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A precise displacement measurement system using a non-contact image-based optical sensor and a hardware-based artificial neural network was developed. Field tests, with the sensors mounted on a tractor-drawn toolbar, were conducted to compare the performance of the image-based displacement system with traditional ground-wheel driven encoder-based and radar-based displacement systems at two different travel speeds (0.45 and 1.36ms−1). The precision of the three methods, expressed as the standard deviation of spot spray activation at 127mm intervals, was 7.3mm, 5.9mm, and 17.3mm on a rough soil surface (50mm to 125mm sized soil clods) at a 0.45ms−1 travel velocity for the image-based, wheel-based, and radar-based displacement sensors respectively. Compared to the radar-based sensor, the image-based sensor had better accuracy on a rough soil surface than the wheel-based sensor, better accuracy at both speeds, and better precision at the low speed. In addition to being non-contact, the main advantage of the image-based sensor over the wheel-based sensor was that it did not require site specific re-calibration to maintain accuracy. [Copyright &y& Elsevier]

Abstract: The evolutionary history of living African amphibians remains poorly understood. This study estimates the phylogeny within the frog genera Arthroleptis and Cardioglossa using approximately 2400 bases of mtDNA sequence data (12S, tRNA-Valine, and 16S genes) from half of the described species. Analyses are conducted using parsimony, maximum likelihood, and Bayesian methods. The effect of alignment on phylogeny estimation is explored by separately analyzing alignments generated with different gap costs and a consensus alignment. The consensus alignment results in species paraphyly, low nodal support, and incongruence with the results based on other alignments, which produced largely similar results. Most nodes in the phylogeny are highly supported, yet several topologies are inconsistent with previous hypotheses. The monophyly of Cardioglossa and of miniature species previously assigned to Schoutedenella was further examined using Templeton and Shimodaira–Hasegawa tests. Cardioglossa monophyly is rejected and C. aureoli is transferred to Arthroleptis. These tests do not reject Schoutedenella monophyly, but this hypothesis receives no support from non-parametric bootstrapping or Bayesian posterior probabilities. This phylogeny provides a framework for reconstructing historical biogeography and analyzing the evolution of body size and life history. Direct development and miniaturization appear at the base of Arthroleptis phylogeny concomitant with a range expansion from Central Africa to throughout most of sub-Saharan Africa. [Copyright &y& Elsevier]

• In-class attentive behavior is an important predictor of mathematics achievement. • Adolescent boys are less attentive in classroom settings than girls (d = −.34). • Controlling for attentive behavior, boys have advantages in mathematics achievement. • The sex difference in mathematics achievement is fully mediated by spatial abilities. The mathematics and reading achievement of 322 adolescents (159 boys) was assessed in seventh and eighth grades, as were their intelligence, working memory, and spatial abilities. Their seventh- and eighth-grade mathematics and English language arts teachers reported on their in-class attentive behavior. The latter emerged as an important predictor of achievement, but more so for mathematics than for reading. Boy were less attentive in classroom settings than girls (d = −.34) and performed better than expected in mathematics given their level of engagement in the classroom. Boys' better-than-expected mathematics achievement was related to advantages on visuospatial measures (d s =.28–.56), which fully mediated a sex difference in mathematics (d s =.27–.28) but not in reading achievement, with control of in-class attentive behavior. The results suggest that boys' advantages in visuospatial skills compensate for lower levels of classroom engagement in the learning of mathematics but not in reading competencies. [ABSTRACT FROM AUTHOR]

Ancient DNA analyses have shown that interbreeding between hominin taxa occurred multiple times. Although admixture is often reflected in skeletal phenotype, the relationship between the two remains poorly understood, hampering interpretation of the hominin fossil record. Direct study of this relationship is often impossible due to the paucity of hominin fossils and difficulties retrieving ancient genetic material. Here, we use a sample of known ancestry hybrids between two closely related nonhuman primate taxa (Indian and Chinese Macaca mulatta) to investigate the effect of admixture on skeletal morphology. We focus on pelvic shape, which has potential fitness implications in hybrids, as mismatches between maternal pelvic and fetal cranial morphology are often fatal to mother and offspring. As the pelvis is also one of the skeletal regions that differs most between Homo sapiens and Neanderthals, investigating the pelvic consequences of interbreeding could be informative regarding the viability of their hybrids. We find that the effect of admixture in M. mulatta is small and proportional to the relatively small morphological difference between the parent taxa. Sexual dimorphism appears to be the main determinant of pelvic shape in M. mulatta. The lack of difference in pelvic shape between Chinese and Indian M. mulatta is in contrast to that between Neanderthals and H. sapiens , despite a similar split time (in generations) between the hybridizing pairs. Greater phenotypic divergence between hominins may relate to adaptations to disparate environments but may also highlight how the unique degree of cultural buffering in hominins allowed for greater neutral divergence. In contrast to some previous work identifying extreme morphologies in first- and second-generation hybrids, here the relationship between pelvic shape and admixture is linear. This linearity may be because most sampled animals have a multigenerational admixture history or because of relatively high constraints on the pelvis compared with other skeletal regions. [ABSTRACT FROM AUTHOR]

The nuclear region of the lens is metabolically quiescent, but it is far from inert chemically. Without cellular renewal and with decades of environmental exposures, the lens proteome, lipidome, and metabolome change. The lens crystallins have evolved exquisite mechanisms for resisting, slowing, adapting to, and perhaps even harnessing the effects of these cumulative chemical modifications to minimize the amount of light-scattering aggregation in the lens over a lifetime. Redox chemistry is a major factor in these damages and mitigating adaptations, and as such, it is likely to be a key component of any successful therapeutic strategy for preserving or rescuing lens transparency, and perhaps flexibility, during aging. Protein redox chemistry is typically mediated by Cys residues. This review will therefore focus primarily on the Cys-rich γ-crystallins of the human lens, taking care to extend these findings to the β- and α-crystallins where pertinent. • As the lens loses glutathione, abundant lens crystallins become a redox buffer. • Early crystallin disulfides are compatible with native structure but strained. • With age, disulfides flow from native to misfolded conformers that aggregate. • Transition metals and PTMs alter crystallin redox chemistry, stability, and aggregation. • Creative approaches are needed to repair or preserve lens redox homeostasis. [ABSTRACT FROM AUTHOR]

Abstract: Many of the regions with the earliest atrophy in Alzheimer''s Disease (AD) do not show prominent deficits on functional imaging studies of flow or metabolism. This paradox may provide unique insights into the pathophysiology of AD. We sought to examine the relationship between function and atrophy in AD using MRI blood flow and anatomic imaging. 22 subjects diagnosed with AD, mean Mini Mental State Exam (MMSE) score 22.2, and 16 healthy elderly controls were imaged with a volumetric arterial spin labeling blood flow MRI technique and an anatomical imaging method using the identical spatial resolution, image orientation, and spatial encoding strategy. Cerebral blood flow (CBF) and gray matter (GM) maps derived from the imaging were transformed to a standard anatomical space. GM and CBF maps were tested for significant differences between groups. Additionally, images were tested for regions with significant mismatch of the CBF and GM differences between groups. CBF was significantly lower in the bilateral precuneus, parietal association cortex and the left inferior temporal lobe but was non-significantly increased in the hippocampus and other medial temporal structures. After correction for GM loss, CBF was significantly elevated in the hippocampus and other medial temporal structures. The hippocampus and other regions affected early in AD are characterized by elevated atrophy-corrected perfusion per cm3 of tissue. This suggests compensatory or pathological elevation of neural activity, inflammation, or elevated production of vasodilators. [Copyright &y& Elsevier]

The article presents information on the mechanisms of action and methods of study for global regulators of transcription in Escherichia coli. An overview of the bactreial multi-subunit RNA polymerase and DNA recognition by RNA polymerase. It describes transcription regulators and global transcription factors. It explores the application of ChIP-chip to the study of nucleoid-associated-omics.

