Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

INTEGRATED NUTRIENT MANAGEMENT IN POTATO WITH COMPOST MADE THROUGH DIFFERENT BIO-DEGRADATION PROCESSES

To achieve the goal of safe and sustainable food, the only realistic option now-a-days lies with the introduction of a low input farming system concept i.e. organic and integrated agriculture. Keeping in view the present scenario, a study was undertaken in Satyapole village, Haringhata block of Nadia district, West Bengal on integrated nutrient management in potatoes during rabi 2018 and 2019. The efficacy of different composts, in terms of their quality, easiness of preparation along with yield and economic attributes were accessed for the high nutrient loving crop, potato. The experiment was planned out in randomized block design (RBD) with 5 treatments and 4 replications. High yield with a marginal difference was found among all the treatments with integrated management. But, the treatment with 50% of recommended inorganic fertilizer dose (recommended dose N:P: K @ 200:150:150 kg/ha, 1/3 N, full P and 1/3 K as basal; 1st and 2nd top dressing with 1/3 N and 1/3 K) and vermicompost @ 5 ton/ha showed the best result. According to the B: C ratio composting with NOVCOM showed the best result whereas, in terms of the bio-degradation process with respect to its end-product quality, easiness of procedure, and cost, compost made through waste decomposer and NOVCOM has better results in comparison with vermicompost

Microcalorimetry and spectroscopic studies on the binding of dye janus green blue to deoxyribonucleic acid

The interaction of the phenazinium dye janus green blue (JGB) with deoxyribonucleic acid was investigated using isothermal titration calorimetry and thermal melting experiments. The calorimetric data were supplemented by spectroscopic studies. Calorimetry results suggested the binding affinity of the dye to DNA to be of the order of 105 M-1. The binding was predominantly entropy driven with a small negative favorable enthalpy contribution to the standard molar Gibbs energy change.The binding became weaker as the temperature and salt concentration was raised. The temperature dependence of the standard molar enthalpy changes yielded negative values of standard molar heat capacity change for the complexation revealing substantial hydrophobic contribution in the DNA binding. An enthalpy–entropy compensation behavior was also observed in the system. The salt dependence of the binding yielded the release of 0.69 number of cations on binding of each dye molecule. The non-polyelectrolytic contribution was found to be the predominant force in the binding interaction. Thermal melting studies revealed that the DNA helix was stabilized against denaturation by the dye. The binding was also characterized by absorbance, resonance light scattering and circular dichroism spectral measurements. The binding constants from the spectral results were close to those obtained from the calorimetric data. The energetic aspects of the interaction of the dye JGB to double stranded DNA are supported by strong binding revealed from the spectral data

