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This research work has been carried out to establish the combinatorial impact of various fermentation medium constituents, used for poly-ß hydroxybutyrate (PHB) biosynthesis. Model development was performed with an optimized medium composition that enhanced the biosynthesis of PHB from the biowaste material Brewers' spent grain (BSG). The latter was used as a carbon substrate in submerged fermentation with Bacillus sphaericus NCIM 2478. Three independent variables: BSG, yeast extract (YE), and salt solution concentration (SS) and one dependent variable (amount of PHB produced) were assigned. A total of 35 microbial fermentation trials were conducted by which a nonlinear mathematical relationship was established in terms of neural network model between independent and dependent variables. The resulting artificial neural networks (ANNs) model for this process was further optimized using a global genetic algorithm optimization technique, which predicted the maximum production of PHB (916.31 mg/L) at a concentration of BSG (50.12 g/L), concentration of YE (0.22 g/L), and concentration of SS (24.06%, v/v). The experimental value of the quantity of PHB (concentration â¼916 mg/L) was found to be very close to the value predicted by the ANN-GA model approach.
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Grano Comestible , Hidroxibutiratos , Fermentación , Poliésteres/análisis , Redes Neurales de la Computación , AlgoritmosRESUMEN
The mother earth is a source of natural resources that, in conjunction with anthropogenic activities, generates a wide spectrum of different biowastes. These biomaterials can be used as low-cost raw feedstock to produce bioenergy, value-added products, and other commodities. However, the improper management and disposal of these biowastes can generate relevant environmental impacts. Consequently, it is imperative to explore alternative technologies for the valorization and exploitation of these wastes to obtain benefits for the society. This review covers different aspects related to valorization of biowastes and their applications in water pollution, soil fertility and green energy generation. The classification and characteristics of different biowastes (biosolids, animal wastes and effluents, plant biomass, wood and green wastes) including their main generation sources are discussed. Different technologies (e.g., pyrolysis, hydrothermal carbonization, anaerobic digestion, gasification, biodrying) for the transformation and valorization of these residues are also analyzed. The application of biowastes in soil fertility, environmental pollution and energy production are described and illustrative examples are provided. Finally, the challenges related to implement low-cost and sustainable biowaste management strategies are highlighted. It was concluded that reliable simulation studies are required to optimize all the logistic stages of management chain of these residues considering the constraints generated from the economic, environmental and social aspects of the biowaste generation sources and their locations. The recollection and sorting of biowastes are key parameters to minimize the costs associated to their management and valorization. Also, the concepts of Industry 4.0 can contribute to achieve a successful commercial production of the value-added products obtained from the biowaste valorization. Overall, this review provides a general outlook of biowaste management and its valorization in the current context of circular economy.
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Suelo , Tecnología , Animales , Suelo/químicaRESUMEN
Primary (or secondary) metabolites are produced by animals, plants, or microbial cell systems either intracellularly or extracellularly. Production capabilities of microbial cell systems for many types of primary metabolites have been exploited at a commercial scale. But the high production cost of metabolites is a big challenge for most of the bioprocess industries and commercial production needs to be achieved. This issue can be solved to some extent by screening and developing the engineered microbial systems via reconstruction of the genome-scale metabolic model. The predicted genetic modification is applied for an increased flux in biosynthesis pathways toward the desired product. Wherein the resulting microbial strain is capable of converting a large amount of carbon substrate to the expected product with minimum by-product formation in the optimal operating conditions. Metabolic engineering efforts have also resulted in significant improvement of metabolite yields, depending on the nature of the products, microbial cell factory modification, and the types of substrate used. The objective of this review is to comprehend the state of art for the production of various primary metabolites by microbial strains system, focusing on the selection of efficient strain and genetic or pathway modifications, applied during strain engineering.
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Genoma Microbiano , Ingeniería Metabólica , Microbiota , Modelos BiológicosRESUMEN
The abundant availability of various kinds of biomass and their use as feedstock for the production of gaseous and liquid biofuels has been considered a viable, eco-friendly, and sustainable mode of energy generation. Gaseous fuels like biogas and liquid fuels, e.g., bioethanol, biodiesel, and biomethanol derived from biological sources, have been theorized to produce numerous industrially relevant organic compounds replacing the traditional practice of employing fossil fuels as a raw material. Among the biofuels explored, biomethanol has shown promising potential to be a future product addressing multifactorial issues concerning sustainable energy and associated process developments. The presented mini-review has explored the importance and application of biomethanol as a value-added product. The biomethanol production process was well reviewed by focusing on different thermochemical and biochemical conversion processes. Syngas and biogas have been acknowledged as potential resources for biomethanol synthesis. The emphasis on biochemical processes is laid on the principal metabolic pathways and enzymatic machinery involved or used by microbial physiology to convert feedstock into biomethanol under normal temperature and pressure conditions. The advantage of minimizing the cost of production by utilizing suggested modifications to the overall process of biomethanol production that involves metabolic and genetic engineering in microbial strains used in the production process has been delineated. The challenges that exist in our current knowledge domain, impeding large-scale commercial production potential of biomethanol at a cost-effective rate, and strategies to overcome them along with its future scenarios have also been pointed out.
