Zebrafish-A Suitable Model for Rapid Translation of Effective Therapies for Pediatric Cancers.

Pediatric cancers are the leading cause of disease-related deaths in children and adolescents. Most of these tumors are difficult to treat and have poor overall survival. Concerns have also been raised about drug toxicity and long-term detrimental side effects of therapies. In this review, we discuss the advantages and unique attributes of zebrafish as pediatric cancer models and their importance in targeted drug discovery and toxicity assays. We have also placed a special focus on zebrafish models of pediatric brain cancers-the most common and difficult solid tumor to treat.

Delayed sowing and its ramifications: biophysical, yield and quality analysis of wheat cultivars in the northwest Indo-Gangetic plains.

BACKGROUND: The continuous cultivation of rice-wheat in the same field is a key element of double-cropping systems in the Indo-Gangetic plains. Yields of such cropping systems are increasingly challenged as climate change drives increases in temperature, terminal stress and uneven rainfall, delaying rice harvesting and subsequently delaying sowing of wheat. In this paper, we evaluate the optimum sowing dates to achieve high grain yield and quality of wheat cultivars in northwest India. Three cultivars of wheat, HD-2967, HD-3086 and PBW-723, were sown on three different dates at the research farm of ICAR-IARI, New Delhi, to generate different weather conditions at different phenological stages. Different biophysical attributes, photosynthetic rate, stomatal conductance and transpiration rate, were measured at different phenological stages. Yield and grain quality parameters such as protein, starch, amylopectin, amylose and gluten were measured in different cultivars sown on different dates. RESULTS: Biophysical parameters were found to be higher in timely sown crops followed by late-sown and very late-sown crops. Further, the different sowing dates had a significant (P < 0.05) impact on the grain quality parameters such as protein, starch, amylopectin, amylose and gluten content. Percentage increases in the value of starch and amylose content under timely sown were ~7% and 11.6%, ~5% and 8.4%, compared to the very late-sown treatment. In contrast, protein and amylopectin contents were found to increase by ~9.7% and 7.5%, ~13.8% and 16.6% under very late-sown treatment. CONCLUSION: High-temperature stress during the grain-filling periods significantly decreased the grain yield. Reduction in the grain yield was associated with a reduction in starch and amylose content in the grains. The protein content in the grains is less affected by terminal heat stress. Cultivar HD-3086 had higher growth, yield as well as quality parameters, compared to HD-2967 and PBW-723 in all treatments, hence could be adopted by farmers in northwest India. © 2024 Society of Chemical Industry.

α2δ1-mediated maladaptive sensory plasticity disrupts adipose tissue homeostasis following spinal cord injury.

Spinal cord injury (SCI) increases the risk of cardiometabolic disorders, including hypertension, dyslipidemia, and insulin resistance. Not only does SCI lead to pathological expansion of adipose tissue, but it also leads to ectopic lipid accumulation in organs integral to glucose and insulin metabolism. The pathophysiological changes that underlie adipose tissue dysfunction after SCI are unknown. Here, we find that SCI exacerbates lipolysis in epididymal white adipose tissue (eWAT). Whereas expression of the α2δ1 subunit of voltage-gated calcium channels increases in calcitonin gene-related peptide-positive dorsal root ganglia neurons that project to eWAT, conditional deletion of the gene encoding α2δ1 in these neurons normalizes eWAT lipolysis after SCI. Furthermore, α2δ1 pharmacological blockade through systemic administration of gabapentin also normalizes eWAT lipolysis after SCI, preventing ectopic lipid accumulation in the liver. Thus, our study provides insight into molecular causes of maladaptive sensory processing in eWAT, facilitating the development of strategies to reduce metabolic and cardiovascular complications after SCI.

Gene Signature Associated with Nervous System in an Experimental Radiation- and Estrogen-Induced Breast Cancer Model.

