Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

This corrects the article DOI: 10.1038/mp.2017.42.

Partitioning heritability analysis reveals a shared genetic basis of brain anatomy and schizophrenia.

Schizophrenia is a devastating neurodevelopmental disorder with a complex genetic etiology. Widespread cortical gray matter loss has been observed in patients and prodromal samples. However, it remains unresolved whether schizophrenia-associated cortical structure variations arise due to disease etiology or secondary to the illness. Here we address this question using a partitioning-based heritability analysis of genome-wide single-nucleotide polymorphism (SNP) and neuroimaging data from 1750 healthy individuals. We find that schizophrenia-associated genetic variants explain a significantly enriched proportion of trait heritability in eight brain phenotypes (false discovery rate=10%). In particular, intracranial volume and left superior frontal gyrus thickness exhibit significant and robust associations with schizophrenia genetic risk under varying SNP selection conditions. Cross-disorder comparison suggests that the neurogenetic architecture of schizophrenia-associated brain regions is, at least in part, shared with other psychiatric disorders. Our study highlights key neuroanatomical correlates of schizophrenia genetic risk in the general population. These may provide fundamental insights into the complex pathophysiology of the illness, and a potential link to neurocognitive deficits shaping the disorder.

Intrinsic functional architecture in the anaesthetized monkey brain.

The traditional approach to studying brain function is to measure physiological responses to controlled sensory, motor and cognitive paradigms. However, most of the brain's energy consumption is devoted to ongoing metabolic activity not clearly associated with any particular stimulus or behaviour. Functional magnetic resonance imaging studies in humans aimed at understanding this ongoing activity have shown that spontaneous fluctuations of the blood-oxygen-level-dependent signal occur continuously in the resting state. In humans, these fluctuations are temporally coherent within widely distributed cortical systems that recapitulate the functional architecture of responses evoked by experimentally administered tasks. Here, we show that the same phenomenon is present in anaesthetized monkeys even at anaesthetic levels known to induce profound loss of consciousness. We specifically demonstrate coherent spontaneous fluctuations within three well known systems (oculomotor, somatomotor and visual) and the 'default' system, a set of brain regions thought by some to support uniquely human capabilities. Our results indicate that coherent system fluctuations probably reflect an evolutionarily conserved aspect of brain functional organization that transcends levels of consciousness.

First experimental demonstration of self-synchronous phase locking of an optical array.

A novel, highly accurate, all electronic technique for phase locking arrays of optical fibers is demonstrated. We report the first demonstration of the only electronic phase locking technique that doesn't require a reference beam. The measured phase error is lambda/20. Excellent phase locking has been demonstrated for fiber amplifier arrays.

Gaze direction modulates finger movement activation patterns in human cerebral cortex.

We investigated whether gaze direction modified the pattern of finger movement activation in human cerebral cortex using functional magnetic resonance imaging (MRI). Participants performed a sequential finger-tapping task or made no finger movements while maintaining gaze in the direction of the moving hand (aligned conditions) or away from the location of the moving hand. Functional MR signals, measured in the hemisphere contralateral to the moving hand, revealed finger movement-related activation in primary motor cortex, lateral and medial premotor cortex, and a wide extent of the lateral superior and inferior parietal lobules. In each area, the extent of the finger movement activation increased when static gaze was more aligned with the moving hand compared to when gaze was directed away from the moving hand. These data suggest the existence of large-scale cortical networks related to finger actions and indicate that skeletomotor processing in the cerebral cortex is consistently modified by gaze direction signals.

Anatomic and prognostic implications of an early positive treadmill exercise test.