Mass Transfer and Volume Changes in French Fries During Air Frying

An erratum to this article can be found at http://dx.doi.org/10.1007/s11947-012-0904-8 (The graph located in the left upper corner of Fig. 2 is incorrect)The production of healthier fried foods requires the adaptation of industrial processes. In this context, air frying is an alternative to deep oil frying to obtain French fries with lower fat content. Kinetic analysis of compositional changes and main fluxes involved in air frying were carried out, and the results were compared to those obtained for deep oil frying. The influence of the type of sample (unpretreated, frozen, or blanched potatoes) was also analyzed. The results showed that oil uptake is much lower in air frying although a much longer processing time is required. Also, water loss and thus the loss of volume were much higher in air frying compared to the conventional process.The authors would like to thank the Universitat Politecnica de Valencia (PAID-06-09-2876) for the financial support given to this investigation.Andrés Grau, AM.; Argüelles Foix, AL.; Castelló Gómez, ML.; Heredia Gutiérrez, AB. (2013). Mass Transfer and Volume Changes in French Fries During Air Frying. Food and Bioprocess Technology. 6(8):1917-1924. https://doi.org/10.1007/s11947-012-0861-2S1917192468Aguilar, C. N., Anzaldúa-Morales, R., Talamás, R., & Gastélum, G. (1997). Low-temperature blanch improves textural quality of French-fries. Journal of Food Science, 62, 568–571.AOAC. (1980). Official methods of analysis (12th ed.). Washington, D.C., USA: Association of Official Analytical Chemists.Califano, A. N., & Calvelo, A. (1987). Adjustment of surface concentration of reducing sugars before frying of potato strips. Journal of Food Processing and Preservation, 12, 1–9.Clark, J. P. (2003). Happy birthday, potato chip! And other snack developments. Food Technology, 57(5), 89–92.Debnath, S., Bhat, K. K., & Rastogi, N. K. (2003). Effect of pre-drying on kinetics of moisture loss and oil uptake during deep fat frying of chickpea flour-based snack food. LWT—Food Science and Technology, 36, 91–98.Du Pont, M. S., Kirby, A. B., & Smith, A. C. (1992). Instrumental and sensory tests of cooked frozen French fries. International Journal of Food Science and Technology, 27, 285–295.Dueik, V., Robert, P., & Bouchon, P. (2010). Vacuum frying reduces oil uptake and improves the quality parameters of carrot crisps. Food Chemistry, 119(3), 1143–1149.Hubbard, L. J., & Farkas, B. E. (2000). Influence of oil temperature on convective heat transfer during immersion frying. Journal of Food Processing and Preservation, 24(2), 143–162.Krokida, M. K., Oreopoulou, V., & Maroulis, Z. B. (2000). Water loss and oil uptake as a function of frying time. Journal of Food Engineering, 44, 39–46.Mestdagh, F., De Wilde, T., Fraselle, S., Govaert, Y., Ooghe, W., Degroodt, J. M., Verhé, R., Van Peteghem, C., & De Meulenaer, B. (2008). Optimization of the blanching process to reduce acrylamide in fried potatoes. LWT- Food Science and Technology, 41(9), 1648–1654.Mohsenin, N. M. (1986). Physical properties of plant and animal materials. Nueva York: Gordon and Breach.Moyano, P. C., & Pedreschi, F. (2006). Kinetics of oil uptake during frying of potato slices: effect of pre-treatments. LWT- Food Science and Technology, 39, 285–291.Ngadi, M. O., Wang, Y., Adedeji, A. A., & Raghavan, G. S. V. (2009). Effect of microwave pretreatment on mass transfer during deep-fat frying of chicken nugget. LWT- Food Science and Technology, 42(1), 438–440.Pedreschi, F., & Moyano, P. (2005). Oil uptake and texture development in fried potato slices. Journal of Food Engineering, 70(4), 557–563.Saguy, S., & Dana, D. (2003). Integrated approach to deep fat frying: engineering, nutrition, health and consumer aspects. Journal of Food Engineering, 56, 143–152.Troncoso, E., & Pedreschi, F. (2009). Modeling water loss and oil uptake during vacuum frying of pre-treated potato slices. LWT- Food Science and Technology, 42(6), 1164–1173

Type I insulin-like growth factor receptor over-expression induces proliferation and anti-apoptotic signaling in a three-dimensional culture model of breast epithelial cells

INTRODUCTION: Activation of the type I insulin-like growth factor receptor (IGFIR) promotes proliferation and inhibits apoptosis in a variety of cell types. Transgenic mice expressing a constitutively active IGFIR or IGF-I develop mammary tumors and increased levels of IGFIR have been detected in primary breast cancers. However, the contribution of IGFIR activation in promoting breast cancer progression remains unknown. Mammary epithelial cell lines grown in three-dimensional cultures form acinar structures that mimic the round, polarized, hollow and growth-arrested features of mammary alveoli. We used this system to determine how proliferation and survival signaling by IGFIR activation affects breast epithelial cell biology and contributes to breast cancer progression. METHODS: Pooled, stable MCF-10A breast epithelial cells expressing wild-type IGFIR or kinase-dead IGFIR (K1003A) were generated using retroviral-mediated gene transfer. The effects of over-expression of wild-type or kinase-dead IGFIR on breast epithelial cell biology were analyzed by confocal microscopy of three-dimensional cultures. The contribution of signaling pathways downstream of IGFIR activation to proliferation and apoptosis were determined by pharmacological inhibition of phosphatidylinositol 3' kinase (PI3K) with LY294002, MAP kinase kinase (MEK) with UO126 and mammalian target of rapamycin (mTOR) with rapamycin. RESULTS: We found that MCF-10A cells over-expressing the IGFIR formed large, misshapen acinar structures with filled lumina and disrupted apico-basal polarization. This phenotype was ligand-dependent, occurring with IGF-I or supraphysiological doses of insulin, and did not occur in cells over-expressing the kinase-dead receptor. We observed increased proliferation, decreased apoptosis and increased phosphorylation of Ser(473 )of Akt and Ser(2448 )of mTOR throughout IGFIR structures. Inhibition of PI3K with LY294002 or MEK with UO126 prevented the development of acinar structures from IGFIR-expressing but not control cells. The mTOR inhibitor rapamycin failed to prevent IGFIR-induced hyperproliferation and survival signaling. CONCLUSION: Increased proliferation and survival signaling as well as loss of apico-basal polarity by IGFIR activation in mammary epithelial cells may promote early lesions of breast cancer. Three-dimensional cultures of MCF-10A cells over-expressing the IGFIR are a useful model with which to study the role of IGFIR signaling in breast cancer progression and for characterizing the effects of chemotherapeutics targeted to IGFIR signaling