Breast cancer is frequently the most diagnosed female cancer in the world. The experimental studies on cancer seldom focus on the relationship between the central nervous system and cancer. Despite extensive research into the treatment of breast cancer, chemotherapy resistance is an important issue limiting the efficacy of treatment. Novel biomarkers to predict prognosis or sensitivity to chemotherapy are urgently needed. This study examined nervous-system-related genes. The profiling of differentially expressed genes indicated that high-LET radiation, such as that emitted by radon progeny, in the presence of estrogen, induced a cascade of events indicative of tumorigenicity in human breast epithelial cells. Bioinformatic tools allowed us to analyze the genes involved in breast cancer and associated with the nervous system. The results indicated that the gene expression of the Ephrin A1 gene (EFNA1), the roundabout guidance receptor 1 (ROBO1), and the kallikrein-related peptidase 6 (KLK6) was greater in T2 and A5 than in the A3 cell line; the LIM domain kinase 2 gene (LIMK2) was greater in T2 than A3 and A5; the kallikrein-related peptidase 7 (KLK7), the neuroligin 4 X-linked gene (NLGN4X), and myelin basic protein (MBP) were greater than A3 only in T2; and the neural precursor cell expressed, developmentally down-regulated 9 gene (NEDD9) was greater in A5 than in the A3 and E cell lines. Concerning the correlation, it was found a positive correlation between ESR1 and EFNA1 in BRCA-LumA patients; with ROBO1 in BRCA-Basal patients, but this correlation was negative with the kallikrein-related peptidase 6 (KLK6) in BRCA-LumA and -LumB, as well as with LIMK2 and ROBO1 in all BRCA. It was also positive with neuroligin 4 X-linked (NLGN4X) in BRCA-Her2 and BRCA-LumB, and with MBP in BRCA-LumA and -LumB, but negative with KLK7 in all BRCA and BRCA-LumA and NEDD9 in BRCA-Her2. The differential gene expression levels between the tumor and adjacent tissue indicated that the ROBO1, KLK6, LIMK2, KLK7, NLGN4X, MBP, and NEDD9 gene expression levels were higher in normal tissues than in tumors; however, EFNA1 was higher in the tumor than the normal ones. EFNA1, LIMK2, ROBO1, KLK6, KLK7, and MBP gene expression had a negative ER status, whereas NEDD9 and NLGN4X were not significant concerning ER status. In conclusion, important markers have been analyzed concerning genes related to the nervous system, opening up a new avenue of studies in breast cancer therapy.

The Kinetics of Transtentorial Brain Herniation: Kernohan-Woltman Notch Phenomenon Revisited.

PURPOSE OF REVIEW: To critically review recent literature in understanding the pathological consequences of transtentorial brain herniation resulting from unilateral expanding supratentorial mass lesions. RECENT FINDINGS: Modern neuroimaging assists in understanding the consequences of transtentorial brain herniation with the development of the Kernohan-Woltman notch phenomenon. MRI studies in post-operative patients undergoing craniotomy and removal of expanding unilateral hemispheric mass lesions (usually an extradural or subdural hematoma) have shown striking findings in the contralateral crus cerebri suggestive of damage as a result of impact against the free margin of the opposite tentorium as suggested by Kernohan and Woltman nearly a century back in autopsy studies. MR changes include T1 hypointensity, T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensity, DW1 hyperintensity with restriction of diffusion, presence of hypointensity in GRE sequences and evidence of axonal damage in the corticospinal tracts in the cerebral peduncle in diffusion tensor imaging and MR tractography. The pathological basis of such changes may be variable or a combination of several pathological processes, which may all be related to the impact/compression of the contralateral crus with the tentorial margin. These include contusion, compression, demyelination, and perhaps most importantly microvascular damage including microbleeds. The role of uncal herniation is debatable. It appears that as a result of massive lateral shift in the supratentorial compartment, there is a transient forceful impact of the opposite cerebral peduncle against the rigid tentorial border to induce one or more of the abovementioned phenomena to explain the imaging findings. The limitation of these studies is that most of them have been done in the post-operative periods and surgical manipulations can surely alter anatomical relationships between intracranial structures. The exact sequence of events happening intracranially in the face of rapidly expanding supratentorial mass lesions is largely unknown. Even with rapid progress in neuroimaging, documentation of such changes during life are difficult, principally for logistic reasons. Consequently, the very truth of the much taught about phenomenon of uncal herniation and the resultant Kernohan-Woltman notch phenomenon and the false localizing sign of unilateral motor weakness and contralateral pupillary dilation have been questioned. Animal experimentation and autopsy studies have not contributed much in our understanding of the actual process happening intracranially in such an emergent situation. The midbrain undoubtedly is the key structure bearing the brunt of the effect of brain shift which is more lateral than downward in cases with unilateral expanding lesions. Structural changes in the cerebral peduncles have now been visualized with modern neuroimaging. These alterations may result from the interplay of one or more factors which include compression, contusion, demyelination, and perhaps most importantly microvascular ischemia and hemorrhage resulting from a forceful yet transient impact of the cerebral peduncle with the tough tentorial margin. The last mentioned hypothesis would be in conformity with Kernohan and Woltman's concept of elastic deformation of the midbrain. In the present article an attempt is made to provide a historical account of the changing concepts in relation to brain herniation as systematically and chronologically as possible, and then, critically review recent neuroimaging observations with a view to hypothesize on the sequence of events during transtentorial brain herniation.

