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BACKGROUND AND AIMS: Chronic liver disease leads to ~2 million deaths annually. Cyclic AMP (cAMP) signaling has long been studied in liver injury, particularly in the regulation of fatty acid (FA) ß-oxidation and pro-inflammatory polarization of tissue-resident lymphocytes. Phosphodiesterase 4B inhibition has been explored as a therapeutic modality, but these drugs have had limited success and are known to cause significant adverse effects. The PDE4 inhibitor 2-(4-([2-(5-Chlorothiophen-2-yl)-5-ethyl-6-methylpyrimidin-4-yl]amino)phenyl)acetic acid) (known as A-33) has yet to be explored for the treatment of metabolic diseases. APPROACH AND RESULTS: Herein, we evaluated the efficacy of A-33 in the treatment of animal models of alcohol-associated liver disease and steatotic liver disease. We demonstrated that A-33 effectively ameliorated the signs and symptoms of chronic liver disease, resulting in significant decreases in serum alanine aminotransferase and aspartate aminotransferase levels, decreased overall fat and collagen deposition in the liver, decreased intrahepatic triglyceride concentrations, and normalized expression of genes related to ß-oxidation of fatty acids, inflammation, and extracellular matrix deposition. We also designed and synthesized a novel analog of A-33, termed MDL3, which inhibited both phosphodiesterase 4B and PDE5A and was more effective in ameliorating pathophysiological signs and symptoms of liver injury and inflammation. In addition, MDL3 re-sensitized obese mice to glucose and significantly inhibited the pathological remodeling of adipose tissue, which was not observed with A-33 administration. CONCLUSIONS: In conclusion, we synthesized and demonstrated that MDL3, a novel phosphodiesterase 4B and PDE5A inhibitor, presents a promising avenue of exploration for treating chronic liver disease.
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Crop residue burning is a common practice in many parts of the world that causes air pollution and greenhouse gas (GHG) emissions. Regenerative practices that return residues to the soil offer a 'no burn' pathway for addressing air pollution while building soil organic carbon (SOC). Nevertheless, GHG emissions in rice-based agricultural systems are complex and difficult to anticipate, particularly in production contexts with highly variable hydrologic conditions. Here we predict long-term net GHG fluxes for four rice residue management strategies in the context of rice-wheat cropping systems in Eastern India: burning, soil incorporation, livestock fodder, and biochar. Estimations were based on a combination of Tier 1, 2, and 3 modelling approaches, including 100-year DNDC simulations across three representative soil hydrologic categories (i.e., dry, median, and wet). Overall, residue burning resulted in total direct GHG fluxes of 2.5, 6.1, and 8.7 Mg CO2-e in the dry, median, and wet hydrologic categories, respectively. Relative to emissions from burning (positive values indicate an increase) for the same dry to wet hydrologic categories, soil incorporation resulted in a -0.2, 1.8, or 3.1 Mg CO2-e change in emissions whereas use of residues for livestock fodder increased emissions by 2.0, 2.1, or 2.3 Mg CO2-e. Biochar reduced emissions relative to burning by 2.9 Mg CO2-e in all hydrologic categories. This study showed that the production environment has a controlling effect on methane and, therefore, net GHG balance. For example, wetter sites had 2.8-4.0 times greater CH4 emissions, on average, than dry sites when rice residues were returned to the soil. To effectively mitigate burning without undermining climate change mitigation goals, our results suggest that geographically-target approaches should be used in the rice-based systems of Eastern India to incentivize the adoption of regenerative 'no burn' residue management practices.
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Here, we report the first complete genome of a psychrotolerant and yellow-pigmented rhizobacteria Chryseobacterium cucumeris PCH239. It was obtained from the rhizospheric soil of the Himalayan plant Bergenia ciliata. The genome consists of a single contig (5.098 Mb), 36.3% G + C content, and 4899 genes. The cold adaptation, stress response, and DNA repair genes promote survivability in a high-altitude environment. PCH239 grows in temperature (10-37 °C), pH (6.0-8.0), and NaCl (2.0%). The genome derived plant growth-promoting activities of siderophore production (siderophore units 53 ± 0.6), phosphate metabolism (PSI 5.0 ± 0.8), protease, indole acetic acid production (17.3 ± 0.5 µg/ml), and ammonia (2.89 ± 0.4 µmoles) were experimentally validated. Interestingly, PCH239 treatment of Arabidopsis seeds significantly enhances germination, primary, and hairy root growth. In contrast, Vigna radiata and Cicer arietinum seeds had healthy radicle and plumule elongation, suggesting varied plant growth-promotion effects. Our findings suggested the potential of PCH239 as a bio-fertilizer and biocontrol agent in the challenging conditions of cold and hilly regions.
