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PubMed2005

CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor alpha (PPARalpha) in mice.

PPARalpha (peroxisome-proliferator-activated receptor alpha) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that regulate the expression of genes associated with lipid metabolism. In the present study, we show that circadian expression of mouse PPARalpha mRNA requires the basic helix-loop-helix PAS (Per-Arnt-Sim) protein CLOCK, a core component of the negative-feedback loop that drives circadian oscillators in mammals. The circadian expression of PPARalpha mRNA was abolished in the liver of homozygous Clock mutant mice. Using wild-type and Clock-deficient fibroblasts derived from homozygous Clock mutant mice, we showed that the circadian expression of PPARalpha mRNA is regulated by the peripheral oscillators in a CLOCK-dependent manner. Transient transfection and EMSAs (electrophoretic mobility-shift assays) revealed that the CLOCK-BMAL1 (brain and muscle Arnt-like protein 1) heterodimer transactivates the PPARalpha gene via an E-box-rich region located in the second intron. This region contained two perfect E-boxes and four E-box-like motifs within 90 bases. ChIP (chromatin immunoprecipitation) also showed that CLOCK associates with this E-box-rich region in vivo. Circadian expression of PPARalpha mRNA was intact in the liver of insulin-dependent diabetic and of adrenalectomized mice, suggesting that endogenous insulin and glucocorticoids are not essential for the rhythmic expression of the PPARalpha gene. These results suggested that CLOCK plays an important role in lipid homoeostasis by regulating the transcription of a key protein, PPARalpha.

ARNTL Transcription Factors↗
PubMed2006

Feeding and circadian clocks.

The mammalian genome encodes at least a dozen of genes directly involved in the regulation of the feedback loops constituting the circadian clock. The circadian system is built up on a multitude of oscillators organized according to a hierarchical model in which neurons of the suprachiasmatic nuclei of the hypothalamus may drive the central circadian clock and all the other somatic cells may possess the molecular components allowing tissues and organs to constitute peripheral clocks. Suprachiasmatic neurons are driving the central circadian clock which is reset by lighting cues captured and integrated by the melanopsin cells of the retina and define the daily rhythms of locomotor activity and associated physiological regulatory pathways like feeding and metabolism. This central clock entrains peripheral clocks which can be synchronized by non-photic environmental cues and uncoupled from the central one depending on the nature and the strength of the circadian signal. The human circadian clock and its functioning in central or peripheral tissues are currently being explored to increase the therapeutic efficacy of timed administration of drugs or radiation, and to offer better advice on lighting and meal timing useful for frequent travelers suffering from jet lag and for night workers' comfort. However, the molecular mechanism driving and coordinating the central and peripheral clocks through a wide range of synchronizers (lighting, feeding, physical or social activities) remains a mystery.

Animals↗
PubMed2003

Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes.

CLOCK is a positive component of a transcription/translation-based negative feedback loop of the central circadian oscillator in the suprachiasmatic nucleus in mammals. To examine CLOCK-regulated circadian transcription in peripheral tissues, we performed microarray analyses using liver RNA isolated from Clock mutant mice. We also compared expression profiles with those of Cryptochromes (Cry1 and Cry2) double knockout mice. We identified more than 100 genes that fluctuated from day to night and of which expression levels were decreased in Clock mutant mice. In Cry-deficient mice, the expression levels of most CLOCK-regulated genes were elevated to the upper range of normal oscillation. Most of the screened genes had a CLOCK/BMAL1 binding site (E box) in the 5'-flanking region. We found that CLOCK was absolutely concerned with the circadian transcription of one type of liver genes (such as DBP, TEF, and Usp2) and partially with another (such as mPer1, mPer2, mDec1, Nocturnin, P450 oxidoreductase, and FKBP51) because the latter were damped but remained rhythmic in the mutant mice. Our results showed that CLOCK and CRY proteins are involved in the transcriptional regulation of many circadian output genes in the mouse liver. In addition to being a core component of the negative feedback loop that drives the circadian oscillator, CLOCK also appears to be involved in various physiological functions such as cell cycle, lipid metabolism, immune functions, and proteolysis in peripheral tissues.

Amino Acid Motifs↗
PubMed2003

Adaptive significance of circadian clocks.