Abstract: A surface-based approach is described for the transcriptional analysis of large, single DNA molecule templates and their imaged reaction products using RNA polymerase (RNAP). Results demonstrated that surfaces with a charge density supporting stretching of single DNA molecules to 70–80% of their full contour length were ideal for analysis of T7 RNAP transcription complexes on bound single template DNAs. Such DNA molecules were shown to sustain efficient transcription reactions and analysis, which enabled localization of transcription complexes on templates at kilobase resolution. Direct labeling of nascent RNA transcripts by the incorporation of a second fluorochrome into DNA templates promotes more robust and sensitive detection of punctates. Further characterization by RNase digestions, atomic force microscopy studies, and fluoro-immunolabeling revealed a “supercomplex” structure within a punctate where elongation complexes aggregate through entanglement of DNA and RNA strands from individual ternary elongation complexes. We have proposed mechanisms that underlie the supercomplex formation process. Whereas supercomplexes develop naturally in free solution, spatial constraints involved in a topologically limited system where template DNA is bound to the surface may facilitate the assembling process by stalling transcriptional elongation. [Copyright &y& Elsevier]

Abstract: Estimation of diversification rates in evolutionary radiations requires a complete accounting of cryptic species diversity. The rapidly evolving songs of acoustically signaling insects make them good model organisms for such studies. This paper examines the timing of diversification of a large (30 taxon) group of New Zealand cicadas (genus Kikihia Dugdale). We use Bayesian relaxed-clock methods and phylogenetic trees based on nuclear and mitochondrial DNA data, and we apply alternative combinations of evolutionary rate priors and geological calibrations. The extant Kikihia taxa began to diversify near the Miocene/Pliocene boundary around the time of increased mountain-building, and both the mitochondrial and nuclear-gene trees confirm early splits of lineages currently represented by lowland forest-dwelling taxa. Most lineages originated in the Pleistocene, and sustained diversification occurred rapidly at over 0.5 lineages/my, a rate comparable to that of the Hawaiian silverswords. Diversification rate tests suggest an increase in the early to mid-Pliocene, followed by constant diversification from the Late Pliocene onward. No descendants of the many Pleistocene-age splits have evolved the ability to coexist in sympatry, and, where they do come into contact, hybrid zones have been documented based on acoustic and DNA evidence. In contrast, lineages separated in time by approximately 2Myr often overlap in distribution with no evidence of hybridization. This suggests that at least 2Myr has been required to achieve the level of divergence required for reproductive isolation. [Copyright &y& Elsevier]

Abstract: The success of riboflavin photochemical cross-linking of the cornea in treating keratoconus and post-surgical keratectasia has prompted interest in cross-linking scleral tissue with a potential application to stabilize myopic progression. Applying an UVA light source to the sclera is difficult, particularly in the posterior region. An alternate pharmacologic approach to scleral cross-linking may be possible. The present study was undertaken in order to identify nitrite related compounds capable of inducing scleral tissue cross-linking and to gain information regarding the possible chemical mechanisms involved. 8×4mm strips of porcine and human sclera were incubated in various concentrations of nitrite related agents (1–100mM) at 37°C. pH 7.4 was used for all experiments except those involving NaNO2. Following a 24–96h incubation period, the samples were tested for cross-linking effects using thermal shrinkage temperature (T s) analysis. Several compounds were studied including NaNO2, 2-nitroethanol, 2-nitro-1-propanol, 3-nitro-2-pentanol, 2-nitrophenol, 2-nitroethane, 2-aminoethanol, isopentyl nitrite, DPTA/NO, DETA/NO, and urea, a nitrous acid trap. The results indicate that short chain aliphatic β-nitro alcohols (2-nitroethanol, 2-nitro-1-propanol, and 3-nitro-2-pentanol) are particularly effective cross-linking agents at pH 7.4, showing both time and concentration dependent effects. Furthermore, nitrosation does not appear to induce tissue cross-linking. In conclusion, aliphatic β-nitro alcohols can cross-link scleral tissue at physiologic pH and temperature. Since β-nitro alcohols are known to have reasonable toxicity profiles, these agents could find utility as pharmacologic cross-linking agents for scleral thinning disease. [Copyright &y& Elsevier]

Abstract: We used results of laboratory experiments to make predictions about a well-established phenomenon, scale-dependent association of organisms with habitat. Based on shelter seeking behaviour in laboratory experiments, we predicted that age 0 cod would be locally decoupled from vegetated habitat at spatial scales on the order of the limits of underwater visibility, becoming associated at larger scales. On transects at 10 sites in Newman Sound, Bonavista Bay, Newfoundland age 0 juvenile cod were usually found either in or adjacent to the band of tall eelgrass running parallel to the coast. At the scale of 5m or less along transects perpendicular and parallel to the coast cod were decoupled from habitat, as expected. At the scale of 5–20m cod were either decoupled or only weakly associated with habitat, contrary to expectation based on underwater visibility and shelter seeking behaviour in the lab. At the scale of 20–100m along transects perpendicular to the coast cod were positively associated with tall eelgrass, while being negatively associated with short eelgrass. This reflects the negative association of tall with short eelgrass due to parallel band structure at this scale. At scales of 20–100m along transects parallel to the coast cod were positively associated with short eelgrass. Decoupling of cod density from the amount of habitat at scales of 5–20m was due to the formation of small shoals near the boundaries between tall and short eelgrasses. The observed change in association of numbers with habitat with change in scale, combined with the theoretical expectation that association with habitat decreases as the risk/reward ratio increases, allowed us to draw the conclusion that the ratio of risk to reward decreases as spatial scale increases from 10 to 100m. The predictive approach we develop here can be extended to other scale-dependent phenomena, such as scale-dependent association of predator with prey. [Copyright &y& Elsevier]

Abstract: Background: We have shown previously that cryopreservation of human internal mammary arteries activates protein kinase C and enhances intracellular Ca2+ [Ca2+]i. We now present evidence that in human saphenous veins (HSV) cryoinjury is associated with activation of the Rho/Rho kinase signaling pathways and enhanced [Ca2+]i. Methods: HSV were investigated in vitro either unfrozen within 12h after removal or after storage at −196°C in a cryomedium containing 1.8M dimethyl sulfoxide and 0.1M sucrose as cryoprotectant additives. Results: Cryostorage diminished responses to receptor-mediated contractile agonists such as noradrenaline, 5-HT and endothelin-1 by up to 30% whereas responses to KCl were attenuated by about 50%. Concentration–response curves for CaCl2 on unfrozen and cryopreserved HSV revealed similar inhibitory activities of both blocking 1,4-dihydropyridine derivatives nifedipine and the (−)-(R) enantiomer of SDZ 202-791 whereas the Ca2+ channel activating (+)-(S) enantiomer of SDZ 202-791 was 10 times less effective at enhancing contractions to CaCl2 when tested after cryostorage. These functional effects were reflected by changes in [Ca2+]i as demonstrated by fluorescence of Fluo-3AM loaded veins. The diminished activity of (+)-(S) SDZ 202-791 in cryopreserved HSV was reversed partially when the potassium channel opener pinacidil (1μM) was present during the freezing/thawing process. Blockade of Rho kinase by HA-1077 proved to be significantly more effective at attenuating contractile responses to both endothelin-1 and KCl after cryostorage. Conclusions: Data suggested that cryopreservation modified [Ca2+]i of venous smooth muscle cells (1) through depolarization-induced changes in Ca2+ influx and (2) through activation of Rho kinase signaling pathways. [Copyright &y& Elsevier]

