Charge Transfer-oxy Radical Mechanism for Anti-cancer Agents

The proposal is advanced that anti-cancer drugs generally function by charge transfer resulting in formation of toxic oxy radicals which destroy the neoplasm. Electrochemical studies were performed with some of the main types of agents: iminium ions (adenine iminium from alkylating species, iminium metabolite of 6-mercaptopurine, nitidine, other polynuclear iminiums) and metal complexes (Pt(II)diaquodiammine-guanosine, copper salicylaldoximes). Reduction potentials ranged from -0.4 to -1.2 V. Literature data for quinones are presented and radiation is discussed. Based on the theoretical framework, a rationale is offered for the carcinogen-anti-cancer paradox and the role of antioxidants

Modelling of laboratory data of bi-directional reflectance of regolith surface containing Alumina

Bidirectional reflectance of a surface is defined as the ratio of the scattered radiation at the detector to the incident irradiance as a function of geometry. The accurate knowledge of the bidirectional reflection function (BRF) of layers composed of discrete, randomly positioned scattering particles is very essential for many remote sensing, engineering, biophysical applications and in different areas of Astrophysics. The computations of BRF's for plane parallel particulate layers are usually reduced to solve the radiative transfer equation (RTE) by the existing techniques. In this work we present our laboratory data on bidirectional reflectance versus phase angle for two sample sizes of 0.3 and 1 $\mu m$ of Alumina for the He-Ne laser at 632.8 nm (red) and 543.5nm(green) wavelength. The nature of the phase curves of the asteroids depends on the parameters like- particle size, composition, porosity, roughness etc. In our present work we analyse the data which are being generated using single scattering phase function i.e. Mie theory considering particles to be compact sphere. The well known Hapke formula will be considered along with different particle phase function such as Mie and Henyey Greenstein etc to model the laboratory data obtained at the asteroid laboratory of Assam University.Comment: 5 pages, 5 figures [accepted for publication in Publications of the Astronomical Society of Australia (PASA) on 8 June, 2011

Genomic signatures of parasite-driven natural selection in north European Atlantic salmon (Salmo salar)

Abstract Understanding the genomic basis of host-parasite adaptation is important for predicting the long-term viability of species and developing successful management practices. However, in wild populations, identifying specific signatures of parasite-driven selection often presents a challenge, as it is difficult to unravel the molecular signatures of selection driven by different, but correlated, environmental factors. Furthermore, separating parasite-mediated selection from similar signatures due to genetic drift and population history can also be difficult. Populations of Atlantic salmon (Salmo salar L.) from northern Europe have pronounced differences in their reactions to the parasitic flatworm Gyrodactylus salaris Malmberg 1957 and are therefore a good model to search for specific genomic regions underlying inter-population differences in pathogen response. We used a dense Atlantic salmon SNP array, along with extensive sampling of 43 salmon populations representing the two G. salaris response extremes (extreme susceptibility vs resistant), to screen the salmon genome for signatures of directional selection while attempting to separate the parasite effect from other factors. After combining the results from two independent genome scan analyses, 57 candidate genes potentially under positive selection were identified, out of which 50 were functionally annotated. This candidate gene set was shown to be functionally enriched for lymph node development, focal adhesion genes and anti-viral response, which suggests that the regulation of both innate and acquired immunity might be an important mechanism for salmon response to G. salaris. Overall, our results offer insights into the apparently complex genetic basis of pathogen susceptibility in salmon and highlight methodological challenges for separating the effects of various environmental factors.Peer reviewe

Footprints of directional selection in wild atlantic salmon populations: Evidence for parasite-driven evolution?

Mechanisms of host-parasite co-adaptation have long been of interest in evolutionary biology; however, determining the genetic basis of parasite resistance has been challenging. Current advances in genome technologies provide new opportunities for obtaining a genome-scale view of the action of parasite-driven natural selection in wild populations and thus facilitate the search for specific genomic regions underlying inter-population differences in pathogen response. European populations of Atlantic salmon (Salmo salar L.) exhibit natural variance in susceptibility levels to the ectoparasite Gyrodactylus salaris Malmberg 1957, ranging from resistance to extreme susceptibility, and are therefore a good model for studying the evolution of virulence and resistance. However, distinguishing the molecular signatures of genetic drift and environment-associated selection in small populations such as land-locked Atlantic salmon populations presents a challenge, specifically in the search for pathogen-driven selection. We used a novel genome-scan analysis approach that enabled us to i) identify signals of selection in salmon populations affected by varying levels of genetic drift and ii) separate potentially selected loci into the categories of pathogen (G. salaris)-driven selection and selection acting upon other environmental characteristics. A total of 4631 single nucleotide polymorphisms (SNPs) were screened in Atlantic salmon from 12 different northern European populations. We identified three genomic regions potentially affected by parasite-driven selection, as well as three regions presumably affected by salinity-driven directional selection. Functional annotation of candidate SNPs is consistent with the role of the detected genomic regions in immune defence and, implicitly, in osmoregulation. These results provide new insights into the genetic basis of pathogen susceptibility in Atlantic salmon and will enable future searches for the specific genes involved

Sulphonamide inhibition studies of the beta-carbonic anhydrase GsaCA beta present in the salmon platyhelminth parasite Gyrodactylus salaris

Peer reviewe

Prevention is better than cure, but...: Preventive medication as a risk to ordinariness?

Preventive health remains at the forefront of public health concerns; recent initiatives, such as the NHS health check, may lead to recommendations for medication in response to the identification of 'at risk' individuals. Little is known about lay views of preventive medication. This paper uses the case of aspirin as a prophylactic against heart disease to explore views among people invited to screening for a trial investigating the efficacy of such an approach. Qualitative interviews (N=46) and focus groups (N=5, participants 31) revealed dilemmas about preventive medication in the form of clashes between norms: first, in general terms, assumptions about the benefit of prevention were complicated by dislike of medication; second, the individual duty to engage in prevention was complicated by the need not to be over involved with one's own health; third, the potential appeal of this alternative approach to health promotion was complicated by unease about the implications of encouraging irresponsible behaviour among others. Though respondents made different decisions about using the drug, they reported very similar ways of trying to resolve these conflicts, drawing upon concepts of necessity and legitimisation and the special ordinariness of the particular dru

Commencement Program, August (1966)

https://red.mnstate.edu/commencement/1105/thumbnail.jp

Cloning, purification, kinetic and anion inhibition studies of a recombinant beta-carbonic anhydrase from the Atlantic salmon parasite platyhelminth Gyrodactylus salaris

A beta-class carbonic anhydrase (CA, EC 4.2.1.1) was cloned from the genome of the Monogenean platyhelminth Gyrodactylus salaris, a parasite of Atlantic salmon. The new enzyme, GsaCA beta has a significant catalytic activity for the physiological reaction, CO2 + H2O (sic) HCO3- + H+ with a k(cat) of 1.1 x 10(5) s(-1) and a k(cat)/K-m of 7.58 x 10(6) M-1 x s(-1). This activity was inhibited by acetazolamide (K-I of 0.46 mu M), a sulphonamide in clinical use, as well as by selected inorganic anions and small molecules. Most tested anions inhibited GsaCA beta at millimolar concentrations, but sulfamide (K-I of 81 mu M), N,N-diethyldithiocarbamate (K-I of 67 mu M) and sulphamic acid (K-I of 6.2 mu M) showed a rather efficient inhibitory action. There are currently very few non-toxic agents effective in combating this parasite. GsaCA beta is subsequently proposed as a new drug target for which effective inhibitors can be designed.Peer reviewe

Vitamin D levels in women with polycystic ovary syndrome: a population-based study

Background: Conflicting evidence supports a role for vitamin D in women with reproductive disorders such as polycystic ovary syndrome (PCOS) but studies on large, unselected populations have been lacking. Methods: We conducted a general population-based study from the prospective Northern Finland Birth Cohort 1966 (NFBC1966). Serum 25-hydroksyvitamin D (25(OH)D) levels were evaluated in women with self-reported PCOS (n = 280) versus non-symptomatic controls (n = 1573) at the age of 31 with wide range of endocrine and metabolic confounders. Results: The levels of 25(OH)D were similar among women with and without self-reported PCOS (50.35 vs. 48.30 nmol/L, p = 0.051). Women with self-reported PCOS presented with a higher body mass index (BMI), increased insulin resistance, and low-grade inflammation and testosterone levels compared to controls. The adjusted linear regression model showed a positive association between total 25(OH)D levels in self-reported PCOS (β = 2.46, 95% confidence interval (CI) 0.84 to 4.08, p = 0.003). The result remained after adjustment for BMI, testosterone, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hs-CRP) levels. Conclusion: In this population-based setting, PCOS was associated with higher vitamin D levels when adjusting for confounding factors, without distinct beneficial effects on metabolic derangements

Understanding the meaning of medications for patients: The medication experience

Objective: To understand and describe the meaning of medications for patients. Methods: A metasynthesis of three different, yet complementary qualitative research studies, was conducted by two researchers. The first study was a phenomenological study of patients’ medication experiences that used unstructured interviews. The second study was an ethnographic study of pharmaceutical care practice, which included participant observation, in-depth interviews and focus groups with patients of pharmaceutical care. The third was a phenomenological study of the chronic illness experience of medically uninsured individuals in the United States and included an explicit aim to understand the medication experience within that context. The two researchers who conducted these three qualitative studies that examined the medication experience performed the meta-synthesis. The process began with the researchers reviewing the themes of the medication experience for each study. The researchers then aggregated the themes to identify the overlapping and similar themes of the medication experience and which themes are sub-themes within another theme versus a unique theme of the medication experience. The researchers then used the analytic technique, “free imaginative variation” to determine the essential, structural themes of the medication experience. Results: The meaning of medications for patients was captured as four themes of the medication experience: a meaningful encounter; bodily effects; unremitting nature; and exerting control. The medication experience is an individual’s subjective experience of taking a medication in his daily life. It begins as an encounter with a medication. It is an encounter that is given meaning before it occurs. The experience may include positive or negative bodily effects. The unremitting nature of a chronic medication often causes an individual to question the need for the medication. Subsequently, the individual may exert control by altering the way he takes the medication and often in part because of the gained expertise with the medication in his own body. Conclusion: The medication experience is a practice concept that serves to understand patients’ experiences and to understand an individual patient’s medication experience and medication-taking behaviors in order to meet his or her medication-related needs