The effects of requiring different response strategies following caching in Clark’s nutcrackers (Nucifraga columbiana)

Clark’s nutcrackers use spatial memory to recover stored food in the field and have performed very well in laboratory tests of spatial memory. During the present experiment, two groups of nutcrackers cached seeds every 4 days. Following each cache session, the stay group was tested with seeds in their caches; the shift group found seeds in novel sites. The stay group performed accurately throughout the experiment, but the shift group gave no indication of being able to learn to avoid sites where they had stored seeds. These results suggest that although nutcrackers can learn to shift away from remembered locations during some memory experiments, they cannot learn to shift away from cache sites. This raises interesting questions about the relationship between task characteristics, response strategies, and memory

Electronic Band Dispersion and Pseudogap in Quasicrystals: Angular-Resolved Photoemission Studies on Icosahedral Al70Pd21.5Mn8.5

Angular-resolved photoelectron spectra from the fivefold surface of single-grain icosahedral Al70Pd21.5Mn8.5 exhibit a quasiperiodic dispersion of 300 meV at 2.3 eV binding energy. Low energy electron diffraction studies confirm quasicrystalline order at the surface. A distinct pseudogap feature is observed with a density of states near the Fermi level decreasing as a square-root power law

Specific Subpopulations of Hypothalamic Leptin Receptor-Expressing Neurons Mediate the Effects of Early Developmental Leptin Receptor Deletion on Energy Balance

ACKNOWLEDGEMENTS We thank MedImmune, Inc. and James Trevaskis, PhD and Christopher Rhodes, PhD for the gift of leptin. We thank members of the Myers and Olson labs for helpful discussions. Research support was provided by the Michigan Diabetes Research Center (NIH P3 0 DK020572, including the Molecular Genetics, Animal Phenotyping, and Clinical Cores), the American Diabetes Association (MGM), the Marilyn H. Vincent Foundation (MGM), the NIH (MGM: D K05673 1; ACR:DK071212; MBA: DK097861), the BBSRC (LKH: BB/NO17838/1) and WellcomeTrust (LKH: 098012).Peer reviewedPublisher PD

A comparative analysis of the cultural representation of disability in school textbooks in Iran and England

The paper details the findings of a study which focused on the analysis of the cultural representation of disability in school textbooks in Iran and England. The paper argues that whilst inclusive education could facilitate the incorporating of disabled pupils into mainstream schools, there needs to be deeper examination as to how this transition should take place for children aged 3-13. The paper suggests that in such examinations school textbooks might be of significance in familiarizing non-disabled pupils, teachers and authorities with the issues related to disability and disabled pupils

HO_x chemistry during INTEX-A 2004: Observation, model calculation, and comparison with previous studies

OH and HO_2 were measured with the Airborne Tropospheric Hydrogen Oxides Sensor (ATHOS) as part of a large measurement suite from the NASA DC-8 aircraft during the Intercontinental Chemical Transport Experiment-A (INTEX-A). This mission, which was conducted mainly over North America and the western Atlantic Ocean in summer 2004, was an excellent test of atmospheric oxidation chemistry. The HOx results from INTEX-A are compared to those from previous campaigns and to results for other related measurements from INTEX-A. Throughout the troposphere, observed OH was generally 0.95 of modeled OH; below 8 km, observed HO_2 was generally 1.20 of modeled HO_2. This observed-to-modeled comparison is similar to that for TRACE-P, another midlatitude study for which the median observed-to-modeled ratio was 1.08 for OH and 1.34 for HO_2, and to that for PEM-TB, a tropical study for which the median observed-to-modeled ratio was 1.17 for OH and 0.97 for HO_2. HO_2 behavior above 8 km was markedly different. The observed-to-modeled HO_2 ratio increased from ∼1.2 at 8 km to ∼3 at 11 km with the observed-to-modeled ratio correlating with NO. Above 8 km, the observed-to-modeled HO_2 and observed NO were both considerably greater than observations from previous campaigns. In addition, the observed-to-modeled HO_2/OH, which is sensitive to cycling reactions between OH and HO_2, increased from ∼1.5 at 8 km to almost 3.5 at 11 km. These discrepancies suggest a large unknown HO_x source and additional reactants that cycle HO_x from OH to HO_2. In the continental planetary boundary layer, the observed-to-modeled OH ratio increased from 1 when isoprene was less than 0.1 ppbv to over 4 when isoprene was greater than 2 ppbv, suggesting that forests throughout the United States are emitting unknown HO_x sources. Progress in resolving these discrepancies requires a focused research activity devoted to further examination of possible unknown OH sinks and HO_x sources

Assessing the ecological risks from the persistence and spread of feral populations of insect-resistant transgenic maize