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Among various natural biowastes availability in the environment, agricultural residues showed great impacts. It is due to huge availability and cheap carbon source, creating big challenges for their utility and systematic reduction. Objective of this review is to address the waste biomass availability and huge quantities issues and also put effort to minimize this nutrient load via biotransforming into value-added products. Different wastes (organic/inorganic) generation with their negative issues are due to numbers of developmental and social activities, reported. Currently, various efforts are found for these wastes minimization via generation of different types of value-added products (biogas, bioH2, alcoholic fuel, organic acids and others products) and these wastes in municipal cities are also reported with production of advanced biofuels as promising outcomes. For hydrolysis of complex organic resources including lignocellulosic biomasses, physicochemical, structural or compositional changes are needed that aid in conversion into sugar and organic compounds such as biofuels. So, efficient and effective pretreatment processes selection (physical, biological, chemical or combined one) is critical to achieve these hydrolysis goals and resultant cellulose or hemicellulose components can be accessible by biological catalysis. These can achieve final hydrolysis and fermentative or monomer sugars. And later, synthesis of fuels or value-added products during microbial fermentation or biotransformation processes can be achieved. This review discusses pretreatment techniques for improved hydrolysis for fermentative sugar with emphasis on reduced quantities of toxic compounds (furfural compound) in hydrolyzed biomasses. Minimum deterioration fuel economy also reported with production of different bioproducts including biofuels. Additionally, impacts of toxic products and gasses emission are also discussed with their minimization.
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Contaminación del Aire , Biocombustibles , Biomasa , Hidrólisis , Fermentación , Carbohidratos , Azúcares , Lignina/metabolismoRESUMEN
The major global concern on energy is focused on conventional fossil resources. The burning of fossil fuels is an origin of greenhouse gas emissions resulting in the utmost threat to the environment and subsequently which leads to global climate changes. As far as sustainability is concerned, fuels and materials derived from organic or plant wastes overcome this downside establishing the solution to the fossil resource crisis. In this context, exploration of agricultural residue appears to be a suitable alternative of non-renewable resources to support the environmental feasibility and meet the high energy crisis. The use of agricultural waste as a feedstock for the biorefinery approach emerges to be an eco-friendly process for the production of biofuel and value-added chemicals, intensifying energy security. Therefore, a prospective choice of this renewable biomass for the synthesis of green fuel and other green biochemicals comes up with a favorable outcome in terms of cost-effectiveness and sustainability. Exploiting different agricultural biomass and exploring various biomass conversion techniques, biorefinery generates bioenergy in a strategic way which eventually fits in a circular bioeconomy. Sources and production of agricultural waste are critically explained in this paper, which provides a path for further value addition by various technologies. Biorefinery solutions, along with a life cycle assessment of agricultural waste biomass toward a wide array of value-added products aiding the bioeconomy, are summarized in this paper.
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Combustibles Fósiles , Plantas , Biocombustibles , Biomasa , Estudios Prospectivos , ReciclajeRESUMEN
Pectin possesses a dual property of resistance and flexibility and thus has diverse commercial value which has generated research interest on this versatile biopolymer. Formulated products using pectin could be useful in food, pharma, foam, plasticiser and paper substitute industries. Pectin is structurally tailor-made for greater bioactivity and diverse applications. Sustainable biorefinery leaves greener footprints while producing high-value bioproducts like pectin. The essential oils and polyphenols obtained as byproducts from a pectin-based biorefinery are useful in cosmetics, toiletries and fragrance industries. Pectin can be extracted from organic sources following eco-friendly strategies, and the extraction techniques, structural alterations and the applications are continually being upgraded and standardized. Pectin has great applications in diverse areas, and its green synthesis is a welcome development. In future, growing industrial application of pectin is anticipated as research orients on biopolymers, biotechnologies and renewable source-based processes. As the world is gradually adopting greener strategies in sync with the global sustainable development goal, active involvement of policy makers and public participation are prime. Governance and policy framing are essential in the transition of the world economy towards circularity since green circular bioeconomy is ill-understood among the public in general and within the administrative circles in particular. Concerted efforts by researchers, investors, innovators, and policy and decision makers to integrate biorefinery technologies as loops within loop of biological structures and bioprocesses is suggested. The review focusses on generation of the different nature of food wastes including fruits and vegetables with cauterization of their components. It discusses the innovative extraction and biotransformation approaches for these waste conversions into value-added products at cost-effective and eco-friendly way. This article compiles numerous effective and efficient and green way pectin extraction techniques with their advantages with varying success in an integrated manner.
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Frutas , Pectinas , Frutas/química , Pectinas/análisis , Biotecnología , VerdurasRESUMEN
The metabolic reaction rate vector is a bridge that links gene and protein expression alterations to the phenotypic endpoint. We present a simple approach for the estimation of flux distribution at key branch points in the metabolic network by using substrate uptake, metabolite secretion rate, and biomass growth rate for transketolase (tkt) deficient Bacillus pumilus ATCC 21951. We find that the glucose-6-phosphate (G6P) and pseudo catabolic/anabolic branch points are flexible in the D: -ribose-producing tkt deficient strain of B. pumilus. The normalized flux through the pentose phosphate pathway (PPP) varied from 1.5 to 86 % under different growth conditions, thereby enabling substantial extracellular accumulation of D: -ribose under certain conditions. Interestingly, the flux through PPP was affected by the extracellular phosphate concentration and dissolved oxygen concentration. This metabolic flexibility may have been the underlying reason for this strain being selected from thousands of others in a screening for D: -ribose producers conducted in the 1970s.
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Bacillus/metabolismo , Redes y Vías Metabólicas , Ribosa/biosíntesis , Bacillus/clasificación , Bacillus/enzimología , Bacillus/crecimiento & desarrollo , Biomasa , Oxígeno/metabolismo , Vía de Pentosa Fosfato , Transcetolasa/genética , Transcetolasa/metabolismoRESUMEN
This study surveys the mental behaviour and purchase behaviour of Indian consumers, especially their online purchase behaviour, during a lockdown. Also, it studies their perceptions of job security during a lockdown. Primary data were collected using judgement sampling, and the sample size was 328. Demographic variables such as age, gender, and income affect online purchases in the present study. An increase in the purchase of essentials and hygiene products during COVID-19 has been observed due to a change in mental behaviour. Government have imposed total lock down and prevented people to come out from their houses which resulted in to uncomfortable position. The theory of fear (Ruiter, et. al., 2001) has been applied to explain the purchase behaviour during COVID-19 in emerging markets like India.
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This review explains the various methods of conversion of Carbon dioxide (CO2) to methanol by using homogenous, heterogeneous catalysts through hydrogenation, photochemical, electrochemical, and photo-electrochemical techniques. Since, CO2 is the major contributor to global warming, its utilization for the production of fuels and chemicals is one of the best ways to save our environment in a sustainable manner. However, as the CO2 is very stable and less reactive, a proper method and catalyst development is most important to break the CO2 bond to produce valuable chemicals like methanol. Litertaure says the catalyt types, ratio and it surface structure along with the temperature and pressure are the most controlling parameters to optimize the process for the production of methanol from CO2. This article explains about the various controlling parameters of synthesis of Methanol from CO2 along with the advantages and drawbacks of each process. The mechanism of each synthesis process in presence of metal supported catalyst is described. Basically the activity of Cu supported catalyst and its stability based on the activity for the methanol synthesis from CO2 through various methods is critically described.
