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.     

Distribution of aluminum in black spruce saplings growing on two New Brunswick forest soils with contrasting acid sulfate sorption

Two adjacent soils with contrasting sulfate sorption were examined in terms of (i) water-soluble and ion-exchangeable Al, Fe, Ca, Mg, K, Mn and Zn, (ii), water- and bicarbonate-extractable sulfate, (iii) Truog-extractable P, (iv) dithionite-extractable Al, Mn and Fe and (v) treatment response to irrigation with simulated acid precipitation. The biomass of 8 year old black spruce saplings growing on the soils, and the distributions of Al, Fe, Ca, Mg, K, Mn, P and Zn within these plants, were also examined. The soils were well to moderately-well drained, with the mineral soil exposed by site preparation prior to planting. The exposed soil underneath individual saplings was treated with acid sulfate solutions (75 mm containing 2 to 50 mg L^?1 H₂SO₄) applied during each of three consecutive growing seasons. The results indicate that Al, much like Fe, Ca, Mn and Zn, accumulated with time in the foliage, but K, Mg and P were highest in young plant tissues. Much of Al and Fe taken up remained in the fine roots. Aluminum uptake increased with the amount of dithionite-extractable Al (free Al oxide) in the soil. Growth of the black spruce saplings was not visibly affected by readily accessed Al in each soil, or by acid irrigation.Instead, growth was restricted by factors other than soil Al and acid irrigation in spite of (i) low soil pH, (ii) high levels of exchangeable Al, and (iii) high levels of Al in fine roots. Sulfate retention across and within the two soils was positively correlated with free Al oxide. The two soils responded to acid irrigation by accelerated silicate weathering and enhanced ion leaching. Sulfate sorption reduced these effects.     

Acidic mist reduces foliar membrane-associated calcium and impairs stomatal responsiveness in red spruce

Acidic deposition can leach essential pools of calcium (Ca) directly from plant foliage. Because of the central role of Ca in environmental signal transduction, disruptions of labile foliar Ca pools could impair physiological responses to a variety of environmental stimuli and stressors. We investigated the possibility that acidic mist-induced depletion of membrane-associated Ca (mCa), which is one form of labile Ca, may alter stomatal responsiveness to water stress, a process known to include Ca in signal transduction cascades. Red spruce (Picea rubens Sarg.) seedlings were exposed to either pH 3.0 or pH 5.0 mist treatments for one growing season. Foliar nutrition was assessed following treatments, and declines in stomatal conductance and net photosynthesis were measured on current-year shoots following stem excision. Seedlings exposed to pH 3.0 acidic mist treatments had reduced mCa relative to the pH 5.0 treated seedlings. Seedlings subjected to the pH 3.0 acidic mist treatment exhibited impaired stomatal functions, including a smaller maximum aperture, slower closure and an increased lag time between stomatal closure and photosynthetic decline following experimental water stress. Delayed stomatal closure could undermine desiccation avoidance mechanisms. Previous work has demonstrated that acidic mist treatments deplete mCa in red spruce and impair cold tolerance, with similar effects in other species. The results we present provide further evidence that acidic mist-induced mCa depletion may cause disruption of a broad range of plant stress responses.     

Fragmentation and flow regulation of the world's large river systems

A global overview of dam-based impacts on large river systems shows that over half (172 out of 292) are affected by dams, including the eight most biogeographically diverse. Dam-impacted catchments experience higher irrigation pressure and about 25 times more economic activity per unit of water than do unaffected catchments. In view of projected changes in climate and water resource use, these findings can be used to identify ecological risks associated with further impacts on large river systems.     

A physical map of the 1-gigabase bread wheat chromosome 3B

As the staple food for 35% of the world's population, wheat is one of the most important crop species. To date, sequence-based tools to accelerate wheat improvement are lacking. As part of the international effort to sequence the 17-billion-base-pair hexaploid bread wheat genome (2n = 6x = 42 chromosomes), we constructed a bacterial artificial chromosome (BAC)-based integrated physical map of the largest chromosome, 3B, that alone is 995 megabases. A chromosome-specific BAC library was used to assemble 82% of the chromosome into 1036 contigs that were anchored with 1443 molecular markers, providing a major resource for genetic and genomic studies. This physical map establishes a template for the remaining wheat chromosomes and demonstrates the feasibility of constructing physical maps in large, complex, polyploid genomes with a chromosome-based approach.     

Diagnosis and surgical removal of brain abscesses in a juvenile alpaca

CASE DESCRIPTION: A 1-month-old female alpaca was examined because of progressive clinical signs consistent with an intracranial lesion. CLINICAL FINDINGS: Clinical signs included signs of depression, lethargy, tetraparesis, and neck weakness. Two large isointense intracranial masses could be seen on T1-weighted magnetic resonance images. On T2-weighted images, the masses contained concentric rings of hypointense and hyperintense material. TREATMENT AND OUTCOME: 2 abscesses were removed via a craniotomy that incorporated removal of the sagittal crest and surrounding skull and transection of the sagittal sinus. The bony deficit was replaced with polypropylene mesh. The alpaca recovered within 2 weeks and was fully integrated into the herd within 1 month after surgery. CLINICAL RELEVANCE: Findings indicated that surgical removal is a feasible means of successfully treating intracranial abscesses in juvenile alpacas.     

A morphological approach to understanding preferential flow using image analysis with dye tracers and X-ray Computed Tomography

A key problem facing soil physics and hydropedology at present is some of the standard theories of water flow in soils do not fully reflect the processes at the pore scale, and thus, cannot be adequately used for prediction. As such, examination of soil structure is vital for hydropedologists. Realisation that solutes move preferentially through soil into groundwaters has meant research in this area has increased in importance. This paper describes a multi-scale approach to analyse transport mechanisms using visualisation techniques. Chloride and Brilliant Blue tracers were applied to undisturbed soil cores to examine the physical and morphological properties associated with preferential flow in a range of soil types. Following collection of serial digital images, it was possible to examine and quantify the nature of active water flow mechanisms in terms of both dye-stained pathways and spatial distribution of dye concentration, using image analysis. Preferential flow linked to water potential and soil structural discontinuity was observed in all but the coarsest textured soil which conformed to uniform flow theory. A high level of variability in flow patterns was noted between the soil types. Such information as to how a soil dynamically re-wets is key for hydropedologists involved in applications such as pollution modelling. This is especially significant when considering a wetting mechanism, such as preferential flow, that cannot be adequately described by conventional soil physics.