Search

The global obesity epidemic cannot be attributed solely to high caloric intake and inactivity. Recent systematic reviews and meta-analyses suggest a correlation between exposure to the insecticide DDT/ DDE and elevated body fat, reduced energy expenditure, and heightened obesity risk. There is evidence that these effects of DDT/DDE are mediated by a decrease in brown adipose tissue (BAT) thermogenesis, which is under the regulatory influence of the sympathetic nervous system. A recent study found that developmental exposure to DDT and DDE decreased sympathetic innervation of BAT and decreased synaptic density in peripheral sympathetic ganglia, suggesting a possible mechanism by which DDT and DDE exposure during development increases risk of obesity. To determine whether these changes to sympathetic morphology observed in vivo are due to direct effects of DDT on sympathetic neurons, we exposed primary sympathetic neurons derived from embryonic rat superior cervical ganglia (SCG) to p,p’-DDT and its main metabolite p,p’-DDE and measured axonal and dendritic morphology. At the concentrations tested (0.01 to 1 µM), neither DDT nor DDE altered the number of axons and dendrites per neuron. However, DDT significantly reduced axonal length in both male and female sympathetic neurons at 1 µM and 0.1 µM, respectively. Both DDT and DDE significantly reduced BMP-7-induced dendritic outgrowth in male neurons at concentrations greater than 0.1 µM and in female neurons at all concentrations that were tested. In cultures not exposed to BMP-7, neither DDT nor DDE altered dendritic growth. These morphological effects of DDT and DDE occurred at concentrations that did not decrease cell viability, as assessed by calcein uptake and release of lactate dehydrogenase into the culture media. Collectively, these data demonstrate that DDT and DDE have a direct effect on morphology of sympathetic neurons with female neurons being more sensitive to exposure than neurons from male rats and dendrites being more vulnerable to DDT and DDE exposure than axons in both sexes.

Abstract of the DissertationClinical Investigations on Human Health Responses to Thirdhand Smoke and Electronic Cigarette ExposurebyShane Sakamaki-ChingDoctor of Philosophy, Graduate Program in Cell, Molecular, and Developmental BiologyUniversity of California, Riverside, March 2022Dr. Prue Talbot, ChairpersonBackground: Cigarette smoking causes diseases such as cancer, heart disease, and stroke. The diseases associated with electronic cigarettes (ECs) are not as well understood. Cigarette smoking leaves a residue, thirdhand smoke (THS), on indoor surfaces. The health effects of THS on humans is limited to one study. Our purposes were to: (1) identify urinary biomarkers of potential harm and exposure and correlate these to metal concentrations in urine from cigarette smokers and EC users; (2) determine the responses of humans dermally exposed to THS; and (3) identify molecular changes in keratinocytes exposed to THS extract.Methods: In Chapter 1, urine from non-smokers, EC users, and cigarette smokers was evaluated for biomarkers of exposure, effect, and potential harm. In Chapter 2, human participants were exposed dermally to clothing impregnated with filtered clean air or THS; their urine was analyzed for biomarkers of exposure and harm, and their plasma was analyzed using proteomics. In Chapter 3, molecular responses of keratinocytes to extracts from THS impregnated fabric were determined.Results: In Chapter #1, urinary biomarkers of exposure, effect, and potential harm were elevated in EC users and cigarette smokers; increased EC usage was correlated with elevated metal concentrations, which correlated with oxidative DNA damage. In Chapter #2, THS-exposure significantly elevated urinary 8-OHdG, 8-isoprostane, and protein carbonyls and activated pathways associated with inflammation, oxidative stress, and skin disease initiation. In Chapter #3, THS in keratinocytes caused proinflammation, and oxidative stress, mitochondrial damage, and elevated keratin 5 levels.Conclusion: Cigarette smoking and EC vaping elevated DNA damage by oxidization which was correlated with total metal concentrations in the urine of cigarette smokers and EC vapers, a change which may lead to disease. Dermal THS exposure significantly increased oxidative damage to DNA, lipids, and proteins in humans. Inflammation was elevated at 3 hours and persisted for 22 hours, which could in the long-term lead to disease. Keratinocytes exposed to THS extracts had elevated molecular risk factors for developing inflammatory skin diseases, including cancer. THS-induced responses in keratinocytes were similar to those in cigarette smokers, implicating THS as an environmental hazard that should be monitored.

