Telmisartan as metabolic modulator: a new perspective in sports doping?

The World Antidoping Agency (WADA) has introduced some changes in the 2012 prohibited list. Among the leading innovations to the rules are that both 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (peroxisome proliferator-activated receptor-δ [PPAR-δ]-5' adenosine monophosphate-activated protein kinase [AMPK] agonist) and GW1516 (PPAR-δ-agonist) are no longer categorized as gene doping substances in the new 2012 prohibited list but as metabolic modulators in the class "Hormone and metabolic modulators." This may also be valid for the angotensin II receptor blocker telmisartan. It has recently been shown that telmisartan might induce similar biochemical, biological, and metabolic changes (e.g., mitochondrial biogenesis and changes in skeletal muscle fiber type) as those reported for the former call of substances. We suspect that metabolic modulators abuse such as telmisartan might become a tangible threat in sports and should be thereby targeted as an important antidoping issue. The 2012 WADA prohibited list does not provide telmisartan for a potential doping drug, but arguments supporting the consideration to include them among "metabolic modulators" are at hand.     

‘Optimal thermal range’ in ectotherms: Defining criteria for tests of the temperature-size-rule

Thermal performance curves for population growth rate r (a measure of fitness) were estimated over a wide range of temperature for three species: Coleps hirtus (Protista), Lecane inermis (Rotifera) and Aeolosoma hemprichi (Oligochaeta). We measured individual body size and examined if predictions for the temperature-size rule (TSR) were valid for different temperatures. All three organisms investigated follow the TSR, but only over a specific range between minimal and optimal temperatures, while maintenance at temperatures beyond this range showed the opposite pattern in these taxa. We consider minimal and optimal temperatures to be species-specific, and moreover delineate a physiological range outside of which an ectotherm is constrained against displaying size plasticity in response to temperature. This thermal range concept has important implications for general size-temperature studies. Furthermore, the concept of 'operating thermal conditions' may provide a new approach to (i) defining criteria required for investigating and interpreting temperature effects, and (ii) providing a novel interpretation for many cases in which species do not conform to the TSR.     

Diffusion of genetic testing in oncology: what criteria for regulation?

Does gene testing indicate a switch from an histopathological to a molecular approach of human diseases ? Disease management in oncology is already improved by gene testing, at least for some specific cancers. It is however necessary to distinguish the analysis of genes specific to the tumour which gives clues about the fate of the tumours, from those unique to the patients, which gives clues about the future of the person. For the latter so-called germline mutations, wide scale gene-default screening would put pressure on resource allocation from the health care systems of developed countries. Currently the cost of detecting of 700 genes in the whole French population would exceed the whole health budget of the country for the next 10 years. Even if we can anticipate a dramatic decrease in the unit cost of these genetic tests in the future, their diffusion should not be controlled exclusively by technological and market forces. In this paper, we propose to discuss four main parameters for regulating these genetic tests, using as an archetypal example their application to cancer prevention and treatment: (1) which specific cancer disease is targeted by the test (prevalence, incidence, likelihood of cure with current therapeutics, number of years of life potentially saved...); (2) what are the characteristics of the genes tested and which level of evidence is required about the predictive value of the test; (3) what are the size and characteristics of the population who will be offered the test, and (4) which process and public control are necessary before market approval of the test and reimbursement of related expenditures by health care insurance schemes.     

Myocardial Hypertrophy in Athletes: Physiology or Pathology?

This paper includes data from the 11th century to the present day on athlete’s heart and its most controversial trait, myocardial hypertrophy. Four historical stages in the evolution of the concept of athlete’s heart are considered: physical, electrocardiographic, echocardiographic, and magnetic resonance imaging stages.     

Breeding of Little Ringed Plovers Charadrius dubius in farmland: do nests in fields suffer from predation?

Capsule Fishponds and fields were equally attractive for breeding plovers, although predation on nests was higher in fishponds and extremely low in fields.     

Are single species toxicity tests alone adequate for estimating environmental hazard?

