minor hypercellularity or gliosis, and 12 (34.3%) contained tumor with a high proportion of necrosis. The sensitivity and specificity for fluorescein fluorescence were 83% and 100%, respectively. CONCLUSIONS: Fluorescein fluorescence is a handy tool to detect the pathological tissue in stereotactic brain biopsy and may improve its diagnostic accuracy and expedite the procedure.

Interactions of urbanisation, climate variability, and infectious disease dynamics: insights from the Coimbatore district of Tamil Nadu.

Climate change and shifts in land use/land cover (LULC) are critical factors affecting the environmental, societal, and health landscapes, notably influencing the spread of infectious diseases. This study delves into the intricate relationships between climate change, LULC alterations, and the prevalence of vector-borne and waterborne diseases in Coimbatore district, Tamil Nadu, India, between 1985 and 2015. The research utilised Landsat-4, Landsat-5, and Landsat-8 data to generate LULC maps, applying the maximum likelihood algorithm to highlight significant transitions over the years. This study revealed that built-up areas have increased by 67%, primarily at the expense of agricultural land, which was reduced by 51%. Temperature and rainfall data were obtained from APHRODITE Water Resources, and with a statistical analysis of the time series data revealed an annual average temperature increase of 1.8 °C and a minor but statistically significant rainfall increase during the study period. Disease data was obtained from multiple national health programmes, revealing an increasing trend in dengue and diarrhoeal diseases over the study period. In particular, dengue cases surged, correlating strongly with the increase in built-up areas and temperature. This research is instrumental for policy decisions in public health, urban planning, and climate change mitigation. Amidst limited research on the interconnections among infectious diseases, climate change, and LULC changes in India, our study serves as a significant precursor for future management strategies in Coimbatore and analogous regions.

Retention of Knowledge and Efficacy of a Hands-on Training Session in Oxygen Therapy for COVID-19 among Healthcare Workers.

Introduction: We conducted basic hands-on training in oxygen therapy and ventilatory management of coronavirus disease-2019 (COVID-19) patients to health care workers (HCWs) at our tertiary care hospital. We designed this study aiming to find out the impact of hands-on training in oxygen therapy for COVID-19 patients on the knowledge and degree of retention of this gained knowledge 6 weeks after the training session among HCWs. Materials and methods: The study was conducted after obtaining approval from the Institutional Ethics Committee. A structured questionnaire consisting of 15 multiple-choice questions was given to the individual HCW. This was followed by a structured 1-hour training session on "Oxygen therapy in COVID-19", following which the same questionnaire was given to the HCWs with the questions in a different order. After 6 weeks, the same questionnaire with questions in a different format was sent to the participants as a Google form. Results: A total of 256 responses were obtained for the pre-training test and post-training test. The median [IQR] pre-training test scores and post-training test scores were 8 [7-10] and 12 [10-13], respectively. The median retention score was 11 [9-12]. The retention scores were significantly higher than the pre-test scores. Conclusion: About 89% of the HCWs had a significant gain of knowledge. About 76% of the HCWs were able to retain knowledge, which also means the training program was successful. A definitive improvement in baseline knowledge was observed after 6 weeks of training. We propose conducting reinforcement training after 6 weeks of primary training to further augment retention. How to cite this article: Singh A, Salhotra R, Bajaj M, Saxena AK, Sharma SK, Singh D, et al. Retention of Knowledge and Efficacy of a Hands-on Training Session in Oxygen Therapy for COVID-19 among Healthcare Workers. Indian J Crit Care Med 2023;27(2):127-131.

Photocatalytic sequential C-H functionalization expediting acetoxymalonylation of imidazo heterocycles.

The importance of functionalized imidazo heterocycles has often been featured in several impactful research both from academia and industry. Herein, we report a direct C-3 acetoxymalonylation of imidazo heterocycles using relay C-H functionalization enabled by organophotocatalysis starring zinc acetate in the triple role of an activator, ion scavenger as well as an acetylating reagent. The mechanistic investigation revealed a sequential sp2 and sp3 C-H activation, followed by functionalization driven by zinc acetate coupled with the photocatalyst PTH. A variety of imidazo[1,2-a]pyridines and related heterocycles were explored as substrates along with several active methylene reagents, all generating the products with excellent yields and regioselectivity, thus confirming excellent functional group tolerability.

Computed tomography evaluation of variations in positions and measurements of appendix in patients with non-appendicular symptoms: time to revise the diagnostic criteria for appendicitis.

