Effects of Epistasis and Pleiotropy on Fitness Landscapes

The factors that influence genetic architecture shape the structure of the fitness landscape, and therefore play a large role in the evolutionary dynamics. Here the NK model is used to investigate how epistasis and pleiotropy -- key components of genetic architecture -- affect the structure of the fitness landscape, and how they affect the ability of evolving populations to adapt despite the difficulty of crossing valleys present in rugged landscapes. Populations are seen to make use of epistatic interactions and pleiotropy to attain higher fitness, and are not inhibited by the fact that valleys have to be crossed to reach peaks of higher fitness.Comment: 10 pages, 6 figures. To appear in "Origin of Life and Evolutionary Mechanisms" (P. Pontarotti, ed.). Evolutionary Biology: 16th Meeting 2012, Springer-Verla

Is a Calorie Really a Calorie? Metabolic Advantage of Low-Carbohydrate Diets

The first law of thermodynamics dictates that body mass remains constant when caloric intake equals caloric expenditure. It should be noted, however, that different diets lead to different biochemical pathways that are not equivalent when correctly compared through the laws of thermodynamics. It is inappropriate to assume that the only thing that counts in terms of food consumption and energy balance is the intake of dietary calories and weight storage. Well-controlled studies suggest that calorie content may not be as predictive of fat loss as is reduced carbohydrate consumption. Biologically speaking, a calorie is certainly not a calorie. The ideal weight loss diet, if it even exists, remains to be determined, but a high-carbohydrate/low-protein diet may be unsatisfactory for many obese individuals

Stimulation programs for pediatric drug research – do children really benefit?

Most drugs that are currently prescribed in pediatrics have not been tested in children. Pediatric drug studies are stimulated in the USA by the pediatric exclusivity provision under the Food and Drug Administration Modernization Act (FDAMA) that grants patent extensions when pediatric labeling is provided. We investigated the effectiveness of these programs in stimulating drug research in children, thereby increasing the evidence for safe and effective drug use in the pediatric population. All drugs granted pediatric exclusivity under the FDAMA were analyzed by studying the relevant summaries of medical and clinical pharmacology reviews of the pediatric studies or, if these were unavailable, the labeling information as provided by the manufacturer. A systematic search of the literature was performed to identify drug utilization patterns in children. From July 1998 to August 2006, 135 drug entities were granted pediatric exclusivity. Most frequent drug groups were anti-depressants and mood stabilizers, ACE inhibitors, lipid-lowering preparations, HIV antivirals, and non-steroidal anti-inflammatory and anti-rheumatic drugs. The distribution of the different drugs closely matched the distribution of these drugs over the adult market, and not the drug utilization by children

Effect of collaborative depression treatment on risk for diabetes: A 9-year follow-up of the IMPACT randomized controlled trial

Considerable epidemiologic evidence and plausible biobehavioral mechanisms suggest that depression is an independent risk factor for diabetes. Moreover, reducing the elevated diabetes risk of depressed individuals is imperative given that both conditions are leading causes of death and disability. However, because no prior study has examined clinical diabetes outcomes among depressed patients at risk for diabetes, the question of whether depression treatment prevents or delays diabetes onset remains unanswered. Accordingly, we examined the effect of a 12-month collaborative care program for late-life depression on 9-year diabetes incidence among depressed, older adults initially free of diabetes. Participants were 119 primary care patients [M (SD) age: 67.2 (6.9) years, 41% African American] with a depressive disorder but without diabetes enrolled at the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial. Incident diabetes cases were defined as diabetes diagnoses, positive laboratory values, or diabetes medication prescription, and were identified using electronic medical record and Medicare/Medicaid data. Surprisingly, the rate of incident diabetes in the collaborative care group was 37% (22/59) versus 28% (17/60) in the usual care group. Even though the collaborative care group exhibited greater reductions in depressive symptom severity (p = .024), unadjusted (HR = 1.29, 95% CI: 0.69-2.43, p = .428) and adjusted (HR = 1.18, 95% CI: 0.61-2.29, p = .616) Cox proportional hazards models indicated that the risk of incident diabetes did not differ between the treatment groups. Our novel preliminary findings raise the possibility that depression treatment alone may be insufficient to reduce the excess diabetes risk of depressed, older adults

Modeling Trap-Awareness and Related Phenomena in Capture-Recapture Studies

Trap-awareness and related phenomena whereby successive capture events are not independent is a feature of the majority of capture-recapture studies. This phenomenon was up to now difficult to incorporate in open population models and most authors have chosen to neglect it although this may have damaging consequences. Focusing on the situation where animals exhibit a trap response at the occasion immediately following one where they have been trapped but revert to their original naïve state if they are missed once, we show that trap-dependence is more naturally viewed as a state transition and is amenable to the current models of capture-recapture. This approach has the potential to accommodate lasting or progressively waning trap effects

Evaluating the Potential Effectiveness of Compensatory Mitigation Strategies for Marine Bycatch

