Cloning adult animals - what is the genetic age of the clones?

The rapid progress in cloning research along with its many ramifications will soon have a significant beneficial impact on basic research, agriculture, and biomedicine. However, for the nuclear transfer technology to reach its fullest potential, it is important to understand whether the cloning procedure can reverse cellular aging and generate clones with normal genetic and physiological age, similar to those produced from natural reproduction. Telomere shortening is believed to correlate with cellular aging both in vitro and in vivo. Telomere lengths in cells of cloned individuals thus may reflect their genetic age. However, controversies have developed over whether the eroded telomere in somatic cells used for nuclear transfer can be restored during the cloning process.     

Prominent ears in children younger than 4 years of age: what is the appropriate timing for otoplasty?

The present study was conducted to determine whether otoplasty performed in children younger than 4 years of age has an acceptable long-term outcome. This two-part study consisted of (1) a questionnaire mailed to 481 members of the American Association of Plastic Surgeons to ask their opinion on the timing of otoplasty, and (2) a consecutive series of 12 patients who had otoplasty performed before the age of 4 years. The survey demonstrated that the majority (57 percent) of the respondents perform otoplasty on patients who are aged 5 years or older. The prospective series consisted of 12 patients ranging in age from 9 months to 3 years at the time of the procedure. Otoplasty was bilateral in nine patients and unilateral in three patients. Length of follow-up ranged from 21 months to 7(1/2) years, with a median follow-up of 41 months. Growth following otoplasty was evaluated in three patients who underwent unilateral otoplasty by measuring the length of both ears at the time of final follow-up. No difference in ear length was noted between the sides that were and were not operated on during a follow-up period of 46 to 63 months. Noticeable recurrence was noted in only one (8 percent) of 12 patients. In response to a follow-up questionnaire to the patients' families, all respondents (n = 10) stated that if again asked to choose the timing of otoplasty in their children, they would opt to have it performed at the same age of younger than 4 years. Otoplasty can be safely performed at ages younger than previously thought without interfering with growth of the operated ear.     

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.     

Early detection of genetic hemochromatosis: should all young adults be offered the genetic test?

Genetic hemochromatosis (GH) is a late-onset, autosomal recessive disorder. The majority of those at risk from iron overload and its clinical consequences may be detected by a simple genetic test. Furthermore, treatment by phlebotomy, if instituted early, removes excess iron and prevents the complications of iron overload which include arthralgia, diabetes, and cirrhosis of the liver. GH seems to be an obvious candidate for inclusion in national screening programs. However, important questions remain concerning the proportion of individuals with the high-risk genotype who eventually show clinical manifestations of iron overload and the significance of heterozygosity for haemochromatosis in terms of morbidity. Until these questions are resolved, the introduction of widespread genetic screening cannot be justified.     

The statistical distribution of the intensity of pixels within spots of DNA microarrays: what is the appropriate single-value representative?

This paper opens a discussion about an important issue in the analysis of data from spotted DNA microarrays: how to summarise into a single value the distribution for the intensity values of the pixels within a spot. Although the most popular statistic used is the median, there is no clear study demonstrating why it is more appropriate than other measures of central tendency such as the mean or the mode. Here, we argue that the median intensity is not the most appropriate measure for many common cases and discuss a frequently encountered case of a 'doughnut'-shaped spot for which the mode is closest to the 'expected' spot intensity. For an 'ideal' spot with a clear boundary and uniformly hybridised, the intensity of its pixels should approximately be normally distributed. In practical situations, these two requirements are often not met due to the physical properties of pins and the particularities of the printing and hybridisation processes. As a consequence, the distribution of the intensity of the pixels is usually negatively skewed. This asymmetry results in a larger displacement for the mean and median than for the mode from the ideal situation mentioned above.     

Performance and fatigue during repeated sprints: what is the appropriate sprint dose?

When testing the ability of sportsmen to repeat maximal intensity efforts, or when designing specific training exercises to improve it, fatigue during repeated sprints is usually investigated through a number of sprints identical for all subjects, which induces a high intersubject variability in performance decrement in a typical heterogeneous group of athletes (e.g., team sport group, students, and research protocol volunteers). Our aim was to quantify the amplitude of the reduction in this variability when individualizing the sprint dose, that is, when requiring subjects to perform the number of sprints necessary to reach a target level of performance decrement. Fifteen healthy men performed 6-second sprints on a cycle ergometer with 24 seconds of rest until exhaustion or until 20 repetitions in case no failure occurred. Peak power output (PPO) was measured and a fatigue index (FI) computed. The variability in PPO decrement was compared between the 10th sprint and the sprint at which subject reached the target FI of 10%. Individual FI values after the 10th sprint were 14.6 ± 6.9 vs. 11.1 ± 1.2%, when individualizing the sprint dose, which corresponded to coefficients of interindividual variability of ～47.3 and ～10.8%, respectively. Individualizing the sprint dose substantially reduced intersubject variability in performance decrement, enabling a more standardized state of fatigue in repeated-sprints protocols designed to induce fatigue and test or train this specific repeated-sprint ability in a heterogeneous group of athletes. A direct feedback on the values of performance parameters is necessary between each sprint for the experimenter to set this individualized sprint dose.     