Vertical distributions of radionuclides along the tourist-attractive Marayon Tong Hill in the Bandarban district of Bangladesh.

This is the first attempt in the world to depict the vertical distribution of radionuclides in the soil samples along several heights (900 feet, 1550 feet, and 1650 feet) of Marayon Tong hill in the Chittagong Hill Tracts, Bandarban by HPGe gamma-ray spectrometry. The average activity concentrations of 232Th, 226Ra, and 40K were found to be 37.15 ± 3.76 Bqkg-1, 19.69 ± 2.15 Bqkg-1, and 347.82 ± 24.50 Bqkg-1, respectively, where in most cases, 232Th exceeded the world average value of 30 Bqkg-1. According to soil characterization, soils ranged from slightly acidic to moderately acidic, with low soluble salts. The radium equivalent activity, outdoor and indoor absorbed dose rate, external and internal hazard indices, external and internal effective dose rates, gamma level index, and excess lifetime cancer risk were evaluated and found to be below the recommended or world average values; but a measurable activity of 137Cs was found at soils collected from ground level and at an altitude of 1550 feet, which possibly arises from the nuclear fallout. The evaluation of cumulative radiation doses to the inhabitants via periodic measurement is recommended due to the elevated levels of 232Th.This pioneering work in mapping the vertical distribution of naturally occurring radioactive materials (NORMs) can be an essential factual baseline data for the scientific community that may be used to evaluate the variation in NORMs in the future, especially after the commissioning of the Rooppur Nuclear Power Plant in Bangladesh in 2024.

Ionizing Radiation and Estrogen Affecting Growth Factor Genes in an Experimental Breast Cancer Model.

Genes associated with growth factors were previously analyzed in a radiation- and estrogen-induced experimental breast cancer model. Such in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line, MCF-10F, to low doses of high linear energy transfer (LET) α particle radiation (150 keV/µm) and subsequent growth in the presence or absence of 17ß-estradiol. The MCF-10F cell line was analyzed in different stages of transformation after being irradiated with either a single 60 cGy dose or 60/60 cGy doses of alpha particles. In the present report, the profiling of differentially expressed genes associated with growth factors was analyzed in their relationship with clinical parameters. Thus, the results indicated that Fibroblast growth factor2 gene expression levels were higher in cells transformed by radiation or in the presence of ionizing radiation; whereas the fibroblast growth factor-binding protein 1gene expression was higher in the tumor cell line derived from this model. Such expressions were coincident with higher values in normal than malignant tissues and with estrogen receptor (ER) negative samples for both gene types. The results also showed that transforming growth factor alpha gene expression was higher in the tumor cell line than the tumorigenic A5 and the transformed A3 cell line, whereas the transforming growth factor beta receptor 3 gene expression was higher in A3 and A5 than in Tumor2 cell lines and the untreated controls and the E cell lines. Such gene expression was accompanied by results indicating negative and positive receptors for transforming growth factor alpha and the transforming growth factor beta receptor 3, respectively. Such expressions were low in malignant tissues when compared with benign ones. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expressions were found to be present in all BRCA patients that are BRCA-Basal, BRCA-LumA, and BRCA-LumB, except in BRCA-Her2 patients. The results also indicated that the insulin growth factor receptor gene expression was higher in the tumor cell line Tumor2 than in Alpha3 cells transformed by ionizing radiation only; then, the insulin growth factor receptor was higher in the A5 than E cell line. The insulin growth factor receptor gene expression was higher in breast cancer than in normal tissues in breast cancer patients. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expression levels were in stages 3 and 4 of breast cancer patients. It can be concluded that, by using gene technology and molecular information, it is possible to improve therapy and reduce the side effects of therapeutic radiation use. Knowing the different genes involved in breast cancer will make possible the improvement of clinical chemotherapy.

