Assessing the potential of the unexploited Atlantic purple sea urchin, Arbacia punctulata, for the edible market

The global demand for sea urchin as seafood is currently unmet. Despite exploitation of \u3e 40 species across the world, there is a need to identify other candidate species, especially in regions where diversification in production is sought where species are considered native. The Eastern US presents an opportunity to determine the marketability of the currently unexploited Arbacia punctulata which is naturally distributed from Massachusetts and southwards into the Gulf of Mexico. To determine whether A. punctulata had market potential, it was fed one of the following diets to determine whether the gonad tissue (uni) could be manipulated to increase gonad mass and improve gonad color for the market: dried Ulva lactuca, Salmon pellets (Skretting), Tilapia pellets (Ziegler) or an Urchinomics diet designed for sea urchins either fed for 8 weeks or 12 weeks. All of the pelleted feeds (Salmon, Tilapia and Urchinomics) increased gonad mass and altered the color. The colors of the uni were generally darker than the colors that the market would typically prefer but some individuals did exhibit colors which have been classed as acceptable to the European market. This work highlights that further research is worthwhile to assess the market potential of A. punctulata

Right Isomerism of the Brain in Inversus Viscerum Mutant Mice

Left-right (L-R) asymmetry is a fundamental feature of higher-order neural function. However, the molecular basis of brain asymmetry remains unclear. We recently reported L-R asymmetry of hippocampal circuitry caused by differential allocation of N-methyl-D-aspartate receptor (NMDAR) subunit GluRε2 (NR2B) in hippocampal synapses. Using electrophysiology and immunocytochemistry, here we analyzed the hippocampal circuitry of the inversus viscerum (iv) mouse that has a randomized laterality of internal organs. The iv mouse hippocampus lacks L-R asymmetry, it exhibits right isomerism in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. This independent right isomerism of the hippocampus is the first evidence that a distinct mechanism downstream of the iv mutation generates brain asymmetry

Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors

<p>Abstract</p> <p>Background</p> <p>Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors.</p> <p>Methods</p> <p>Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3–5) were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45–60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months.</p> <p>Results</p> <p>Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease.</p> <p>Conclusion</p> <p>Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.</p

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene

The Center for Eukaryotic Structural Genomics

The Center for Eukaryotic Structural Genomics (CESG) is a “specialized” or “technology development” center supported by the Protein Structure Initiative (PSI). CESG’s mission is to develop improved methods for the high-throughput solution of structures from eukaryotic proteins, with a very strong weighting toward human proteins of biomedical relevance. During the first three years of PSI-2, CESG selected targets representing 601 proteins from Homo sapiens, 33 from mouse, 10 from rat, 139 from Galdieria sulphuraria, 35 from Arabidopsis thaliana, 96 from Cyanidioschyzon merolae, 80 from Plasmodium falciparum, 24 from yeast, and about 25 from other eukaryotes. Notably, 30% of all structures of human proteins solved by the PSI Centers were determined at CESG. Whereas eukaryotic proteins generally are considered to be much more challenging targets than prokaryotic proteins, the technology now in place at CESG yields success rates that are comparable to those of the large production centers that work primarily on prokaryotic proteins. We describe here the technological innovations that underlie CESG’s platforms for bioinformatics and laboratory information management, target selection, protein production, and structure determination by X-ray crystallography or NMR spectroscopy

Cardiovascular risk factors and cognitive decline in older people with type 2 diabetes

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p </= 0.05). CONCLUSIONS/INTERPRETATION: Increased smoking and poorer glycaemic control (with relatively weaker findings for BP) during the life-course were independently associated with accelerated late-life cognitive decline. Where possible, evaluation is warranted of these risk factors as targets for intervention to reduce the burden of cognitive impairment in diabetes

Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder causing dementia. Massive deposition of amyloid β peptide (Aβ) as senile plaques in the brain is the pathological hallmark of AD, but oligomeric, soluble forms of Aβ have been implicated as the synaptotoxic component. The apolipoprotein E epsilon 4 (apoE ε4) allele is known to be a genetic risk factor for developing AD. However it is still unknown how apoE impacts the process of Aβ oligomerization. Here, we found that the level of Aβ oligomers in APOEε4/ε4 AD patient brains is 2.7 times higher than those in APOEε3/ε3 AD patient brains, matched for total plaque burden, suggesting that apoE4 impacts the metabolism of Aβ oligomers. To test this hypothesis, we examined apoE’s effect on Aβ oligomer formation. Using both synthetic Aβ and a split-luciferase method for monitoring Aβ oligomers, we observed that apoE increased the level of Aβ oligomers in an isoform dependent manner (E2 < E3 < E4). This effect appears to be dependent on the ApoE carboxy-terminal domain. Moreover, these results were confirmed using endogenous apoE isolated from the TBS-soluble fraction of human brain, which increased the formation of Aβ oligomers. Taken together, these data show that lipidated apoE, especially apoE4, increases Aβ oligomers in the brain. Higher levels of Aβ oligomers in the brains of APOEε4/ε4 carriers compared to APOEε3/ε3 carriers may increase the loss of dendritic spines and accelerate memory impairments, leading to earlier cognitive decline in AD

Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB

A Solution to the Strong CP Problem with Gauge-Mediated Supersymmetry Breaking

We demonstrate that a certain class of low scale supersymmetric ``Nelson-Barr'' type models can solve the strong and supersymmetric CP problems while at the same time generating sufficient weak CP violation in the $K^{0}-\bar{K}^{0}$ system. In order to prevent one-loop corrections to $\bar{\theta}$ which violate bounds coming from the neutron electric dipole moment (EDM), one needs a scheme for the soft supersymmetry breaking parameters which can naturally give sufficient squark degeneracies and proportionality of trilinear soft supersymmetry-breaking parameters to Yukawa couplings. We show that a gauge-mediated supersymmetry breaking sector can provide the needed degeneracy and proportionality, though that proves to be a problem for generic Nelson-Barr models. The workable model we consider here has the Nelson-Barr mass texture enforced by a gauge symmetry; one also expects a new U(1) gauge superfield with mass in the TeV range. The resulting model is predictive. We predict a measureable neutron EDM and the existence of extra vector-like quark superfields which can be discovered at the LHC. Because the $3\times 3$ Cabbibo-Kobayashi-Maskawa matrix is approximately real, the model also predicts a flat unitarity triangle and the absence of substantial CP violation in the $B$ system at future $B$ factories. We discuss the general issues pertaining to the construction of such a workable model and how they lead to the successful strategy. A detailed renormalization group study is then used to establish the feasibility of the model considered.Comment: Proof-read version to appear in Phys. Rev.

Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS–related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans