A worldwide correlation of lactase persistence phenotype and genotypes

Background: The ability of adult humans to digest the milk sugar lactose - lactase persistence - is a dominant Mendelian trait that has been a subject of extensive genetic, medical and evolutionary research. Lactase persistence is common in people of European ancestry as well as some African, Middle Eastern and Southern Asian groups, but is rare or absent elsewhere in the world. The recent identification of independent nucleotide changes that are strongly associated with lactase persistence in different populations worldwide has led to the possibility of genetic tests for the trait. However, it is highly unlikely that all lactase persistence-associated variants are known. Using an extensive database of lactase persistence phenotype frequencies, together with information on how those data were collected and data on the frequencies of lactase persistence variants, we present a global summary of the extent to which current genetic knowledge can explain lactase persistence phenotype frequency. Results: We used surface interpolation of Old World lactase persistence genotype and phenotype frequency estimates obtained from all available literature and perform a comparison between predicted and observed trait frequencies in continuous space. By accommodating additional data on sample numbers and known false negative and false positive rates for the various lactase persistence phenotype tests (blood glucose and breath hydrogen), we also apply a Monte Carlo method to estimate the probability that known lactase persistence-associated allele frequencies can explain observed trait frequencies in different regions. Conclusion: Lactase persistence genotype data is currently insufficient to explain lactase persistence phenotype frequency in much of western and southern Africa, southeastern Europe, the Middle East and parts of central and southern Asia. We suggest that further studies of genetic variation in these regions should reveal additional nucleotide variants that are associated with lactase persistence

Adaptive prior variance calibration in the Bayesian continual reassessment method

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98219/1/sim5621.pd

The Relationship Between Interleukin-6 in Saliva, Venous and Capillary Plasma, at Rest and in Response to Exercise

IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise. The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma. Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA). In Trial A venous plasma IL-6 increased significantly from 0.4. 0.14. pg/ml to 0.99 0.29. pg/ml (. P<. 0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change. In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22. ±. 0.18 to 0.74. ±. 0.28. pg/ml; capillary: 0.37. ±. 0.22 to 1.08. ±. 0.30. pg/ml (. P<. 0.01). Venous and capillary plasma responses did not correlate at rest (. r=. 0.59, P=. 0.07) but did correlate post exercise (. r=. 0.79) and when expressed as an exercise induced change (. r=. 0.71, P=. 0.02). Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise. © 2014 Elsevier Ltd

Imaging ‘Invisible' Dopant Atoms in Semiconductor Nanocrystals

Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 - August 2, 201

Goodness-of-Fit Tests to study the Gaussianity of the MAXIMA data

Goodness-of-Fit tests, including Smooth ones, are introduced and applied to detect non-Gaussianity in Cosmic Microwave Background simulations. We study the power of three different tests: the Shapiro-Francia test (1972), the uncategorised smooth test developed by Rayner and Best(1990) and the Neyman's Smooth Goodness-of-fit test for composite hypotheses (Thomas and Pierce 1979). The Smooth Goodness-of-Fit tests are designed to be sensitive to the presence of ``smooth'' deviations from a given distribution. We study the power of these tests based on the discrimination between Gaussian and non-Gaussian simulations. Non-Gaussian cases are simulated using the Edgeworth expansion and assuming pixel-to-pixel independence. Results show these tests behave similarly and are more powerful than tests directly based on cumulants of order 3, 4, 5 and 6. We have applied these tests to the released MAXIMA data. The applied tests are built to be powerful against detecting deviations from univariate Gaussianity. The Cholesky matrix corresponding to signal (based on an assumed cosmological model) plus noise is used to decorrelate the observations previous to the analysis. Results indicate that the MAXIMA data are compatible with Gaussianity.Comment: MNRAS, in pres

Accurate age estimation in small-scale societies

Precise estimation of age is essential in evolutionary anthropology, especially to infer population age structures and understand the evolution of human life history diversity. However, in small-scale societies, such as hunter-gatherer populations, time is often not referred to in calendar years, and accurate age estimation remains a challenge. We address this issue by proposing a Bayesian approach that accounts for age uncertainty inherent to fieldwork data. We developed a Gibbs sampling Markov chain Monte Carlo algorithm that produces posterior distributions of ages for each individual, based on a ranking order of individuals from youngest to oldest and age ranges for each individual. We first validate our method on 65 Agta foragers from the Philippines with known ages, and show that our method generates age estimations that are superior to previously published regression-based approaches. We then use data on 587 Agta collected during recent fieldwork to demonstrate how multiple partial age ranks coming from multiple camps of hunter-gatherers can be integrated. Finally, we exemplify how the distributions generated by our method can be used to estimate important demographic parameters in small-scale societies: here, age-specific fertility patterns. Our flexible Bayesian approach will be especially useful to improve cross-cultural life history datasets for small-scale societies for which reliable age records are difficult to acquire