Most biologists agree that at each succeeding level of biological organization new properties appear that would not have been evident even by the most intense and careful examination of lower levels of organization. These levels might be crudely characterized as subcellular, cellular, organ, organism, population, multispecies, community, and ecosystem. The field of ecology developed because even the most meticulous study of single species could not accurately predict how several such species might interact competitively or in predator-prey interactions and the like. Moreover, interactions of biotic and abiotic materials at the level of organization called ecosystem are so complex that they could not be predicted from a detailed examination of isolated component parts. This preamble may seem platitudinous to most biologists who have heard this many times before. This makes it all the more remarkable that in the field of toxicity testing an assumption is made that responses at levels of biological organization above single species can be reliably predicted with single species toxicity tests. Unfortunately, this assumption is rarely explicitly stated and, therefore, often passes unchallenged. When the assumption is challenged, a response is that single species tests have been used for years and no adverse ecosystem or multispecies effects were noted. This could be because single species tests are overly protective when coupled with an enormous application factor or that such effects were simply not detected because there were no systematic, scientifically sound studies carried out to detect them. Probably both of these possibilities occur. However, the important factor is that no scientifically justifiable evidence exists to indicate that degree of reliability with which one may use single species tests to predict responses at higher levels of biological organization. One might speculate that the absence of such information is due to the paucity of reliable tests at higher levels of organization. This situation certainly exists but does not explain the lack of pressure to develop such tests. The most pressing need in the field of toxicity testing is not further perfection of single species tests, but rather the development of parallel tests at higher levels of organization. These need not be inordinately expensive, time consuming, or require any more skilled professionals than single species tests. Higher level tests merely require a different type of biological background. Theoretical ecologists have been notoriously reluctant to contribute to this effort, and, as a consequence, such tests must be developed by associations of professional biologists and other organizations with similar interests.     

Are mimics monophyletic? The necessity of phylogenetic hypothesis tests in character evolution

Background  

The processes governing the origin and maintenance of mimetic phenotypes can only be understood in a phylogenetic framework. Phylogenetic estimates of evolutionary relationships can provide a context for analyses of character evolution; however, when phylogenetic estimates conflict, rigorous analyses of alternative evolutionary histories are necessary to determine the likelihood of a specific history giving rise to the observed pattern of diversity. The polyphenic butterfly Limenitis arthemis provides a case in point. This species is comprised of three lineages, two of which are mimetic and one of which is non-mimetic. Conflicting estimates of the relationships among these three lineages requires direct evaluation of the alternative hypotheses of mimicry evolution.     

Angling-Induced Barotrauma in Snapper Chrysophrys auratus: Are There Consequences for Reproduction?

In response to concerns regarding the potential for sub-lethal impacts of barotrauma on reproductively active Chrysophrys auratus during catch and release, 90 males and 90 females representing five reproductive stages (immature or resting-28%, developing-8%, developed-7%, ripe or spawning-23% and spent-34%) were angled from 8–70 m and macroscopically assessed (on-board and then in a laboratory). Irrespective of sex, all fish exhibited various clinical signs of barotrauma, including a prolapsed cloaca (60% of fish); gastric herniation (46%); ruptured swim bladder (73%); organ displacement (48%); and kidney (3%), liver (73%) and coloemic-cavity haemorrhaging (33%);with the frequency of nearly all positively associated with capture depth. Reproductive stage was also an important barotrauma predictor (reflecting related morphological changes) with a general trend towards spent fish least likely to incur the various clinical signs—especially for a prolapsed cloaca (also common among immature or resting fish and significantly affected by food in the digestive tract) and a ruptured swim bladder (common among ripe or spawning fish). The only macroscopically visible gonad damage was haemorrhaging, which was least common among immature or resting and spent fish and, irrespective of reproductive stage, temporally reduced in frequency, and more quickly among males than females. While further research is required to accurately describe the effects of angling at each stage of the reproductive cycle and the physiological consequences of barotrauma on the gonads of C. auratus, given the observed influences of reproductive stage and depth on barotrauma found in this study, any adverse effects might be partially managed by regulating either temporal or spatial fishing effort.     

Drug Users in Amsterdam: Are They Still at Risk for HIV?

Background and Aims

To examine whether drug users (DU) in the Amsterdam Cohort Study (ACS) are still at risk for HIV, we studied trends in HIV incidence and injecting and sexual risk behaviour from 1986 to 2011.

Methods

The ACS is an open, prospective cohort study on HIV. Calendar time trends in HIV incidence were modelled using Poisson regression. Trends in risk behaviour were modelled via generalized estimating equations. In 2010, a screening for STI (chlamydia, gonorrhoea and syphilis) was performed. Determinants of unprotected sex were studied using logistic regression analysis.

Results

The HIV incidence among 1298 participants of the ACS with a total follow-up of 12,921 person-years (PY) declined from 6.0/100 PY (95% confidence interval [CI] 3.2–11.1) in 1986 to less than 1/100 PY from 1997 onwards. Both injection and sexual risk behaviour declined significantly over time. Out of 197 participants screened for STI in 2010–2011, median age 49 years (IQR 43–59), only 5 (2.5%) were diagnosed with an STI. In multivariable analysis, having a steady partner (aOR 4.1, 95% CI 1.6–10.5) was associated with unprotected sex. HIV-infected participants were less likely to report unprotected sex (aOR 0.07, 95% CI 0.02–0.37).

Conclusions

HIV incidence and injection risk behaviour declined from 1986 onwards. STI prevalence is low; unprotected sex is associated with steady partners and is less common among HIV-infected participants. These findings indicate a low transmission risk of HIV and STI, which suggests that DU do not play a significant role in the current spread of HIV in Amsterdam.     