Cell Adhesion Molecules Affected by Ionizing Radiation and Estrogen in an Experimental Breast Cancer Model.

Cancer develops in a multi-step process where environmental carcinogenic exposure is a primary etiological component, and where cell-cell communication governs the biological activities of tissues. Identifying the molecular genes that regulate this process is essential to targeting metastatic breast cancer. Ionizing radiation can modify and damage DNA, RNA, and cell membrane components such as lipids and proteins by direct ionization. Comparing differential gene expression can help to determine the effect of radiation and estrogens on cell adhesion. An in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line MCF-10F to low doses of high linear energy transfer α particle radiation and subsequent growth in the presence of 17ß-estradiol. The MCF-10F cell line was analyzed in different stages of transformation that showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth, and invasive capability before becoming tumorigenic in nude mice. This model was used to determine genes associated with cell adhesion and communication such as E-cadherin, the desmocollin 3, the gap junction protein alpha 1, the Integrin alpha 6, the Integrin beta 6, the Keratin 14, Keratin 16, Keratin 17, Keratin 6B, and the laminin beta 3. Results indicated that most genes had greater expression in the tumorigenic cell line Tumor2 derived from the athymic animal than the Alpha3, a non-tumorigenic cell line exposed only to radiation, indicating that altered expression levels of adhesion molecules depended on estrogen. There is a significant need for experimental model systems that facilitate the study of cell plasticity to assess the importance of estrogens in modulating the biology of cancer cells.

Geometric thermodynamics of strain-induced crystallization in polymers.

Going beyond the classical Gaussian approximation of Einstein's fluctuation theory, Ruppeiner gave it a Riemannian geometric structure with an entropic metric. This yielded a fundamental quantity, the Riemannian curvature, which was used to extract information on the nature of interactions between molecules in fluids, ideal gases, and other open systems. In this article, we examine the implications of this curvature in a nonequilibrium thermodynamic system where relaxation is sufficiently slow so as not to invalidate the local equilibrium hypothesis. The nonequilibrium system comprises a rubbery polymer undergoing strain induced crystallization. The curvature is found to impart information on a spurious isochoric energy arising from the conformational stretching of already crystallized segments. This unphysical component perhaps arises as the crystallized manifold is considered Euclidean with the stretch measures defined via the Euclidean metric. The thermodynamic state associated with curvature is the key to determine the isochoric stretch and hence the spurious energy. We determine this stretch and propose a form for the spurious free energy that must be removed from the total energy in order for the correct stresses to be recovered.

Protocol for assessing ex vivo lipolysis of murine adipose tissue.

Here, we provide a detailed protocol for assessing ex vivo lipolysis of subcutaneous and visceral white adipose tissue. We describe a robust approach to detect depot-specific changes in lipolytic potential under basal and beta-adrenergic receptor-stimulated conditions. Given that adipose tissue plays a critical role in systemic metabolic health, this experimental protocol can be used to determine changes in adipose tissue function in health and disease.

Evaluation of cytogenotoxic potential and embryotoxicity of KRS-Cauvery River water in zebrafish (Danio rerio).