Circadian clocks are ubiquitous and are found in organisms ranging from bacteria to mammals. This ubiquity of occurrence implies adaptive significance, but to date there has been no rigorous empirical evidence to support this. It is believed that an organism possessing circadian clocks gains fitness advantage in two ways: (i) by synchronizing its behavioral and physiological processes to cyclic environmental factors (extrinsic adaptive value); (ii) by coordinating its internal metabolic processes (intrinsic adaptive value). There is preliminary circumstantial evidence to support both. Several studies using organisms living in constant environments have shown that these organisms possess functional circadian clocks, suggesting that circadian clocks may have some intrinsic adaptive value. Studies to assess the adaptive value of circadian clocks in periodic environments suggest that organisms may have a fitness advantage in those periodic environments, which closely match their own intrinsic periodicity. Furthermore, evidence from organisms living in the wild, selection studies, and studies on latitudinal clines suggest that circadian clocks may have an extrinsic adaptive value as well. In this paper, I have presented several hypotheses for the emergence of circadian clocks and have reviewed some major empirical studies suggesting adaptive significance of circadian clocks.

Adaptation, Physiological↗
PubMed2003

Involvement of CLOCK:BMAL1 heterodimer in serum-responsive mPer1 induction.

A rapid induction of mouse period1 (mPer1) gene expression is supposed to be critical in the clock gene regulation, especially in the phase resetting of the clock, but its molecular mechanism is poorly understood. Based on the previous finding that the process does not involve de novo synthesis of proteins, we postulated the involvement of CLOCK:BMAL1 heterodimer, a positive regulator of circadian oscillator, in the rapid induction of mPer1 transcription. To test this hypothesis, we utilized CLOCKdelta19, a dominant-negative mutant, to suppress the function of CLOCK:BMAL1 in vitro. Serum-evoked rapid increases of mPer1 mRNA expression and promoter activity were significantly blunted when CLOCK:BMAL1 function was interfered with. Furthermore, DNA binding activity of CLOCK:BMAL1 heterodimer to five E-boxes of mPer1 promoter markedly increased shortly after serum shock. Taken together, these results suggest that CLOCK:BMAL1 heterodimer is not only a core component of negative feedback loop driving circadian oscillator, but also involved in the rapid induction of mPer1during phase resetting of the clock.

3T3 Cells↗
PubMed1998

The short-period mutant, toc1-1, alters circadian clock regulation of multiple outputs throughout development in Arabidopsis thaliana.

The coordination of developmental and physiological events with environmental signals is facilitated by the action of the circadian clock. Here we report a new set of circadian clock-controlled phenotypes for Arabidopsis thaliana. We use these markers together with the short-period mutant, toc1-1, and the clock-controlled cab2::luciferase reporter gene to assess the nature of the circadian clock throughout development and to suggest the position of TOC1 within the circadian clock system. In dark-grown seedlings, the toc1-1 lesion conferred a short period to the cycling of cab2::luciferase luminescence, as previously found in light-grown plants, indicating that the circadian clocks in these two divergent developmental states share at least one component. Stomatal conductance rhythms were similarly approximately 3 hours shorter than wild type in toc1-1, suggesting that a cell-autonomous clockwork may be active in guard cells in 5- to 6-week-old leaves. The effect of daylength on flowering time in the C24 ecotype was diminished by toc1-1, and was nearly eliminated in the Landsberg erecta background where the plants flowered equally early in both short and long days. Throughout a 500-fold range of red light intensities, both the wild type and the mutant showed an inverse log-linear relationship of fluence rate to period, with a 2-3 hour shorter period for the mutant at all intensities. These results indicate that TOC1 acts on or within the clock independently of light input. Temperature entrainment appears normal in toc1-1, and the period-shortening effects of the mutant remain unchanged over a 20 degrees C temperature range. Taken together our results are consistent with the likelihood that TOC1 codes for an oscillator component rather than for an element of an input signaling pathway. In addition, the pervasive effect of toc1-1 on a variety of clock-controlled processes throughout development suggests that a single circadian system is primarily responsible for controlling most, if not all, circadian rhythms in the plant.

Arabidopsis↗
PubMed2005

Circadian oscillations of clock genes, cytolytic factors, and cytokines in rat NK cells.