Eighty men (group A) with clinical coronary artery disease underwent coronary angiography regardless of symptoms and previous therapy because they had a positive treadmill exercise test in stage I or II of the Bruce protocol. Thirty-four other men (group B) who also had an early positive treadmill test underwent coronary angiography because they had disabling angina pectoris despite medical therapy. We found left main coronary artery stenosis of 50% or greater of the vessel diameter in 28% of group A and 35% of group B (p greater than 0.3). In contrast, only 10% of 93 other catheterized patients who had treadmill tests that were not early positive had left main coronary disease (p less than 0.001). Fifty-four patients from group A who did not have left main stenosis of 50% or greater were treated medically. In this subgroup, 85% had 2 or 3 major coronary vessels with 75% or greater stenosis. These patients had a 36 month survival rate of 89.2%. We conclude that an early positive treadmill test identifies patients who have an increased likelihood of having left main coronary stenosis, even if they are minimally symptomatic. To identify left main coronary stenosis, catheterization may be justified in patients whose angina pectoris has been mild or not intensively treated when they have an early positive treadmill response. After left main coronary stenosis has been excluded, these patients may be treated medically with a low mortality.

Neural correlates of verbal memory encoding during semantic and structural processing tasks.

Eighteen participants were imaged using fMRI to explore whether brain regions predicting successful verbal memory encoding during semantic decisions would continue to predict encoding during structural (non-semantic) decisions. Consistent with prior studies, left inferior frontal and fusiform regions were more active during semantic than structural decisions, and activity was greater for remembered than forgotten words during semantic decisions. Critically, structural decisions yielded significantly greater activity for remembered than forgotten words in these regions providing evidence that a common frontal-temporal network supports verbal memory encoding irrespective of orienting task. Further analysis revealed activity associated with successful encoding in the right precentral gyrus, suggesting other regions may also play a role in verbal encoding during non-semantic processing.

Effect of intense training on plasma leptin in male and female swimmers.

PURPOSE: The purpose of this study was to determine whether fasting plasma leptin concentration was altered with an increase in training volume in competitive male and female athletes. METHODS: Intercollegiate male (N = 9) and female (N = 12) swimmers were examined during the preseason and at two times during the mid-season (mid-season 1 and mid-season 2) when training volume was relatively high (33,000 m.wk(-1)). Body composition (hydrostatic weighing), energy intake and expenditure, and fasting plasma leptin concentration were measured. RESULTS: In the women, there was a significant (P < 0.05) decline in fat mass (2 kg) with the increase in training volume, which was not accompanied by a reduction in fasting leptin (12.8 +/- 1.5 vs 11.0 +/- 1.2 vs 11.0 +/- 1.5 ng.mL(-1) for preseason, mid-season 1, and mid-season 2, respectively). In the men, there were no significant changes in body composition, body mass, or fasting leptin (4.4 +/- 0.8 vs 4.3 +/- 0.8 vs 4.6 +/- 0.8 ng.mL(-1), respectively). CONCLUSION: These findings suggest 1) plasma leptin is not sensitive to an increase in training volume and 2) leptin may not be indicative of changes in fat mass with an increase in training volume in female athletes. These data suggest that leptin may not be useful in monitoring relative training stress in athletes.

Assessment of the impact of rising carbon dioxide and other potential climate changes on vegetation.

The projected doubling of current levels of atmospheric carbon dioxide concentration ([CO(2)]) during the next century along with increases in other radiatively active gases have led to predictions of increases in global air temperature and shifts in precipitation patterns. Additionally, stratospheric ozone depletion may result in increased ultraviolet-B (UV-B) radiation incident at the Earth's surface in some areas. Since these changes in the Earth's atmosphere may have profound effects on vegetation, the objectives of this paper are to summarize some of the recent research on plant responses to [CO(2)], temperature and UV-B radiation. Elevated [CO(2)] increases photosynthesis and usually results in increased biomass, and seed yield. The magnitude of these increases and the specific photosynthetic response depends on the plant species, and are strongly influenced by other environmental factors including temperature, light level, and the availability of water and nutrients. While elevated [CO(2)] reduces transpiration and increases photosynthetic water-use efficiency, increasing air temperature can result in greater water use, accelerated plant developmental rate, and shortened growth duration. Experiments on UV-B radiation exposure have demonstrated a wide range of photobiological responses among plants with decreases in photosynthesis and plant growth among more sensitive species. Although a few studies have addressed the interactive effects of [CO(2)] and temperature on plants, information on the effects of UV-B radiation at elevated [CO(2)] is scarce. Since [CO(2)], temperature and UV-B radiation may increase concurrently, more research is needed to determine plant responses to the interactive effects of these environmental variables.

