Does governance play a role in the distribution of invasive alien species?

Invasive alien species (IAS) constitute a major threat to global biological diversity. In order to control their spread, a detailed understanding of the factors influencing their distribution is essential. Although international trade is regarded as a major force structuring spatial patterns of IAS, the role of other social factors remains unclear. Despite studies highlighting the importance of strong governance in slowing drivers of biodiversity loss such as logging, deforestation, and agricultural intensification, no study has yet analyzed its contribution to the issue of IAS. Using estimates of governance quality and comprehensive spatiotemporal IAS data, we performed multiple linear regressions to investigate the effect of governance quality upon the distribution of species listed under “100 of the worst” IAS in 38 Eurasian countries as defined by DASIE. Our model suggested that for countries with higher GDP, stronger governance was associated with a greater number of the worst IAS; in contrast, for the lowest GDP countries under analysis, stronger governance was associated with fewer of these IAS. We elucidate how the quality of governance within a country has implications for trade, tourism, transport, legislation, and economic development, all of which influence the spread of IAS. While our findings support the common assumption that strengthening governance benefits conservation interventions in countries of smaller economy, we find that this effect is not universal. Stronger governance alone cannot adequately address the problem of IAS, and targeted action is required in relatively high‐GDP countries in order to stem the influx of IAS associated with high volumes of trade.     

Embryonic expression of an Nkx2‐5/Cre gene using ROSA26 reporter mice

Summary: Nkx2‐5, one of the earliest cardiac‐specific markers in vertebrate embryos, was used as a genetic locus to knock in the Cre recombinase gene by homologous recombination. Offspring resulting from heterozygous Nkx2‐5/Cre mice mated to ROSA26 (R26R) reporter mice provided a model system for following Nkx2‐5 gene activity by β‐galactosidase (β‐gal) activity. β‐gal activity was initially observed in the early cardiac crescent, cardiomyocytes of the looping heart tube, and in the epithelium of the first pharyngeal arch. In later stage embryos (10.5–13.5 days postcoitum, dpc), β‐gal activity was observed in the stomach and spleen, the dorsum of the tongue, and in the condensing primordium of the tooth. The Nkx2‐5/Cre mouse model should provide a useful genetic resource to elucidate the role of loxP manipulated genetic targets in cardiogenesis and other developmental processes. genesis 31:176–180, 2001. © 2001 Wiley‐Liss, Inc.     

PERIOD–TIMELESS Interval Timer May Require an Additional Feedback Loop

In this study we present a detailed, mechanism-based mathematical framework of Drosophila circadian rhythms. This framework facilitates a more systematic approach to understanding circadian rhythms using a comprehensive representation of the network underlying this phenomenon. The possible mechanisms underlying the cytoplasmic “interval timer” created by PERIOD–TIMELESS association are investigated, suggesting a novel positive feedback regulatory structure. Incorporation of this additional feedback into a full circadian model produced results that are consistent with previous experimental observations of wild-type protein profiles and numerous mutant phenotypes.     

Comparison and evaluation of biomechanical,electrical, and biological methods for assessment of damage to tissue collagen

In regard to evaluating tissue banking methods used to preserve or otherwise treat (process) soft allograft tissue, current tests may not be sufficiently sensitive to detect potential damage inflicted before, during, and after processing. Using controlled parameters, we aim to examine the sensitivity of specific biomechanical, electrical, and biological tests in detecting mild damage to collagen. Fresh porcine pulmonary heart valves were treated with an enzyme, collagenase, and incubated using various times. Controls received no incubation. All valves were cryopreserved and stored at ?135 °C until being rewarmed for evaluation using biomechanical, permeability, and cell viability tests. Statistically significant time dependent changes in leaflet ultimate stress, (p = 0.006), permeability (p = 0.01), and viability (p ≤ 0.02, four different days of culture) were found between heart valves subjected to 0–15 min of collagenase treatment (ANOVA). However, no statistical significance was found between the tensile modulus of treated and untreated valves (p = 0.07). Furthermore, the trends of decreasing and increasing ultimate stress and viability, respectively, were somewhat inconsistent across treatment times. These results suggest that permeability tests may offer a sensitive, quantitative assay to complement traditional biomechanical and viability tests in evaluating processing methods used for soft tissue allografts, or when making changes to current validated methods. Multiple test evaluation may also offer insight into the mechanism of potential tissue damage such as, as is the case here, reduced collagen content and increased tissue porosity.     

Binding of TPX2 to Aurora A alters substrate and inhibitor interactions

The Aurora kinases are a family of serine/threonine kinases involved in mitosis. The expression of AurA is ubiquitous and cell cycle regulated. It is overexpressed in many tumor types, including breast, colon, and ovarian. TPX2 is a binding partner and activator of AurA. A fragment of TPX2 (residues 1-43) has been shown to be sufficient for binding, kinase activation, and protection from dephosphorylation. We have shown that the addition of TPX2(1-43) increases the catalytic efficiency of AurA. While TPX2 binding has no effect on the turnover number of AurA and does not change the reaction mechanism (characterized here to be a rapid equilibrium random mechanism), it increases the binding affinity of both ATP and a peptide substrate. We have also demonstrated differences in the inhibitor structure-activity relationship (SAR) in the presence or absence of TPX2(1-43). To better understand the differential SAR, we carried out computer modeling studies to gain insight into the effect of TPX2 on the binding interactions between AurA and inhibitors. Our working hypothesis is that TPX2 binding decreases the size and accessibility of a hydrophobic pocket, adjacent to the ATP site, to inhibitors.     