This survey was conducted to document the distribution, market potential, medicinal properties, and conservation status of wild food plants (WFPs) which are consumed by local communities of poor socioeconomic background, residing near the Pakistan-Afghan border. Data were collected via semi-structured during 2017–2020 and a total of 288 informers were interviewed in a different locality. In this survey, a total of 95 WFPs species of 39 families and 58 genera were documented. Among these WFPS, 70% of species are ethno-medicinally known. August was the peak month for the accessibility of WFPs (i.e., 17%). The most consumed parts were leaves (37%) and fruit (36%). Plant species of 36 families out of 39 were marketable and reported for the first time, which was further interrelated with taste, ethnobotanical, ethnomedicinal value, FC, and relative frequency of citation (RFC). Rhamnaceae and Rosaceae were the dominant families with the highest number of frequencies of citation (FC) and number of species. The highest FC (77) and RFC (0.267) were calculated for Ziziphus jujuba. This study presents the market potential and distribution of the WFPs for the first time in a war-affected zone. These findings would facilitate local people along the Pakistan-Afghan border and researchers to utilize WFPs to fulfill food requirements. We suggest that further pharmacological and biological assessments of these plants can contribute to economic prosperity, and increase the dietary diversity of this region.

The proton-coupled folate transporter (PCFT; SLC46A1) was discovered in 2006 as the principal mechanism by which folates are absorbed in the intestine and the causal basis for hereditary folate malabsorption (HFM). In 2011, it was found that PCFT is highly expressed in many tumors. This stimulated interest in using PCFT for cytotoxic drug targeting, taking advantage of the substantial levels of PCFT transport and acidic pH conditions commonly associated with tumors.We summarize the literature from 2006 to 2022 that explores the role of PCFT in the intestinal absorption of dietary folates and its role in HFM and as a transporter of folates and antifolates such as pemetrexed (Alimta) in relation to cancer. We provide the rationale for the discovery of a new generation of targeted pyrrolo[2,3-We summarize the promising future and potential challenges of implementing PCFT-targeted therapeutics for HFM and a variety of cancers.

An increase in beet production at the present stage is possible only with the use of intensive technologies, where the integrated protection of crops from harmful organisms is of great social and economic importance. In the system of measures aimed at increasing the production of beetroots, an important place is the protection of sugar beets from diseases. Successful control of sugar beet diseases is an important reserve for increasing the yield and sugar content of root crops and improving their technological quality. A rather dangerous disease of sugar beet is the root eater, which is widespread throughout Ukraine, especially in the zone of sufficient moisture. Conducting studies to study the effect of certain agro technical measures, as more economically affordable, on the formation of harmful microorganisms that contribute to the development of root and other root diseases during the growing season, the effect of sugar beet concentration in crop rotation. In the experiments, various types of crop rotation were studied: grain-sowing, grain-cultivating (with green manure) and fruit-bearing. The technology for growing crops is generally accepted. Pesticides were not used in the experiments, with the exception of seed dressing. Studies have established that the main causative agent of the root in the conditions of the western forest-steppe of Ukraine are various species of fungi of the genus Fusarium i Aphanomyces cochliondes. The dominance of these pathogens among pathogens causes the most severe defeat of beets in the phase of the first pair of leaflets, as well as the death of plant diseases in a later period - after the formation of planting density. Studies have shown that the lowest prevalence of sugar beet diseases was observed at a saturation level of 17% when they were grown in one place after 5 years (the average degree of development of the root was 14.7%). The development of the disease increased with a decrease in the time of returning to the previous place of cultivation in the rotation. So, on average, over a three-year period, the reduction of this period to four to two years increased the degree of root beetle damage to 15.4-19.8%. At a one-year break and re-sowing, this indicator was 24.4% and 27.2%, respectively. Based on the results obtained, it can be argued that an increase in the concentration of sugar beets in the crop rotation leads to an increase in the distribution of the root.

Despite the high prevalence of alcoholic liver disease, its identification and characterization remain poor, especially in early stages such as alcoholic fatty liver disease and alcoholic steatohepatitis. This latter implies diagnostic difficulties, few therapeutic options and unclear mechanisms of action. To elucidate the metabolic alterations and pinpoint affected biochemical pathways, alcoholic steatohepatitis was simulated in vitro by exposing HepaRG cells to ethanol (IC10, 368 mM) and tumor necrosis factor alpha (TNF-α, 50 ng/mL) for 24 h. This combined exposure was compared to solely ethanol-exposed as well as -nonexposed cells. Four different metabolomics platforms were used combining liquid chromatography, high-resolution mass spectrometry and drift tube ion mobility to elucidate both intracellular and extracellular metabolic alterations. Some of the key findings include the influence of TNF-α in the upregulation of hepatic triglycerides and the downregulation of hepatic phosphatidylethanolamines and phosphatidylcholines. S-Adenosylmethionine showed to play a central role in the progression of alcoholic steatohepatitis. In addition, fatty acyl esters of hydroxy fatty acid (FAHFA)-containing triglycerides were detected for the first time in human hepatocytes and their alterations showed a potentially important role during the progression of alcoholic steatohepatitis. Ethoxylated phosphorylcholine was identified as a potential new biomarker of ethanol exposure.

Black rice (Zizania aqatica) is famous for its high nutritional value. Other names given for this rice are forbidden rice, emperor’s rice and royal’s rice. Mainly this rice is originated from Asian countries. The richest country in cultivation of black rice is China (62%) followed by Sri Lanka (8.6 %), Indonesia (6.2%) and India holds the 4th placed with (5.1%) follows by different countries. It contains a high amount of antioxidant which is known as anthocyanin and tocopherols (which is one of the most powerful antioxidants and it is also known as vitamin E). Foods which consist of antioxidant are black in colour or dark purple. It is also rich in fibre, protein, carbohydrates, potassium and B vitamins respectively. Activity of “free radicals” in our body is naturally dominated by another group of chemical compounds called ‘antioxidant’ which are present in our regularly consumed food. Therefore, consuming of black rice in your regular diet can prevent many non-communicable diseases (NCD) like occurrence of cancer cells, atherosclerosis, hypertension, diabetes, osteoporosis, asthma, digestive health, reduces stroke risk level in women. Black rice is also use in developing a new novel food product.

Cardiometabolic disorders such as metabolic syndrome, obesity, diabetes, cardiovascular disease, and non-alcoholic fatty liver disease are growing public health problems across the world. Among known cardiometabolic risk factors are obesogens such as endocrine disrupting chemicals (EDCs), exogenous chemical compounds that induce endocrine and metabolic dysfunctions. To date, the species- and tissue-specific influence of EDCs on molecular programs and cardiometabolic risks has not been fully elucidated. We performed a comprehensive data-driven transcriptome-wide analysis of 44 publicly available datasets for 4 EDCs, namely Bisphenol(BPA), Bis(2-ethylhexyl) phthalate (DEHP), Tributyltin (TBT), and Perfluorooctanoic acid (PFOA), to elucidate the perturbation in genes and pathways induced by these chemicals in a species- and tissue-specific manner. Our study identified various metabolic pathways including lipid metabolism, cholesterol biosynthesis and fatty acid metabolism to be up-regulated across all chemicals and species, whereas down-regulated pathways were largely species- and tissue-specific, including immune response, cell cycle, and metabolism terms. Taken together, the genes and pathways identified highlight differential responses of the transcriptome between tissue and species and help infer the mechanisms underlying the connections between EDCs and cardiometabolic diseases.

Sodium azide, referred to as “NaN3” or “azide” in this thesis, is a common pesticide, laboratory preservative, and propellent in vehicular airbags due to its explosive properties. Despite its practical utilities, azide is highly toxic. Ingestion of several grams can cause death in 1-2 hours. Azide’s high toxicity in conjunction to its commercial availability are causes for concern and the chemical is listed as a potential terrorism threat (Holstege et al. 2007). There are two proposed mechanisms of azide toxicity: inhibition of cellular respiration via cytochrome C oxidase inhibition and generation of nitric oxide. Inhibition of cytochrome C by azide is well documented but generation of nitric oxide has only recently been found in vivo. Since there is no FDA-approved antidote for azide poisoning, development of an antidote for azide poisoning is a public health priority. Members of the Boss Lab have shown that cobinamide (Cbi), a vitamin B12 analog, scavenges azide and nitric oxide. We hypothesized that cobinamide could antagonize azide poisoning based on azide’s mechanism of toxicity and how cobinamide functions. We determined that azide inhibited cell growth and cobinamide offered protection. We saw that D. melanogaster (fruit flies) raised on food containing cobinamide were partially protected from azide toxicity, with survival as a readout. We found that azide induced nitric oxide generation in mice. Finally, we observed that cobinamide rescued mice poisoned with a lethal dose of azide. Altogether our results demonstrated azide toxicity in vitro and in vivo and that cobinamide could reverse these toxic effects.

Background: Anemia is one of the most common complications of Chronic Kidney Disease (CKD). The vast majority of Egyptian CKD patients are interchangeably treated with Darbepoetin Alfa (DPA) and Epoetin Alfa (EPA) to achieve and maintain target hemoglobin levels. Our study aimed to compare the efficacy and safety of DPA versus EPA for managing anemia amongst Egyptian patients with CKD undergoing dialysis. Methods: A multicenter, open label, randomized, prospective, parallel study was conducted. Patients with CKD undergoing dialysis with Hb level < 10 g/dl were enrolled. The primary efficacy endpoint was the change in hemoglobin concentration at the evaluation period (weeks 20-24). Prespecified adverse events of interest following administration, including blood transfusions requirement, blood pressure and hemoglobin excursions, the relationship between C - Reactive Protein (CRP) and hemoglobin, were assessed. Results: Only 98 of 104 enrolled patients completed the study, fifty patients received EPA, and 48 patients received DPA. Our results showed that a significantly higher percentage of patients who achieved target Hb level ≥ 11 g/dL in DPA treated group vs. EPA as well as the meantime to achieve Hb level ≥ 10 g/dL was shorter in DPA treated group. Safety profiles of both treatments were similar. A negative correlation was observed between serum CRP and hemoglobin level in hemodialysis patients. Conclusion: Our study showed that DPA was more effective and well tolerated in achieving and maintaining Hb levels with lower dosing frequency compared to EPA. Furthermore, CRP is recommended to be routinely measured where patients with higher CRP require high ESA doses.

Helicoverpa armigera is one of the most devastating, cosmopolitan, polyphagous and multivoltine pests of agricultural crops. The growing side-effects of synthetic insecticides used to control agricultural pests, have amplified demand for the relatively safe and biodegradable compounds which offer benefits over synthetic chemical insecticides. Hence, the current study investigates the effects of Nerium oleander methanol leaf extracts on the physiological and reproductive fitness of H. armigera. Addition of the range of extract concentration; 0.5%–10.0%; in the larval diet induced an appreciable and dose-dependent effect on the developmental parameters of H. armigera. The extract, though resulted in moderate larval and pupal mortality, caused significant growth regulatory effects. A prolonged larval duration, formation of larval-pupal intermediates and significant reduction in the average larval weight gain by 26.5% - 63.4%; and pupal weight by 23.9% - 63.4% was recorded. The 74.6% to 54.9% reduction in the oviposition duration in the emerged adults, and diminished fecundity and egg hatch in the corresponding range of 0.78–0.63 and 0.89–0.62 demonstrated negative impact of the extract on the adult reproductive fitness. The adverse impact of N. oleander methanol leaf extracts on the growth and development of H. armigera leading to the reproductive disadvantage in adults can be beneficial in the field management; though its use can only be ascertained after identification of bioactive constituents and elucidating their mode of action.

Animal dissection remains a common practice in American biology classrooms, despite the availability of dissection alternatives to study anatomy and physiology. Indeed, there is a growing body of evidence in the literature suggesting that the use of alternatives leads to the greater achievement of learning objectives, as compared to dissection. To better understand the current use of and attitudes toward dissection and alternatives, a nationwide survey of (mainly high-school) biology teachers ( n = 2687) was conducted. Most educators believed that learning objectives related to biology subject content could be met through the use of alternatives, yet they preferred the hands-on experience of dissection. Most educators allow their students to use alternatives if requested, although few teachers ask students about their preference for using an animal specimen versus an alternative. Educators cited student engagement as the main factor driving their decision to choose between dissection specimens and alternatives, and felt that cost is the biggest barrier to implementing alternatives at their schools. Additional perspectives on dissection and alternatives were shared by survey participants. Since alternatives can be used to meet learning objectives associated with dissection, we recommend their use as replacements for traditional animal specimens, in line with the replacement, reduction and refinement of animal use in education, according to the Three Rs principles.

Chillies and chilli-based products are important spices on a global basis. The production, processing, transport and storage phases of chillies are prone to infection by Aspergillus Section Flavi and contamination with aflatoxins (AFs), especially aflatoxin B1 (AFB1) for which legislative limits exist in many countries. We have examined the effect of the interacting abiotic factors of water availability (water activity, aw; 0.995-0.850 aw) and temperature (15-37 °C) on (a) lag phases prior to growth, (b) growth, (c) AFB1 production and (d) contour maps of optimum and boundary conditions for colonisation and toxin production by three Aspergillus flavus strains on a 10% chilli-based medium. Additional studies with whole red chillies + A. flavus conidial inoculum on AFB1 contamination during storage for 10-20 days at 30 °C were also carried out. In vitro, the lag phases before growth were delayed by lower temperatures (15, 20 °C) and aw levels (0.928-0.901 aw). There was no statistical difference in growth between the three strains. Optimal growth was at 37 °C and 0.982 aw with no growth at 0.85 aw. Optimal temperature × aw conditions for AFB1 production were at 30 °C and 0.982 aw with no statistical difference in production between strains. No AFB1 was produced at 15-20 °C at 0.901 and 0.928 aw levels, respectively. In situ studies with A. flavus inoculated whole red chillies at 0.90 and 0.95 aw found that this species became the major component of the total fungal populations at 30 °C after 10-20 days storage. AFB1 contamination was above the European legislative limits (5 μg/kg) for spices at 0.90 aw after 20 days storage and at 0.95 aw after 10 and 20 days. This suggests that storage conditions of ≥0.90 aw, especially at ≥25-30 °C represents a significant risk of contamination with AFB1 at levels where rejection might occur, even after only 10-20 days storage.

Maize is consumed world-wide as staple food, livestock feed, and industrial raw material. However, it is susceptible to fungal attack and at risk of aflatoxin contamination under certain conditions. Such contamination is a serious threat to human and animal health. Ensuring that the maize used by food industry meets standards for aflatoxin levels requires significant investment across the supply chain. Good Agricultural Practices (GAP) form a critical part of a broader, integrated strategy for reduction of aflatoxin contamination. We reviewed and summarised the GAP of maize that would be effective and practicable for aflatoxin control within high-risk regions for smallholder farmers. The suggested practicable GAP for smallholder farmers were: use of drought-tolerant varieties; timely harvesting before physiological maturity; sorting to remove damaged ears and those having poor husk covering; drying properly to 13% moisture content; storage in suitable conditions to keep the crop clean and under condition with minimally proper aeration, or ideally under hermetic conditions. This information is intended to provide guidance for maize growers that will help reduce aflatoxin in high-risk regions, with a specific focus on smallholder farmers. Following the proposed guidelines would contribute to the reduction of aflatoxin contamination during pre-harvest, harvest, and post-harvest stages of the maize value chain.

Aflatoxin M1 (AFM1) contamination in milk and milk products may pose a major public health concern. The present cross-sectional study was aimed to estimate the prevalence of AFM1 in bovine milk across all districts of Punjab, India and to identify the associated animal and farm level risk factors. A total of 402 milk samples (266 cow milk and 136 buffalo milk) were analysed using commercial ELISA and representative samples were confirmed using HPLC-FLD. The results revealed that 56.2 and 13.4% of the milk samples exceeded the maximum levels of the European Union, i.e. 0.05 μg/l and Food Safety and Standards Authority of India (FSSAI), i.e. 0.5 μg/l for AFM1 in milk, respectively. On analysis of species variation, buffalo milk (prevalence: 56.6%; mean concentration: 0.42±0.9 μg/l) was found to have higher AFM1 levels than cow milk (prevalence: 56.0%; mean concentration: 0.19±0.3 μg/l), with statistically significant difference between mean concentrations (P1 prevalence (P=0.91). Furthermore, milk from commercial dairy farms (prevalence: 64.7%; mean concentration: 0.34±0.65 μg/l) was found to be more contaminated than from household dairy establishments (prevalence: 47.8%; mean concentration: 0.19±0.65 μg/l). The risk factors ‘above average milk yield/day’ (odds ratio (OR): 2.4) and ‘poor animal hygiene’ (OR: 1.9) were identified at animal level, and ‘intensive dairy farming’ (OR: 3.1) and ‘animal feed without aflatoxin binder’ (OR: 4.7) as farm level risk factors for AFM1 excretion above maximum levels of European Union in milk. Among cow breeds, the milk from ‘non-descript’ breed (OR: 11.5) was found to be most contaminated with AFM1 and the least from Jersey breed (OR: 1.0). The present study highlighted the presence of AFM1 in milk samples; therefore, regular monitoring of AFM1 in milk is required so that high risk regions and associated risk factors can be addressed appropriately.

Control failure of pests and selectivity of insecticides to beneficial arthropods are key data for the implementation of Integrated Pest Management (IPM) programs. Therefore, the aim of this study was to assess the control failure likelihood of Plutella xylostella and the physiological selectivity active ingredients to parasitoid Oomyzus sokolowskii (Hymenoptera: Eulophidae) and to predators Polybia scutellaris (Hymenoptera: Vespidae) and Lasiochilus sp. (Hemiptera: Anthocoridae). In bioassays, P. xylostella larvae and O. sokolowskii, P. scutellaris and Lasiochilus sp. adults were used. Concentration-mortality curves of six insecticides for P. xylostella were established. These curves were used to estimate the mortality of P. xylostella at the recommended concentration, in order to check a control failure of insecticides to this pest. Furthermore, the lethal concentration for 90% of populations (LC90) and the half of LC90 were used in bioassays with the natural enemies to determine the selectivity of these insects to insecticides. All tested insecticides showed control failure to P. xylostella, indicated by high LC90 and low estimated mortalities (less than 80%). The cartap insecticide was selective in half of LC90 to Lasiochilus sp. and moderately selective in LC90 and the half of LC90, to Lasiochilus sp. and P. scutellaris, respectively. Deltamethrin was moderately selective in the half of LC90 to predator Lasiochilus sp. Cartap, carbaryl, and deltamethrin reduced the mortality of Lasiochilus sp. in the half LC90. The results also showed that the insecticides methamidophos, carbaryl, parathion methyl and permethrin were not selective to any of the tested natural enemies. The role of insecticides in IPM systems of Brassica crops is discussed based on their control failures to P. xylostella and selectivity to their natural enemies.

The aim of this study was to monitor pesticide residues in the blood of agricultural workers (farmers, pesticide dealers, and spraying workers) living in the Dakahlia Governorate, Egypt. Residue analysis revealed that 48, 76, and 84% of the farmers, pesticide dealers, and spraying workers had pesticide residues in their bloods, respectively. Eleven compounds were detected in the blood of examined individuals. According to the World Health Organization (WHO) classification, most of these pesticides (nine pesticides) were in moderately hazardous compounds. Carbofuran, a highlyhazardous compound was the most toxic. The compound with the lowest toxicity was hexytiazox, which is unlikely to pose an acute hazard in normal use. Chlorpyrifos was found in the blood of 38.3% of the study subjects, followed by acetamiprid (11.7%) and profenofos (10.7%), while fenvalerate was the lowest occurring compound (1.3%). Of the collected samples 41.3% was free of pesticide residues, while 58.7% of the samples was contaminated. Furthermore, the amounts of all detected pesticides were below the no observable adverse effect levels (NOAEL). Also, 38.7% of the samples had only one pesticide, while 8% of them contained residues of two pesticides, and 5.3% contained more than two compounds. The worker’s age did not affect the accumulations of pesticide residues in their bodies. However, there was a strong correlation between pesticide residues accumulation and an individual’s exposure time. Therefore, from these results it can be seen that encouraging greater awareness among pesticide users of the need to improve safe usage and handling of pesticides by education, advice, and warning them of the risks involved in the misuse of these poisonous materials is highly recommended.