Richardson''s ground squirrels produce alarm calls that warn conspecifics of potential predatory threat. Variation in the acoustic structure of individual syllables within a call carries information regarding the extent of threat. Given this variation, along with the production of multiple syllables within a repeated call, the syntactical structure of the call could also encode meaningful information. To test for evidence of syntax in Richardson''s ground squirrel alarm communication, we presented adult and juvenile subjects with repeated alarm calls with unaltered syllable order and those same calls with syllable order randomized. There was limited evidence that syllable order affected receiver response, but squirrels were more responsive to primary syllables of repeated calls even when these syllables were embedded within randomized calls. This suggests that primary syllables serve a general alerting function, possibly priming receivers for information that follows. Distinctive structural elements of primary syllables, including reduced syllable duration and reduced harmonic durations relative to the fundamental frequency, were correlated with the heightened vigilance responses that these syllables evoked. [Copyright &y& Elsevier]

Abstract: This study was designed to evaluate effects of specific p38 MAP kinase inhibition on gene and protein expression of essential hematopoietic cytokines in primary human bone marrow stromal cells (HBMSC) and to identify downstream transcription factors (TF) regulated by the p38 MAP kinase signalling pathway. In vitro effects of p38 inhibitors (p38i) on cytokine regulation were compared to inhibitors of other major signalling pathways including PI3 kinase, JNK, MEK-1, NF-κB or protein kinase C (PKC). HBMSC were pre-treated with p38i (SB-203580) for 1 h and then stimulated with 200 ng/ml lipopolysaccharide (LPS). Supernatants and RNA were collected 6 h post LPS treatment for quantitative protein and mRNA analyses by ELISA and real-time RT–PCR, respectively, for interleukin-6 (IL-6), interleukin-11 (IL-11), granulocyte–monocyte colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and Activin A. Effects of the inhibitors of PI3 kinase (LY294002), JNK (synthetic inhibitory peptide), MEK-1 (PD90859), NF-κB (pyrrolidinedithiocarbamate (PDTC)) and protein kinase C (calphostin C) on HBMSC expression hematopoietic cytokines were evaluated and compared. SB-203580 caused dose-dependent decreases in cytokine protein expression and decreased IL-6 and IL-11 mRNA expression. Of the pathway inhibitors examined, only NF-κB elicited similar effects on cytokine protein and mRNA expression. p38-regulated transcription factor activity was assessed using a DNA/Protein array. Several TFs linked to cytokine regulation were modulated by SB-203580, with 10 of 21 p38-regulated TFs identified have not been previously linked to downstream p38 signalling. These observations in cultured HBMSC have illustrated the involvement of cytokine proteins, mRNA and TF activities and may improve the current understanding of the in vivo p38i suppression of erythropoiesis. In addition, these results suggest that IL-6, IL-11, GM-CSF, G-CSF and Activin A are similarly regulated by p38 and NF-κB and that the MEK1, JNK and PKC pathways appear to play a more limited role in modulating cytokine expression in HBMSC. [Copyright &y& Elsevier]

Abstract: The Melaleuca leucadendra complex (broad-leaf paperbarks; Myrtaceae) is a dominant component of the tropical and sub-tropical biota of Australia, particularly in wetlands of high conservation significance. In Florida and other parts of the Americas, however, one member of the group (Melaleuca quinquenervia) is a serious ecological and economic weed. Understanding the relationships and evolution of the group is integral to both conservation and biocontrol efforts. Although the complex is currently considered to include up to 14 species, there has been some concern over taxonomic boundaries within the complex because most species are circumscribed only by combinations of characters, each of which also occurs in other species. Here, DNA sequence data derived from the chloroplast and two nuclear regions are used to explore the relationships of M. quinquenervia. We find little evidence for clear species boundaries within the M. leucadendra complex in general, with regional sharing of chloroplast haplotypes across morphologically defined taxa, indicating asymmetrical introgression or retention of ancestral haplotypes (lineage sorting). Phylogenies were further confounded by the recovery of multiple copies of both nuclear regions sequenced (ITS and rpb2) from many individuals. There was no clear evidence of polyploidy or pseudogenes, but multiple duplications of rpb2 could not be ruled out. Parsimony networks of the nuclear ITS region show some clustering of haplotypes by morphospecies but there is also evidence of both hybridisation and recombination. Signals of introgression were also evident in rpb2, supporting an hypothesis of recent or ongoing gene flow between M. quinquenervia and other members of the M. leucadendra complex. Both relaxed and fixed molecular-clock dating estimate the introgression to have occurred sometime within the past seven million years (95% CI: 0.7–18). The New Caledonian population of M. quinquenervia appears to have been established by dispersal from Australia during this period. M. quinquenervia is found to have alleles closely related to multiple different morphotaxa within the M. leucadendra complex, suggesting considerable past introgression into this taxon from some other members of the M. leucadendra complex, and this has implications for biocontrol efforts. The M. leucadendra complex appears to reflect early to intermediate stages of speciation, possibly driven by different ecologies. [Copyright &y& Elsevier]

Abstract: The lens and cornea are transparent and usually avascular. Controlling nutrient supply while maintaining transparency is a physiological challenge for both tissues. During sleep and with contact lens wear the endothelial layer of the cornea may become hypoxic, compromising its ability to maintain corneal transparency. The mechanism responsible for establishing the avascular nature of the corneal stroma is unknown. In several pathological conditions, the stroma can be invaded by abnormal, leaky vessels, leading to opacification. Several molecules that are likely to help maintain the avascular nature of the corneal stroma have been identified, although their relative contributions remain to be demonstrated. The mammalian lens is surrounded by capillaries early in life. After the fetal vasculature regresses, the lens resides in a hypoxic environment. Hypoxia is likely to be required to maintain lens transparency. The vitreous body may help to maintain the low oxygen level around the lens. The hypothesis is presented that many aspects of the aging of the lens, including increased hardening, loss of accommodation (presbyopia), and opacification of the lens nucleus, are caused by exposure to oxygen. Testing this hypothesis may lead to prevention for nuclear cataract and insight into the mechanisms of lens aging. Although they are both transparent, corneal pathology is associated with an insufficient supply of oxygen, while lens pathology may involve excessive exposure to oxygen. [Copyright &y& Elsevier]