A growing body of knowledge is revealing the critical role of circadian physiology in the development of specific pathological entities such as cancer. NK cell function participates in the immune response against infection and malignancy. We have reported previously the existence of a physiological circadian rhythm of NK cell cytolytic activity in rats, suggesting the existence of circadian mechanisms subjacent to NK cell function. At the cellular level, circadian rhythms are originated by the sustained transcriptional-translational oscillation of clock genes that form the cellular clock apparatus. Our aim in this study was to investigate the presence of molecular clock mechanisms in NK cells as well as the circadian expression of critical factors involved in NK cell function. For that purpose, we measured the circadian changes in the expression of clock genes (Per1, Per2, Bmal1, Clock), Dbp (a clock-controlled output gene), CREB (involved in clock signaling), cytolytic factors (granzyme B and perforin), and cytokines (IFN-gamma and TNF-alpha) in NK cells enriched from the rat spleen. The results obtained from this study demonstrate for the first time the existence of functional molecular clock mechanisms in NK cells. Moreover, the circadian expression of cytolytic factors and cytokines in NK cells reported in this study emphasizes the circadian nature of NK cell function.

ARNTL Transcription Factors↗
PubMed2004

[Advances in study on molecular mechanism of circadian clock in pineal gland].

The pineal gland functions as a central circadian oscillator in a variety of nonmammalian vertebrates. More recently, clock genes such as Per, Cry, Clock, and Bmal have been found in a variety of vertebrate clock structures including the avian pineal gland. The profiles of the temporal change of the clock gene expression in the avian pineal gland are more similar to those in the mammalian suprachiasmatic nucleus (SCN) of the hypothalamus. Avian pineal gland and mammalian SCN seem to share a fundamental molecular framework of the clock oscillator composed of a transcription/translation-based autoregulatory feedback loop. Some products of the clock genes serve as positive or negative regulators influencing the clock oscillation. The circadian time-keeping mechanism is also involved in several post-translational events. The above-mentioned processes play a quite important role in the stability of the oscillator and/or the photic-input pathway for entrainment of the clock.

Animals↗
PubMed2002

Alterations of the circadian clock in the heart by streptozotocin-induced diabetes.

The heart, like other organs, possesses an internal circadian clock. These clocks provide the selective advantage of anticipation, enabling the organ to prepare for a given stimulus, thereby optimizing the appropriate response. The heart in diabetes is associated with alterations in morphology, gene expression, metabolism and contractile performance. The present study investigated whether diabetes also alters the circadian clock in the heart. Insulin-dependent diabetes mellitus was induced in rats by treatment with streptozotocin (STZ; 65 mg/kg). STZ increased humoral (glucose and non-esterified fatty acids) and heart gene expression (myosin heavy chain beta, pyruvate dehydrogenase kinase 4 and uncoupling protein 3) markers of diabetes. The circadian patterns of gene expression of seven components of the mammalian clock (bmal1, clock, cry1, cry2, per1, per2 and per3), as well as three clock output genes (dbp, hlf and tef), were compared in hearts isolated from control and STZ-induced diabetic rats. All components of the clock investigated possessed circadian rhythms of gene expression. In the hearts isolated from STZ-induced diabetic rats, the phases of these circadian rhythms were altered (approximately 3 h early) compared to those observed for control hearts. The clock in the heart has therefore lost normal synchronization with its environment during diabetes. Whether this loss of synchronization plays a role in the development of contractile dysfunction of the heart in diabetes remains to be determined.

Animals↗
PubMed2006

The mPer1 clock gene expression in the rd mouse suprachiasmatic nucleus is affected by the retinal degeneration.