Australian deliberations on access to its terrestrial and marine biodiversity.

The predominantly developed country business principle that the natural resource is effectively free, or of very low monetary value, has been significantly challenged in recent years, not only through the recognition of the accelerated rate of depletion of native forest resources and of the space and food demands of increasing populations, but also through international conventions which deal with a wide range of topics from the rights of indigenous people to the Law of the Sea Convention. Australia, classified as a developed country, but located in a geographic region of many developing countries, has, in the past 25 years, demonstrated particular concern for the rights of the people of those countries, as well as for the rights of indigenous people of Australia. The practical international aspects were clearly exemplified in the time, from 1985, when the Australian Institute of Marine Science (AIMS) negotiated, within the National Cancer Institute (NCI) contract, that collections of biological samples in developing countries would be accompanied by an agreement to provide benefits arising from field work, and from any commercial product developments, to those countries. Australia, as a signatory to the Convention on Biological Diversity (Appendix I), continues to analyze the challenge presented by the need to freely exchange genetic resources of common value, e.g. food crops, while insuring an appropriate reward to developing and developed countries, should discoveries be made from their biological resources, which lead directly or indirectly, to high value commercial non-food products. The Prime Minister's Coordinating Committee on Science and Technology established a special working group to recommend on access to Australia's biodiversity. The report arising from the study, and other related issues, are discussed.

Effects of pulsed electromagnetic fields on bone healing in a rabbit tibial osteotomy model.

OBJECTIVE: The purpose of this study was to determine the effect of pulsed electromagnetic field (PEMF) exposure on healing tibial osteotomies in New Zealand White rabbits. DESIGN: One-millimeter Gigli saw osteotomies were stabilized by external fixation. One day after surgery, rabbits were randomly assigned to receive either no exposure (sham control) or thirty minutes or sixty minutes per day of low-frequency, low-amplitude PEMF. Radiographs were obtained weekly throughout the study. Rabbits were euthanized at fourteen, twenty-one, or twenty-eight days, and tibiae underwent either destructive torsional testing or histologic analysis. To determine the baseline torsional strength and stiffness of rabbit tibiae, eleven normal intact tibiae were tested to failure. RESULTS: Sixty-minute PEMF-treated osteotomies had significantly higher torsional strength than did sham controls at fourteen and twenty-one days postoperatively. Thirty-minute PEMF-treated osteotomies were significantly stronger than sham controls only after twenty-one days. Normal intact torsional strength was achieved by fourteen days in the sixty-minute PEMF group, by twenty-one days in the thirty-minute PEMF group, and by twenty-eight days in the sham controls. Maximum fracture callus area correlated with the time to reach normal torsional strength. CONCLUSION: In this animal model, low-frequency, low-amplitude PEMF significantly accelerated callus formation and osteotomy healing in a dose-dependent manner.

Value of emergency cardiac enzymes: audit in a coronary care unit.

Medical audit in a district general hospital coronary care unit led to the introduction of an emergency cardiac enzyme service. 91.2% of patients eligible for thrombolysis therapy received treatment following this introduction compared to 73.7% before (P = .05). No patient was treated inappropriately on the basis of a raised cardiac enzyme.

Measurement of a single tendon reflex in conjunction with a myogram: the second manned Skylab mission.

