Autosomal Dominant Optic Atrophy Plus Syndrome

Background: Dominant optic atrophy (DOA) is the most commonly encountered hereditary optic neuropathy in clinical practice and is the result of a mutation in the OPA1 or OPA3 genes encoding mitochondrial membrane proteins. The resultant mitochondrial dysfunction causes a distinct set of ophthalmic findings and may progress to extra-ocular systems known as OPA plus syndrome. We present a case of late-onset OPA plus syndrome encompassing both typical ophthalmic findings and the rarer extra-ocular findings. Case Report: A 41 year-old Caucasian male presents for a second opinion regarding a previously diagnosed traumatic optic neuropathy. Examination revealed decreased best-corrected acuities, optic nerve pallor, optical coherence tomography thinning of the retinal nerve fiber layers, progressive centrocecal visual field defects and tritanomalous color vision defects. All findings proved to be bilateral and symmetric. As the ophthalmic findings were inconsistent with a traumatic optic neuropathy, genetic testing was pursued resulting in a DOA diagnosis. Specialty consults demonstrated high-frequency hearing loss and mitochondrial myopathy consistent with OPA plus syndrome. Conclusion: While not a common diagnosis, hereditary optic neuropathies are most likely to present initially to primary eye care. The practitioner should be familiar with the ophthalmic findings and the need for specialty consult should a DOA diagnosis be confirmed

The wheat ω-gliadin genes: structure and EST analysis

A survey and analysis is made of all available ω-gliadin DNA sequences including ω-gliadin genes within a large genomic clone, previously reported gene sequences, and ESTs identified from the large wheat EST collection. A contiguous portion of the Gli-B3 locus is shown to contain two apparently active ω-gliadin genes, two pseudogenes, and four fragments of the 3′ portion of ω-gliadin sequences. Comparison of ω-gliadin sequences allows a phylogenetic picture of their relationships and genomes of origin. Results show three groupings of ω-gliadin active gene sequences assigned to each of the three hexaploid wheat genomes, and a fourth group thus far consisting of pseudogenes assigned to the A-genome. Analysis of ω-gliadin ESTs allows reconstruction of two full-length model sequences encoding the AREL- and ARQL-type proteins from the Gli-A3 and Gli-D3 loci, respectively. There is no DNA evidence of multiple active genes from these two loci. In contrast, ESTs allow identification of at least three to four distinct active genes at the Gli-B3 locus of some cultivars. Additional results include more information on the position of cysteines in some ω-gliadin genes and discussion of problems in studying the ω-gliadin gene family

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

Characterisation of the bacterial and fungal communities associated with different lesion sizes of Dark Spot Syndrome occurring in the Coral Stephanocoenia intersepta

The number and prevalence of coral diseases/syndromes are increasing worldwide. Dark Spot Syndrome (DSS) afflicts numerous coral species and is widespread throughout the Caribbean, yet there are no known causal agents. In this study we aimed to characterise the microbial communities (bacteria and fungi) associated with DSS lesions affecting the coral Stephanocoenia intersepta using nonculture molecular techniques. Bacterial diversity of healthy tissues (H), those in advance of the lesion interface (apparently healthy AH), and three sizes of disease lesions (small, medium, and large) varied significantly (ANOSIM R = 0.052 p,0.001), apart from the medium and large lesions, which were similar in their community profile. Four bacteria fitted into the pattern expected from potential pathogens; namely absent from H, increasing in abundance within AH, and dominant in the lesions themselves. These included ribotypes related to Corynebacterium (KC190237), Acinetobacter (KC190251), Parvularculaceae (KC19027), and Oscillatoria (KC190271). Furthermore, two Vibrio species, a genus including many proposed coral pathogens, dominated the disease lesion and were absent from H and AH tissues, making them candidates as potential pathogens for DSS. In contrast, other members of bacteria from the same genus, such as V. harveyii were present throughout all sample types, supporting previous studies where potential coral pathogens exist in healthy tissues. Fungal diversity varied significantly as well, however the main difference between diseased and healthy tissues was the dominance of one ribotype, closely related to the plant pathogen, Rhytisma acerinum, a known causal agent of tar spot on tree leaves. As the corals’ symbiotic algae have been shown to turn to a darker pigmented state in DSS (giving rise to the syndromes name), the two most likely pathogens are R. acerinum and the bacterium Oscillatoria, which has been identified as the causal agent of the colouration in Black Band Disease, another widespread coral disease