Endogenous rhythms of mammals are controlled by the clock located in the suprachiasmatic nucleus (SCN). The molecular mechanism of a clock involves transcription/translation-based feedback loops in which the expression of the so called "clock genes" is suppressed periodically by their protein products. Previous studies reported influence of the eye itself on the circadian oscillation of the SCN, apart from the well-known photic readjustment of the central clock. With this in mind, we decided to analyze the mPer1 clock gene expression in the retinally degenerate (rd) mouse SCN by means of immunohistochemical techniques. Our objective was to detect possible alterations of the daily endogenous oscillation of PER1 protein in the SCN of these rd mice, as well as to make clear whether or not this protein was involved in the resetting of the central clock in a manner similar to wild-type animals. We found that the endogenous levels of PER1 protein were reduced in the SCN of rd mice throughout the 24-h cycle, which suggests that loss of classic photoreceptors influences somehow the main mechanism of the SCN clock. Light stimulation induced a parallel increase of Per1 expression at the subjective night, but not at the subjective day, in both rd and wild-type mice. Therefore, SCN readjustment by light in the rd mice occurs with a pattern similar to wild-type controls, despite the reduced PER1 protein levels detected. The effect of retinal degeneration on the circadian system and the possible interactions between the retinal and the SCN clocks are discussed.

Analysis of Variance↗
PubMed2006

Sleeping with the enemy: clock monitoring in the maintenance of insomnia.

Two experiments that aimed to investigate the association between clock monitoring, pre-sleep worry and sleep are presented. In Experiment 1, 30 good and 30 poor sleepers were instructed either to monitor or not to monitor a clock as they were trying to get to sleep. Worry was indexed by self-rating. Sleep was measured by self-report and actigraphy. Compared to non-monitors, clock-monitors reported more pre-sleep worry and they experienced longer sleep onset latency (SOL). These findings held true for both good and poor sleepers. In Experiment 2, following one night of baseline measurement, 38 individuals diagnosed with primary insomnia were instructed to monitor either a clock or a digit display unit (a control monitoring task) as they were trying to get to sleep. The clock-monitoring task was rated to be more worry provoking and sleep interfering than the display unit-monitoring task. Whilst display unit-monitors experienced less pre-sleep worry, the clock-monitors experienced more pre-sleep worry and reported a longer SOL on the experimental night, relative to baseline. Further, compared to the display unit-monitors, the clock-monitors overestimated their SOL more on the experimental night. Together, these findings suggest that clock monitoring may trigger pre-sleep worry and serve to maintain insomnia by fuelling pre-sleep worry and exacerbating misperception of sleep.

Adult↗
PubMed2002

Accuracy of the clock drawing test for detecting dementia in a multicultural sample of elderly Australian patients.

OBJECTIVE: To assess the accuracy of clock drawing for detecting dementia in a multicultural, non-English-speaking-background population. DESIGN: A prospective cohort study. SETTING: A general geriatric medical outpatient clinic in southwest Sydney, Australia. PARTICIPANTS: Ninety-three consecutive new patients to the clinic who had a non-English-speaking-background country of birth (mean age 78.0 years). MEASUREMENTS: The clock drawing test was conducted at the beginning of each clinic visit by a blinded investigator. Each patient was then assessed by a geriatrician who collected demographic data, administered the Modified Barthel Index, the Geriatric Depression Scale, and the Folstein Mini-Mental State Examination, and categorized each patient as normal or demented, according to DSM-IV criteria. Interpreters were used for participants who spoke a language other than English or who requested them. Each clock drawing was scored according to the 4-point CERAD scale and the previously published methods of Mendez, Shulman, Sunderland, Watson, and Wolf-Klein. Scoring was evaluated for reliability and predictive accuracy, using receiver operating characteristic (ROC) curve analysis. Logistic regression analysis was used to assess the potential interaction between level of education and each of the clock scoring methods. RESULTS: Using ROC curve analysis, there was no significant difference between the clock scoring methods (area under the curve varied from 0.60 to 0.72). The most sensitive was the Mendez scoring method (98%), with a specificity of 16%. Specificity above 50% was found only for the Wolf-Klein method, with an intermediate sensitivity of 78%. CONCLUSIONS: There were no significant differences in the clock scoring methods used to detect dementia. Performance of the clock drawing test was modest at best with low levels of specificity across all methods. Scored according to these methods, clock drawing was not a useful predictor of dementia in our multicultural population.

Aged↗
PubMedDate not supplied

Circadian clock in Xenopus eye controlling retinal serotonin N-acetyltransferase.

