Search

DNA methylation is an epigenetic modification that changes with age in human tissues, although the mechanisms and specificity of this process are still poorly understood. We compared CpG methylation changes with age across 283 human blood, brain, kidney, and skeletal muscle samples using methylation arrays to identify tissue-specific age effects. We found age-associated CpGs (ageCGs) that are both tissue-specific and common across tissues. Tissue-specific ageCGs are frequently located outside CpG islands with decreased methylation, and common ageCGs show the opposite trend. AgeCGs are significantly associated with poorly expressed genes, but those with decreasing methylation are linked with higher tissue-specific expression levels compared with increasing methylation. Therefore, tissue-specific gene expression may protect against common age-dependent methylation. Distinguished from other tissues, skeletal muscle ageCGs are more associated with expression, enriched near genes related to myofiber contraction, and closer to muscle-specific CTCF binding sites. Kidney-specific ageCGs are more increasingly methylated compared to other tissues as measured by affiliation with kidney-specific expressed genes. Underlying chromatin features also mark common and tissue-specific age effects reflective of poised and active chromatin states, respectively. In contrast with decreasingly methylated ageCGs, increasingly methylated ageCGs are also generally further from CTCF binding sites and enriched within lamina associated domains. Our data identified common and tissue-specific DNA methylation changes with age that are reflective of CpG landscape and suggests both common and unique alterations within human tissues. Our findings also indicate that a simple epigenetic drift model is insufficient to explain all age-related changes in DNA methylation.

ABSTRACT

Subjects' physiological responses and rated reactions to a medical film and an erotic film were assessed. Later cardiovascular fitness levels were determined by subjects' physiological responses to an exercise task. The greater the increase in the subject's systolic blood pressure after exercise and the slower the recovery, the lower the fitness level. A median split on the fitness scores of males and females separately was used to determine levels of relatively low and high fitness. Subjects in low fitness had significantly greater sympathetic-arousal responses to the two films as measured in systolic blood-pressure increases and skin-temperature decreases. Subjects in the two fitness levels did not differ in ratings of their own physiological or emotional responses to the films. Reported interoception of the magnitude of physiological responses was inaccurate, especially for subjects in low fitness.

IT IS NOW eight years since Lempert first reported a successful one stage fenestration operation for relieving the deafness of otosclerosis. Enough time has elapsed to prove the efficacy and permanency of this procedure. Even the most skeptical otologists must admit that this operation has proved successful in restoring practical hearing for speech in some cases. Undoubtedly, it is the greatest otologic contribution of the present generation. More and more reports are being submitted by men who have undertaken this intricate and difficult operation, with varying degrees of success. This is a new form of reconstructive plastic surgical treatment, and, while still far from reaching a stage of perfection, the results to date, as reported by different operators, seem to show a definite trend toward a higher percentage of successes. However, what is needed is not simply reports of successes and failures but an attempt to analyze the reasons for

During the past generation there have been many heated arguments as to the pathogenesis and nature of cholesteatoma of the ear. As yet there are no universally accepted theories. The nomenclature itself is confusing. In this paper I shall attempt to clarify the situation and suggest a more uniform nomenclature. DEFINITION "True cholesteatoma," or "cholesteatoma verum," is the term used for a congenital tumor. I believe the term "cholesteatoma" should be limited to the true congenital tumor which develops from a congenital misplaced epidermal anlage. There are a few rare instances of such a tumor developing in the temporal bone. The so-called primary congenital cholesteatoma developing in the temporal bone, however, is in most instances not congenital but develops as a direct result of an invasion of the epidermal epithelium through a perforation of Shrapnell's membrane. Any cholesteatoma which develops as a result of an ingrowth of epidermis into the

50 male university students each participated in one of five film conditions. In all conditions subjects were provoked, exposed to communications, and then given an opportunity to retaliate against their tormentor. Subjects in Condition 1, the control, viewed 150 sec. of a neutral film as opposed to 150 sec. of a violent film viewed in Conditions 2 through 5. Retaliation was delayed in Conditions 3, 4, and 5 by appending 100, 200, or 300 sec., respectively, of the neutral film of the control to the violent film viewed in these conditions. Postcommunication aggression was significantly greater than the control in Conditions 3 and 4 only

ALTHOUGH individuals with Down's syndrome nearly always develop the clinical and pathological features of Alzheimer's disease, some clearly do not become demented despite living into their sixth and seventh decades. Genetic variation at the apolipoprotein E locus has recently been shown to be an important determinant of Alzheimer's disease, with the 4 allele having been shown to be associated with the disease and, at least in some cases, the 2 allele being negatively associated with the disease. Here we show, in a series of clinically assessed individuals with Down's syndrome, that the 2 allele of ApoE is associated with both longevity and the absence of clinical evidence of dementia. These data show that the clinical phenotype of Down's syndrome can be modulated by genes on chromosomes other than chromosome 21. The importance of this observation to the pathogenesis of Alzheimer's disease, both in Down's syndrome and in general, is discussed.

Presents a correction to the article "Dixon," which appeared in the May 2005 issue of the "Landscape Contractor National" magazine.