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Chryseobacterium , Sideróforos , Sideróforos/metabolismo , Desenvolvimento Vegetal , Chryseobacterium/metabolismo , Genômica , Microbiologia do Solo , Raízes de Plantas/microbiologiaRESUMO
Context or problem: In the Indian state of Odisha, rice-based system productivity is poor due to: (i) low rice yield in the monsoon (wet) season (2-4 t ha-1 compared to 6-8 t ha-1 in Punjab or Haryana); and (ii) limited cropping during the post-monsoon (dry) season (59% of the wet season rice area is left fallow in the dry season). Objective: Our study identifies strategies for increasing rice-based system productivity through: (i) alternative crop establishment methods in the wet season (Dry-Direct Seeded Rice or DSR, and mechanical puddled transplanted rice or PTR-M) to traditional methods such as broadcasting followed by post-emergence tillage (locally known as beushening) and manual random puddled transplanted rice (PTR-R); (ii) to identify rice-fallow areas suitable for pulse and oilseed cultivation in the dry season; and (iii) to evaluate the performance of short-duration pulses (green gram, Vigna radiata; black gram, Vigna mungo), and oilseeds (Brassica rapa var. toria, Helianthus annuus) in rice-fallow areas in the dry season. Methods: On-farm experiments were conducted between 2017 and 2019 in three districts of Odisha (Bhadrak, Cuttack and Mayurbhanj) to evaluate DSR compared to beushening and PTR-R; and PTR-M compared to PTR-R and manual line puddled transplanted rice (PTR-L) in the wet season. The data from Landsat-8 Operational Land Imager (OLI) and Sentinel-1satellite sensors was used to identify rice-fallow areas, and the daily SMAP (Soil Moisture Active Passive) L-band soil moisture was used for mapping suitable rice-fallow areas for growing pulses and oilseeds. Short duration crops were evaluated in suitable rice-fallow areas. Results: In the wet season, DSR (range -4 to + 53%) had a significant effect on rice yield over beushening. Similarly, PTR-M consistently increased rice yield by 16-26% over PTR-R, and by 5-23% over PTR-L. In the dry season, pulse crops (green gram and black gram) performed well compared to Indian mustard under rainfed cultivation. However, under irrigated conditions, dry-season rice yield was more productive than the rice equivalent yield of green gram, black gram and sunflower. We found that 1.03 M ha (i.e., â¼50%) of total rice-fallow areas of 2.1 M ha were suitable for growing short duration green gram and black gram in the dry season. Conclusions: We conclude that system productivity and cropping intensity can be increased by adoption of DSR and PTR-M in the wet season, and growing of green gram and black gram in the dry season. Implications: Odisha state can potentially produce an additional 0.67 million tonnes pulses if suitable rice-fallow areas are brought under green gram and black gram cultivation in the dry the season.
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BACKGROUND: The Sugar Will Eventually Be Exported Transporters (SWEET), consisting of the MtN3 and salvia domain, are sugar transporters having an active role in diverse activities in plants such as pollen nutrition, phloem loading, nectar secretion, reproductive tissue development, and plant-pathogen interaction. The SWEET genes have been characterized only in a few fruit crop species. METHODS AND RESULTS: In this study, a total of 15 SWEET genes were identified in the pomegranate (Punica granatum) genome. The gene structure, transmembrane (TM) helices, domain architecture, and phylogenetic relationships of these genes were evaluated using computational approaches. Genes were further classified as Semi-SWEETs or SWEETs based on the TM domains. Similarly, pomegranate, Arabidopsis, rice, and soybean SWEETs were studied together to classify into major groups. In addition, analysis of RNAseq transcriptome data was performed to study SWEEET gene expression dynamics in different tissue. The expression suggests that SWEETs are mostly expressed in pomegranate peel. In addition, PgSWEET13 was found to be differentially expressed under high salinity stress in pomegranate. Further, quantitative PCR analysis confirmed the expression of four candidate genes in leaf and stem tissues. CONCLUSION: The information provided here will help to understand the role of SWEET genes in fruit development and under abiotic stress conditions in pomegranate.