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Dióxido de Carbono , Metanol , Dióxido de Carbono/química , Catálisis , Técnicas Electroquímicas , Hidrogenación , Metanol/químicaRESUMEN
Still, in the current period, non-renewable energy sources have contributed to fulfill the current energy requirement and it causes the deficit of available stocks with emission of pollutant byproducts components. In recent years, efforts were made to harness the sustainable/ renewable fuels from renewable sources/ waste, complex organic matters including biomass at global level. Researchers have put attention on harnessing energy from wastewater and MFCs systems. This MFC approach utilizes the wastewater as feed/ carbon sources to generate bioenergy such as bio- hydrogen and electricity in a sustainable and efficient way via completing the wastewater treatment. This approach consists of anode and cathode electrodes with proton exchange membrane (PEM). Microbial fuel cells are utilized with other effective approaches (anaerobic digestion/ fermentation, local demand-based-MFC approach) that are applied to utilize biowastes for microbial cell growth and electron emission. This review discusses the recent and technologically advanced approach such as microbial fuel cells (MFCs). MFCs can apply to fulfill the increasing trends of global energy demand, found with more utilization in home appliances in urban areas, industrial tasks and transportation sectors. Last few decades, there have been recent modifications in MFCs configurations and design that have improved performance of MFCs. Recent design and configuration of MFCs have shown the removal of maximum chemical oxygen demand (up to 94-97%) with generation maximum current output (up to 5.23 mA) from wastewater. This review presents a comprehensive collection of recent information about technologies and design of MFCs with implementation of microbial electrogene with development of wastewater treatment having sustainable fuel/ energy generation at an effective level.
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Fuentes de Energía Bioeléctrica , Contaminantes Ambientales , Carbono , Hidrógeno , Nutrientes , Protones , Aguas ResidualesRESUMEN
Agricultural residues play a pivotal role in meeting the growing energy and bulk chemicals demand and food security of society. There is global concern about the utilization of fossil-based fuels and chemicals which create serious environmental problems. Biobased sustainable fuels can afford energy and fuels for future generations. Agro-industrial waste materials can act as the alternative way for generating bioenergy and biochemicals strengthening low carbon economy. Processing of pineapple generates about 60% of the weight of the original pineapple fruit in the form of peel, core, crown end, and pomace that can be converted into bioenergy sources like bioethanol, biobutanol, biohydrogen, and biomethane along with animal feed and vermicompost as described in this paper. This paper also explains about bioconversion process towards the production of various value-added products such as phenolic anti-oxidants, bromelain enzyme, phenolic flavour compounds, organic acids, and animal feed towards bioeconomy.
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Ananas , Biocombustibles , Agricultura , Animales , Biocombustibles/análisis , Carbono , Residuos Industriales/análisisRESUMEN
Semen was recently shown to contain amyloid fibrils formed from a self-assembling peptide fragment of the protein prostatic acid phosphatase. These amyloid fibrils, termed semen-derived enhancer of virus infection, or SEVI, have been shown to strongly enhance HIV infectivity and may play an important role in sexual transmission of HIV, making them a potential microbicide target. One novel approach to target these fibrils is the use of small molecules known to intercalate into the structure of amyloid fibrils, such as derivatives of thioflavin-T. Here, we show that the amyloid-binding small molecule BTA-EG(6) (the hexa(ethylene glycol) derivative of benzothiazole aniline) is able to bind SEVI fibrils and effectively inhibit both SEVI-mediated and semen-mediated enhancement of HIV infection. BTA-EG(6) also blocks the interactions of SEVI with HIV-1 virions and HIV-1 target cells but does not cause any inflammation or toxicity to cervical epithelial cells. These results suggest that an amyloid-binding small molecule may have utility as a microbicide, or microbicidal supplement, for HIV-1.
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Amiloide/metabolismo , Benzotiazoles/farmacología , VIH-1/efectos de los fármacos , Semen/metabolismo , Animales , Benzotiazoles/química , Benzotiazoles/metabolismo , Línea Celular Tumoral , Células Cultivadas , Propuestas de Licitación , Relación Dosis-Respuesta a Droga , Citometría de Flujo , VIH-1/fisiología , Humanos , Células Jurkat , Cinética , Masculino , Estructura Molecular , Unión Proteica , Tiazoles/química , Virión/metabolismo , Acoplamiento Viral/efectos de los fármacosRESUMEN
The availability of organic matters in vast quantities from the agricultural/industrial practices has long been a significant environmental challenge. These wastes have created global issues in increasing the levels of BOD or COD in water as well as in soil or air segments. Such wastes can be converted into bioenergy using a specific conversion platform in conjunction with the appropriate utilization of the methods such as anaerobic digestion, secondary waste treatment, or efficient hydrolytic breakdown as these can promote bioenergy production to mitigate the environmental issues. By the proper utilization of waste organics and by adopting innovative approaches, one can develop bioenergy processes to meet the energy needs of the society. Waste organic matters from plant origins or other agro-sources, biopolymers, or complex organic matters (cellulose, hemicelluloses, non-consumable starches or proteins) can be used as cheap raw carbon resources to produce biofuels or biogases to fulfill the ever increasing energy demands. Attempts have been made for bioenergy production by biosynthesizing, methanol, n-butanol, ethanol, algal biodiesel, and biohydrogen using different types of organic matters via biotechnological/chemical routes to meet the world's energy need by producing least amount of toxic gases (reduction up to 20-70% in concentration) in order to promote sustainable green environmental growth. This review emphasizes on the nature of available wastes, different strategies for its breakdown or hydrolysis, efficient microbial systems. Some representative examples of biomasses source that are used for bioenergy production by providing critical information are discussed. Furthermore, bioenergy production from the plant-based organic matters and environmental issues are also discussed. Advanced biofuels from the organic matters are discussed with efficient microbial and chemical processes for the promotion of biofuel production from the utilization of plant biomasses.
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Biocombustibles , Carbono , Biomasa , Etanol , SueloRESUMEN
Sperm contributes diverse RNAs to the zygote. While sperm small RNAs have been shown to impact offspring phenotypes, our knowledge of the sperm transcriptome, especially the composition of long RNAs, has been limited by the lack of sensitive, high-throughput experimental techniques that can distinguish intact RNAs from fragmented RNAs, known to abound in sperm. Here, we integrate single-molecule long-read sequencing with short-read sequencing to detect sperm intact RNAs (spiRNAs). We identify 3440 spiRNA species in mice and 4100 in humans. The spiRNA profile consists of both mRNAs and long non-coding RNAs, is evolutionarily conserved between mice and humans, and displays an enrichment in mRNAs encoding for ribosome. In sum, we characterize the landscape of intact long RNAs in sperm, paving the way for future studies on their biogenesis and functions. Our experimental and bioinformatics approaches can be applied to other tissues and organisms to detect intact transcripts.
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Secuencia Conservada/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , ARN/genética , Imagen Individual de Molécula , Espermatozoides/metabolismo , Animales , Evolución Molecular , Ontología de Genes , Humanos , Masculino , Ratones Endogámicos C57BL , ARN/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ribosomas/metabolismo , Testículo/metabolismo , Transcriptoma/genéticaRESUMEN
Coronavirus (COVID-19) started its invasion as an epidemic from Wuhan, China and propagated to become the scary pandemic that reached more than 200 countries all over the world. High number of infected people and unfortunately high mortality are the result of this invasion. The Indian scenario is no exception to this deadly infection attack, though it started a bit late. The first case in India came into notice in January and the number of cases showed an enormous growth in mid March and still continue to grow. This timely report focuses on the current invasion scenario in India as of 11th May 2020; with total cases of 67,152, active cases of 44, 029, deaths totaling to 2206 and over-all recoveries of â¼20,917 patients.
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This review emphasizes utilization of waste organic matters from water bodies and soil sources for sustainable energy development. These organic waste matters (including microplastics) from a variety of environmental sources have created a big challenge to utilize them for energy development for human needs, maintaining a cleaner environment and thereby, producing useful bioproducts (sustainable bioenergy or other primary metabolites). Anaerobic digestions as well as other effective wastewater treatment approaches are discussed. From the water bodies, waste organic matter reduction can be achieved by a reduction of chemical oxygen demand and biological oxygen demand after the waste treatment. Other forms of organic waste matter are available in the form of agro wastes or residues (stalk of wheat or rice, maize, corn etc.) due to crop cultivation, which are generally burnt into ashes. Such wastes can be utilized for bioenergy energy production, which would help for the reduction of climate changes or other toxic gases. Hydrogen, bioelectricity, ethanol, butanol, methane and algal diesel or other types of fuel sources would help to provide sustainable source of bioenergy that can be produced from these wastes via degradation by the biological processes. This review will discuss in depths about the sustainable nature of organic matters to produce clean energy via application of efficient biological methods to maintain a clean environment, thereby providing alternative options to fossil energy fuels.