Abstract: Sulfonyl chlorides substituted with functional groups having high proton affinity can serve as derivatization reagents to enhance the sensitivity for steroidal estrogens in liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The most commonly used reagent for derivatization of estrogens for LC-ESI-MS/MS is dansyl chloride. In this study, we compared dansyl chloride, 1,2-dimethylimidazole-4-sulfonyl (DMIS) chloride, pyridine-3-sulfonyl (PS) chloride, and 4-(1H-pyrazol-1-yl)benzenesulfonyl (PBS) chloride for derivatization of 17β-estradiol (E2) prior to LC-ESI-MS/MS. The product ion spectra of the dansyl and DMIS derivatives were dominated by ions representing derivatization reagent moieties. In contrast, the product ion spectrum of the PS derivative of E2 and, to a lesser extent, the PBS derivative, showed analyte-specific fragment ions. Derivatization with PS chloride was therefore chosen for further investigation. The product ion spectrum of the PS derivative of E2 showed intense ions at m/z 272, assigned to the radical E2 cation, and at m/z 350, attributed to the loss of SO2 from the [M+H]+ ion. Third-stage mass spectrometry of the PS derivative of E2 with isolation and collisional activation of the m/z 272 ion resulted in steroid C and D ring cleavages analogous to those observed in electron ionization mass spectrometry. The product ion spectra of the PS derivatives of estrone, 17α-ethinylestradiol, equilin, and equilenin showed similar estrogen-specific ions. Using derivatization with PS chloride, we developed an LC-ESI-MS/MS method with multiple reaction monitoring of primary and confirmatory precursor-to-product ion transitions for the determination of E2 in serum. [Copyright &y& Elsevier]

Abstract: Bursicon is the ultimate hormone in insect ecdysis, which is involved in cuticle hardening. Here we show that mRNAs encoding the heterodimeric cystine knot protein bursicon (Burs α, β), are present in crustaceans, suggesting ubiquity of this hormone in arthropods. We firstly report the cloning, sequencing of mRNAs encoding subunits from the water flea, Daphnia arenata and the CNS of the crab, Carcinus maenas, in comparison with insect bursicon subunits. Expression patterns of α and β burs mRNAs were examined by in-situ hybridisation (ISH) and quantitative RT-PCR. In the thoracic ganglion, burs α and β mRNAs were completely colocalised in neurones expressing crustacean cardioactive peptide (CCAP). However, in the brain and eyestalk, bursicon transcripts were never observed, despite a complex expression pattern of CCAP interneurones. Patterns of expression of burs α and β mRNAs were constitutive during the moult cycle of adult crabs, in stark contrast to the situation in insects. Whilst copy numbers of burs β transcripts closely matched those of CCAP, those of burs α mRNA were around 3-fold higher than burs β. This pattern was apparent during embryogenesis, where bursicon transcripts were first observed at around 50% development—the same time as first expression of CCAP mRNA. Transcript ratios (burs α: β) increased during development. Our studies have shown, for the first time, that bursicon mRNAs are expressed in identified neurones in the nervous system of crustaceans. These findings will now promote further investigation into the functions of bursicon during the moult cycle and development of crustaceans. [Copyright &y& Elsevier]

Abstract: Acidic waters of the Rio Tinto, southwestern Spain, evaporate seasonally, precipitating a variety of iron sulfide and oxide minerals. Schwertmannite and nanophase goethite form thin laminae on biological and detrital grain surfaces, replicating, among other things, the morphologies of insect cuticle, plant tissues, fungi, algae, and bacteria. Intergrain cements also incorporate bacterial cells and filaments. Other sulfate minerals precipitated in Rio Tinto environments are transient and contribute little to short-term preservation. Because the Rio Tinto has been cutting its current valley for several million years, terrace deposits provide a window on longer term fossil preservation. Early and later diagenesis are recorded in terrace deposits formed about one thousand and two million years ago, respectively. The sedimentary structures and mineralogies of these deposits suggest that they formed under physical and chemical conditions comparable to those of modern Rio Tinto sediments. The terrace deposits show quantitative loss of sulfate minerals, increasing crystallinity of goethite and, in the older terrace, replacement of goethite by hematite. Fossils formed originally by schwertmannite and nanophase goethite replication persist through diagenesis, preserving a long term record of local biological diversity. Fossil preservation by iron oxides in the acidic environment of Rio Tinto suggests that if life was present when sedimentary rocks formed at Meridiani Planum, Mars, precipitated minerals could record their presence. [Copyright &y& Elsevier]

Abstract: Same-sex friendships are an important source of social support and typically contribute to positive adjustment. However, there can be adjustment trade-offs if the friends co-ruminate (i.e., talk excessively about problems) in that co-rumination is related to having close friendships but also to increased internalizing symptoms. The current study utilized an experimental manipulation that elicited co-rumination in young women and thus mirrored an everyday response to stress. Observed co-rumination was associated with a significant increase in the stress hormone, cortisol (after controlling for self-reported co-rumination and for cortisol levels assessed before the discussion of problems). These findings suggest that co-rumination can amplify, rather than mitigate, the hormonal stress response to personal life stressors. [Copyright &y& Elsevier]

Abstract: Signal peptide peptidase (Spp) is the enzyme responsible for cleaving the remnant signal peptides left behind in the membrane following Sec-dependent protein secretion. Spp activity appears to be present in all cell types, eukaryotic, prokaryotic and archaeal. Here we report the first structure of a signal peptide peptidase, that of the Escherichia coli SppA (SppAEC). SppAEC forms a tetrameric assembly with a novel bowl-shaped architecture. The bowl has a dramatically hydrophobic interior and contains four separate active sites that utilize a Ser/Lys catalytic dyad mechanism. Our structural analysis of SppA reveals that while in many Gram-negative bacteria as well as characterized plant variants, a tandem duplication in the protein fold creates an intact active site at the interface between the repeated domains, other species, particularly Gram-positive and archaeal organisms, encode half-size, unduplicated SppA variants that could form similar oligomers to their duplicated counterparts, but using an octamer arrangement and with the catalytic residues provided by neighboring monomers. The structure reveals a similarity in the protein fold between the domains in the periplasmic Ser/Lys protease SppA and the monomers seen in the cytoplasmic Ser/His/Asp protease ClpP. We propose that SppA may, in addition to its role in signal peptide hydrolysis, have a role in the quality assurance of periplasmic and membrane-bound proteins, similar to the role that ClpP plays for cytoplasmic proteins. [Copyright &y& Elsevier]

Abstract: The present studies examined whether the retrieval of an old ‘reactivated’ memory could be brought under the control of new contextual cues. In Experiment 1 rats trained in one context were exposed to different contextual cues either immediately, 60 or 120min after a cued reactivation of the training memory. When tested in the shifted context, subjects exposed shortly after reactivation treated the shifted context as the original context. This transfer diminished with longer post-reactivation delays. Experiment 2 replicated the basic finding and demonstrated that the transfer of the old retrieval cues was specific to the contextual cues present during exposure. These findings are consistent with previous research [i.e., Briggs, J. F., Fitz, K. I., & Riccio, D. C. (in press). Transfer of memory retrieval cues in rats. Psychonomic Bulletin &Review] showing the transfer of retrieval cues for a new memory, and demonstrating a similarity (in this case) between newly acquired and old reactivated memories. [Copyright &y& Elsevier]