A generalized hyperreflexia was observed in Skylab 2 crewmembers during the immediate postflight clinical evaluations. Unfortunately, no provisions had been made to quantitate the observed phenomenon. The cause of the hyperreflexia was not readily apparent at the time of the observation. Reflex changes have been noted in several of the Russian cosmonauts after extended spaceflight. Prior to the launch of Skylab 3, it was decided to measure and record a single tendon reflex and, if possible, the associated muscle potential. Duration of the Achilles reflex immediately postflight showed a significant (p greater than 0.01) shortening for all three crewmen. The reflex duration exhibited further significant shortening from preflight values on the fourth day after recovery. At the 16th day measurement, there was a signficant lengthening of the reflex for crewmenber 2 and 3 while crewmember 1 showed some lengthening which was not significant. By 29 d postrecovery, the reflex time of crewmember 1 had returned to his preflight value while the other two crewmen continued to show a significant lengthening of the reflex, although both were showing trends toward their preflight values. The muscle potential intervals were shortened immediately postflight and remained shortened during the 29 d of postflight evaluation. Currently, work is in progress to correlate these findings with other observed anatomical, physical, and biochemical changes. Final conclusions and an in-depth statistical analysis will be presented at a later date.

Adrenal disorders. A primary care approach.

Small in size but powerful in influence, the adrenal glands and their hormones are necessary to sustain life and maintain homeostasis. If not detected in a timely fashion, adrenal disorders can have fatal consequences. This articles reviews the anatomy and physiology of the adrenal glands and, with the use of case studies, considers many disorders of the adrenal glands, including Cushing's disease, aldosteronism, hyperaldosteronism, and Addison's disease.

Dependence of p-aminohippurate transport on calcium in canine renal cortical slices.

1. Experiments were conducted on renal cortical slices from sixty-one adult mongrel dogs in order to evaluate the relationship between p-aminohippurate (PAH) transport and calcium. Tissues were found to be viable for at least 180 min.2. PAH uptake and the slice/medium (S/M) concentration ratio increased in normal tissues from 3 to 90 min whether data were expressed on a tissue weight or protein content basis. PAH uptake increased with time in calcium-depleted tissues, but all values were lower than normal. At 90 min, PAH S/M in calcium-depleted tissues (4.20 +/- 0.18) was reduced 40% compared to normal tissues (6.90 +/- 0.23).3. Over the time period of 3-90 min incubation, protein concentration ranged from 89.4 to 99.4 mg/g cortex in calcium-depleted tissues. During the same time period in normal tissues, protein concentration ranged from 105 to 117.6 mg/g cortex. No change was observed in medium protein concentration of calcium-depleted tissues.4. Lineweaver-Burke analysis showed similar values for K(m) in normal and calcium-depleted tissues (0.45-0.50 mumole ml.(-1)) although V(max) fell from control values of 0.082 to 0.052 mumole g(-1) min(-1) during calcium depletion.5. After 90 min incubation, addition of EGTA (7, 14 or 21 x 10(-3)M) to media containing calcium was associated with decreased S/M and uptake rates compared to control values from the same animals. The decreases observed were similar to those seen in tissues incubated in calcium-free media.6. Increased cell volume in the presence of calcium was not associated with decreased PAH uptake. Removal of calcium in association with constant cell volume was associated with reduced PAH uptake. Replacement of calcium, but not magnesium, is associated with a return of uptake to normal rates.7. It is concluded that (a) calcium removal causes increased water uptake into cells, (b) calcium removal causes a reduced V(max), (c) calcium is required for maintenance of intracellular PAH, (d) the effect of calcium on PAH is specific and reversible, and (e) the effect of calcium is not mediated by volume changes.

Extraction fraction at any urine flow and extraction percentage.

Extraction fraction of renal solutes is ordinarily calculated as a ratio of arterial and venous concentration differences. Calculations provided in the present manuscript illustrate the need to correct for changes in renal venous concentration when solute extraction is low and urine flow simultaneously high.