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Energía Renovable , Hidrógeno , Metano , Plásticos , Aguas ResidualesRESUMEN
Fermentation with transketolase (tkt) deficient strain of Bacillus is the only reported industrially viable process for production of D-ribose, a commercially important pentose sugar. In addition to direct effects of tkt deficiency, the mutation in non-oxidative part of pentose phosphate pathway (PPP) is known to display several unexpected physiological characteristics such as decreased ability to utilize D-glucose, altered carbon catabolite repression, lack of motility, etc. Here we demonstrate the morphological plasticity of tkt deficient strain of Bacillus pumilus ATCC 21951 and its possible relation with D-ribose productivity, a measure of carbon flux through PPP. The bacilli divide normally in nutrient rich media such as Luria-Bertani (LB) broth while showing cell elongation of up to 20-fold without a visible septum accompanied by moderate to high extracellular D-ribose accumulation in glucose-rich media. The cells stained with DAPI (4'-6-diamidino-2-phenylindole) and anti FtsZ antibody showed nucleoid separation and Z-ring formation in LB broth but not in glucose-rich media. FtsZ protein is known to localize at the future division site forming a ring, called Z-ring, at an early stage in cytokinesis. The strain experiences inhibition or delay in Z-ring formation resulting in cell elongation, possibly due to its altered cell membrane composition resulting from tkt deficiency. We hypothesize that the lack of PPP intermediates may have two effects on the strain: (i) altered the cell membrane leading to delay in Z-ring formation and cell elongation; and (ii) induction of genes of the oxidative part of PPP resulting in D-ribose accumulation. Nutrient rich media such as LB broth may alleviate these metabolite deficiencies thereby restoring normal cell division and inhibiting excessive D-ribose accumulation. The D-ribose productivity and cell elongation may therefore be co-morbid. The results have implications in designing optimal media and monitoring strategy based on morphological analysis.
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Bacillus/citología , Bacillus/metabolismo , Proteínas Bacterianas/genética , Ribosa/metabolismo , Transcetolasa/genética , Bacillus/crecimiento & desarrollo , Proteínas Bacterianas/metabolismo , Biomasa , Medios de Cultivo/química , Proteínas del Citoesqueleto/metabolismo , Fermentación , Eliminación de Gen , Concentración de Iones de Hidrógeno , Viabilidad MicrobianaRESUMEN
Synthetic pyrethroids are the recent major class of broad spectrum, photostable, organic insecticides used in agricultural, domestic and veterinary applications and now account for more than 30% of global insecticide use. Cypermethrin is metabolized and eliminated significantly more slowly by fish than by mammals or birds, which may explain this compound's high toxicity in fish compared to other organisms. The present communication deals with histoanatomical alterations in the gonads of a local fresh water food fish, Channa punctatus exposed to 0.033 ppm (96 hr LC50 X 1/10) concentration of a synthetic pyrethroid, devicyprin (cypermethrin 25%) in aquatic medium of aged tap water for 15, 30 and 45 days respectively. In testis, exposure dependent histological damage has been observed in terms of vacuolization, condensation of spermatogonic cells, distortion of tubular epithelium, shrinkage of interstitial cells and general inflammatory responses. Longest exposure of 45 days has resulted in peculiar starry-sky appearance of the testicular tissue. Gross histo-anatomy of ovarian tissue reveals epithelial lesions, inflammatory responses, stromal hemorrhage, increased interstitium and shrinkage of yolk vesicles towards periphery These findings are quite suggestive of reproductive impairments leading to delayed gonadal maturity and adversely affecting processes of sperm production and ovulation and thus, the fish production.
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Gónadas/efectos de los fármacos , Gónadas/fisiopatología , Insecticidas/toxicidad , Perciformes/fisiología , Piretrinas/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Femenino , Agua Dulce , Humanos , Concentración de Iones de Hidrógeno , Insecticidas/metabolismo , Masculino , Piretrinas/metabolismo , Temperatura , Factores de Tiempo , Pruebas de Toxicidad , Contaminantes Químicos del Agua/metabolismoRESUMEN
Obesity is considered detrimental to women's reproductive health. Although most of the attention has been focused on the effects of obesity on hypothalamic function, studies suggest a multifactorial impact. In fact, obesity is associated with reduced fecundity even in women with regular cycles, indicating that there may be local ovarian effects modulating fertility. Here we describe a novel mechanism for leptin actions directly in the ovary that may account for some of the negative effects of obesity on ovarian function. We find that normal cycling, obese, hyperleptinemic mice fed with a high-fat diet are subfertile and ovulate fewer oocytes compared with animals fed with a normal diet. Importantly, we show that leptin induces expression of the neuropeptide cocaine- and amphetamine-regulated transcript (CART) in the granulosa cells (GCs) of ovarian follicles both in vitro and in vivo. CART then negatively affects intracellular cAMP levels, MAPK signaling, and aromatase mRNA expression, which leads to lower estradiol synthesis in GCs and altered ovarian folliculogenesis. Finally, in human samples from patients undergoing in vitro fertilization, we show a significant positive correlation between patient body mass index, CART mRNA expression in GCs, and CART peptide levels in follicular fluid. These observations suggest that, under obese conditions, CART acts as a local mediator of leptin in the ovary to cause ovarian dysfunction and reduced fertility.