Purpose: To estimate the frequency distribution of different anatomical positions, and to measure the diameter, wall thickness, and length of appendix in patients with non-appendicular symptoms. Material and methods: This retrospective observational study was conducted among 1,575 patients, who had undergone computed tomography (CT) scan of abdomen for various non-appendicular signs and symptoms. Frequency of distribution of different anatomic locations and measurements of various morphologic parameters were recorded. Results: The most common location of appendix was retrocecal, followed by sub-cecal, post-ileal, and pelvic locations. The mean length of appendix was 66.7 mm (range, 6.3-123 mm), and the diameter was 6.3 mm (range, 2.8-11.3 mm). Diameter of > 6 mm was noted in 48.12% patients. The mean wall thickness was 2.37 mm, ranging 1.2-4.2 mm. The most common intra-luminal content was air-mixed with hypodense or hyperdense material observed in 70.5% of cases. Conclusions: Although an appendix with diameter less than 6 mm may be considered normal, a diameter above 6 mm has an overlap between a normal and inflamed appendix. Therefore, it should be considered in association with clinical and secondary findings to avoid overdiagnosis and unnecessary appendicectomies. We strongly recommend that diameter-based CT criteria to diagnose appendicitis should be revised and standardized.

Enhanced fitness of hepatitis C virus increases resistance to direct-acting antivirals.

Drug resistance mutations of hepatitis C virus (HCV) negatively impact viral replicative fitness. RNA viruses are known to change their replication behaviour when subjected to suboptimal selection pressure. Here, we assess whether mutation supply in HCV is sufficiently large to allow the selection of its variants during dual or triple direct-acting antiviral (DAA) treatment associated with augmented virus fitness or impairment. We engineered randomly mutagenized full-genome libraries to create a highly diverse population of replication-competent HCV variants in cell culture. These variants exhibited escape when treated with NS5A/NS5B inhibitors (daclatasvir/sofosbuvir), and relapse on treatment with a combination of NS3/NS5A/NS5B inhibitors (simeprevir or paritaprevir/daclatasvir/sofosbuvir). Analysis of the relationship between virus fitness and drug resistance of JFH1-derived NS5A-5B variants showed a significant positive correlation (P=0.003). At the earliest time points, intracellular RNA levels remain unchanged in both the subgenomic replicon and infection assays, whereas extracellular RNA levels increased upto ten-fold compared to wild-type JFH1. Beneficial substitutions hyperstimulated phosphatidylinositol 4-phosphate during DAA treatment, and showed decreased dependence on cyclophilins during cyclosporine A treatment, indicating an interplay of virus-host molecular mechanisms in beneficial substitution selection that may necessitate infectious virus production. This comprehensive study demonstrates a possible role for HCV fitness of overcoming drug-mediated selection pressure.

LncRNA-mediated regulation of SOX9 expression in basal subtype breast cancer cells.

Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer (BC) subtypes with a poor prognosis and high recurrence rate. Recent studies have identified vital roles played by several lncRNAs (long noncoding RNAs) in BC pathobiology. Cell type-specific expression of lncRNAs and their potential role in regulating the expression of oncogenic and tumor suppressor genes have made them promising cancer drug targets. By performing a transcriptome screen in an isogenic TNBC/basal subtype BC progression cell line model, we recently reported ∼1800 lncRNAs that display aberrant expression during breast cancer progression. Mechanistic studies on one such nuclear-retained lncRNA, linc02095, reveal that it promotes breast cancer proliferation by facilitating the expression of oncogenic transcription factor, SOX9. Both linc02095 and SOX9 display coregulated expression in BC patients as well in basal subtype BC cell lines. Knockdown of linc02095 results in decreased BC cell proliferation, whereas its overexpression promotes cells proliferation. Linc02095-depleted cells display reduced expression of SOX9 concomitant with reduced RNA polymerase II occupancy at the SOX9 gene body as well as defective SOX9 mRNA export, implying that linc02095 positively regulates SOX9 transcription and mRNA export. Finally, we identify a positive feedback loop in BC cells that controls the expression of both linc02095 and SOX9 Thus, our results unearth tumor-promoting activities of a nuclear lncRNA linc02095 by facilitating the expression of key oncogenic transcription factor in BC.

Characterizing plant trait(s) for improved heat tolerance in field pea (Pisum sativum L.) under subtropical climate.

Field pea is highly sensitive to climatic vagaries, particularly high-temperature stress. The crop often experiences terminal heat stress in tropical climates indicating the need for the development of heat-tolerant cultivars. Characterization and identification of stress-adaptive plant traits are pre-requisites for breeding stress-tolerant/adaptive cultivar(s). In the study, a panel of 150 diverse field pea genotypes was tested under three different temperature environments (i.e., normal sowing time or non-heat stress environment (NSTE), 15 days after normal sowing time or heat stress environment-I (LSHTE-I), and 30 days after normal sowing time or heat stress environment-II (LSHTE-II)) to verify the effect of high-temperature environment, genotype, and genotype × environment interaction on different plant traits and to elucidate their significance in heat stress adaptation/tolerance. The delayed sowing had exposed field pea crops to high temperatures during flowering stage by + 3.5 °C and + 8.1 °C in the LSHTE-I and LSHTE-II, respectively. Likewise, the maximum ambient temperature during the grain-filling period was + 3.3 °C and + 6.1 °C higher in the LSHTE-I and LSHTE-II over the NSTE. The grain yield loss with heat stress was 25.8 ± 2.2% in LSHTE-I, and 59.3 ± 1.5% in LSHTE-II compared to the NSTE. Exposure of crops to a high-temperature environment during the flowering stage had a higher impact on grain yield than the heat stress at the grain filling period. Results suggested that the reduced sink capacity (pod set (pod plant-1), seed set (seed pod-1)) was the primary cause of yield loss under the heat stress environments, while, under the NSTE, yield potential was mostly attributed to the source capacity (plant biomass). The high-temperature stress resulted in forced maturity as revealed by shrinkage in crop period (5-11%) and reproductive period (15-36%), prominently in long-duration genotypes. The failure of pod set in the upper nodes and higher ovule abortion (7-16%) was noticed under the high-temperature environments, particularly in the LSHTE-II. Multivariate analysis results revealed seed set, pods plant-1, last pod bearing node, and plant biomass as a critical yield determinant under the heat stress. The GGE biplot suggested that the genotypes G-112, G-114, and G-33 had higher potential to sustain yield coupled with higher stability across the environments and, thus, could serve as a source for breeding heat-tolerant high yielding cultivars.