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Punica granatum/genética , Estresse Fisiológico/genética , Arabidopsis/genética , Transporte Biológico , Frutas/metabolismo , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Lythraceae/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Oryza/genética , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Plantas/genética , Punica granatum/crescimento & desenvolvimento , Glycine max/genética , Transcriptoma/genéticaRESUMO
Pigments are an essential part of life on earth, ranging from microbes to plants and humans. The physiological and environmental cues induce microbes to produce a broad spectrum of pigments, giving them adaptation and survival advantages. Microbial pigments are of great interest due to their natural origin, diverse biological activities, and wide applications in the food, pharmaceutical, cosmetics, and textile industries. Despite noticeable research on pigment-producing microbes, commercial successes are scarce, primarily from higher, remote, and inaccessible Himalayan niches. Therefore, substantial bioprospection integrated with advanced biotechnological strategies is required to commercialize microbial pigments successfully. The current review elaborates on pigment-producing microbes from a Himalayan perspective, offering tremendous opportunities for industrial applications. Additionally, it illustrates the ecological significance of microbial pigments and emphasizes the current status and prospects of microbial pigments production above the test tube scale.
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Recent studies of diabetes suggest an obesity paradox: mortality risk increases with weight in people without diabetes but decreases with weight in people with diabetes. A recent study also reports the paradox more generally with health care utilization. Whether this paradox in health care utilization and spending is causal or instead the result of empirical biases and confounding factors has yet to be examined in detail. This study set out to examine changes in the relationship between BMI and health care expenditures in populations with versus without diabetes, controlling for confounding risk factors. It found that the obesity paradox does not exist and is the result of statistical biases such as confounding and reverse causation. Obesity is not cost-saving for people with diabetes. Thus, insurers and physicians should renew efforts to prevent obesity in people with diabetes.
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Weeds are one of the key threats in sustaining the productivity of the rice-wheat cropping system in the Indo-Gangetic Plains. The development of sound integrated weed management technologies requires knowledge of mechanisms that influence weed flora composition and weed seedbank dynamics. A long-term study was initiated in 2015 at Patna, Bihar, India to evaluate the effect of seven tillage and crop establishment methods on weed density, weed seedbank composition, and crop productivity in rice-wheat-mungbean rotation. All the treatments included zero-till mungbean after wheat. Tillage and crop establishment methods had differential effects on weed and weed seedbank composition. In rice, zero-till direct-seeded rice recorded 62% lower emergence of Cyperus iria, 82-90% of Echinochloa colona, and 81-83% of total weeds compared to tilled systems, but the system of rice and wheat intensification favoured E. colona. In wheat, the system of wheat intensification favoured the Phalaris minor and Solanum nigrum. Zero-till rice and wheat reduced the seedbank of Trianthema portulacastrum by 95%, and total weed seedbank by 62% compared to the system of rice and wheat intensification. Nearly, 72% of C. iria seeds, 62% of grasses, and 64% of broad-leaved weeds were in 0-15 cm soil layer. Zero-till direct-seeded rice produced a 13% lower rice grain yield than conventional puddled transplanted rice. Compared to the system of wheat intensification, zero-till wheat under triple zero-till systems produced an 11.5% higher grain yield. Managing weed seedbank is a long-term endeavour. The present study revealed that tillage and crop establishment methods influence weed density and diversity. Under zero-till rice-wheat system, rice yield decreases marginally, but the system productivity maintains due to improvement in succeeding wheat yield. This system is also helpful in reducing the weed flora density and soil weed seedbank. Regular monitoring and management of emerging pests such as armyworm (Mythimna separata) are, however, required. The study suggests that the adoption of triple zero-tillage can be a viable option for reducing the weed density and weed seedbank concurrently increasing the system productivity of the rice-wheat-mungbean cropping system in eastern Indo-Gangetic Plains.
