Identification of large-scale human-specific copy number differences by inter-species array comparative genomic hybridization

Copy number differences (CNDs), and the concomitant differences in gene number, have contributed significantly to the genomic divergence between humans and other primates. To assess its relative importance, the genomes of human, common chimpanzee, bonobo, gorilla, orangutan and macaque were compared by comparative genomic hybridization using a high-resolution human BAC array (aCGH). In an attempt to avoid potential interference from frequent intra-species polymorphism, pooled DNA samples were used from each species. A total of 322 sites of large-scale inter-species CND were identified. Most CNDs were lineage-specific but frequencies differed considerably between the lineages; the highest CND frequency among hominoids was observed in gorilla. The conserved nature of the orangutan genome has already been noted by karyotypic studies and our findings suggest that this degree of conservation may extend to the sub-microscopic level. Of the 322 CND sites identified, 14 human lineage-specific gains were observed. Most of these human-specific copy number gains span regions previously identified as segmental duplications (SDs) and our study demonstrates that SDs are major sites of CND between the genomes of humans and other primates. Four of the human-specific CNDs detected by aCGH map close to the breakpoints of human-specific karyotypic changes [e.g., the human-specific inversion of chromosome 1 and the polymorphic inversion inv(2)(p11.2q13)], suggesting that human-specific duplications may have predisposed to chromosomal rearrangement. The association of human-specific copy number gains with chromosomal breakpoints emphasizes their potential importance in mediating karyotypic evolution as well as in promoting human genomic diversity. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Wild bird mortality and West Nile virus surveillance: biases associated with detection, reporting, and carcass persistence

Surveillance targeting dead wild birds, in particular American crows (Corvus brachyrhynchos), plays a critical role in West Nile virus (WNV) surveillance in the United States. Using crow decoy surrogates, detection and reporting of crow carcasses within urban and rural environments of DeKalb County, Georgia were assessed for potential biases that might occur in the county's WNV surveillance program. In each of two replicated trials, during July and September 2003, 400 decoys were labeled with reporting instructions and distributed along randomly chosen routes throughout designated urban and rural areas within DeKalb County. Information-theoretic methods were used to compare alternative models incorporating the effects of area and trial on probabilities of detection and reporting. The model with the best empirical support included the effects of area on both detection and reporting of decoys. The proportion of decoys detected in the urban area (0.605, SE=0.024) was approximately twice that of the rural area (0.293, SE=0.023), and the proportion of decoys reported in the urban area (0.273, SE=0.023) was approximately three times that of the rural area (0.103, SE=0.028). These results suggest that human density and associated factors can substantially influence dead crow detection and reporting and, thus, the perceived distribution of WNV. In a second and separate study, the persistence and fate of American crow and house sparrow (Passer domesticus) carcasses were assessed in urban and rural environments in Athens-Clarke, Madison, and Oconee counties, Georgia. Two replicated trials using 96 carcasses of each species were conducted during July and September 2004. For a portion of the carcasses, motion sensitive cameras were used to monitor scavenging species visits. Most carcasses (82%) disappeared or were decayed by the end of the 6-day study. Carcass persistence averaged 1.6 days in rural areas and 2.1 days in urban areas. We analyzed carcass persistence rates using a known-fate model framework in program MARK. Model selection based on Akaike's Information Criteria (AIC) indicated that the best model explaining carcass persistence rates included species and number of days of exposure; however, the model including area and number of days of exposure received approximately equal support. Model-averaged carcass persistence rates were higher for urban areas and for crow carcasses. Six mammalian and one avian species were documented scavenging upon carcasses. Dead wild birds could represent potential sources of oral WNV exposure to these scavenging species. Species composition of the scavenger assemblage was similar in urban and rural areas but "scavenging pressure" was greater in rural areas.     

Dim light melatonin onset in alcohol-dependent men and women compared with healthy controls

Sleep disturbances in alcohol-dependent (AD) individuals may persist despite abstinence from alcohol and can influence the course of the disorder. Although the mechanisms of sleep disturbances of AD are not well understood and some evidence suggests dysregulation of circadian rhythms, dim light melatonin onset (DLMO) has not previously been assessed in AD versus healthy control (HC) individuals in a sample that varied by sex and race. The authors assessed 52 AD participants (mean?±?SD age: 36.0?±?11.0 yrs of age, 10 women) who were 3-12 wks since their last drink (abstinence: 57.9?±?19.3 d) and 19 age- and sex-matched HCs (34.4?±?10.6 yrs, 5 women). Following a 23:00-06:00?h at-home sleep schedule for at least 5 d and screening/baseline nights in the sleep laboratory, participants underwent a 3-h extension of wakefulness (02:00?h bedtime) during which salivary melatonin samples were collected every 30?min beginning at 19:30?h. The time of DLMO was the primary measure of circadian physiology and was assessed with two commonly used methodologies. There was a slower rate of rise and lower maximal amplitude of the melatonin rhythm in the AD group. DLMO varied by the method used to derive it. Using 3 pg/mL as threshold, no significant differences were found between the AD and HC groups. Using 2 standard deviations above the mean of the first three samples, the DLMO in AD occurred significantly later, 21:02?±?00:41?h, than in HC, 20:44?±?00:21?h (t?=?-2.4, p?=?.02). Although melatonin in the AD group appears to have a slower rate of rise, using well-established criteria to assess the salivary DLMO did not reveal differences between AD and HC participants. Only when capturing melatonin when it is already rising was DLMO found to be significantly delayed by a mean 18?min in AD participants. Future circadian analyses on alcoholics should account for these methodological caveats.     

Structural basis of membrane invagination by F-BAR domains

BAR superfamily domains shape membranes through poorly understood mechanisms. We solved structures of F-BAR modules bound to flat and curved bilayers using electron (cryo)microscopy. We show that membrane tubules form when F-BARs polymerize into helical coats that are held together by lateral and tip-to-tip interactions. On gel-state membranes or after mutation of residues along the lateral interaction surface, F-BARs adsorb onto bilayers via surfaces other than their concave face. We conclude that membrane binding is separable from membrane bending, and that imposition of the module's concave surface forces fluid-phase bilayers to bend locally. Furthermore, exposure of the domain's lateral interaction surface through a change in orientation serves as the crucial trigger for assembly of the helical coat and propagation of bilayer bending. The geometric constraints and sequential assembly of the helical lattice explain how F-BAR and classical BAR domains segregate into distinct microdomains, and provide insight into the spatial regulation of membrane invagination.     

Weight regain and health-related quality of life in postmenopausal women

Weight loss improves health-related quality of life (HRQoL). However, regain after loss is common; little is known about the impact of weight regain on HRQoL in postmenopausal women. Woman on the Move through Activity and Nutrition (WOMAN) is a randomized lifestyle intervention trial of diet, physical activity, and weight loss in 508 postmenopausal women aged 52-62 years. This analysis focused on the women who lost > or =5 lb during the initial phase of the study, baseline to 6 months (n = 248). This cohort was divided into three groups based on subsequent weight change between 6 and 18 months: weight loss (WL; > or =5 lb loss), weight stable (WS; <+/-5 lb change), and weight regain (WR; > or =5 lb gain). HRQoL was measured at baseline, 6, and 18 months using the Short Form-36. Of the 248 women studied, 51 (21%) continued to lose weight after initial weight loss, while 127 (51%) maintained a stable weight, and 70 (28%) regained weight. Between baseline and 6 months, women in WR group had decreased mental health and social-functioning scores, while the WL and WS groups improved in these subscales. Between baseline and 18 months, energy improved most significantly in those with continued weight loss (P = 0.0003). Weight loss was correlated with a small to moderate improvement in perceived general health and energy, which was reversed by weight gain. Further study is needed to investigate the impact of a decline in mental health and social functioning on future weight regain.     

Advanced computer graphics technology reveals cortical asymmetry in endocasts of rhesus monkeys

Lengths of cortical sulci were measured on ten endocranial casts (endocasts) from skulls of rhesus monkeys, using advanced computer technology that permits analysis and imaging of surface morphology in three dimensions. Sulcal lengths were compared in left and right hemispheres and, contrary to earlier reports, the length of the left Sylvian fissure was found to be significantly longer than its right counterpart, as is the case for chimpanzees and humans. This asymmetry in humans is thought to be associated with asymmetrical representation of language functions in the left hemisphere and, although this report is the first to demonstrate a significantly longer left Sylvian fissure in rhesus monkeys, our results are in keeping with psychophysical evidence that suggests that Macaca is left hemisphere dominant for perception of meaningful vocalizations. We attribute the difference between our findings and previous reports to the sensitivity of the new computer technology used to collect data from endocasts.