Aneuploidy in oocytes is prevented by sustained CDK1 activity through degron masking in cyclin B1

Successful mitosis requires that cyclin B1:CDK1 kinase activity remains high until chromosomes are correctly aligned on the mitotic spindle. It has therefore been unclear why, in mammalian oocyte meiosis, cyclin B1 destruction begins before chromosome alignment is complete. Here, we resolve this paradox and show that mouse oocytes exploit an imbalance in the ratio of cyclin B1 to CDK1 to control CDK1 activity; early cyclin B1 destruction reflects the loss of an excess of non-CDK1-bound cyclin B1 in late prometaphase, while CDK1-bound cyclin B1 is destroyed only during metaphase. The ordered destruction of the two forms of cyclin B1 is brought about by a previously unidentified motif that is accessible in free cyclin B1 but masked when cyclin B1 is in complex with CDK1. This protects the CDK1-bound fraction from destruction in prometaphase, ensuring a period of prolonged CDK1 activity sufficient to achieve optimal chromosome alignment and prevent aneuploidy

Higher-order mutual coherence of optical and matter waves

We use an operational approach to discuss ways to measure the higher-order cross-correlations between optical and matter-wave fields. We pay particular attention to the fact that atomic fields actually consist of composite particles that can easily be separated into their basic constituents by a detection process such as photoionization. In the case of bosonic fields, that we specifically consider here, this leads to the appearance in the detection signal of exchange contributions due to both the composite bosonic field and its individual fermionic constituents. We also show how time-gated counting schemes allow to isolate specific contributions to the signal, in particular involving different orderings of the Schr\"odinger and Maxwell fields.Comment: 11 pages, 2 figure

Integrating distribution kinetics and toxicodynamics to assess repeat dose neurotoxicity in vitro using human BrainSpheres: a case study on amiodarone.

For ethical, economical, and scientific reasons, animal experimentation, used to evaluate the potential neurotoxicity of chemicals before their release in the market, needs to be replaced by new approach methodologies. To illustrate the use of new approach methodologies, the human induced pluripotent stem cell-derived 3D model BrainSpheres was acutely (48 h) or repeatedly (7 days) exposed to amiodarone (0.625-15 µM), a lipophilic antiarrhythmic drug reported to have deleterious effects on the nervous system. Neurotoxicity was assessed using transcriptomics, the immunohistochemistry of cell type-specific markers, and real-time reverse transcription-polymerase chain reaction for various genes involved in the lipid metabolism. By integrating distribution kinetics modeling with neurotoxicity readouts, we show that the observed time- and concentration-dependent increase in the neurotoxic effects of amiodarone is driven by the cellular accumulation of amiodarone after repeated dosing. The development of a compartmental in vitro distribution kinetics model allowed us to predict the change in cell-associated concentrations in BrainSpheres with time and for different exposure scenarios. The results suggest that human cells are intrinsically more sensitive to amiodarone than rodent cells. Amiodarone-induced regulation of lipid metabolism genes was observed in brain cells for the first time. Astrocytes appeared to be the most sensitive human brain cell type in vitro. In conclusion, assessing readouts at different molecular levels after the repeat dosing of human induced pluripotent stem cell-derived BrainSpheres in combination with the compartmental modeling of in vitro kinetics provides a mechanistic means to assess neurotoxicity pathways and refine chemical safety assessment for humans

Increased abundance of MTD1 and MTD2 mRNAs in nodules of decapitated Medicago truncatula.

To gain insight into the molecular processes occurring in root nodule metabolism after stress, we used a mRNA differential display (DDRT-PCR) approach to identify cDNAs corresponding to genes whose expression is enhanced in nodules of decapitated Medicago truncatula plants. Two full-length cDNAs of plant origin were isolated (MTD1 and MTD2). Sequence analysis revealed that MTD1 is identical to an EST clone (accession number AW559774) expressed in roots of M. truncatula upon infection with Phytophthora medicaginis, while MTD2 is highly homologous to an Arabidopsis thaliana gene (accession number AL133292) coding for a RNA binding-like protein. The two mRNAs started to accumulate in root nodules at 4 h after plant decapitation and reached even higher transcript levels at 24 h from the imposition of the treatment. MTD1 and MTD2 mRNAs were mainly induced in nodules, with very little induction in roots. The abundance of the two transcripts did not change in response to other perturbations known to decrease nitrogenase activity, such as nitrate and Ar/O2 treatments. Our results suggest that MTD1 and MTD2 represent transcripts that accumulate locally in nodules and may be involved in changes in nodule metabolism in response to decapitation