One source of potential harm from the cultivation of transgenic crops is their dispersal, persistence and spread in non-agricultural land. Ecological damage may result from such spread if the abundance of valued species is reduced. The ability of a plant to spread in non-agricultural habitats is called its invasiveness potential. The risks posed by the invasiveness potential of transgenic crops are assessed by comparing in agronomic field trials the phenotypes of the crops with the phenotypes of genetically similar non-transgenic crops known to have low invasiveness potential. If the transgenic and non-transgenic crops are similar in traits believed to control invasiveness potential, it may be concluded that the transgenic crop has low invasiveness potential and poses negligible ecological risk via persistence and spread in non-agricultural habitats. If the phenotype of the transgenic crop is outside the range of the non-transgenic comparators for the traits controlling invasiveness potential, or if the comparative approach is regarded as inadequate for reasons of risk perception or risk communication, experiments that simulate the dispersal of the crop into non-agricultural habitats may be necessary. We describe such an experiment for several commercial insect-resistant transgenic maize events in conditions similar to those found in maize-growing regions of Mexico. As expected from comparative risk assessments, the transgenic maize was found to behave similarly to non-transgenic maize and to be non-invasive. The value of this experiment in assessing and communicating the negligible ecological risk posed by the low invasiveness potential of insect-resistant transgenic maize in Mexico is discussed

Investigating the effect of independent blinded digital image assessment on the STOP GAP trial

Background Blinding is the process of keeping treatment assignment hidden and is used to minimise the possibility of bias. Trials at high risk of bias have been shown to report larger treatment effects than low risk studies. In dermatology, one popular method of blinding is to have independent outcome assessors who are unaware of treatment allocation assessing the end point using digital photographs. However, this can be complex, expensive and time-consuming. The objective of this study was to compare the effect of blinded and unblinded outcome assessment on the results of the STOP GAP trial. Methods The STOP GAP trial compared prednisolone to ciclosporin in treating pyoderma gangrenosum. Participants’ lesions were measured at baseline and 6 weeks to calculate the primary outcome, speed of healing. Independent blinded assessors obtained measurements from digital photographs using specialist software. In addition, unblinded treating clinicians estimated lesion area by measuring length and width. The primary outcome was determined using blinded measurements where available, otherwise unblinded measurements were used (method referred to as trial measurements). In this study, agreement between the trial and unblinded measurements was determined using the intraclass correlation coefficient (ICC). The STOP GAP primary analysis was repeated using unblinded measurements only. We introduced differential and non-differential error in unblinded measurements and investigated the effect on the STOP GAP primary analysis. Results 86 (80%) of the 108 patients were assessed using digital images. Agreement between trial and unblinded measurements was excellent (ICC=0.92 at baseline; 0.83 at 6 weeks). There was no evidence that the results of the trial primary analysis differed according to how the primary outcome was assessed (p-value for homogeneity = 1.00). Conclusions Blinded digital image assessment in STOP GAP did not meaningfully alter trial conclusions compared with unblinded assessment. However, as the process brought added accuracy and credibility to the trial it was considered worthwhile. These findings question the usefulness of digital image assessment in a trial with an objective outcome and where bias is not expected to be excessive. Further research should investigate if there are alternative, less complex ways of incorporating blinding in clinical trials

Co-Crystal Structures of Inhibitors with MRCKβ, a Key Regulator of Tumor Cell Invasion

MRCKα and MRCKβ (myotonic dystrophy kinase-related Cdc42-binding kinases) belong to a subfamily of Rho GTPase activated serine/threonine kinases within the AGC-family that regulate the actomyosin cytoskeleton. Reflecting their roles in myosin light chain (MLC) phosphorylation, MRCKα and MRCKβ influence cell shape and motility. We report further evidence for MRCKα and MRCKβ contributions to the invasion of cancer cells in 3-dimensional matrix invasion assays. In particular, our results indicate that the combined inhibition of MRCKα and MRCKβ together with inhibition of ROCK kinases results in significantly greater effects on reducing cancer cell invasion than blocking either MRCK or ROCK kinases alone. To probe the kinase ligand pocket, we screened 159 kinase inhibitors in an in vitro MRCKβ kinase assay and found 11 compounds that inhibited enzyme activity >80% at 3 µM. Further analysis of three hits, Y-27632, Fasudil and TPCA-1, revealed low micromolar IC50 values for MRCKα and MRCKβ. We also describe the crystal structure of MRCKβ in complex with inhibitors Fasudil and TPCA-1 bound to the active site of the kinase. These high-resolution structures reveal a highly conserved AGC kinase fold in a typical dimeric arrangement. The kinase domain is in an active conformation with a fully-ordered and correctly positioned αC helix and catalytic residues in a conformation competent for catalysis. Together, these results provide further validation for MRCK involvement in regulation of cancer cell invasion and present a valuable starting point for future structure-based drug discovery efforts