In the Cauvery River (CR), indiscriminate discharge of waste causes unexplained skeletal deformity in some fish species present in the water. To investigate this phenomenon, we analyzed the biological, physical, and chemical parameters present in the water and then evaluated the toxicity effects on the zebrafish (Danio rerio) model. The zebrafish were treated with KRS-CR water samples collected from three stations (fast-flowing water [X], slow-flowing [Y], and stagnant [Z] water), before and after filtration. Firstly, we detected microscopic organisms (MO) such as Cyclops, Daphnia, Spirogyra, Spirochaeta, and total coliform (Escherichia coli), which are bioindicators of water pollution present in the samples. All physicochemical parameters analyzed, including heavy metals before and after filtration of the water with Millipore filter paper (0.45 µm), were within the acceptable limits set by standard organizations, except for decreased dissolved oxygen (DO), and increased biochemical oxygen demand (BOD), and chemical oxygen demand (COD), which are indicators of hypoxic water conditions, as well as the presence of microplastics (polybutene (< 15 µm), polyisobutene (≤ 20 µm), and polymethylpentene (≤3 mm)) and cyclohexyl in CR water samples. Zebrafish embryos treated with the water samples, both before and after filtration exerts the same cytogenotoxic effects by inducing increased reactive oxygen species (ROS) production, which triggers subcellular organelle dysfunctions, DNA damage, apoptosis, pericardial edema, skeletal deformities, and increased mortality. As a result, we observed that both water samples and zebrafish larvae had significantly less oxygen using SEM and EDS. Our findings show that KRS-CR water can induce cytogenotoxic and embryotoxic defects in zebrafish due to hypoxic water conditions triggered by the microplastics influx. The present study would provide valuable insights for health hazards evaluation and future river water treatment strategies.

Evaluation of developmental toxicity and genotoxicity of aqueous seed extract of Croton tiglium L. using zebrafish.

Croton tiglium L. has been used in Ayurvedic and Chinese herbal medicinal formulations from ancient times. Although its seeds are widely prescribed as traditional medicine, there is a dearth of information, regarding its toxic effects, and the mechanisms underlying its toxicity. This study aims to investigate the developmental toxicity and genotoxicity of the aqueous seed extract of C. tiglium L. (AECT) in zebrafish. We have examined the effects of AECT on the early embryonic development of zebrafish. Zebrafish embryos, treated with different concentrations of the AECT, suffered embryonic lethality and displayed various developmental defects. The 96 h-LC50 of AECT was found to be 162.78 µg/ml. Interestingly, the developmental abnormalities observed, such as pericardial edema (PE), yolk sac edema (YSE), spinal curvature (SC), and delayed hatching, varied in severity, in a dose-dependent manner. Zebrafish embryos, treated with different concentrations of AECT, exhibited exaggerated cell death in the anatomical regions of brain, heart, and trunk. Our data suggest that the phenomenon of apoptosis is probably responsible for both embryonic lethality and developmental toxicity in zebrafish embryos. Furthermore, the genotoxic potential of the AECT, in vivo, was evaluated using micronucleus assay and comet assay, on the peripheral blood of zebrafish. The results suggest that AECT has the potential to cause genotoxicity in the peripheral blood of zebrafish.

Gene Signatures Induced by Ionizing Radiation as Prognostic Tools in an In Vitro Experimental Breast Cancer Model.

This study aimed to analyze the expression of genes involved in radiation, using an Affymetrix system with an in vitro experimental breast cancer model developed by the combined treatment of low doses of high linear energy transfer (LET) radiation α particle radiation and estrogen yielding different stages in a malignantly transformed breast cancer cell model called Alpha model. Altered expression of different molecules was detected in the non-tumorigenic Alpha3, a malignant cell line transformed only by radiation and originally derived from the parental MCF-10F human cell line; that was compared with the Alpha 5 cell line, another cell line exposed to radiation and subsequently grown in the presence 17ß-estradiol. This Alpha5, a tumorigenic cell line, originated the Tumor2 cell line. It can be summarized that the Alpha 3 cell line was characterized by greater gene expression of ATM and IL7R than control, Alpha5, and Tumor2 cell lines, it presented higher selenoprotein gene expression than control and Tumor2; epsin 3 gene expression was higher than control; stefin A gene expression was higher than Alpha5; and metallothionein was higher than control and Tumor2 cell line. Therefore, radiation, independently of estrogen, induced increased ATM, IL7R, selenoprotein, GABA receptor, epsin, stefin, and metallothioneins gene expression in comparison with the control. Results showed important findings of genes involved in cancers of the breast, lung, nervous system, and others. Most genes analyzed in these studies can be used for new prognostic tools and future therapies since they affect cancer progression and metastasis. Most of all, it was revealed that in the Alpha model, a breast cancer model developed by the authors, the cell line transformed only by radiation, independently of estrogen, was characterized by greater gene expression than other cell lines. Understanding the effect of radiotherapy in different cells will help us improve the clinical outcome of radiotherapies. Thus, gene signature has been demonstrated to be specific to tumor types, hence cell-dependency must be considered in future treatment planning. Molecular and clinical features affect the results of radiotherapy. Thus, using gene technology and molecular information is possible to improve therapies and reduction of side effects while providing new insights into breast cancer-related fields.

The Role of Lipids, Lipid Metabolism and Ectopic Lipid Accumulation in Axon Growth, Regeneration and Repair after CNS Injury and Disease.

Axons in the adult mammalian nervous system can extend over formidable distances, up to one meter or more in humans. During development, axonal and dendritic growth requires continuous addition of new membrane. Of the three major kinds of membrane lipids, phospholipids are the most abundant in all cell membranes, including neurons. Not only immature axons, but also severed axons in the adult require large amounts of lipids for axon regeneration to occur. Lipids also serve as energy storage, signaling molecules and they contribute to tissue physiology, as demonstrated by a variety of metabolic disorders in which harmful amounts of lipids accumulate in various tissues through the body. Detrimental changes in lipid metabolism and excess accumulation of lipids contribute to a lack of axon regeneration, poor neurological outcome and complications after a variety of central nervous system (CNS) trauma including brain and spinal cord injury. Recent evidence indicates that rewiring lipid metabolism can be manipulated for therapeutic gain, as it favors conditions for axon regeneration and CNS repair. Here, we review the role of lipids, lipid metabolism and ectopic lipid accumulation in axon growth, regeneration and CNS repair. In addition, we outline molecular and pharmacological strategies to fine-tune lipid composition and energy metabolism in neurons and non-neuronal cells that can be exploited to improve neurological recovery after CNS trauma and disease.

Long-term conservation agriculture and best nutrient management improves productivity and profitability coupled with soil properties of a maize-chickpea rotation.

Conservation agriculture (CA)-based practices have been promoted and recouped, as they hold the potential to enhance farm profits besides a consistent improvement in soil properties. A 7 years' field experiment consisting of three crop establishment practices viz., zero-till flatbed (ZTFB), permanent beds (PNB), conventional system (CT) along with the three-nutrient management; nutrient expert-based application (NE), recommended fertilization (RDF), and farmers' fertilizer practice (FFP), was carried out from 2013 to 2020. The CA-based practices (ZTFB/PNB) produced 13.9-17.6% greater maize grain-equivalent yield (MGEY) compared to the CT, while NE and RDF had 10.7-20% greater MGEY than the FFP. PNB and ZTFB gave 28.8% and 24% additional net returns than CT, while NE and RDF had 22.8% and 17.4% greater returns, respectively over FFP. PNB and ZTFB had 2.3-4.1% (0.0-0.20 m soil layers) lower bulk density than the CT. Furthermore, microbial biomass carbon (MBC) increased by 8-19% (0.0-0.50 m soil layers) in ZTFB/PNB over the CT, and by 7.6-11.0% in NE/RDF over FFP. Hence, CA-based crop establishment coupled with the NE or RDF could enhance the yields, farm profits, soil properties of the maize-chickpea rotation, thereby, could sustain production in the long run.

Signs of carcinogenicity induced by parathion, malathion, and estrogen in human breast epithelial cells (Review).

