Counting Orbifolds

We present several methods of counting the orbifolds C^D/Gamma. A correspondence between counting orbifold actions on C^D, brane tilings, and toric diagrams in D-1 dimensions is drawn. Barycentric coordinates and scaling mechanisms are introduced to characterize lattice simplices as toric diagrams. We count orbifolds of C^3, C^4, C^5, C^6 and C^7. Some remarks are made on closed form formulas for the partition function that counts distinct orbifold actions.Comment: 69 pages, 9 figures, 24 tables; minor correction

The broad phenotypic spectrum of 17α-hydroxylase/17,20-lyase (CYP17A1) deficiency: a case series

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterised by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. OBJECTIVE: To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. DESIGN: Case series. PATIENTS AND RESULTS: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr) and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of WT activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. CONCLUSION: Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol has not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity. SIGNIFICANCE STATEMENT: Here we report, supported by careful phenotyping, genotyping and functional analysis, a prismatic case series of patients with congenital adrenal hyperplasia due to 17α-hydroxylase (CYP17A1) deficiency (17OHD). These range in severity from the abolition of function, presenting in early infancy, and unusually mild with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients. These findings will guide improved diagnostic detection of CYP17A1 deficiency

Native aggregation as a cause of origin of temporary cellular structures needed for all forms of cellular activity, signaling and transformations

According to the hypothesis explored in this paper, native aggregation is genetically controlled (programmed) reversible aggregation that occurs when interacting proteins form new temporary structures through highly specific interactions. It is assumed that Anfinsen's dogma may be extended to protein aggregation: composition and amino acid sequence determine not only the secondary and tertiary structure of single protein, but also the structure of protein aggregates (associates). Cell function is considered as a transition between two states (two states model), the resting state and state of activity (this applies to the cell as a whole and to its individual structures). In the resting state, the key proteins are found in the following inactive forms: natively unfolded and globular. When the cell is activated, secondary structures appear in natively unfolded proteins (including unfolded regions in other proteins), and globular proteins begin to melt and their secondary structures become available for interaction with the secondary structures of other proteins. These temporary secondary structures provide a means for highly specific interactions between proteins. As a result, native aggregation creates temporary structures necessary for cell activity

Early anthropogenic transformation of the Danube-Black Sea system

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 2 (2012): 582, doi:10.1038/srep00582.Over the last century humans have altered the export of fluvial materials leading to significant changes in morphology, chemistry, and biology of the coastal ocean. Here we present sedimentary, paleoenvironmental and paleogenetic evidence to show that the Black Sea, a nearly enclosed marine basin, was affected by land use long before the changes of the Industrial Era. Although watershed hydroclimate was spatially and temporally variable over the last ~3000 years, surface salinity dropped systematically in the Black Sea. Sediment loads delivered by Danube River, the main tributary of the Black Sea, significantly increased as land use intensified in the last two millennia, which led to a rapid expansion of its delta. Lastly, proliferation of diatoms and dinoflagellates over the last five to six centuries, when intensive deforestation occurred in Eastern Europe, points to an anthropogenic pulse of river-borne nutrients that radically transformed the food web structure in the Black Sea.This study was supported by grants OISE 0637108, EAR 0952146, OCE 0602423 and OCE 0825020 from the National Science Foundation and grants from the Woods Hole Oceanographic Institution

Unexpected Ecological Resilience in Bornean Orangutans and Implications for Pulp and Paper Plantation Management

Ecological studies of orangutans have almost exclusively focused on populations living in primary or selectively logged rainforest. The response of orangutans to severe habitat degradation remains therefore poorly understood. Most experts assume that viable populations cannot survive outside undisturbed or slightly disturbed forests. This is a concern because nearly 75% of all orangutans live outside protected areas, where degradation of natural forests is likely to occur, or where these are replaced by planted forests. To improve our understanding of orangutan survival in highly altered forest habitats, we conducted population density surveys in two pulp and paper plantation concessions in East Kalimantan, Indonesia. These plantations consist of areas planted with fast-growing exotics intermixed with stands of highly degraded forests and scrublands. Our rapid surveys indicate unexpectedly high orangutan densities in plantation landscapes dominated by Acacia spp., although it remains unclear whether such landscapes can maintain long-term viable populations. These findings indicate the need to better understand how plantation-dominated landscapes can potentially be incorporated into orangutan conservation planning. Although we emphasize that plantations have less value for overall biodiversity conservation than natural forests, they could potentially boost the chances of orangutan survival. Our findings are based on a relatively short study and various methodological issues need to be addressed, but they suggest that orangutans may be more ecologically flexible than previously thought

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration

Self-reported sex differences in high-functioning adults with autism: a meta-analysis

Background: Sex differences in autistic symptomatology are believed to contribute to the mis- and missed diagnosis of many girls and women with an autism spectrum condition (ASC). Whilst recent years have seen the emergence of clinical and empirical reports delineating the profile of young autistic girls, recognition of sex differences in symptomatology in adulthood is far more limited. Methods: We chose here to focus on symptomatology as reported using a screening instrument, the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R). In a meta-analysis, we pooled and analysed RAADS-R data from a number of experimental groups. Analysis of variance (ANOVA) searched for the presence of main effects of Sex and Diagnosis and for interactions between these factors in our sample of autistic and non-autistic adults. Results: In social relatedness and circumscribed interests, main effects of Diagnosis revealed that as expected, autistic adults reported significantly greater lifetime prevalence of symptoms in these domains; an effect of Sex, in circumscribed interests, also suggested that males generally reported more prevalent symptoms than females. An interaction of Sex and Diagnosis in language symptomatology revealed that a normative sex difference in language difficulties was attenuated in autism. An interaction of Sex and Diagnosis in the sensorimotor domain revealed the opposite picture: a lack of sex differences between typically-developing men and women and a greater prevalence of sensorimotor symptoms in autistic women than autistic men. Conclusions: We discuss the literature on childhood sex differences in relation to those which emerged in our adult sample. Where childhood sex differences fail to persist in adulthood, several interpretations exist, and we discuss, for example, an inherent sampling bias that may mean that only autistic women most similar to the male presentation are diagnosed. The finding that sensorimotor symptomatology is more highly reported by autistic women is a finding requiring objective confirmation, given its potential importance in diagnosis

Mild Mitochondrial Uncoupling and Calorie Restriction Increase Fasting eNOS, Akt and Mitochondrial Biogenesis

Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1α, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis