Potentiation of ribonuclease cytotoxicity by a poly(amidoamine) dendrimer

Variants of bovine pancreatic ribonuclease (RNase A) engineered to evade the endogenous ribonuclease inhibitor protein (RI) are toxic to human cancer cells. Increasing the basicity of these variants facilitates their entry into the cytosol and thus increases their cytotoxicity. The installation of additional positive charge also has the deleterious consequence of decreasing ribonucleolytic activity or conformational stability. Here, we report that the same benefit can be availed by co-treating cells with a cationic dendrimer. We find that adding the generation 2 poly(amidoamine) dendrimer in trans increases the cytotoxicity of RI-evasive RNase A variants without decreasing their activity or stability. The increased cytotoxicity is not due to increased RI-evasion or cellular internalization, but likely results from improved translocation into the cytosol after endocytosis. These data indicate that co-treatment with highly cationic molecules could enhance the efficacy of ribonucleases as chemotherapeutic agents.     

Dynamics of Male–Female Multimodal Signaling Behavior across the Estrous Cycle in Giant Pandas (Ailuropoda melanoleuca)

Giant panda courtship behavior includes multimodal signaling assemblages consisting of olfactory, vocal, and postural elements. While signaling is generally conspicuous, successful copulation is inconsistently achieved in captivity, even when female behavioral and physiological data indicate that ovulation is imminent. We set out to characterize these complex patterns of social behavior by observing interactions between 26 unique pairs of giant pandas housed in adjoining pens throughout the females' reproductive cycle. We categorized social behaviors from a transactional perspective and examined social exchanges via analyses of the relative frequency of social behaviors, and via the sequential relationship between male and female social behavior. From non‐estrus to peak‐estrus, we found that the relative frequency of female affiliative and sexual behavior increased and that the relative frequency of ambivalent and aggressive behavior decreased. Male behavior was fairly constant, except for sexual behavior, which increased during peak‐estrus, when it was facilitated by female sexual behavior. Sequential analysis of social interactions showed that preceding behavior had a significant influence over the other panda's response behavior primarily during peak‐estrus, suggesting that pandas are most responsive to conspecific signaling during the peri‐ovulatory period. However, behavioral momentum was a dominant feature of the intra‐individual transitions. Females maintained sexual, ambivalent, and neutral behavior during interactions significantly more than would be expected by chance, with male behavior bearing little influence once the behavior was initiated. A similar pattern was also observed in males, who maintained affiliative, interested, and neutral behaviors. Overall, our data suggest that the multimodal signals used by giant pandas during courtship do not consistently evoke a discrete, immediate response from receivers. Instead, signals appear to advertise reproductive condition and influence potential mates over longer timeframes, suggesting the potential tonic role of communication.     

The role of maternal effects on offspring performance in familiar and novel environments

Maternal effects are an important evolutionary force that may either facilitate adaptation to a new environment or buffer against unfavourable conditions. The degree of variation in traits expressed by siblings from different mothers is often sensitive to environmental conditions. This could generate a Maternal-by-Environment interaction (M × E) that inflates estimates of Genotype-by-Environment effects (G × E). We aimed to test for environment-specific maternal effects (M × E) using a paternal full-sib/half-sib breeding design in the seed beetle Callosobruchus maculatus, where we split and reared offspring from the same mother on two different bean host types—original and novel. Our quantitative genetic analysis indicated that maternal effects were very small on both host types for all the measured life-history traits. There was also little evidence that maternal oviposition preference for a particular host type predicted her offspring’s performance on that host. Further, additive genetic variance for most traits was relatively high on both hosts. While there was higher heritability for offspring reared in the novel host, there was no evidence for G × Es, and most cross-host genetic correlations were positive. This suggests that offspring from the same family ranked similarly for performance on both host types. Our results point to a genetic basis of host adaptation in the seed beetle, rather than maternal effects. Even so, we encourage researchers to test for potential M × Es because, due to a lack of testing, it remains unclear how often they arise.Subject terms: Evolutionary genetics, Quantitative trait     

The changing role of veterinary expertise in the food chain

This paper analyses how the changing governance of animal health has impacted upon veterinary expertise and its role in providing public health benefits. It argues that the social sciences can play an important role in understanding the nature of these changes, but also that their ideas and methods are, in part, responsible for them. The paper begins by examining how veterinary expertise came to be crucial to the regulation of the food chain in the twentieth century. The relationship between the veterinary profession and the state proved mutually beneficial, allowing the state to address the problems of animal health, and the veterinary profession to become identified as central to public health and food supply. However, this relationship has been gradually eroded by the application of neoliberal management techniques to the governance of animal health. This paper traces the impact of these techniques that have caused widespread unease within and beyond the veterinary profession about the consequences for its role in maintaining the public good of animal health. In conclusion, this paper suggests that the development of the social sciences in relation to animal health could contribute more helpfully to further changes in veterinary expertise.     

Benefits of a Working Memory Training Program for Inattention in Daily Life: A Systematic Review and Meta-Analysis

Background

Many common disorders across the lifespan feature impaired working memory (WM). Reported benefits of a WM training program include improving inattention in daily life, but this has not been evaluated in a meta-analysis. This study aimed to evaluate whether one WM training method has benefits for inattention in daily life by conducting a systematic review and meta-analysis.