Circadian rhythms are controlled by endogenous oscillators or clocks. These clocks exhibit a persistent period of approximately 24 h in constant conditions, a specific phase relationship to a periodic cue (zeitgeber) in the external environment, and plasticity in that the phase of the clock may be altered in response to a phase change in the zeitgeber. Although many processes exhibit circadian rhythmicity, the nature and location of endogenous clocks remain poorly defined. Recent evidence in vertebrates suggests that the mammalian suprachiasmatic nucleus and the avian pineal gland contain clocks that affect the rhythmicity of indoleamine metabolism. The vertebrate retina also exhibits a circadian rhythm of serotonin N-acetytransferase activity (NAT, EC 2.1.1.4), a key enzyme controlling melatonin synthesis, and of photoreceptor disk shedding. The latter process may be regulated by melatonin, and the immediate cellular events seem to be controlled locally within the eye. Although sustained oscillation and entrainment were not demonstrated, data suggesting that an ocular circadian clock influences disk shedding have been reported. We sought evidence for an ocular clock by studying retinal NAT activity in Xenopus eye cups maintained in culture and report here both sustained oscillation and entrainment of the in vitro system. The data indicate that in addition to the suprachiasmatic nucleus and pineal gland, the eye itself must be regarded as the locus of a circadian clock in vertebrates.

Acetyltransferases↗
PubMed1996

Does clock-watching make you clockwise?

French and Richards (1993) found that subjects asked to draw from memory a clock that had Roman numerals on its face typically represented the number four on the clock face as "IV" rather than the correct "IIII", whereas those merely asked to copy it typically drew "IIII". The current experiments followed the methodology of French and Richards, but then went on to examine the subsequent memorial representation of the number four. Subjects drew a clock with Roman numerals on its face, either from memory (with or without forewarning) or while the clock remained in full view. Subsequently, subjects were asked to recall the exact form in which the numbers were represented on the clock (Experiment 1) or were asked to recognise which of two clocks had been presented earlier (Experiment 2). Findings supported the idea that subjects in the copy condition were more likely than subjects in other conditions to draw the clock without invoking schematic knowledge of Roman numerals. The basic effect reported by French and Richards was replicated in both experiments. Furthermore, in both experiments, subjects who correctly drew the clock with the number four represented as "IIII" were more likely to misrepresent it as "IV" in the subsequent memory task if they were in the copy condition rather than the two memory conditions. The results are interpreted in terms of schema theory.

England↗
PubMed2002

Temperature effect on entrainment, phase shifting, and amplitude of circadian clocks and its molecular bases.

Effects of temperature and temperature changes on circadian clocks in cyanobacteria, unicellular algae, and plants, as well as fungi, arthropods, and vertebrates are reviewed. Periodic temperature with periods around 24 h even in the low range of 1-2 degrees C (strong Zeitgeber effect) can entrain all ectothermic (poikilothermic) organisms. This is also reflected by the phase shifts-recorded by phase response curves (PRCs)-that are elicited by step- or pulsewise changes in the temperature. The amount of phase shift (weak or strong type of PRC) depends on the amplitude of the temperature change and on its duration when applied as a pulse. Form and position of the PRC to temperature pulses are similar to those of the PRC to light pulses. A combined high/low temperature and light/dark cycle leads to a stabile phase and maximal amplitude of the circadian rhythm-when applied in phase (i.e., warm/light and cold/dark). When the two Zeitgeber cycles are phase-shifted against each other the phase of the circadian rhythm is determined by either Zeitgeber or by both, depending on the relative strength (amplitude) of both Zeitgeber signals and the sensitivity of the species/individual toward them. A phase jump of the circadian rhythm has been observed in several organisms at a certain phase relationship of the two Zeitgeber cycles. Ectothermic organisms show inter- and intraspecies plus seasonal variations in the temperature limits for the expression of the clock, either of the basic molecular mechanism, and/or the dependent variables. A step-down from higher temperatures or a step-up from lower temperatures to moderate temperatures often results in initiation of oscillations from phase positions that are about 180 degrees different. This may be explained by holding the clock at different phase positions (maximum or minimum of a clock component) or by significantly different levels of clock components at the higher or lower temperatures. Different permissive temperatures result in different circadian amplitudes, that usually show a species-specific optimum. In endothermic (homeothermic) organisms periodic temperature changes of about 24 h often cause entrainment, although with considerable individual differences, only if they are of rather high amplitudes (weak Zeitgeber effects). The same applies to the phase-shifting effects of temperature pulses. Isolated bird pineals and rat suprachiasmatic nuclei tissues on the other hand, respond to medium high temperature pulses and reveal PRCs similar to that of light signals. Therefore, one may speculate that the self-selected circadian rhythm of body temperature in reptiles or the endogenously controlled body temperature in homeotherms (some of which show temperature differences of more than 2 degrees C) may, in itself, serve as an internal entraining system. The so-called heterothermic mammals (undergoing low body temperature states in a daily or seasonal pattern) may be more sensitive to temperature changes. Effects of temperature elevation on the molecular clock mechanisms have been shown in Neurospora (induction of the frequency (FRQ) protein) and in Drosophila (degradation of the period (PER) and timeless (TIM) protein) and can explain observed phase shifts of rhythms in conidiation and locomotor activity, respectively. Temperature changes probably act directly on all processes of the clock mechanism some being more sensitive than the others. Temperature changes affect membrane properties, ion homeostasis, calcium influx, and other signal cascades (cAMP, cGMP, and the protein kinases A and C) (indirect effects) and may thus influence, in particular, protein phosphorylation processes of the clock mechanism. The temperature effects resemble to some degree those induced by light or by light-transducing neurons and their transmitters. In ectothermic vertebrates temperature changes significantly affect the melatonin rhythm, which in turn exerts entraining (phase shifting) functions.