The interactions of polycyclic aromatic hydrocarbons (PAH) and cytochromes P450 (CYP) are complex; PAHs are enzyme inducers, substrates, and inhibitors. In T-47D breast cancer cells, exposure to 0.1 to 1 μM benzo(k)fluoranthene (BKF) induced CYP1A1/1B1-catalyzed 17β-estradiol (E2) metabolism, whereas BKF levels greater than 1 μM inhibited E2 metabolism. Time course studies showed that induction of CYP1-catalyzed E2 metabolism persisted after the disappearance of BKF or co-exposed benzo(a)pyrene, suggesting that BKF metabolites retaining Ah receptor agonist activity were responsible for prolonged CYP1 induction. BKF metabolites were shown, through the use of ethoxyresorufin O-deethylase and CYP1A1-promoter-luciferase reporter assays to induce CYP1A1/1B1 in T-47D cells. Metabolites formed by oxidation at the C-2/C-3 region of BKF had potencies for CYP1 induction exceeding those of BKF, whereas C-8/C-9 oxidative metabolites were somewhat less potent than BKF. The activities of expressed human CYP1A1 and 1B1 with BKF as substrate were investigated by use of HPLC with fluorescence detection, and by GC/MS. The results showed that both enzymes efficiently catalyzed the formation of 3-, 8-, and 9-OHBKF from BKF. These studies indicate that the inductive effects of PAH metabolites as potent CYP1 inducers are likely to be additional important factors in PAH-CYP interactions that affect metabolism and bioactivation of other PAHs, ultimately modulating PAH toxicity and carcinogenicity. [Copyright &y& Elsevier]

Abstract: Individual variability of the human cerebral cortex is a source of both fascination and frustration. The fascination arises because variability in cortical structure and function may account for many aspects of our unique personalities and cognitive capabilities. For neuroimagers, the frustration arises because variability presents serious obstacles when attempting to assign particular functional activation patterns to specific cortical areas. Devlin and Poldrack cogently summarize many of the key issues, and they make useful suggestions for linking function to anatomy using a standardized stereotaxic space. This commentary provides a broader perspective on the nature of individual variability that has implications for the choice of strategies used to compensate for variability. It also includes information about the actual differences between various registration strategies and introduces a new strategy for converting neuroimaging data to a standard stereotaxic space. [Copyright &y& Elsevier]

In the present study, the authors propose a new framework that integrates literature on achievement, supports the testing of novel hypotheses, and stresses the importance of examining a large number of factors in the same study. This framework assumes that high achievement is a function of three categories of factors: (a) opportunity factors (e.g., coursework), (b) propensity factors (e.g., prerequisite skills, motivation), and (c) distal factors (e.g., SES). A secondary analysis of the National Longitudinal Educational Study (NELS:88) using hierarchical regression and structural equation modeling revealed that 58–81% of the variance in achievement was explained by family variables and specific opportunity and propensity factors. The findings are discussed in terms of their potential implications for intervention efforts. [Copyright &y& Elsevier]

Plant invasions are a serious threat to natural and semi-natural ecosystems worldwide. Most management-orientated research on invasions focuses on invaders that are already widespread and often have major impacts. This paper deals with “emerging” invaders—those alien species with the potential to become important problems without timely intervention. A climate matching procedure was developed to define areas of South Africa, Lesotho and Swaziland that could be invaded by 28 plant species that had previously been classified as emerging invaders. Information on the location of populations of these species in the study area was combined with information on their distributions (as native or alien) in parts of Australia and the United States of America. These two countries had the best available distribution data for this study. They also share many invasive alien plant species with South Africa. Climatic data obtained for weather stations near points of known occurrence in these countries were used to define the climatically suitable areas for each species in the study area. Almost 80% of the remaining natural environment in southern Africa was found to be vulnerable to invasion by at least one of these species, 50% by six or more and 24% by 16 or more species. The most vulnerable areas are the highveld grasslands and the eastern escarpment. The emerging invaders with the greatest potential range included Acacia podalyriifolia and Cortaderia selloana. The globally important invaders Ulex europaeus and Lythrum salicaria had a more limited invasion potential but could still become major invaders. There was no relationship between the extent of the climatically suitable areas for the different species and an expert ranking of their invasion potential, emphasising the uncertainties inherent in making expert assessments based on very little information. The methods used in this analysis establish a protocol for future modelling exercises to assess the invasion potential of other emerging invaders. [Copyright &y& Elsevier]

Abstract: We used mitochondrial DNA sequences of 12S and 16S ribosomal RNA genes to reconstruct phylogenetic relationships of the nine species of South American aquatic hylids known as paradoxical frogs. Pseudis minuta and P. cardosoi form the sister-group to a clade comprising Lysapsus and the remaining Pseudis. We suggest the resurrection of Podonectes, including P. minutus and P. cardosoi, to avoid the nonmonophyly of Pseudis. Some doubt is cast on the species status of P. cardosoi. Lysapsus limellum, P. bolbodactyla, and P. paradoxa each may comprise more than one species, but lack of comprehensive geographic and morphological appraisals precludes taxonomic changes. Biogeographic implications of the phylogeny are discussed. The correlation between hydrographic basins and Pseudis species is not fully supported, and a recent contact between Amazon populations in eastern Bolivia and western Brazil (Rondônia) and Paraná basin populations in the Pantanal is suggested. A dispersal-vicariance analysis showed that major diversification of Pseudis and Lysapsus species occurred in the Brazilian Shield, and that the presence of P. paradoxa and L. limellum in the Amazon and Paraná basins is due to recent dispersals. Evidence suggests a vicariant event, most likely caused by Miocene marine introgressions, as the cause for the restricted distribution of L. laevis in the Guiana Shield. [Copyright &y& Elsevier]

Background: Health literacy skills (HLS) have been shown to have a major impact on patient outcomes. To identify patients with limited or marginal HLS, the accuracy of three established screening items were examined. Materials and methods: We studied English-speaking adults (≥21 years) attending a university-based vascular surgery clinic. Structured interviews were conducted to assess sociodemographic characteristics, screening items, and HLS. Area under the receiver operating characteristic (AUROC) curves were plotted to assess the discriminatory capacity of each screening item in detecting patients with limited/marginal HLS. Results: One hundred patients agreed to enter the study and met inclusion criteria. The mean age was 62.0 ± 12.9; 65 were female; 96 were Caucasian; and 32 had not completed high school. The three screening items were effective in detecting patients with limited (n = 18) or marginal (n = 21) HLS. “How often do you have someone (like a family member, friend, or hospital worker) help you read hospital materials?” (AUROC of 0.83; 95% confidence interval [CI] = 0.73, 0.92), “How often do you have problems learning about your medical condition because of difficulty understanding written information?” (AUROC of 0.77; 95% CI = 0.67, 0.86), and “How confident are you filling out medical forms by yourself?” (AUROC of 0.76; 95% CI = 0.66, 0.86) were effective in detecting those with limited/marginal HLS skills. Conclusions: Our findings provide further evidence of the clinical usefulness of these screening items for detecting inadequate HLS in this patient population. Surgeons should consider administering these easy screening items to identify patients at greatest risk of limited or marginal HLS. [Copyright &y& Elsevier]

Abstract: The present article examines personality as a predictor of college achievement beyond the traditional predictors of high school grades and SAT scores. In an undergraduate sample (N =131), self and informant-rated conscientiousness using the Big Five Inventory (BFI; ) robustly correlated with academic achievement as indexed by both freshman GPA and senior GPA. A model including traditional predictors and informant ratings of conscientiousness accounted for 18% of the variance in freshman GPA and 37% of the variance in senior GPA; conscientiousness alone explained unique variance in senior GPA beyond the traditional predictors, even when freshman GPA was included in the model. Conscientiousness is a valid and unique predictor of college performance, and informant ratings may be useful in its assessment for this purpose. [Copyright &y& Elsevier]