Screening for hereditary hemochromatosis: are DNA-based tests the answer?

Universal screening for hereditary hemochromatosis (HH) has been proposed by many experts, with understandable enthusiasm: HH can cause fatal complications, which are preventable with early treatment. The disorder involves excess iron accumulation that can result in tissue iron overload, with secondary cirrhosis, diabetes, heart failure, impotence and arthritis. These complications are preceded by years of iron accumulation, and most are believed to be preventable by removal of excess iron by phlebotomy. Thus, early identification and treatment - the quintessential functions of health screening - seem to make sense for HH. However, the available screening tests are imperfect. While they can identify many persons at increased risk from HH, the proportion that will develop serious clinical manifestations related to iron overload is not known with certainty. DNA-based tests do not provide a simple resolution to these questions.     

Hypoglycemia in falciparum malaria: is fasting an unrecognized and insufficiently emphasized risk factor?

Hypoglycemia is a frequently encountered complication in falciparum malaria that is usually ascribed to increased glucose use and impaired glucose production caused by the inhibition of gluconeogenesis. Here, in light of recent data showing that glucose production and gluconeogenesis are often increased in falciparum malaria, we review the causes and the risk factors leading to hypoglycemia in malaria. Fasting emerges as an important potential risk factor. Length of fasting should be included in studies on hypoglycemia in malaria. Full recognition of this risk factor for hypoglycemia in malaria could change both advice to the population, especially mothers, and treatment guidelines in the health sector.     

Genome editing in livestock: Are we ready for a revolution in animal breeding industry?

Genome editing is a powerful technology that can efficiently alter the genome of organisms to achieve targeted modification of endogenous genes and targeted integration of exogenous genes. Current genome-editing tools mainly include ZFN, TALEN and CRISPR/Cas9, which have been successfully applied to all species tested including zebrafish, humans, mice, rats, monkeys, pigs, cattle, sheep, goats and others. The application of genome editing has quickly swept through the entire biomedical field, including livestock breeding. Traditional livestock breeding is associated with rate limiting issues such as long breeding cycle and limitations of genetic resources. Genome editing tools offer solutions to these problems at affordable costs. Generation of gene-edited livestock with improved traits has proven feasible and valuable. For example, the CD163 gene-edited pig is resistant to porcine reproductive and respiratory syndrome (PRRS, also referred to as “blue ear disease”), and a SP110 gene knock-in cow less susceptible to tuberculosis. Given the high efficiency and low cost of genome editing tools, particularly CRISPR/Cas9, it is foreseeable that a significant number of genome edited livestock animals will be produced in the near future; hence it is imperative to comprehensively evaluate the pros and cons they will bring to the livestock breeding industry. Only with these considerations in mind, we will be able to fully take the advantage of the genome editing era in livestock breeding.     

Conservation Targets for Viable Species Assemblages in Canada: Are Percentage Targets Appropriate?

Percentage targets for conservation have become a popular tool (advocated in both the scientific literature and the conservation community) for setting minimum goals for the amount of land to be set aside as protected areas. However, there is little literature to support a consistent percentage target that might be widely applied. Moreover, most percentage targets have not taken into account issues of species persistence. A recent study of herbivores in Kruger National Park took into account issues of representation and persistence in setting conservation targets and found that results were consistently about 50% and were unaffected by different permutations of the reserve selection process. Here, we carry out a similar analysis for representation of mammals within sites that are predicted to allow for their persistence, across eight ecologically defined regions in Canada to test whether we see similar consistent patterns emerging. We found that percentage targets varied with the different permutations of the reserve selection algorithms, both within and between the study regions. Thus, we conclude that the use of percentage targets is not an appropriate conservation strategy.     

Are endophytic fungi from Rhododendron tomentosum preadapted for its essential oil?

Endophytic fungi have to cope with various secondary metabolites produced by their host plant. Rhododendron tomentosum is an evergreen shrub with a high content of essential oil showing antimicrobial effects. The first aim of our study was to reveal the diversity of culturable endophytic fungi colonizing leaves of R. tomentosum. We isolated and identified 30 species, mostly ubiquitous species colonizing various plants as endophytes and later turning into saprotrophs. The second aim was to explore whether strains obtained from R. tomentosum (RT-strain) are better adapted to growth in environments with essential oils, compared to strains of the same species obtained from different substrates. In five of the six species pairs tested, the growth of RT-strains was more inhibited by three components of the essential oil added to the medium, compared to the corresponding strains. Only the RT-strain of Desmazierella acicola was less susceptible compared to its corresponding strain. Our results show that the essential oil in leaves of R. tomentosum do not represent a selective barrier that can be crossed only by preadapted strains.