Amphibians↗
PubMed2026

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

Healthspan↗
PubMed2001

Cellular signalling and the complexity of biological timing: insights from the ultradian clock of Schizosaccharomyces pombe.

The molecular bases of circadian clocks are complex and cannot be sufficiently explained by the relatively simple feedback loops, based on transcription and translation, of current models. The existence of additional oscillators has been demonstrated experimentally, but their mechanism(s) have so far resisted elucidation and any universally conserved clock components have yet to be identified. The fission yeast, Schizosaccharomyces pombe, as a simple and well-characterized eukaryote, is a useful model organism in the investigation of many aspects of cell regulation. In fast-growing cells of the yeast an ultradian clock operates, which can serve as a model system to analyse clock complexity. This clock shares strict period homeostasis and efficient entrainment with circadian clocks but, because of its short period of 30 min, mechanisms other than a transcription/translation-based feedback loop must be working. An initial systematic screen involving over 200 deletion mutants has shown that major cellular signalling pathways (calcium/phosphoinositide, mitogen-activated protein kinase and cAMP/protein kinase A) are crucial for the normal functioning of this ultradian clock. A comparative examination of the role of cellular signalling pathways in the S.pombe ultradian clock and in the circadian timekeeping of different eukaryotes may indicate common principles in biological timing processes that are universally conserved amongst eukaryotes.

Activity Cycles↗
PubMedDate not supplied

The 7-o'clock posteroinferior portal for shoulder arthroscopy.

BACKGROUND: Access to the inferior glenohumeral joint of the shoulder is very limited through the traditional 2- or 3-o'clock anterior portals. HYPOTHESIS: The 7-o'clock posteroinferior portal offers an excellent alternative approach. STUDY DESIGN: Descriptive anatomic study. METHODS: Six paired cadaveric shoulders were used to arthroscopically develop and test a 7-o'clock posteroinferior portal. The distances between the portal and the subscapular and axillary nerves were measured with the arm in six different positions, combining flexion, extension, abduction, and adduction. RESULTS: The distance from the 7-o'clock posteroinferior portal to the axillary nerve was 39 +/- 4 mm and to the suprascapular nerve was 28 +/- 2 mm. There was no statistically significant nerve-to-portal differential distance when the arm was placed in flexion, extension, abduction, or adduction. The inside-to-outside technique produced a 7-o'clock posteroinferior portal approximately 5 mm further from both the axillary and suprascapular nerves than did the outside-to-inside method. The angle of divergence from the 7-o'clock posterior portal skin incision to the axillary nerve was 47 degrees and to the suprascapular nerve was 33 degrees. CONCLUSIONS: The 7-o'clock portal affords safe, direct working access to the inferior capsular recess of the glenohumeral joint. CLINICAL RELEVANCE: The 7-o'clock portal is a safe and effective technique for use by shoulder surgeons.

Arthroscopy↗