Abstract: A new single-molecule system, Transchip, was developed for analysis of transcription products at their genomic origins. The bacteriophage T7 RNA polymerase and its promoters were used in a model system, and resultant RNAs were imaged and detected at their positions along single template DNA molecules. The Transchip system has drawn from critical aspects of Optical Mapping, a single-molecule system that enables the construction of high-resolution ordered restriction maps of whole genomes from single DNA molecules. Through statistical analysis of hundreds of single-molecule template/transcript complexes, Transchip enables analysis of the locations and strength of promoters, the direction and processivity of transcription reactions, and the termination of transcription. These novel results suggest that the new system may serve as a high-throughput platform to investigate transcriptional events on a large genome-wide scale. [Copyright &y& Elsevier]

Abstract: This paper explores the historical relationships between Methodist Sunday school tea treats and parades and the formation of religious identity in west Cornwall between c. 1830 and 1930. Through these ritual activities, people were entrained into the symbolic identity-forming apparatus of Methodist faith and practice. Moving beyond the spaces of school rooms and chapels, the paper focuses on the organisation, the use of public space and the territorial significance of annual tea treats and parades in the nurturing and maintenance of a Methodist constituency. In so doing, the paper draws on work in the history of Nonconformity, geographies of religion and the historical geography of parades to conduct a critical analysis of tea treats and parades as ritual, spectacle and carnival. [Copyright &y& Elsevier]

Abstract: Objectives. : Although early reports suggested that smoking was not associated with ovarian cancer risk, recent studies have reported positive associations for cancers of the mucinous subtype. We sought to clarify the relationship between smoking and ovarian cancer by histological subtype. Methods. : We conducted a systematic literature review and meta-analysis of studies investigating the association between smoking and risk of the different histological subtypes of epithelial ovarian cancer. Eight population-based case–control studies, one pooled analysis of case–control studies, and one cohort study met the inclusion criteria. Summary relative risks (RR), 95% confidence intervals (CI), and tests for heterogeneity were generated from random effects models. Results. : Combined, these studies included a total of 910 women with mucinous and 5564 with non-mucinous ovarian cancers. There was a significant doubling of risk of mucinous ovarian cancer in current smokers compared to never smokers (summary RR 2.1, 95%CI 1.7–2.7), but no increased risk of serous (1.0, 95%CI 0.8–1.2) or endometrioid (0.8, 95%CI 0.6–1.1) cancers and a significant risk reduction for clear cell cancers (0.6, 95%CI 0.3–0.9). The risk of mucinous cancer increased with increasing amount smoked but returned to that of never smokers within 20–30 years of stopping smoking. Conclusions. : Meta-analysis suggests that current smoking doubles a woman''s risk of developing mucinous ovarian cancer. Stopping smoking returns the risk to normal in the long term. Smoking may thus be one of the few modifiable factors offering potential for primary prevention of mucinous ovarian cancer. [Copyright &y& Elsevier]

Abstract: Radiation damping induced by the strong water magnetization in Z-spectroscopy experiments can be sufficient to perturb significantly the resultant Z-spectrum. With a probe tuned to exact electrical resonance the effects are relatively straightforward, narrowing the central feature of the Z-spectrum. Where, as is commonly the case, the probe is tuned sufficiently well to give optimum signal-to-noise ratio and radiofrequency field strength but is not at exact resonance, radiation damping introduces an unexpected asymmetry into the Z-spectrum. This has the potential to complicate the use of Z-spectrum asymmetry to study chemical exchange, for example in the estimation of pH in vivo. [Copyright &y& Elsevier]

Abstract: The primary purpose of this study was to measure the influence of ibuprofen use during the 160-km Western States Endurance Run on endotoxemia, inflammation, and plasma cytokines. Subjects included 29 ultramarathoners who consumed 600 and 1200mg ibuprofen the day before and on race day, respectively, and 25 controls that competed in the race but avoided ibuprofen and all other medications. Blood and urine samples were collected the morning prior to and immediately following the race, and subjects recorded muscle soreness during the week following the race using a 10-point Likert scale (DOMS). Race time (25.8±.6 and 25.6±.8h, respectively) and ratings of perceived exertion (RPE, 6–20 scale) (14.6±.4 and 14.5±.2, respectively) did not differ significantly between ibuprofen users and nonusers. Ibuprofen use compared to nonuse was linked to a smaller increase in urine creatinine (P =.038), higher plasma levels of lipopolysaccharide (group effect, P =.042), and greater increases (pre-to-post race) in serum C-reactive protein and plasma cytokine levels for interleukin (IL)-6, IL-10, IL-8, IL-1ra, granulocyte colony-stimulating factor, monocyte chemotactic protein 1, and macrophage inflammatory protein 1 beta, but not tumor necrosis factor alpha. Post-race DOMS and serum creatine kinase levels did not differ significantly between ibuprofen users and nonusers (20,621±3565 and 13,886±3068μcal/L, respectively, P =.163). In conclusion, ibuprofen use compared to nonuse by athletes competing in a 160-km race did not alter muscle damage or soreness, and was related to elevated indicators of endotoxemia and inflammation. [Copyright &y& Elsevier]

Abstract: As polyomavirus major capsid protein VP1-derived virus-like particles (VLPs) have been demonstrated to be highly immunogenic, we studied their interaction with human dendritic cells (hDCs). Exposure of hDCs to VLPs originating from murine (MPyV) or hamster polyomavirus (HaPyV) induced hDC maturation. In contrast, exposure of hDCs to VLPs derived from human polyomaviruses (BK and JC) and simian virus 40 (SV40) only marginally induced DC maturation. The hDCs stimulated by HaPyV- or MPyV-derived VLPs readily produced interleukin-12 and stimulated CD8-positive T-cell responses in vitro. The highest frequencies of activated T cells were again observed after pulsing with HaPyV- and MPyV-derived VLPs. Monocyte-derived hDCs both bound and internalized the various tested polyomavirus VP1-derived VLPs with different levels of efficiency, partially explaining their individual maturation potentials. In conclusion, our data suggest a high variability in uptake of polyomavirus-derived VLPs and potency to induce hDC maturation. [Copyright &y& Elsevier]

Abstract: The capsaicin receptor TRPV1 is an emerging target for the treatment of pain with a unique expression profile in peripheral nociceptors and the ability to show polymodal activation, TRPV1 is an important integrator of responses to inflammatory mediators. Sensitization of TRPV1 during chronic pain is believed to contribute to the transduction of noxious signaling for normally innocuous stimuli and consequently the search for novel TRPV1 therapeutics is intense. The current understanding of the physiological role the receptor, as well as the potential therapeutic utility and emerging liabilities of TRPV1 modulators are discussed. [Copyright &y& Elsevier]

Abstract: Edwards’ functional integral approach to the statistical mechanics of polymer liquids is amenable to a diagrammatic analysis in which free energies and correlation functions are expanded as infinite sums of Feynman diagrams. This analysis is shown to lead naturally to a perturbative cluster expansion that is closely related to the Mayer cluster expansion developed for molecular liquids by Chandler and co-workers. Expansion of the functional integral representation of the grand-canonical partition function yields a perturbation theory in which all quantities of interest are expressed as functionals of a monomer–monomer pair potential, as functionals of intramolecular correlation functions of non-interacting molecules, and as functions of molecular activities. In different variants of the theory, the pair potential may be either a bare or a screened potential. A series of topological reductions yields a renormalized diagrammatic expansion in which collective correlation functions are instead expressed diagrammatically as functionals of the true single-molecule correlation functions in the interacting fluid, and as functions of molecular number density. Similar renormalized expansions are also obtained for a collective Ornstein–Zernicke direct correlation function, and for intramolecular correlation functions. A concise discussion is given of the corresponding Mayer cluster expansion, and of the relationship between the Mayer and perturbative cluster expansions for liquids of flexible molecules. The application of the perturbative cluster expansion to coarse-grained models of dense multi-component polymer liquids is discussed, and a justification is given for the use of a loop expansion. As an example, the formalism is used to derive a new expression for the wave-number dependent direct correlation function and recover known expressions for the intramolecular two-point correlation function to first-order in a renormalized loop expansion for coarse-grained models of binary homopolymer blends and diblock copolymer melts. [Copyright &y& Elsevier]