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Microbial remediation of synthetic dyes from industrial effluents offers a sustainable and eco-friendly alternative. Herein, laccase-producing bacteria were isolated from decaying wood niches in the Himalayan region. A bacterial consortium (BC-I) was developed to decolorize synthetic dyes cocktail of three major groups (azo, anthraquinone, and triphenylmethane). BC-I consisted of Klebsiella sp. PCH427, Enterobacter sp. PCH428, and Pseudomonas sp. PCH429 can decolorize 77% of 240 mg/L dyes cocktail in 44 h at 37 °C. BC-I works under wide pH (4.0-10.0), a high salt concentration (NaCl, 10%), and low nutrients. Further, FT-IR and LC-MS validated the dyes cocktail degradation and identified the degraded products. Additionally, phytotoxicity analysis of BC-I treated dyes cocktail significantly reduced the toxicity to Vigna radiata and Cicer arietinum compared to untreated dyes cocktail. The present study has simulated environmental challenges of acidic, alkaline, and saline industrial dyes effluents, which are significant to bioremediation.
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Corantes , Lacase , Compostos Azo/metabolismo , Bactérias/metabolismo , Biodegradação Ambiental , Corantes/metabolismo , Lacase/metabolismo , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Diversification of smallholder rice-based cropping systems has the potential to increase cropping system intensity and boost food security. However, impacts on resource use efficiencies (e.g., nutrients, energy, and labor) remain poorly understood, highlighting the need to quantify synergies and trade-offs among different sustainability indicators under on-farm conditions. In southern coastal Bangladesh, aman season rice is characterized by low inputs and low productivity. We evaluated the farm-level impacts of cropping system intensification (adding irrigated boro season rice) and diversification (adding chili, groundnut, mungbean, or lathyrus) on seven performance indicators (rice equivalent yield, energy efficiency, partial nitrogen productivity, partial potassium productivity, partial greenhouse gas footprint, benefit-cost ratio, and hired labor energy productivity) based on a comprehensive survey of 501 households. Indicators were combined into a multi-criteria performance index, and their scope for improvement was calculated by comparing an individual farmer's performance to top-performing farmers (highest 20%). Results indicate that the baseline system (single-crop aman season rice) was the least productive, while double cropped systems increased rice equivalent yield 72-217%. Despite gains in productivity, higher cropping intensity reduced resource use efficiencies due to higher inputs of fertilizer and energy, which also increased production costs, particularly for boro season rice. However, trade-offs were smaller for diversified systems including legumes, largely owing to lower N fertilizer inputs. Aman season rice had the highest multi-criteria performance index, followed by systems with mungbean and lathyrus, indicating the latter are promising options to boost food production and profitability without compromising sustainability. Large gaps between individual and top-performing farmers existed for each indicator, suggesting significant scope for improvement. By targeting indicators contributing most to the multi-criteria performance index (partial nitrogen productivity, energy efficiency, hired labor energy productivity), results suggest further sustainability gains can be achieved through future field research studies focused on optimizing management within diversified systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s13593-022-00795-3.
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Deteriorating soil health, diminishing soil organic carbon (SOC), development of subsurface hard compact layer and declining system productivity are barriers to achieving sustainable production in the traditional rice-wheat cropping system (TA) in the eastern Indo-Gangetic Plain of India. Conservation agriculture (CA), which favours minimum soil disturbance, crop residue retention and crop diversification could be a viable alternative to the TA to address most of those major problems. With that in mind, a long-term experiment is being implemented at ICAR-RCER, Patna, Bihar, India, with four treatments: (a) TA, (b) full CA (fCA) and (c and d) partial CA (pCA1 and pCA2), differing in crop establishment methods, cropping system and crop residue management in a randomized complete block design. Measurement of soil health parameters was carried out in the 11th year of the experiment. The results revealed a beneficial effect of CA and 46 and 40% increase in SOC concentration and stock, respectively, under fCA over TA in the 0-7.5-cm soil layer. The effect of partial CA (pCA1 and pCA2) was variable, but an increasing trend was always observed under pCA compared to TA. There was an enrichment in SOC content of aggregates under CA irrespective of size class; however, no relation was found between SOC content and aggregate diameter. The contribution of macroaggregates to SOC stock was larger (36-66%) under CA in the 0-7.5-cm soil layer. Adoption of CA improved the macroaggregate content, MWD and GMD of aggregates, and aggregation ratio. Soil macropore content was greater under fCA, whereas other parameters were similar among treatments. The impact of CA was mostly limited to 0-7.5 cm soil layer and a maximum up to 15 cm soil depth while evaluation until 60 cm soil depth was realized. The yield of rice in CA was comparable to or higher than in TA, whereas the system rice equivalent yield was always higher (38-53%) under CA than under the conventional practices. Therefore, a CA-based cropping system must be encouraged, to increase SOC status, improve aggregation stability and, consequently, sustain or increase system productivity, in order to achieve food and nutritional security in the eastern Indo-Gangetic Plain of India. HIGHLIGHTS: Effects of long-term conservation agriculture (CA) on soil C, aggregation and yield were evaluated.CA improved SOC concentration and stock by 46 and 40%, as well as macroaggregate SOC stock by 36-66%.Macro-aggregation and mean weight diameter improved in CA but was mostly limited to a shallow soil depth.CA can be promoted for sustainability of a rice-wheat system due to higher productivity (38-53%).
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Himalayan niches provide unprecedented opportunities for finding novel microbes of commercial importance. The present study investigated the genome sequence of Glaciimonas sp. PCH181 isolated from the glacial stream of Indian trans-Himalaya. The draft genome sequence has six contigs with 5.3â¯Mb size, 51.1% Gâ¯+â¯C content, and possesses 4876 genes. Phylogenomic analysis revealed PCH181 as a putative novel bacterium in the genus Glaciimonas. Genomic insight showed Glaciimonas sp. PCH181 enriched with genes for diverse physiology, cold/stress adaptation, and industrial potential. The presence of genes for CO2 fixation and hydrogen metabolism suggested for chemolithoautotrophy. However, genes for sugars and organic acids usage showed heterotrophy and validated by physiological experiments. Genes for the metabolism of phenol (up to 500â¯ppm) and biosynthesis of polyhydroxyalkanoate (25% of dry cell mass) were also verified. Collectively, we present the first whole genome sequencing in the genus Glaciimonas, a taxonomically, physiologically, and industrially noteworthy bacterium.
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Aclimatação , Congelamento , Genoma Bacteriano , Camada de Gelo/microbiologia , Microbiologia Industrial , Oxalobacteraceae/genética , Filogenia , Oxalobacteraceae/isolamento & purificação , Oxalobacteraceae/metabolismo , Sequenciamento Completo do GenomaRESUMO
In the eastern Indo-Gangetic Plains (EIGP), conventional rice-wheat system has led to a decline in productivity, input-use efficiency, and profitability. To address these, a four-year field study was conducted to evaluate the performance of tillage and crop establishment (TCE) methods in rice-wheat-greengram rotation. The treatments included: 1) random puddled transplanted rice (RPTR) - conventional-till broadcast wheat (BCW) - zero-till greengram (ZTG); 2) line PTR (LPTR) - conventional-till drill sown wheat (CTW) - ZTG; 3) machine transplanted rice in puddled soil (CTMTR) - zero tillage wheat (ZTW) - ZTG; 4) machine transplanted rice in zero-till wet soil (ZTMTR) - ZTW - ZTG; 5) system of rice intensification (SRI) - system of wheat intensification (SWI) - ZTG; 6) direct-seeded rice (DSR) - ZTW - ZTG; and 7) zero-till DSR - ZTW - ZTG. During the initial two years, conventional rice system (PTR) recorded a 16.2 % higher rice grain yield than DSR system. Whereas in the fourth year, the rice yields under DSR and PTR were comparable. As compared to SRI/SWI, the average wheat yield in ZT system was significantly high, whereas in rice, SRI/SWI system was comparable with CT system. ZTW after non-puddled rice was at par to CTW after PTR. The ZT wheat produced 4.6 % more yield than CT system. DSR production system consumed 6.8 % less water compared to transplanted system. On the system basis, 10.8 % higher net returns were recorded with CA-based system compared to conventional system. The system energy productivity under CA-based production system was 14-36 % higher than PTR-based systems. CA-based system also led to 8-10 % lower global warming potential (GWP) than conventional methods. The current study indicated that as compared to conventional system, a significant gain in productivity, profitability and energy-use efficiency, and reduction in the environmental mitigation are possible with emerging alternative TCE methods. Long-term expansion and further refinement of these technologies in local areas need to be explored for the second green revolution.
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While Direct Seeded Rice (DSR) has numerous potential benefits to smallholder farmers in the Eastern Gangetic Plains of South Asia, it's out-scaling has been limited by both a lack of demand by farmers and limited supply of DSR services by machinery owners. This contrasts with the comparatively more rapid scaling of zero tillage wheat in the region. This trend is yet to be fully explored, particularly when focus has been placed almost exclusively on understanding DSR adoption though the lens of farm-level agronomic, economic and environmental performance. Given that limited DSR service provision is likely to be governed outside of these considerations, this study explores with zero tillage drill owners the decision processes they apply in deciding how to use their zero tillage drills. Respondents highlight a complex web of interrelated considerations that highlight the additional complexities of DSR as compared to existing practices. Using a novel 'Decision-making Dartboard' qualitative framework, these complexities are unpacked and a set of potential changes to the assumed theory of change for DSR scaling are identified, including considerations for selection of potential DSR service providers and responsibilities for promotion and extension of DSR to overcome the prevalent negative perceptions of DSR held broadly across the communities explored. The proposed framework and analysis process are also potentially useful for exploration of other farmer decision making processes more broadly.
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Laser land levelling is expanding rapidly in the rice-wheat (RW) and maize-wheat (MW) systems of the Indo-Gangetic Plains of India and Pakistan. Current practice is to level to zero (0%) gradient, whereas a small gradient (e.g. 0.1%) is typically used in developed countries. Therefore, experiments were conducted in farmers' plots (~15 m x 40 m) in the Eastern Gangetic Plains to evaluate laser levelling with a 0.1% gradient in comparison with 0% and farmer levelling practice (FL). The study was conducted over two years in RW and MW systems. In the MW system, raised beds in plots lasered with 0% and 0.1% gradients were also evaluated. Laser levelling with 0% gradient significantly reduced irrigation amount and/or increased irrigation water productivity (WPi) in all crops/systems grown on the flat compared to FL except for wheat in the MW system. While there was a consistent trend for higher yield with a 0% gradient compared with FL, the differences were not significant in any crop/system. For the RW system, the results suggest no to marginal benefits in irrigation amount and WPi from levelling with a 0.1% gradient in comparison with 0% gradient. In that system, by far the bigger gains were from changing from FL to laser levelling with 0% gradient. This resulted in substantial reductions in irrigation amount, which greatly increased WPi in both crops (by ~40%), while yield was not affected. Rice grown with FL was not profitable, but lasering with 0% gradient significantly increased gross margin for rice, wheat and the total RW system. As for the RW system, levelling to 0% with a flat configuration significantly increased WPi of both crops in the MW system compared to FL, but by a lesser proportion. Raised beds significantly increased yield of maize by 8% (0.5 t ha-1), reduced irrigation amount by 20% (40 mm) and increased WPi by 34% (1.0 kg m-3) in comparison with the laser levelled flat plots. Gross margin of the MW system on beds was 17-20% higher than FL, and gross margin with beds on a 0.1% gradient was significantly higher than either gradient on the flat. The results suggest that the gains from levelling with a 0.1% gradient compared to 0% are marginal; however, this may change if the goal of consolidation of small farmer plots into larger fields becomes a reality provided there is a proportionate increase in irrigation flow rates, and ability to drain.
