Individual variation evades the Prisoner's Dilemma

Background  

The Prisoner's Dilemma (PD) is a widely used paradigm to study cooperation in evolutionary biology, as well as in fields as diverse as moral philosophy, sociology, economics and politics. Players are typically assumed to have fixed payoffs for adopting certain strategies, which depend only on the strategy played by the opponent. However, fixed payoffs are not realistic in nature. Utility functions and the associated payoffs from pursuing certain strategies vary among members of a population with numerous factors. In biology such factors include size, age, social status and expected life span; in economics they include socio-economic status, personal preference and past experience; and in politics they include ideology, political interests and public support. Thus, no outcome is identical for any two different players.     

Pulmonary complications of smoked substance abuse.

After tobacco, marijuana is the most widely smoked substance in our society. Studies conducted within the past 15 years in animals, isolated tissues, and humans indicate that marijuana smoke can injure the lungs. Habitual smoking of marijuana has been shown to be associated with chronic respiratory tract symptoms, an increased frequency of acute bronchitic episodes, extensive tracheobronchial epithelial disease, and abnormalities in the structure and function of alveolar macrophages, key cells in the lungs'' immune defense system. In addition, the available evidence strongly suggests that regularly smoking marijuana may predispose to the development of cancer of the respiratory tract. "Crack" smoking has become increasingly prevalent in our society, especially among habitual smokers of marijuana. New evidence is emerging implicating smoked cocaine as a cause of acute respiratory tract symptoms, lung dysfunction, and, in some cases, serious, life-threatening acute lung injury. A strong physician message to users of marijuana, cocaine, or both concerning the harmful effects of these smoked substances on the lungs and other organs may persuade some of them, especially those with drug-related respiratory complications, to quit smoking.     

Melatonin,immune function and aging

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.     

Evolution of the WANCY region in amniote mitochondrial DNA

In most vertebrate mitochondrial genomes, the site for initiation of light-strand replication, OL, is found within a cluster of five transfer RNA (tRNA) genes (tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), and tRNA(Tyr)). This region and part of the adjacent cytochrome c oxydase subunit I (COI) gene were sequenced for two crocodilian, two turtle, and one snake species and for Sphenodon punctatus; part of the adjacent nicotinamide adenine dinucleotide dehydrogenase subunit 2 (ND2) gene was also sequenced for the crocodilian and turtle species. All had the typical vertebrate gene order. The turtles and the snake have a lengthy noncoding sequence between the tRNA(Asn) and tRNA(Cys) genes that we assumed to be homologous to the mammalian OL. The crocodilians and Sphenodon lack such a sequence, a condition they share with birds. Most proposed phylogenies for the amniotes require that OL at this position was lost at least twice during their diversification or was evolved independently more than once. Within the five tRNA genes, frequencies of substitutions are much higher in loops than in stems. Many loops vary dramatically in size among the species; in the most extreme case, the D-arm of the Sphenodon tRNA(Cys) is a "D-arm replacement" loop of seven nucleotides. Frequency of transitions in stems is relatively uniform across tRNAs, but frequency of transversions varies greatly. Mismatches in stems are infrequent, and their relative frequency in a specific tRNA is unrelated to the frequency of substitution in the corresponding gene. Several features of mammalian mitochondrial tRNAs are conserved in WANCY tRNAs throughout amniotes. The inferred initiation codon for COI is GTG in crocodilians, turtles, and the snake, a condition they share with fishes, certain amphibians, and birds. TTG appears to be the initiation codon for COI in Sphenodon; if correct, this would be a novel initiation codon for vertebrate mitochondrial DNA. Phylogenetic analyses of the inferred amino acid sequences of ND2 and COI support the sister-group relationship of birds and crocodilians and suggest that mammals are an early derived lineage within the amniotes.      

Combination bronchodilator therapy in the management of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) represents a significant cause of global morbidity and mortality, with a substantial economic impact. Recent changes in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidance refined the classification of patients for treatment using a combination of spirometry, assessment of symptoms, and/or frequency of exacerbations. The aim of treatment remains to reduce existing symptoms while decreasing the risk of future adverse health events. Long-acting bronchodilators are the mainstay of therapy due to their proven efficacy. GOLD guidelines recommend combining long-acting bronchodilators with differing mechanisms of action if the control of COPD is insufficient with monotherapy, and recent years have seen growing interest in the additional benefits that combination of long-acting muscarinic antagonists (LAMAs), typified by tiotropium, with long-acting β₂-agonists (LABAs), such as formoterol and salmeterol. Most studies have examined free combinations of currently available LAMAs and LABAs, broadly showing a benefit in terms of lung function and other patient-reported outcomes, although evidence is limited at present. Several once- or twice-daily fixed-dose LAMA/LABA combinations are under development, most involving newly developed monotherapy components. This review outlines the existing data for LAMA/LABA combinations in the treatment of COPD, summarizes the ongoing trials, and considers the evidence required to inform the role of LAMA/LABA combinations in treatment of this disease.     

Novel clinical in vivo roles for indigo carmine: high-magnification chromoscopic colonoscopy

Since the adenoma-carcinoma sequence was first proposed by Morson in the 1970s, it has become widely accepted that detection and subsequent removal of polypoid adenomas from the colon reduces the incidence of colorectal cancer. These adenomas are relatively easy to detect by conventional colonoscopy; however, large population studies have shown that despite resection of polypoid adenomas, interval colorectal cancers still occurred. Recent advances in technology have given today's endoscopists access to high-resolution and high-magnification scopes, which has facilitated detection of flat and depressed colorectal lesions. Current data suggest that such morphologically distinct lesions may account for up to 30% of all colorectal adenomas. Furthermore, flat and depressed lesions of the large bowel may confer greater malignant potential compared to polypoid adenomas. The majority of flat lesions show only subtle changes by conventional colonoscopy, but the use of stains, such as indigocarmine, in addition to magnification colonoscopy can enhance their detection significantly. In this paper, we discuss the rationale for detecting flat colorectal lesions. We explore the use of high-magnification colonoscopy and chromoendoscopy, with particular reference to the application of indigocarmine, in this patient group. We also discuss the novel therapeutic techniques now available for these lesions.     

Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians

Background  

A close association between Sst I polymorphism in the 3' untranslated region of the apolipoproteinC3 (APOC3 ) gene and levels of plasma triglycerides (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a known risk factor for coronary artery disease (CAD) in the context of Asian Indians. We conducted a study on the relationship between APOC3 SstI polymorphism (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male healthy volunteers from Northern India.