Expression of pokeweed antiviral protein in mammalian cells activates c-Jun NH2-terminal kinase without causing apoptosis

Pokeweed antiviral protein (PAP) is a ribosome inactivating protein isolated from the pokeweed plant (Phytolacca americana L.) that exhibits broad range antiviral activity against several human viruses including HIV and influenza. This characteristic suggests that PAP may have therapeutic applications; however, it is not known whether the protein elicits a ribotoxic stress response that would result in cell death. Therefore, we expressed PAP in 293T cells and showed that the enzyme did not inhibit protein translation even though approximately 15% of the ribosomal RNA (rRNA) was depurinated. PAP expression induced the activation of c-Jun NH2-terminal kinase (JNK), which was specific to rRNA depurination, as the enzymatically inactive mutant PAPx did not affect kinase activity. Moreover, incubation of PAP-expressing cells with translation inhibitors diminished JNK activation, indicating that the signal for induction of the kinase pathway originated from ribosomes. JNK activation did not result in apoptosis as demonstrated by the absence of caspase-3 and poly(ADP-ribose) polymerase cleavage and by the lack of cell staining for morphological changes in membrane permeability. Unlike all ribosome inactivating proteins tested thus far, the stress response triggered by PAP expression did not result in cell death, which supports further investigation of the enzyme in the design of novel antiviral agents.     

Genetic variation in an individual human exome

There is much interest in characterizing the variation in a human individual, because this may elucidate what contributes significantly to a person's phenotype, thereby enabling personalized genomics. We focus here on the variants in a person's 'exome,' which is the set of exons in a genome, because the exome is believed to harbor much of the functional variation. We provide an analysis of the approximately 12,500 variants that affect the protein coding portion of an individual's genome. We identified approximately 10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs) in this individual, of which approximately 15-20% are rare in the human population. We predict approximately 1,500 nsSNPs affect protein function and these tend be heterozygous, rare, or novel. Of the approximately 700 coding indels, approximately half tend to have lengths that are a multiple of three, which causes insertions/deletions of amino acids in the corresponding protein, rather than introducing frameshifts. Coding indels also occur frequently at the termini of genes, so even if an indel causes a frameshift, an alternative start or stop site in the gene can still be used to make a functional protein. In summary, we reduced the set of approximately 12,500 nonsilent coding variants by approximately 8-fold to a set of variants that are most likely to have major effects on their proteins' functions. This is our first glimpse of an individual's exome and a snapshot of the current state of personalized genomics. The majority of coding variants in this individual are common and appear to be functionally neutral. Our results also indicate that some variants can be used to improve the current NCBI human reference genome. As more genomes are sequenced, many rare variants and non-SNP variants will be discovered. We present an approach to analyze the coding variation in humans by proposing multiple bioinformatic methods to hone in on possible functional variation.     

Modulation of kinase-inhibitor interactions by auxiliary protein binding: crystallography studies on Aurora A interactions with VX-680 and with TPX2

VX-680, also known as MK-0457, is an ATP-competitive small molecule inhibitor of the Aurora kinases that has entered phase II clinical trials for the treatment of cancer. We have solved the cocrystal structure of AurA/TPX2/VX-680 at 2.3 A resolution. In the crystal structure, VX-680 binds to the active conformation of AurA. The glycine-rich loop in AurA adopts a unique bent conformation, forming a pi-pi interaction with the phenyl group of VX-680. In contrast, in the published AurA/VX-680 structure, VX-680 binds to AurA in the inactive conformation, interacting with a hydrophobic pocket only present in the inactive conformation. These data suggest that TPX2, a protein cofactor, can alter the binding mode of VX-680 with AurA. More generally, the presence of physiologically relevant cofactor proteins can alter the kinetics, binding interactions, and inhibition of enzymes, and studies with these multiprotein complexes may be beneficial to the discovery and optimization of enzyme inhibitors as therapeutic agents.     

Behavioral response of termites to tunnel surface irregularity

Subterranean termites construct underground tunnels, tens to hundreds of meters in length, in order to search for and transport resources. Diverse soil conditions surrounding the tunnels, such as soil pores and differing moisture concentrations, may cause different sized- and shaped-irregularities in the tunnels. To understand how individual termites respond to the irregularities, the present study monitored the movement of termites, Coptotermes formosanus Shiraki, in artificially excavated tunnels with rectangular irregularities of varying sizes in two-dimensional sand substrates. Termites tunneled at some of the irregularities and not at the others. The tunneling or non-tunneling behavior resulted from four different responses. The non-tunneling response may result from a behavioral adaptation that allows termites to avoid wasting energy that may be used in foraging.