The EBLM project: VI. Mass and radius of five low-mass stars in F+M binaries discovered by the WASP survey

Some M-dwarfs around F-/G-type stars have been measured to be hotter and larger than predicted by stellar evolution models. Inconsistencies between observations and models need to be addressed with more mass, radius, and luminosity measurements of low-mass stars to test and refine evolutionary models. Our aim is to measure the masses, radii and ages of the stars in five low-mass eclipsing binary systems discovered by the WASP survey. We used WASP photometry to establish eclipse-time ephemerides and to obtain initial estimates for the transit depth and width. Radial velocity measurements were simultaneously fitted with follow-up photometry to find the best-fitting orbital solution. This solution was combined with measurements of atmospheric parameters to interpolate evolutionary models and estimate the mass of the primary star, and the mass and radius of the M-dwarf companion. We assess how the best fitting orbital solution changes if an alternative limb-darkening law is used and quantify the systematic effects of unresolved companions. We also gauge how the best-fitting evolutionary model changes if different values are used for the mixing length parameter and helium enhancement. We report the mass and radius of five M-dwarfs and find little evidence of inflation with respect to evolutionary models. The primary stars in two systems are near the “blue hook” stage of their post sequence evolution, resulting in two possible solutions for mass and age. We find that choices in helium enhancement and mixing-length parameter can introduce an additional 3−5% uncertainty in measured M-dwarf mass. Unresolved companions can introduce an additional 3−8% uncertainty in the radius of an M-dwarf, while the choice of limb-darkening law can introduce up to an additional 2% uncertainty. The choices in orbital fitting and evolutionary models can introduce significant uncertainties in measurements of physical properties of such systems

Characterizing HMW-GS alleles of decaploid Agropyron elongatum in relation to evolution and wheat breeding

Bread wheat quality is mainly correlated with high molecular weight glutenin subunits (HMW-GS) of endosperm. The number of HMW-GS alleles with good processing quality is limited in bread wheat cultivars, while there are plenty of HMW-GS alleles in wheat-related grasses to exploit. We report here on the cloning and characterization of HMW-GS alleles from the decaploid Agropyron elongatum. Eleven novel HMW-GS alleles were cloned from the grass. Of them, five are x-type and six y-type glutenin subunit genes. Three alleles Aex4, Aey7, and Aey9 showed high similarity with another three alleles from the diploid Lophopyrum elongatum, which provided direct evidence for the Ee genome origination of A. elongatum. It was noted that C-terminal regions of three alleles of the y-type genes Aey8, Aey9, and Aey10 showed more similarity with x-type genes than with other y-type genes. This demonstrates that there is a kind of intermediate state that appeared in the divergence between x- and y-type genes in the HMW-GS evolution. One x-type subunit, Aex4, with an additional cysteine residue, was speculated to be correlated with the good processing quality of wheat introgression lines. Aey4 was deduced to be a chimeric gene from the recombination between another two genes. How the HMW-GS genes of A. elongatum may contribute to the improvement of wheat processing quality are discussed

Assessment of animal African trypanosomiasis (AAT) vulnerability in cattle-owning communities of sub-Saharan Africa

