ALBERT

Description: Human gene mutations have revealed that a significant number of ADAMTS (a disintegrin-like and metalloproteinase (reprolysin type) with thrombospondin type 1 motifs) proteins are necessary for normal ocular development and eye function. Mutations in human ADAMTSL4 , encoding an ADAMTS-like protein which has been implicated in fibrillin microfibril biogenesis, cause ectopia lentis (EL) and EL et pupillae. Here, we report the first ADAMTSL4 mouse model, tvrm267 , bearing a nonsense mutation in Adamtsl4 . Homozygous Adamtsl4 tvrm267 mice recapitulate the EL phenotype observed in humans, and our analysis strongly suggests that ADAMTSL4 is required for stable anchorage of zonule fibers to the lens capsule. Unexpectedly, homozygous Adamtsl4 tvrm267 mice exhibit focal retinal pigment epithelium (RPE) defects primarily in the inferior eye. RPE dedifferentiation was indicated by reduced pigmentation, altered cellular morphology and a reduction in RPE-specific transcripts. Finally, as with a subset of patients with ADAMTSL4 mutations, increased axial length, relative to age-matched controls, was observed and was associated with the severity of the RPE phenotype. In summary, the Adamtsl4 tvrm267 model provides a valuable tool to further elucidate the molecular basis of zonule formation, the pathophysiology of EL and ADAMTSL4 function in the maintenance of the RPE.

Description: Aims The diversity–productivity relationship is one of the most critical questions in ecology and can be altered by environmental factors. Hydrological fluctuation affects growth of wetland plants, and such effects vary with plant species. Therefore, we hypothesized that hydrological fluctuation changes effects of species richness on productivity of wetland plant communities. Methods We constructed wetland plant communities consisting of three or six wetland plant species and subjected them to hydrological fluctuation (i.e. gradually changing water level) of two frequencies and two ranges, with unchanged water level as the control. We measured height, root and shoot dry mass of each plant at harvest. Important Findings Hydrological fluctuation significantly decreased biomass of wetland plant communities, which was due to impacts of fluctuation range, but not those of fluctuation frequency. Community biomass was significantly higher when species richness was higher, and such an effect did not depend on hydrological fluctuation. Therefore, hydrological fluctuation can decrease the productivity of wetland plant communities but may not alter the diversity–productivity relationship.

Description: The North Carolina Racial Justice Act allows defendants to submit statistical studies of prosecutorial actions pertaining to their seeking the death penalty or in making peremptory challenges. These studies may consider data from four geographical regions: the state, county, judicial division or prosecutorial district. A study of the effect of race on peremptory challenges in death penalty cases demonstrating statistically significant disparities disadvantaging Black defendants has been submitted in several cases. This comment shows that a more appropriate statistical analysis yields much stronger statistical evidence that race entered into the peremptory challenge process in Randolph County than the affidavit submitted by the authors of the study. A subsequent sensitivity analysis indicates that in order for a characteristic to explain the highly statistically significant disparity, it would need to increase the odds of an individual being challenged by a factor of three and more than twice as many Black venire members would need to possess that characteristic as non-Blacks. Since the data examined excluded potential jurors who had been removed for cause, it may be difficult for the state to find a legitimate reason justifying the racial disparity.

Description: The mechanical damage characteristics of sandstone subjected to cyclic loading is very significant to evaluate the stability and safety of deep excavation damage zones. However to date, there are very few triaxial experimental studies of sandstone under cyclic loading. Moreover, few X-ray micro-computed tomography (micro-CT) observations have been adopted to reveal the damage mechanism of sandstone under triaxial cyclic loading. Therefore, in this research, a series of triaxial cyclic loading tests and X-ray micro-CT observations were conducted to analyse the mechanical damage characteristics of sandstone with respect to different confining pressures. The results indicated that at lower confining pressures, the triaxial strength of sandstone specimens under cyclic loading is higher than that under monotonic loading; whereas at confining pressures above 20 MPa, the triaxial strength of sandstone under cyclic loading is approximately equal to that under monotonic loading. With the increase of cycle number, the crack damage threshold of sandstone first increases, and then significantly decreases and finally remains constant. Based on the damage evolution of irreversible deformation, it appears that the axial damage value of sandstone is all higher than the radial damage value before the peak strength; whereas the radial damage value is higher than the axial damage value after the peak strength. The evolution of Young's modulus and Poisson's ratio of sandstone can be characterized as having four stages: (i) Stage I: material strengthening; (ii) Stage II: material degradation; (iii) Stage III: material failure and (iv) Stage IV: structure slippage. X-ray micro-CT observations demonstrated that the CT scanning surface images of sandstone specimens are consistent with actual surface crack photographs. The analysis of the cross-sections of sandstone supports that the system of crack planes under triaxial cyclic loading is much more complicated than that under triaxial monotonic loading. More axial and lateral tensile cracks were observed in the specimens under cyclic loading than under monotonic loading.