Cancer development is a multistep process that may be induced by a variety of compounds. Environmental substances, such as pesticides, have been associated with different human diseases. Organophosphorus pesticides (OPs) are among the most commonly used insecticides. Despite the fact that organophosphorus has been associated with an increased risk of cancer, particularly hormone­mediated cancer, few prospective studies have examined the use of individual insecticides. Reported results have demonstrated that OPs and estrogen induce a cascade of events indicative of the transformation of human breast epithelial cells. In vitro studies analyzing an immortalized non­tumorigenic human breast epithelial cell line may provide us with an approach to analyzing cell transformation under the effects of OPs in the presence of estrogen. The results suggested hormone­mediated effects of these insecticides on the risk of cancer among women. It can be concluded that, through experimental models, the initiation of cancer can be studied by analyzing the steps that transform normal breast cells to malignant ones through certain substances, such as pesticides and estrogen. Such substances cause genomic instability, and therefore tumor formation in the animal, and signs of carcinogenesis in vitro. Cancer initiation has been associated with an increase in genomic instability, indicated by the inactivation of tumor­suppressor genes and activation of oncogenes in the presence of malathion, parathion, and estrogen. In the present study, a comprehensive summary of the impact of OPs in human and rat breast cancer, specifically their effects on the cell cycle, signaling pathways linked to epidermal growth factor, drug metabolism, and genomic instability in an MCF­10F estrogen receptor­negative breast cell line is provided.

Egr1 mediates the effect of insulin on leptin transcription in adipocytes.

In mammals, leptin production in adipocytes is up-regulated by feeding and insulin. Although this regulatory connection is central to all physiological effects of leptin, its molecular mechanism remains unknown. Here, we show that the transcription factor early growth response 1, Egr1, is rapidly but transiently induced by insulin in adipose cells both in vitro and in vivo, and its induction is followed by an increase in leptin transcription. ChIP and luciferase assays demonstrate that Egr1 directly binds to and activates the leptin promoter. Interestingly, the lipid droplet protein FSP27 may work as a co-factor for Egr1 in regulating leptin expression. By using siRNA-mediated knockout of Egr1 along with its overexpression in adipocytes, we demonstrate that Egr1 is both necessary and sufficient for the stimulatory effect of insulin on leptin transcription.

A novel wavefront measuring camera for quantitative measurement of density in high-speed gas flows.

This paper presents the development of a novel wavefront measuring camera capable of detecting both the amplitude and phase of the captured light wave simultaneously. The main objective of the present work is to develop a simple "aim and shoot" camera system for quantitative estimation of density variations in high-speed gas flow fields. The interrogating beam which is a plane wave used here gets distorted by flow induced change in refractive index gradients. Wavefront distortion is quantitatively measured by inspecting the projected pattern through the embedded mask of a modified CMOS image sensor, which samples the incoming wavefront space continuously. Post-processing of the captured images through Fourier- and windowed Fourier transform schemes reveals the change in phase and amplitude of the captured wave. The captured phase of the wavefront is used in an iterative tomography scheme to estimate the density distribution of the flow field. The utility of the developed camera is demonstrated in the quantitative visualization of the high-speed flow fields around test objects subjected to hypersonic flows at Mach numbers 8.89 and 5.82 in hypersonic shock tunnel facility (HST2) and also to visualize the flow field generated at the exit of a convergent-divergent nozzle (Mach number 2.9). It is observed that the recovered quantitative density values from the experiments match well with the results obtained through computational fluid dynamic simulations demonstrating the proficiency of the proposed wavefront measuring camera for high-speed flow diagnostics.

Shock-wave imaging by density recovery from intensity measurements.

A method for quantitative estimation of density variation in high-speed flow, which uses light as an interrogating tool, is described. The wavefront distortion of the interrogating beam induced by the compressible flow field is estimated quantitatively, in which the density gradient of the flow field is seen as refractive-index gradient by the probing beam. The distorted wavefront is measured quantitatively by using the cross-sectional intensities of the distorted wavefront along the optical axis. Iterative algorithms are developed using both deterministic (Gauss-Newton) and stochastic (ensemble Kalman filter) update strategies to recover unknown parameters such as the phase of the wavefront or the refractive index distribution in the flow directly from the measured intensities. With phase recovered in the first step, a ray tomography algorithm is used to obtain the refractive index and density distributions in the flow from the phase. Experiments are conducted to quantitatively visualize the shock-wave-induced flow field in a shock-tunnel facility. The reconstructed density cross sections, obtained using different reconstruction methods, are presented and compared with those obtained by solving the Navier-Stokes equation using computational fluid dynamic routines. It is observed that the iterative algorithms always outperform those depending on solution of the transport-of-intensity equation. In particular, when using the iterative algorithms, the stochastic search scheme outperforms the Gauss-Newton method.