Abstract: Here, we use a vaccine consisting of DNA priming followed by MVA boosting in rhesus macaques to investigate the ability of GM-CSF DNA to serve as an adjuvant for the elicitation of neutralizing Ab against an HIV-1 Env. The trial used Gag, Pol, and Env sequences from SHIV-89.6 in the immunogens and a neutralization escape variant of SHIV-89.6, SHIV-89.6P, for challenge. Co-delivery of GM-CSF and vaccine DNAs enhanced the temporal appearance of neutralizing Ab and broadened the specificity of the neutralizing activity to include SHIV-89.6P. Two long-term SHIV-89.6 infections elicited neutralizing activity for SHIV-89.6 but not SHIV-89.6P. Studies on the avidity of the anti-Env antisera revealed that the GM-CSF-adjuvanted vaccine had elicited higher avidity Ab than the non-adjuvanted vaccine or the infection. The GM-CSF-adjuvanted group showed a trend towards better control of the challenge infection and had better control of re-emergent virus (P < 0.01) than the non-adjuvanted group. [Copyright &y& Elsevier]

Abstract: A rapid method for measuring 3-methylhistidine (3MH) in rat and human urine with higher sensitivity and precision than any previously reported method is described using internal standard [1-13C]3MH (M+1) and negative chemical ionization (NCI) gas chromatography/mass spectrometry (GC/MS). Internal standard [1-13C]3MH (M+1) was added to rat and human urine samples, hydrolyzed, and absorbed onto cation exchange columns. The column eluent was dried and derivatized for GC/MS analysis. Quantification of 3MH levels was accomplished by monitoring the m/z 204 fragment. The m/z 204 fragment was chosen due to the fragment’s abundance and stability as determined by analysis of [methyl-2H3, 18O2]3MH (M+7) and [methyl-13C]3MH (M+1) fragmentation patterns under NCI conditions. This method shows excellent linearity (0.9989) over the range studied (0–0.5mol), high recovery (95.9%), and low coefficient of variation (4.7%). The described method is sensitive enough to detect 6.8pmol amount of urinary 3MH with a precision of 9.1%. The in vivo utility of this method to quantify urinary 3MH was tested in a burn injury rat model and on urine specimens from pediatric burn patients. Data obtained from the urine of burn-injured rats and pediatric burn patients match previously reported trends and validate the in vivo utility of this method. [Copyright &y& Elsevier]

Abstract: The expression of proteins using recombinant baculoviruses is a mature and widely used technology. However, some aspects of the technology continue to detract from high throughput use and the basis of the final observed expression level is poorly understood. Here, we describe the design and use of a set of vectors developed around a unified cloning strategy that allow parallel expression of target proteins in the baculovirus system as N-terminal or C-terminal fusions. Using several protein kinases as tests we found that amino-terminal fusion to maltose binding protein rescued expression of the poorly expressed human kinase Cot but had only a marginal effect on expression of a well-expressed kinase IKK-2. In addition, MBP fusion proteins were found to be secreted from the expressing cell. Use of a carboxyl-terminal GFP tagging vector showed that fluorescence measurement paralleled expression level and was a convenient readout in the context of insect cell expression, an observation that was further supported with additional non-kinase targets. The expression of the target proteins using the same vectors in vitro showed that differences in expression level were wholly dependent on the environment of the expressing cell and an investigation of the time course of expression showed it could affect substantially the observed expression level for poorly but not well-expressed proteins. Our vector suite approach shows that rapid expression survey can be achieved within the baculovirus system and in addition, goes some way to identifying the underlying basis of the expression level obtained. [Copyright &y& Elsevier]

Abstract: In this paper, the effect of measurement noise on damage detection performance of the minimum rank perturbation theory is investigated. Closed-form solutions for the sensitivity of the minimum rank perturbation theory damage vectors and calculated stiffness perturbations with respect to errors in the measured modes shapes or frequency response functions are developed. This sensitivity allows one to establish confidence in damage existence, location and extent assessment. The use of this information in interpreting damage detection results is discussed in the context of an experimental study. [Copyright &y& Elsevier]

Background: Intestinal malabsorption disorders and short bowel syndrome lead to significant morbidity. We recently demonstrated that grafting of intestinal organoids can grow a bioengineered intestinal neomucosa and cure bile acid malabsorption in rats. Now we have developed a novel system that permits direct observation of intestinal organoids in vivo to optimize conditions for engraftment. Methods: Optical Windows were created in C57BL/6J mice by externalizing an omental pedicle into a dorsal skin flap chamber. Following creation of windows, 5000 intestinal organoids from green-fluorescent protein transgene (GFP)(+) donor mice were seeded directly either on omentum or on polyglycolic acid (PGA) disks that had been placed on omentum at 1 or 5 days. Engraftment of green fluorescent cells was evaluated on postseeding days 1, 3, 5, 7, 10, 12, and 21 using fluorescence microscopy. Results: An initial group had seeding onto omentum (n = 5) or biopolymer disks (n = 5) on postoperative day 1. After 7 days, there was mucosal cell engraftment onto omental tissue and biopolymers. GFP(+) organoids engrafted significantly better when seeded onto biopolymers compared to omentum (P < 0.05). In a second study with increased sample size (n = 24) up to day 12, all four groups demonstrated adherence and growth. However, GFP(+) organoids seeded onto delayed PGA biopolymer demonstrated significantly better engraftment (P < 0.05). Conclusions: This novel system allows continuous in vivo observation of engrafted cells that are seeded on externalized omentum. The use of PGA mesh biopolymer may improve engraftment of intestinal organoids. [Copyright &y& Elsevier]

Abstract: The field of developmental psychology is part of a continuum of disciplines, from cell biology to cultural anthropology, that are focused on understanding developing and potentially evolving phenotypes; the reciprocal interactions between genetics and experiences produce variation in developing phenotypes and this variation is the grist for evolutionary selection. The articles in this issue provide cutting edge and multidisciplinary analyses of developing and potentially evolving phenotypes in areas that are of central interest to developmental scientists, including mother–infant attachments, stress responses in children, social cognition, and life span development. The articles and other recent works signal the reemergence of developmental psychology as an evolutionarily informed, multidisciplinary field. In this view, it is not about nature versus nurture or biology versus psychology, it is about tackling difficult problems at multiple levels of analysis, each of which has something to contribute and none of which is sufficient in and of itself. [Copyright &y& Elsevier]

Background: Transplantation of intestinal mucosal stem cells is an important step in the development of intestinal gene therapy and treatment of intestinal mucosal diseases. We hypothesized that engraftment rates increase proportionally with increasing doses of seeded stem cells and increasing jejunal débridment. Materials and methods: Intestinal mucosal organoids were harvested from neonatal mice carrying a green-fluorescent protein (GFP) transgene and transplanted into adult GFP(−) mice (n = 66). In recipients, two jejunal segments (1.5 cm) were isolated with their blood circulation left intact with anastomosis of the distal and proximal segments to restore continuity. Debridement of native enterocytes was performed by perfusing luminally with ethylene diamine tetraacetc acid solutions for 20 min. A total of 5,000, 10,000, or 25,000 organoids were then seeded. Three weeks later, cross sections (n = 398) of the segments were evaluated for the presence of GFP(+) neomucosa using fluorescence microscopy. Additional segments were débrided for 30 and 40 min (n = 83). Other conditions were not tested because of the rate of high mortality in these experiments. Results: The group seeded with 10,000 organoid units at 20 min showed the highest engraftment of GFP(+) epithelium. Engraftment was improved by increasing débridment times at this seeding density. Overall mortality was 70%. Conclusions: These findings suggest that there is an optimal seeding density of stem cell clusters for enhanced engraftment in this model. Mortality prohibited complete testing of all combinations of seeding density and debridement times. [Copyright &y& Elsevier]

Abstract: Myocardial ischemia/reperfusion (IR) induces myocyte apoptosis, and the pro-apoptotic/tumor suppressor protein p53 may contribute to this process. However, the signaling mechanism by which IR induces p53 activation remains largely unknown. Here, we show that MEKK1 undergoes proteolytic cleavage in a caspase-3 dependent manner in both in vivo and in vitro models of ischemic injury. Overexpression studies both in vivo and in vitro indicated that the caspase-3 mediated cleavage of MEKK1 promotes phosphorylation and transcriptional activity of p53. In addition, caspase-3 inhibited the ability of the wild-type full-length form of MEKK1 to activate ATF2, suggesting that caspase-3, by way of proteolytic cleavage, abrogates the ability of MEKK1 to signal JNK. We propose that IR induces caspase-3 mediated proteolytic cleavage of MEKK1 and promotes p53 transcriptional activity via JNK-independent mechanisms, which in turn may contribute to pathological insults associated with IR injury, such as myocyte apoptosis. [Copyright &y& Elsevier]

Cyclotides are mini-proteins of 28–37 amino acid residues that have the unusual feature of a head-to-tail cyclic backbone surrounding a cystine knot. This molecular architecture gives the cyclotides heightened resistance to thermal, chemical and enzymatic degradation and has prompted investigations into their use as scaffolds in peptide therapeutics. There are now more than 80 reported cyclotide sequences from plants in the families Rubiaceae, Violaceae and Cucurbitaceae, with a wide variety of biological activities observed. However, potentially limiting the development of cyclotide-based therapeutics is a lack of understanding of the mechanism by which these peptides are cyclized in vivo. Until now, no linear versions of cyclotides have been reported, limiting our understanding of the cyclization mechanism. This study reports the discovery of a naturally occurring linear cyclotide, violacin A, from the plant Viola odorata and discusses the implications for in vivo cyclization of peptides. The elucidation of the cDNA clone of violacin A revealed a point mutation that introduces a stop codon, which inhibits the translation of a key Asn residue that is thought to be required for cyclization. The three-dimensional solution structure of violacin A was determined and found to adopt the cystine knot fold of native cyclotides. Enzymatic stability assays on violacin A indicate that despite an increase in the flexibility of the structure relative to cyclic counterparts, the cystine knot preserves the overall stability of the molecule. [Copyright &y& Elsevier]

Abstract: Self-assembling peptides have emerged as an attractive scaffold material for tissue engineering, yet the expense associated with solid phase chemical synthesis has limited their broad use. In addition, the fidelity of chemical synthesis constrains the length of polypeptides that can be produced homogeneously by this method. Template-derived biosynthesis by recombinant DNA technology may overcome both of these problems. However, recovery of polypeptides from recombinant protein expression systems typically involves multi-step purification schemes. In this study, we report an integrated approach to recombinantly produce and purify self-assembling peptides from the recently developed expression host Ralstonia eutropha. The purification is based on the specific affinity of carbohydrate binding modules (CBMs) to cellulose. In a first step, we identified CBMs that express well in R. eutropha by assembling a fusion library of green fluorescent protein (GFP) and CBMs and determining the fluorescence of cell-free extracts. Three GFP::CBM fusions were found to express at levels similar to GFP alone, of which two CBMs were able to mediate cellulose binding of the GFP::CBM fusion. These two CBMs were then fused to multiple repeats of the self-assembling peptide RAD16-I::E (n-RADARADARADARADAE-c). The fusion protein CBM::E::(RAD16-I::E)4 was expressed in R. eutropha and purified using the CBM’s affinity for cellulose. Subsequent proteolytic cleavage with endoproteinase GluC liberated RAD16-I::E peptide monomers with similar properties to the chemically synthesized counterpart RAD16-I. [Copyright &y& Elsevier]

Abstract: We examine hypotheses for the formation of light-toned layered deposits in Juventae Chasma using a combination of data from Mars Global Surveyor''s Mars Orbiter Camera (MOC), Mars Orbiter Laser Altimeter (MOLA), and Thermal Emission Spectrometer (TES), as well as Mars Odyssey''s Thermal Emission Imaging System (THEMIS). We divide Juventae Chasma into geomorphic units of (i) chasm wall rock, (ii) heavily cratered hummocky terrain, (iii) a mobile and largely crater-free sand sheet on the chasm floor, (iv) light-toned layered outcrop (LLO) material, and (v) chaotic terrain. Using surface temperatures derived from THEMIS infrared data and slopes from MOLA, we derive maps of thermal inertia, which are consistent with the geomorphic units that we identify. LLO thermal inertias range from ∼400 to 850 J m−2 K−1 s−1/2. Light-toned layered outcrops are distributed over a remarkably wide elevation range () from the chasm floor to the adjacent plateau surface. Geomorphic features, the absence of small craters, and high thermal inertia show that the LLOs are composed of sedimentary rock that is eroding relatively rapidly in the present epoch. We also present evidence for exhumation of LLO material from the west wall of the chasm, within chaotic and hummocky terrains, and within a small depression in the adjacent plateau. The data imply that at least some of the LLO material was deposited long before the adjacent Hesperian plateau basalts, and that Juventae Chasma underwent, and may still be undergoing, enlargement along its west wall due to wall rock collapse, chaotic terrain evolution, and exposure and removal of LLO material. The new data allow us to reassess possible origins of the LLOs. Gypsum, one of the minerals reported elsewhere as found in Juventae Chasma LLO material, forms only at low temperatures () and thus excludes a volcanic origin. Instead, the data are consistent with either multiple occurrences of lacustrine or airfall deposition over an extended period of time prior to emplacement of Hesperian lava flows on the plateau above the chasm. [Copyright &y& Elsevier]

Abstract: The issue of the variant vs. invariant in personality often arises in different forms of the “person–situation” debate, which is based on a false dichotomy between the personal and situational determination of behavior. Previously reported data are summarized that demonstrate how behavior can vary as a function of subtle situational changes while individual consistency is maintained. Further discussion considers the personal source of behavioral invariance, the situational source of behavioral variation, the person–situation interaction, the nature of behavior, and the “personality triad” of persons, situations, and behaviors, in which each element is understood and predicted in terms of the other two. An important goal for future research is further development of theories and methods for conceptualizing and measuring the functional aspects of situations and of behaviors. One reason for the persistence of the person situation debate may be that it serves as a proxy for a deeper, implicit debate over values such as equality vs. individuality, determinism vs. free will, and flexibility vs. consistency. However, these value dichotomies may be as false as the person–situation debate that they implicitly drive. [Copyright &y& Elsevier]