Conservationists are continually seeking new strategies to reverse population declines and safeguard against species extinctions. Here we evaluate the potential efficacy of a recently proposed approach to offset a major anthropogenic threat to many marine vertebrates: incidental bycatch in commercial fisheries operations. This new approach, compensatory mitigation for marine bycatch (CMMB), is conceived as a way to replace or reduce mandated restrictions on fishing activities with compensatory activities (e.g., removal of introduced predators from islands) funded by levies placed on fishers. While efforts are underway to bring CMMB into policy discussions, to date there has not been a detailed evaluation of CMMB's potential as a conservation tool, and in particular, a list of necessary and sufficient criteria that CMMB must meet to be an effective conservation strategy. Here we present a list of criteria to assess CMMB that are tied to critical ecological aspects of the species targeted for conservation, the range of possible mitigation activities, and the multi-species impact of fisheries bycatch. We conclude that, overall, CMMB has little potential for benefit and a substantial potential for harm if implemented to solve most fisheries bycatch problems. In particular, CMMB is likely to be effective only when applied to short-lived and highly-fecund species (not the characteristics of most bycatch-impacted species) and to fisheries that take few non-target species, and especially few non-seabird species (not the characteristics of most fisheries). Thus, CMMB appears to have limited application and should only be implemented after rigorous appraisal on a case-specific basis; otherwise it has the potential to accelerate declines of marine species currently threatened by fisheries bycatch

Multi-objective optimization of genome-scale metabolic models: the case of ethanol production

Ethanol is among the largest fermentation product used worldwide, accounting for more than 90% of all biofuel produced in the last decade. However current production methods of ethanol are unable to meet the requirements of increasing global demand, because of low yields on glucose sources. In this work, we present an in silico multi-objective optimization and analyses of eight genome-scale metabolic networks for the overproduction of ethanol within the engineered cell. We introduce MOME (multi-objective metabolic engineering) algorithm, that models both gene knockouts and enzymes up and down regulation using the Redirector framework. In a multi-step approach, MOME tackles the multi-objective optimization of biomass and ethanol production in the engineered strain; and performs genetic design and clustering analyses on the optimization results. We find in silico E. coli Pareto optimal strains with a knockout cost of 14 characterized by an ethanol production up to 19.74mmolgDW−1h−1 (+832.88% with respect to wild-type) and biomass production of 0.02h−1 (−98.06% ). The analyses on E. coli highlighted a single knockout strategy producing 16.49mmolgDW−1h−1 (+679.29% ) ethanol, with biomass equals to 0.23h−1 (−77.45% ). We also discuss results obtained by applying MOME to metabolic models of: (i) S. aureus; (ii) S. enterica; (iii) Y. pestis; (iv) S. cerevisiae; (v) C. reinhardtii; (vi) Y. lipolytica. We finally present a set of simulations in which constrains over essential genes and minimum allowable biomass were included. A bound over the maximum allowable biomass was also added, along with other settings representing rich media compositions. In the same conditions the maximum improvement in ethanol production is +195.24%

Mucosal sensitization to German cockroach involves protease-activated receptor-2

<p>Abstract</p> <p>Background</p> <p>Allergic asthma is on the rise in developed countries. A common characteristic of allergens is that they contain intrinsic protease activity, and many have been shown to activate protease-activated receptor (PAR)-2 <it>in vitro</it>. The role for PAR-2 in mediating allergic airway inflammation has not been assessed using a real world allergen.</p> <p>Methods</p> <p>Mice (wild type or PAR-2-deficient) were sensitized to German cockroach (GC) feces (frass) or protease-depleted GC frass by either mucosal exposure or intraperitoneal injection and measurements of airway inflammation (IL-5, IL-13, IL-17A, and IFNγ levels in the lung, serum IgE levels, cellular infiltration, mucin production) and airway hyperresponsiveness were performed.</p> <p>Results</p> <p>Following systemic sensitization, GC frass increased airway hyperresponsiveness, Th2 cytokine release, serum IgE levels, cellular infiltration and mucin production in wild type mice. Interestingly, PAR-2-deficient mice had similar responses as wild type mice. Since these data were in direct contrast to our finding that mucosal sensitization with GC frass proteases regulated airway hyperresponsiveness and mucin production in BALB/c mice (Page et. al. 2007 Resp Res 8:91), we backcrossed the PAR-2-deficient mice into the BALB/c strain. Sensitization to GC frass could now occur via the more physiologically relevant method of intratracheal inhalation. PAR-2-deficient mice had significantly reduced airway hyperresponsiveness, Th2 and Th17 cytokine release, serum IgE levels, and cellular infiltration compared to wild type mice when sensitization to GC frass occurred through the mucosa. To confirm the importance of mucosal exposure, mice were systemically sensitized to GC frass or protease-depleted GC frass via intraperitoneal injection. We found that removal of proteases from GC frass had no effect on airway inflammation when administered systemically.</p> <p>Conclusions</p> <p>We showed for the first time that allergen-derived proteases in GC frass elicit allergic airway inflammation via PAR-2, but only when allergen was administered through the mucosa. Importantly, our data suggest the importance of resident airway cells in the initiation of allergic airway disease, and could make allergen-derived proteases attractive therapeutic targets.</p

FinTech revolution: the impact of management information systems upon relative firm value and risk

The FinTech or ‘financial technology’ revolution has been gaining increasing interest as technologies are fundamentally changing the business of financial services. Consequently, financial technology is playing an increasingly important role in providing relative performance growth to firms. It is also well known that such relative performance can be observed through pairs trading investment. Therefore pairs trading have implications for understanding financial technology performance, yet the relationships between relative firm value and financial technology are not well understood. In this paper we investigate the impact of financial technology upon relative firm value in the banking sector. Firstly, using pairs trade data we show that financial technologies reveal differences in relative operational performance of firms, providing insight on the value of financial technologies. Secondly, we find that contribution of relative firm value growth from financial technologies is dependent on the specific business characteristics of the technology, such as the business application and activity type. Finally, we show that financial technologies impact the operational risk of firms and so firms need to take into account both the value and risk benefits in implementing new technological innovations. This paper will be of interest to academics and industry professionals