Mining a Cathepsin Inhibitor Library for New Antiparasitic Drug Leads

The targeting of parasite cysteine proteases with small molecules is emerging as a possible approach to treat tropical parasitic diseases such as sleeping sickness, Chagas' disease, and malaria. The homology of parasite cysteine proteases to the human cathepsins suggests that inhibitors originally developed for the latter may be a source of promising lead compounds for the former. We describe here the screening of a unique ∼2,100-member cathepsin inhibitor library against five parasite cysteine proteases thought to be relevant in tropical parasitic diseases. Compounds active against parasite enzymes were subsequently screened against cultured Plasmodium falciparum, Trypanosoma brucei brucei and/or Trypanosoma cruzi parasites and evaluated for cytotoxicity to mammalian cells. The end products of this effort include the identification of sub-micromolar cell-active leads as well as the elucidation of structure-activity trends that can guide further optimization efforts

A multiscale systems perspective on cancer, immunotherapy, and Interleukin-12

Monoclonal antibodies represent some of the most promising molecular targeted immunotherapies. However, understanding mechanisms by which tumors evade elimination by the immune system of the host presents a significant challenge for developing effective cancer immunotherapies. The interaction of cancer cells with the host is a complex process that is distributed across a variety of time and length scales. The time scales range from the dynamics of protein refolding (i.e., microseconds) to the dynamics of disease progression (i.e., years). The length scales span the farthest reaches of the human body (i.e., meters) down to the range of molecular interactions (i.e., nanometers). Limited ranges of time and length scales are used experimentally to observe and quantify changes in physiology due to cancer. Translating knowledge obtained from the limited scales observed experimentally to predict patient response is an essential prerequisite for the rational design of cancer immunotherapies that improve clinical outcomes. In studying multiscale systems, engineers use systems analysis and design to identify important components in a complex system and to test conceptual understanding of the integrated system behavior using simulation. The objective of this review is to summarize interactions between the tumor and cell-mediated immunity from a multiscale perspective. Interleukin-12 and its role in coordinating antibody-dependent cell-mediated cytotoxicity is used illustrate the different time and length scale that underpin cancer immunoediting. An underlying theme in this review is the potential role that simulation can play in translating knowledge across scales

Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development

Seven classes of mitogen-activated protein kinase (MAPK) intracellular signalling cascades exist, four of which are implicated in breast disease and function in mammary epithelial cells. These are the extracellular regulated kinase (ERK)1/2 pathway, the ERK5 pathway, the p38 pathway and the c-Jun N-terminal kinase (JNK) pathway. In some forms of human breast cancer and in many experimental models of breast cancer progression, signalling through the ERK1/2 pathway, in particular, has been implicated as being important. We review the influence of ERK1/2 activity on the organised three-dimensional association of mammary epithelial cells, and in models of breast cancer cell invasion. We assess the importance of epidermal growth factor receptor family signalling through ERK1/2 in models of breast cancer progression and the influence of ERK1/2 on its substrate, the oestrogen receptor, in this context. In parallel, we consider the importance of these MAPK-centred signalling cascades during the cycle of mammary gland development. Although less extensively studied, we highlight the instances of signalling through the p38, JNK and ERK5 pathways involved in breast cancer progression and mammary gland development