A systematic survey of loss-of-function variants in human protein-coding genes

Genome-sequencing studies indicate that all humans carry many genetic variants predicted to cause loss of function (LoF) of protein-coding genes, suggesting unexpected redundancy in the human genome. Here we apply stringent filters to 2951 putative LoF variants obtained from 185 human genomes to determine their true prevalence and properties. We estimate that human genomes typically contain ~100 genuine LoF variants with ~20 genes completely inactivated. We identify rare and likely deleterious LoF alleles, including 26 known and 21 predicted severe disease-causing variants, as well as common LoF variants in nonessential genes. We describe functional and evolutionary differences between LoF-tolerant and recessive disease genes and a method for using these differences to prioritize candidate genes found in clinical sequencing studies.     

Congenital ocular anomalies and ventricular septal defect in a dromedary camel (Camelus dromedarius).

A 5-wk-old female dromedary camel (Camelus dromedarius) was clinically diagnosed with bilateral corneal dermoids, incomplete congenital cataracts, a left persistent hyaloid artery (PHA), and a ventricular septal defect (VSD). The corneal dermoids were removed by lamellar keratectomy, and vision improved in the left eye. Thirteen months after dermoid surgery, the calf was presented for enlargement of the right eye. Glaucoma was confirmed in the right eye, and corneal fibrosis and cataract were noted in the left eye. Persistence of the VSD was confirmed by cardiac ultrasonography. The calf was euthanized, and necropsy findings confirmed VSD. Histopathologic examination revealed bilateral corneal thinning and fibrosis, cataracts with retrolental fibroplasia, and retinal dysplasia. Additional changes in the right globe were anterior segment dysgenesis, ruptured lens capsule, chronic phacoclastic uveitis, and retinal separation. The PHA was confirmed in the left eye.     

Does Administrative Status Matter for Urban Growth? Evidence from Present and Former County Capitals in East Germany

Public sector activities are often neglected in the economic approaches used to analyze the driving forces behind urban growth. The institutional status of a regional capital is a crucial aspect of public sector activities. This paper reports on a quasi‐natural experiment on county towns in East Germany. Since 1990, East German cities have demonstrated remarkable differences in population development. During this same period, many towns have lost their status as a county seat due to several administrative reforms. Using a difference‐in‐differences approach, we compare the annual population development of former county capitals to population change in towns that have successfully held on to their capital status throughout the observed period. The estimations show that losing county capital status has a statistically significant negative effect on annual changes in population. This effect continues to increase over time after the respective reforms have been implemented.     

The effect of temperature on sensory quality,chemical composition and growth of carrots (Daucus carota L.). III. Different diurnal temperature amplitudes

Summary

Data from experiments with carrots grown in phytotrons under different day and night temperatures at two locations in Norway and three harvesting dates were treated by means of Principal Component Analysis (PCA). No effect of the single temperature amplitudes were found, the significant main effects were due to the mean temperature levels of 12 and 188C, location and harvest date. The PCA visualized the effect of mean temperature level on sensory, chemical and physical variables. Differences between the two groups were mainly caused by variation in sensory variables, the first group being characterized by high score for whiteness, sweetness, acidic taste, crispness, juiciness, glucose, fructose and root length. The other group had a high score for colour, odour, overall taste and flavour parameters, firmness, dry matter, sucrose, a and b-carotene, root weight and root diameters.     

Heralded entanglement between widely separated atoms

Entanglement is the essential feature of quantum mechanics. Notably, observers of two or more entangled particles will find correlations in their measurement results that cannot be explained by classical statistics. To make it a useful resource, particularly for scalable long-distance quantum communication, the heralded generation of entanglement between distant massive quantum systems is necessary. We report on the creation and analysis of heralded entanglement between spins of two single rubidium-87 atoms trapped independently 20 meters apart. Our results illustrate the viability of an integral resource for quantum information science, as well as for fundamental tests of quantum mechanics.     

Effects of maternal diet and exposure to bisphenol A on sexually dimorphic responses in conceptuses and offspring

Whereas sexual differentiation is considered as the onset of differentiation of the male or female gonads, mounting evidence indicates that sex differences in developmental programming are established as early as the zygotic stage. Genetic and epigenetic differences between the sexes might govern how each responds to shifts in their early environment, including in the uterus or culture dish, as in the case of in vitro cultured pre-implantational embryos. Even if no differences are evident between the sexes at birth, divergent conceptus responses to surrounding changes, such as maternal diet and exposure to endocrine disrupting compounds (EDC), such as bisphenol A (BPA), might predispose one sex over the other to later adult-onset diseases, otherwise termed developmental origin of health and disease (DOHaD). Overall, males subjected to less than optimal in utero conditions tend to be at greater risk for various diseases, including neurobehavioural disorders. As the placenta is the primary nutrient acquisition and communication organ between the dam and foetus, its ability to adapt rapidly to environmental shifts might buffer the conceptus against environmental insults. The placenta of one sex over the other might possess greater ability to respond to environmental fluctuations. In utero environmental changes, including maternal nutrient excess or reduction or exposure to the EDC, BPA, might govern sex-dependent behavioural alterations. In sum, this review examines the evidence to date that male and female zygotes and conceptuses diverge in their responses to shifting environmental conditions and whether these contrasting sexually dimorphic responses underpin later DOHaD outcomes, namely neurobehavioural changes.