Harnessing landfill gas (LFG) for electricity: A strategy to mitigate greenhouse gas (GHG) emissions in Jakarta (Indonesia).

Due to its increasing demands for fossil fuels, Indonesia needs an alternative energy to diversify its energy supply. Landfill gas (LFG), which key component is methane (CH4), has become one of the most attractive options to sustain its continued economic development. This exploratory study seeks to demonstrate the added value of landfilled municipal solid waste (MSW) in generating sustainable energy, resulting from CH4 emissions in the Bantargebang landfill (Jakarta). The power generation capacity of a waste-to-energy (WTE) plant based on a mathematical modeling was investigated. This article critically evaluated the production of electricity and potential income from its sale in the market. The project's environmental impact assessment and its socio-economic and environmental benefits in terms of quantitative and qualitative aspects were discussed. It was found that the emitted CH4 from the landfill could be reduced by 25,000 Mt annually, while its electricity generation could reach one million kW â‹…h annually, savings on equivalent electricity charge worth US$ 112 million/year (based on US' 8/kW ⋅ h). An equivalent CO2 mitigation of 3.4 × 106 Mt/year was obtained. The income from its power sale were US$ 1.2 ×106 in the 1st year and 7.7 ×107US$ in the 15th year, respectively, based on the projected CH4 and power generation. The modeling study on the Bantargebang landfill using the LFG extraction data indicated that the LFG production ranged from 0.05 to 0.40 m3 per kg of the landfilled MSW. The LFG could generate electricity as low as US' 8 per kW ⋅ h. With respect to the implications of this study, the revenue not only defrays the cost of landfill's operations and maintenance (O&M), but also provides an incentive and means to further improve its design and operations. Overall, this work not only leads to a diversification of primary energy, but also improves environmental protection and the living standard of the people surrounding the plant.

Genome-Wide Mutagenesis of Hepatitis C Virus Reveals Ability of Genome To Overcome Detrimental Mutations.

To gain insight into the impact of mutations on the viability of the hepatitis C virus (HCV) genome, we created a set of full-genome mutant libraries, differing from the parent sequence as well as each other, by using a random mutagenesis approach; the proportion of mutations increased across these libraries with declining template amount or dATP concentration. The replication efficiencies of full-genome mutant libraries ranged between 71 and 329 focus-forming units (FFU) per 105 Huh7.5 cells. Mutant libraries with low proportions of mutations demonstrated low replication capabilities, whereas those with high proportions of mutations had their replication capabilities restored. Hepatoma cells transfected with selected mutant libraries, with low (4 mutations per 10,000 bp copied), moderate (33 mutations), and high (66 mutations) proportions of mutations, and their progeny were subjected to serial passage. Predominant virus variants (mutants) from these mutant libraries (Mutantl, Mutantm, and Mutanth, respectively) were evaluated for changes in growth kinetics and particle-to-FFU unit ratio, virus protein expression, and modulation of host cell protein synthesis. Mutantm and Mutantl variants produced >3.0-log-higher extracellular progeny per ml than the parent, and Mutanth produced progeny at a rate 1.0-log lower. More than 80% of the mutations were in a nonstructural part of the mutant genomes, the majority were nonsynonymous, and a moderate to large proportion were in the conserved regions. Our results suggest that the HCV genome has the ability to overcome lethal/deleterious mutations because of the high reproduction rate but highly selects for random, beneficial mutations.IMPORTANCE Hepatitis C virus (HCV) in vivo displays high genetic heterogeneity, which is partly due to the high reproduction and random substitutions during error-prone genome replication. It is difficult to introduce random substitutions in vitro because of limitations in inducing mutagenesis from the 5' end to the 3' end of the genome. Our study has overcome this limitation. We synthesized full-length genomes with few to several random mutations in the background of an HCV clone that can recapitulate all steps of the life cycle. Our study provides evidence of the capability of the HCV genome to overcome deleterious mutations and remain viable. Mutants that emerged from the libraries had diverse phenotype profiles compared to the parent, and putative adaptive mutations mapped to segments of the conserved nonstructural genome. We demonstrate the potential utility of our system for the study of sequence variation that ensures the survival and adaptation of HCV.