Dyspepsia: is a trial of therapy appropriate?

Dyspepsia is a common, benign condition that may be distinguished from gastroesophageal reflux, irritable bowel syndrome and pancreatobiliary, coronary or musculoskeletal disease by a careful history and physical examination. However, the presence or absence of a peptic ulcer in dyspepsia can be determined only by an endoscopic examination or a barium-contrast radiograph. Although the American College of Physicians has recommended trying drug therapy for patients with dyspepsia before diagnostic tests are done, new data support early diagnosis. Although therapy is initially cheaper than endoscopic examination, over a year the costs even out because most patients with dyspepsia eventually need an endoscopic examination, and many patients with nonulcer dyspepsia are given medication unnecessarily. Endoscopic examination, if available to general practitioners, is the most cost-effective approach to dyspepsia. An approach that does not include endoscopy lacks the opportunity to offer patients convincing reassurance that their illness is not serious, which is arguably the most important treatment in cases of nonulcer dyspepsia. Studies supporting the use of endoscopic examination predate the treatment of peptic ulcers with antibiotics, which makes an initial endoscopic examination to determine whether the patient has an ulcer even more important.     

Ribosomal DNA phylogenies of Cyathus: is the current infrageneric classification appropriate?

Phylogenetic relationships within the genus Cyathus (bird's nest fungi) were investigated with neighbor joining, maximum likelihood, weighted maximum parsimony and MrBayes analyses of ITS and LSU ribosomal DNA sequences datasets. Twenty-two taxa of Cyathus were used in the analyses based primarily on type and authentic specimens. The current infrageneric classification system of Brodie recognizes seven infrageneric groups based on morphological characters, including peridium plications and variations in peridium hair anatomy, peridiole structure and fruit-body color. These groups are not supported by molecular data. Instead the ITS and LSU datasets support recognition of three infrageneric groups herein named the ollum, pallidum and striatum groups. Morphological characters useful in distinguishing these groups include basidiospore size, fruit-body coloration and peridium anatomy. Cyathus africanus var. latisporus is considered a synonym of Cyathus jiayuguanensis, and a new combination Cyathus lanatus (Brodie) R.L. Zhao is proposed based on morphological and molecular data.     

Coxiella burnetii: what is the reality?

After the Second World War, in Italy Q Fever or Coxiellosis has been shown a significant relevance, a recrudescence with an epidemic state for over ten years. Later, the infectious disease occurred as endemic since the 80s, the outbreaks were just isolated. Workflows analysis of some authors has demonstrated the spread out of the infection throughout Italian herds with a prevalence ranging from 1.2 per cent to 10 per cent. Our survey carried out throughout Campania area in cattle has shown a real positivity over 14 per cent performing the IFAT for the detection of IgG antibodies for Coxiella burnetii. Therefore, it has been so important to stress the influence of cattle farming management in stables as a real risk of Coxiellosis. For example, the Relative Risk (RR) has been registrated about 6.84 (2.18相似文献   

Optimization of energy coupling: what is all the argument about?

Although it may be asked how effective glycolysis is in retaining the chemical energy in the bonds of glucose during its breakdown in the formation of ATP, the reasons for the coupled pathway of glycolysis having evolved as it has are probably as much as a consequence of the need to find reactions that can lead to formation of phosphoryl groups able to transfer to ADP as to the overall thermodynamics of the pathway. It is not meaningful to talk of optimization of energy coupling solely in terms of free energy changes.     

Developmental programming of reproduction and fertility: what is the evidence?

The concept of the foetal/developmental origins of adult disease has been around for ~20 years and from the original epidemiological studies in human populations much more evidence has accumulated from the many studies in animal models. The majority of these have focused upon the role of early dietary intake before conception, through gestation and/or lactation and subsequent interactions with the postnatal environment, e.g. dietary and physical activity exposures. Whilst a number of theoretical models have been proposed to place the experimental data into a biological context, the underlying phenomena remain the same; developmental deficits (of single (micro) nutrients) during critical or sensitive periods of tissue growth alter the developmental pathway to ultimately constrain later functional capacity when the individual is adult. Ageing, without exception, exacerbates any programmed sequelae. Thus, adult phenotypes that have been relatively easy to characterise (e.g. blood pressure, insulin sensitivity, body fat mass) have received most attention in the literature. To date, relatively few studies have considered the effect of differential early environmental exposures on reproductive function and fecundity in predominantly mono-ovular species such as the sheep, cow and human. The available evidence suggests that prenatal insults, undernutrition for example, have little effect on lifetime reproductive capacity despite subtle effects on the hypothalamic-pituitary-gonadal axis and gonadal progenitor cell complement. The postnatal environment is clearly important, however, since neonatal/adolescent growth acceleration (itself not independent from prenatal experience) has been shown to significantly influence fecundity in farm animals. The present paper will expand these interesting areas of investigation and review the available evidence regarding developmental programming of reproduction and fertility. However, it appears there is little strong evidence to indicate that offspring fertility and reproductive senescence in the human and in farm animal species are overtly affected by prenatal nutrient exposure. Nevertheless, it is clear that the developing gonad is sensitive to its immediate environment but more detailed investigation is required to specifically test the long-term consequences of nutritional perturbations during pregnancy on adult reproductive well-being.