Description: Clostridium difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and colitis in developed countries. The disease is mainly mediated via two major exotoxins TcdA and TcdB secreted by the bacterium. We have previously developed a novel, potently neutralizing, tetravalent and bispecific heavy-chain-only single domain (V H H) antibody to both TcdA and TcdB (designated as ABA) that reverses fulminant CDI in mice. Since ABA has a short serum half-life, in this study a replication-deficient recombinant adenovirus expressing ABA was generated and the long-lasting expression of functional ABA was demonstrated in vitro and in vivo . Mice transduced with one dose of the adenovirus displayed high levels of serum ABA for more than1 month and were fully protected against systemic toxin challenges. More importantly, the ABA delivered by the adenovirus protected mice from both primary and recurrent CDI. Thus, replication-deficient adenoviral vector may be used to deliver neutralizing antibodies against the toxins in order to prevent CDI and recurrence.

Description: Aims Soil heterogeneity is common in natural habitats. It may trigger foraging responses (placing more ramets and/or roots in nutrient-rich patches than in nutrient-poor patches) and further affect the growth of plants. However, the impact of soil heterogeneity on competitive interactions has been little tested. Methods We conducted a greenhouse experiment to investigate the effects of soil heterogeneity on intraspecific competition with a stoloniferous herb Hydrocotyle vulgaris . We grew one (without competition) or nine ramets (with competition) of H . vulgaris under a homogeneous environment and two heterogeneous environments differing in patch size (large or small patches). In the heterogeneous treatment, the soil consisted of the same number of nutrient-rich and nutrient-poor patches arranged in a chessboard manner, and in the homogeneous treatment, the soil was an even mixture of the same amount of the nutrient-rich and the nutrient-poor soil. Important Findings Irrespective of intraspecific competition, H. vulgaris showed foraging responses to soil heterogeneity in the large patch treatment, e.g. it produced significantly more biomass, ramets, aboveground mass and root mass in the nutrient-rich patches than in the nutrient-poor patches. In the small patch treatment, foraging responses were observed when intraspecific competition was present, but responses were not observed when there was no competition. However, we find a significant effect of soil heterogeneity on neither overall growth nor competitive intensity of H. vulgaris . Our results suggest that foraging responses to soil heterogeneity may not necessarily be adaptive and intraspecific competition may not be influenced by soil heterogeneity.

Description: The boundaries of R-loops are well-documented at immunoglobulin heavy chain loci in mammalian B cells. Within primary B cells or B cell lines, the upstream boundaries of R-loops typically begin early in the repetitive portion of the switch regions. Most R-loops terminate within the switch repetitive zone, but the remainder can extend a few hundred base pairs further, where G-density on the non-template DNA strand gradually drops to the genome average. Whether the G-density determines how far the R-loops extend is an important question. We previously studied the role of G-clusters in initiating R-loop formation, but we did not examine the role of G-density in permitting the elongation of the R-loop, after it had initiated. Here, we vary the G-density of different portions of the switch region in a murine B cell line. We find that both class switch recombination (CSR) and R-loop formation decrease significantly when the overall G-density is reduced from 46% to 29%. Short 50 bp insertions with low G-density within switch regions do not appear to affect either CSR or R-loop elongation, whereas a longer (150 bp) insertion impairs both. These results demonstrate that G-density is an important determinant of the length over which mammalian genomic R-loops extend.

Description: Over the past 10 years, genomes of cultivated rice cultivars and their wild counterparts have been sequenced although most efforts are focused on genome assembly and annotation of two major cultivated rice ( Oryza sativa L.) subspecies, 93-11 ( indica ) and Nipponbare ( japonica ). To integrate information from genome assemblies and annotations for better analysis and application, we now introduce a comparative rice genome database, the Rice Genome Knowledgebase (RGKbase, http://rgkbase.big.ac.cn/RGKbase/ ). RGKbase is built to have three major components: (i) integrated data curation for rice genomics and molecular biology, which includes genome sequence assemblies, transcriptomic and epigenomic data, genetic variations, quantitative trait loci (QTLs) and the relevant literature; (ii) User-friendly viewers, such as Gbrowse, GeneBrowse and Circos, for genome annotations and evolutionary dynamics and (iii) Bioinformatic tools for compositional and synteny analyses, gene family classifications, gene ontology terms and pathways and gene co-expression networks. RGKbase current includes data from five rice cultivars and species: Nipponbare ( japonica ), 93-11 ( indica ), PA64s ( indica ), the African rice ( Oryza glaberrima ) and a wild rice species ( Oryza brachyantha ). We are also constantly introducing new datasets from variety of public efforts, such as two recent releases—sequence data from ~1000 rice varieties, which are mapped into the reference genome, yielding ample high-quality single-nucleotide polymorphisms and insertions–deletions.