Background: Animal African trypanosomiasis (AAT) is one of the biggest constraints to livestock production and a threat to food security in sub-Saharan Africa. In order to optimise the allocation of resources for AAT control, decision makers need to target geographic areas where control programmes are most likely to be successful and sustainable and select control methods that will maximise the benefits obtained from resources invested. Methods: The overall approach to classifying cattle-owning communities in terms of AAT vulnerability was based on the selection of key variables collected through field surveys in five sub-Saharan Africa countries followed by a formal Multiple Correspondence Analysis (MCA) to identify factors explaining the variations between areas. To categorise the communities in terms of AAT vulnerability profiles, Hierarchical Cluster Analysis (HCA) was performed. Results: Three clusters of community vulnerability profiles were identified based on farmers’ beliefs with respect to trypanosomiasis control within the five countries studied. Cluster 1 communities, mainly identified in Cameroon, reported constant AAT burden, had large trypanosensitive (average herd size = 57) communal grazing cattle herds. Livestock (cattle and small ruminants) were reportedly the primary source of income in the majority of these cattle-owning households (87.0 %). Cluster 2 communities identified mainly in Burkina Faso and Zambia, with some Ethiopian communities had moderate herd sizes (average = 16) and some trypanotolerant breeds (31.7 %) practicing communal grazing. In these communities there were some concerns regarding the development of trypanocide resistance. Crops were the primary income source while communities in this cluster incurred some financial losses due to diminished draft power. The third cluster contained mainly Ugandan and Ethiopian communities which were mixed farmers with smaller herd sizes (average = 8). The costs spent diagnosing and treating AAT were moderate here. Conclusions: Understanding how cattle-owners are affected by AAT and their efforts to manage the disease is critical to the design of suitable locally-adapted control programmes. It is expected that the results could inform priority setting and the development of tailored recommendations for AAT control strategies

A Schur complement approach to preconditioning sparse linear least-squares problems with some dense rows

The effectiveness of sparse matrix techniques for directly solving large-scale linear least-squares problems is severely limited if the system matrix A has one or more nearly dense rows. In this paper, we partition the rows of A into sparse rows and dense rows (A s and A d ) and apply the Schur complement approach. A potential difficulty is that the reduced normal matrix AsTA s is often rank-deficient, even if A is of full rank. To overcome this, we propose explicitly removing null columns of A s and then employing a regularization parameter and using the resulting Cholesky factors as a preconditioner for an iterative solver applied to the symmetric indefinite reduced augmented system. We consider complete factorizations as well as incomplete Cholesky factorizations of the shifted reduced normal matrix. Numerical experiments are performed on a range of large least-squares problems arising from practical applications. These demonstrate the effectiveness of the proposed approach when combined with either a sparse parallel direct solver or a robust incomplete Cholesky factorization algorithm

Three newly discovered sub-Jupiter-mass planets: WASP-69b and WASP-84b transit active K dwarfs and WASP-70Ab transits the evolved primary of a G4+K3 binary

We report the discovery of the transiting exoplanets WASP-69b, WASP-70Ab and WASP-84b, each of which orbits a bright star (V ∼ 10). WASP-69b is a bloated Saturn-mass planet (0.26 MJup, 1.06 RJup) in a 3.868-d period around an active, ∼1-Gyr, mid-K dwarf. ROSAT detected X-rays 60±27 arcsec from WASP-69. If the star is the source then the planet could be undergoing mass-loss at a rate of ∼1012 g s−1. This is one to two orders of magnitude higher than the evaporation rate estimated for HD 209458b and HD 189733b, both of which have exhibited anomalously large Lyman α absorption during transit. WASP-70Ab is a sub-Jupiter-mass planet (0.59 MJup, 1.16 RJup) in a 3.713-d orbit around the primary of a spatially resolved, 9–10-Gyr, G4+K3 binary, with a separation of 3.3 arcsec (≥800 au). WASP-84b is a sub-Jupiter-mass planet (0.69 MJup, 0.94 RJup) in an 8.523-d orbit around an active, ∼1-Gyr, early-K dwarf. Of the transiting planets discovered from the ground to date, WASP-84b has the third-longest period. For the active stars WASP-69 and WASP-84, we pre-whitened the radial velocities using a low-order harmonic series. We found that this reduced the residual scatter more than did the oft-used method of pre-whitening with a fit between residual radial velocity and bisector span. The system parameters were essentially unaffected by pre-whitening