Methods

We searched Medline and PsycINFO, relevant journals and contacted authors for studies with an intervention and control group reporting post-training estimates of inattention in daily life. To reduce the influence of different WM training methods on the findings, the review was restricted to trials evaluating the Cogmed method. A meta-analysis calculated the pooled standardised difference in means (SMD) between intervention and control groups.

Results

A total of 622 studies were identified and 12 studies with 13 group comparisons met inclusion criteria. The meta-analysis showed a significant training effect on inattention in daily life, SMD=-0.47, 95% CI -0.65, -0.29, p<.00001. Subgroup analyses showed this significant effect was observed in groups of children and adults as well as users with and without ADHD, and in studies using control groups that were active and non-adaptive, wait-list and passive as well as studies using specific or general measures. Seven of the studies reported follow-up assessment and a meta-analysis showed persisting training benefits for inattention in daily life, SMD=-0.33, 95% CI -0.57 -0.09, p=.006. Additional meta-analyses confirmed improvements after training on visuospatial WM, SMD=0.66, 95% CI 0.43, 0.89, p<.00001, and verbal WM tasks, SMD=0.40, 95% CI 0.18, 0.62, p=.0004.

Conclusions

Benefits of a WM training program generalise to improvements in everyday functioning. Initial evidence shows that the Cogmed method has significant benefits for inattention in daily life with a clinically relevant effect size.     

Pleiotropic quantitative trait loci contribute to population divergence in traits associated with life-history variation in Mimulus guttatus

Evolutionary biologists seek to understand the genetic basis for multivariate phenotypic divergence. We constructed an F2 mapping population (N = 539) between two distinct populations of Mimulus guttatus. We measured 20 floral, vegetative, and life-history characters on parents and F1 and F2 hybrids in a common garden experiment. We employed multitrait composite interval mapping to determine the number, effect, and degree of pleiotropy in quantitative trait loci (QTL) affecting divergence in floral, vegetative, and life-history characters. We detected 16 QTL affecting floral traits; 7 affecting vegetative traits; and 5 affecting selected floral, vegetative, and life-history traits. Floral and vegetative traits are clearly polygenic. We detected a few major QTL, with all remaining QTL of small effect. Most detected QTL are pleiotropic, implying that the evolutionary shift between these annual and perennial populations is constrained. We also compared the genetic architecture controlling floral trait divergence both within (our intraspecific study) and between species, on the basis of a previously published analysis of M. guttatus and M. nasutus. Eleven of our 16 floral QTL map to approximately the same location in the interspecific map based on shared, collinear markers, implying that there may be a shared genetic basis for floral divergence within and among species of Mimulus.     

Plant Recruitment and Soil Microbial Characteristics of Rehabilitation Seedings Following Wildfire in Northern Utah

One goal of post‐fire native species seeding is to increase plant community resistance to exotic weed invasions, yet few studies address the impacts of seeding on exotic annual establishment and persistence. In 2010 and 2011, we investigated the influence of seedings on exotic annuals and the underlying microbial communities. The wildfire site in northern Utah was formerly dominated by Artemisia tridentata ssp. wyomingensis, but burned in September 2008. Experimental seeding treatments were installed in November 2008 to examine strategies for establishing native species using two drills, hand broadcasts and different timing of seed applications (resulting in 13 seeding treatments). We collected aboveground biomass of invasive annuals (Halogeton glomeratus, Salsola kali, and Bromus tectorum), other volunteer plants from the extant seed bank, and seeded species from all treatments in the second and third years after fire. We sampled soils within microsites beneath native perennial bunchgrass and exotic annuals to characterize underlying soil microbial communities. High precipitation following seeding led to strong seedling establishment and we found few differences between seeding treatments established with either drill. All seeded treatments reduced exotic biomass by at least 90% relative to unseeded controls. Soil microbial communities (phospholipid fatty acid analysis), beneath B. tectorum, Poa secunda, and Pseudoroegneria spicata microsites differed little 3 years after fire. However, microbial abundance beneath P. spicata increased from June to July, suggesting that microbial communities beneath successful seedings can vary greatly within a single growing season.     

An isotopic perspective on the transport of Byzantine mining camp laborers into southwestern Jordan

The Byzantine Empire managed a complex administrative network that controlled the mining and processing of natural resources from within its boundaries. Scholars relying upon archeological and textual evidence debate the level of imperial involvement in these ventures, particularly in the provinces. Ancient sources note that many mining camps, for instance, purportedly contained criminal laborers and elite administrators transported from distant locales, indicating significant organization and expenditures by the imperial administration to run the mines. This analysis explores the presence of these nonlocal individuals in a cemetery associated with the third to seventh century A.D. mining camp of Phaeno (Faynan), located in modern Jordan. Strontium isotope analysis of 31 burials indicates that most spent their childhood in a similar geological region as Phaeno, implying that they were locally born. The δ¹⁸O results mirror the homogeneous ⁸⁷Sr/⁸⁶Sr values, confirming a local origin for most of the sample. Isotopic evidence therefore suggests that the Phaeno mining camp was largely a local operation, contrary to the picture presented in textual sources, although the profits surely padded imperial coffers. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.