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ß-Galactosidase is a crucial glycoside hydrolase enzyme with potential applications in the dairy, food, and pharmaceutical industries. The enzyme is produced in the intracellular environment by bacteria and yeast. The present study reports yeast Kluyveromyces sp. PCH397 isolated from yak milk, which has displayed extracellular ß-galactosidase activity in cell-free supernatant through the growth phase. To investigate further, cell counting and methylene blue staining of culture collected at different growth stages were performed and suggested for possible autolysis or cell lysis, thereby releasing enzymes into the extracellular medium. The maximum enzyme production (9.94 ± 2.53U/ml) was achieved at 37 °C in a modified deMan, Rogosa, and Sharpe (MRS) medium supplemented with lactose (1.5%) as a carbon source. The enzyme showed activity at a wide temperature range (4-50 °C), maximum at 50 °C in neutral pH (7.0). In addition to the hydrolysis of lactose (5.0%), crude ß-galactosidase also synthesized vital prebiotics (i.e., lactulose and galacto-oligosaccharides (GOS)). Additionally, ß-fructofuranosidase (FFase) activity in the culture supernatant ensued the synthesis of a significant prebiotic, fructo-oligosaccharides (FOS). Hence, the unique features such as extracellular enzymes production, efficient lactose hydrolysis, and broad temperature functionality by yeast isolate PCH397 are of industrial relevance. In conclusion, the present study unrevealed for the first time, extracellular production of ß-galactosidase from a new yeast source and its applications in milk lactose hydrolysis and synthesis of valuable prebiotics of industrial importance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-021-00955-1.
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Conventionally managed rice-wheat systems of the eastern Indo-Gangetic Plains (E-IGP) that rely on soil puddling for rice and intensive tillage for wheat are low-yielding and resource-inefficient, leading to low profitability. While a host of alternative tillage and crop establishment (TCE) methods have been advocated as solutions for sustainably enhancing productivity and profitability, few systematic comparisons of these methods are reported. To address this gap, a three-year field study was conducted in Bihar, India with the goal of identifying TCE methods for rice-wheat systems that are high yielding, less resource-intensive, and more profitable. The following systems were evaluated: 1) puddled transplanted rice (PTR) followed by (fb) conventional tillage wheat (CTW) or zero-tillage wheat (ZTW); 2) machine transplanted rice in non-puddled soil (MTR) fb ZTW; 3) the system of rice intensification (SRI) fb system of wheat intensification (SWI); and 4) dry-seeded rice (DSR) fb ZTW. Rice cultivar duration (short versus medium-duration) was incorporated as a subplot treatment in all systems. Rice yields were similar with all methods, except DSR yield was 11 % lower and MTR yield was 7% higher than PTR in the third year. Cost of production was US$ 149 and 77â¯ha-1 lower in DSR and MTR, respectively, and US$ 84â¯ha-1 higher in SRI than PTR. The gross margin and benefit-cost (B:C) ratio was highest in MTR followed by DSR and lowest in SRI. In wheat, ZT resulted in a higher yield than CTW, especially when ZTW was cultivated after non-puddled rice (e.g., DSR or MTR). ZTW reduced production costs by US$ 69â¯ha-1, whereas SWI increased it by US$ 139â¯ha-1 relative to CTW. The higher yield and lower cost of production resulted in a higher gross margin (US$ 82-355â¯ha-1 and US$ 129-409â¯ha-1 higher than CTW and SWI, respectively) and a higher B:C ratio in ZTW treatments than CTW and SWI. At the system level, MTR or DSR followed by ZTW had both superior crop yields and consistently higher gross margins (US $133 to 382â¯ha-1) than other practices. On the other hand, the SRI fb SWI system had no yield advantage and poorer economic performance than conventional practices. In all systems, the inclusion of a medium-duration rice hybrid resulted in higher rice and system yields. These results suggest that significant gains in profitability are possible with emerging TCE practices in rice-wheat systems, but alternatives such as the SRI and SWI will likely erode farmer incomes.
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In many parts of Eastern India that have a very high prevalence of rural poverty and food insecurity, the prevailing rice establishment practice of 'beushening' is characterized by low yields and modest profitability, while labor and energy inputs are high. Beushening consists of broadcasting ungerminated rice seed at high rates (>100 kg ha-1) prior to the onset of monsoon rain, followed by ploughing at 4-6 weeks after crop emergence to control weeds with subsequent manual gap filling through seedling redistribution to ensure stand uniformity. Dry-direct seeding of rice (DSR), both drill-DSR and precision broadcast-DSR in combination with integrated weed management (IWM) may offer a pathway for simultaneously reducing costs and markedly increasing productivity. On-farm trials were conducted from 2016 to 2018 in four districts of Odisha (Mayurbhanj, Cuttack, Bhadrak, and Puri) to evaluate the yield and economic performance of dry-DSR (drill and precision broadcast), coupled with herbicide-based IWM strategies, in comparison with conventional beushening. Drill-DSR with IWM increased grain yield by 1.7 t ha-1 in Mayurbhanj and 1.3 t ha-1 in Cuttack, but not in Bhadrak, compared to beushening. The combination of increased yield and lower variable cost in drill-DSR increased net benefit by 550, 395, and 166 US$ ha-1 in Mayurbhanj, Cuttack, and Bhadrak, respectively. For farmers without access to seed drills, precision broadcast-DSR with IWM increased yields by 0.91, 1.22 and 0.60 t ha-1, and net benefits by 270, 312, and 188 US$ ha-1 in Mayurbhanj, Puri, and Bhadrak, respectively. Among the IWM practices evaluated in dry-DSR, application of pretilachlor + safener @ 500 g ai ha-1 as pre-emergence, followed by bispyribac-sodium @ 20 g ai ha-1 at 15-25 days after sowing as post-emergence, and then one spot hand weeding at 30-35 days after sowing was effective in controlling weeds. These results suggest that rice yield gaps in eastern India can be reduced, and farmers' income from rice can be increased by more than 50 % by replacing beushening with drill-DSR or precision broadcast-DSR. The results could be applicable to approximately 6.4 million ha of lowland rice where beushening is currently practiced in Eastern India.
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Hedgehog (Hh) signaling is involved in the initiation and progression of various cancers and is essential for embryonic and postnatal development. This pathway remains in the quiescent state in adult tissues but gets activated upon inflammation and injuries. Inhibition of Hh signaling pathway using natural and synthetic compounds has provided an attractive approach for treating cancer and inflammatory diseases. While the majority of Hh pathway inhibitors target the transmembrane protein Smoothened (SMO), some small molecules that target the signaling cascade downstream of SMO are of particular interest. Substantial efforts are being made to develop new molecules targeting various components of the Hh signaling pathway. Here, we have discussed the discovery of small molecules as Hh inhibitors from the diverse chemical background. Also, some of the recently identified natural products have been included as a separate section. Extensive structure-activity relationship (SAR) of each chemical class is the focus of this review. Also, clinically advanced molecules are discussed from the last 5 to 7 years. Nanomedicine-based delivery approaches for Hh pathway inhibitors are also discussed concisely.
Assuntos
Proteínas Hedgehog/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Transdução de Sinais , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Proteínas Hedgehog/metabolismo , Humanos , Receptor Smoothened/metabolismo , Relação Estrutura-AtividadeRESUMO
Trans-differentiation of quiescent hepatic stellate cells (HSCs) into active myofibroblasts secretes excess amounts of extracellular matrix (ECM) proteins. miR-29b1 has the potential to treat liver fibrosis, because it targets several profibrotic genes. We previously demonstrated that miR-29b1 and the hedgehog (Hh) pathway inhibitor GDC-0449 could, together, inhibit the activation of HSCs and ECM production in common bile-duct-ligated (CBDL) mice. Herein, we determined the effect of chemical modifications of miR-29b1 on its stability, immunogenicity, and Argonaute-2 (Ago2) loading in vitro, after modifying its antisense strand with phosphorothioate (PS-miR-29b1), 2'-O-methyl-phosphorothioate (OMe-miR-29b1), locked nucleic acid (LNA-miR-29b1), and N,N'-diethyl-4-(4-nitronaphthalen-1-ylazo)-phenylamine (ZEN-miR-29b1). Chemical modifications significantly improved stability of miR-29b1 in 50% FBS. Among all the modified miRNAs tested, OMe-PS-miR-29b1 showed the highest stability with low immunogenicity, without the loss of efficacy in vitro. Therefore, OMe-PS-miR-29b1 was complexed with poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft-tetraethylenepentamine (mPEG-b-PCC-g-DC-g-TEPA) cationic micelles, and anti-fibrotic efficacy was evaluated in CBDL mice. There was a significant improvement in liver histology and decrease in the levels of injury markers. Further, mRNA/protein levels of collagen, α-SMA, and TIMP-1 were significantly lower for the OMe-PS-miR-29b1-loaded micelles compared to miR-29b1-loaded micelles. In conclusion, micellar delivery of OMe-PS-miR-29b1 is a promising strategy to treat liver fibrosis.