The molecular basis of high-altitude adaptation in deer mice

Elucidating genetic mechanisms of adaptation is a goal of central importance in evolutionary biology, yet few empirical studies have succeeded in documenting causal links between molecular variation and organismal fitness in natural populations. Here we report a population genetic analysis of a two-locus α-globin polymorphism that underlies physiological adaptation to high-altitude hypoxia in natural populations of deer mice, Peromyscus maniculatus. This system provides a rare opportunity to examine the molecular underpinnings of fitness-related variation in protein function that can be related to a well-defined selection pressure. We surveyed DNA sequence variation in the duplicated α-globin genes of P. maniculatus from high- and low-altitude localities (i) to identify the specific mutations that may be responsible for the divergent fine-tuning of hemoglobin function and (ii) to test whether the genes exhibit the expected signature of diversifying selection between populations that inhabit different elevational zones. Results demonstrate that functionally distinct protein alleles are maintained as a long-term balanced polymorphism and that adaptive modifications of hemoglobin function are produced by the independent or joint effects of five amino acid mutations that modulate oxygen-binding affinity.     

Toll-like receptor 9 agonists promote cellular invasion by increasing matrix metalloproteinase activity

Toll-like receptor 9 (TLR9) recognizes microbial DNA. We show here that TLR9 protein is expressed in human breast cancer cells and clinical breast cancer samples. Stimulation of TLR9-expressing breast cancer cells with the TLR9 agonistic CpG oligonucleotides (1-10 mumol/L) dramatically increased their in vitro invasion in both Matrigel assays and three-dimensional collagen cultures. Similar effects on invasion were seen in TLR9-expressing astrocytoma and glioblastoma cells and in the immortalized human breast epithelial cell line MCF-10A. This effect was not, however, dependent on the CpG content of the TLR9 ligands because the non-CpG oligonucleotides induced invasion of TLR9-expressing cells. CpG or non-CpG oligonucleotide-induced invasion in MDA-MB-231 cells was blunted by chloroquine and they did not induce invasion of TLR9(-) breast cancer cells. Treatment of MDA-MB-231 cells with CpG or non-CpG oligonucleotides induced the formation of approximately 50-kDa gelatinolytic band in zymograms. This band and the increased invasion were abolished by a matrix metalloproteinase (MMP) inhibitor GM6001 but not by a serine proteinase inhibitor aprotinin. Furthermore, CpG oligonucleotide treatment decreased tissue inhibitor of metalloproteinase-3 expression and increased levels of active MMP-13 in TLR9-expressing but not TLR9(-) breast cancer cells without affecting MMP-8. Neutralizing anti-MMP-13 antibodies inhibited the CpG oligonucleotide-induced invasion. These findings suggest that infections may promote cancer progression through a novel TLR9-mediated mechanism. They also propose a new molecular target for cancer therapy, because TLR9 has not been associated with cancer invasiveness previously.     

Evidence that Soil Carbon Pool Determines Susceptibility of Semi-Natural Ecosystems to Elevated Nitrogen Leaching

Deposition of reactive nitrogen (N) compounds has the potential to cause severe damage to sensitive soils and waters, but the process of ‘nitrogen saturation’ is difficult to demonstrate or predict. This study compares outputs from a simple carbon–nitrogen model with observations of (1) regional- and catchment-scale relationships between surface water nitrate and dissolved organic carbon (DOC), as an indicator of catchment carbon (C) pool; (2) inter-regional variations in soil C/N ratios; and (3) plot scale soil and leachate response to long-term N additions, for a range of UK moorlands. Results suggest that the simple model applied can effectively reproduce observed patterns, and that organic soil C stores provide a critical control on catchment susceptibility to enhanced N leaching, leading to high spatial variability in the extent and severity of current damage within regions of relatively uniform deposition. Results also support the hypothesis that the N richness of organic soils, expressed as C/N ratio, provides an effective indicator of soil susceptibility to enhanced N leaching. The extent to which current C/N is influenced by N deposition, as opposed to factors such as climate and vegetation type, cannot be unequivocally determined on the basis of spatial data. However, N addition experiments at moorland sites have shown a reduction in organic soil C/N. A full understanding of the mechanisms of N-enrichment of soils and waters is essential to the assessment of current sensitivity to, and prediction of future damage from, globally increasing reactive nitrogen deposition.     

Shifting Baselines on a Tropical Forest Frontier: Extirpations Drive Declines in Local Ecological Knowledge

The value of local ecological knowledge (LEK) to conservation is increasingly recognised, but LEK is being rapidly lost as indigenous livelihoods change. Biodiversity loss is also a driver of the loss of LEK, but quantitative study is lacking. In our study landscape in SW China, a large proportion of species have been extirpated. Hence, we were interested to understand whether species extirpation might have led to an erosion of LEK and the implications this might have for conservation. So we investigated peoples'' ability to name a selection of birds and mammals in their local language from pictures. Age was correlated to frequency of forest visits as a teenager and is likely to be closely correlated to other known drivers of the loss of LEK, such as declining forest dependence. We found men were better at identifying birds overall and that older people were better able to identify birds to the species as compared to group levels (approximately equivalent to genus). The effect of age was also stronger among women. However, after controlling for these factors, species abundance was by far the most important parameter in determining peoples'' ability to name birds. People were unable to name any locally extirpated birds at the species level. However, contrary to expectations, people were better able to identify extirpated mammals at the species level than extant ones. However, extirpated mammals tend to be more charismatic species and several respondents indicated they were only familiar with them through TV documentaries. Younger people today cannot experience the sights and sounds of forest animals that their parents grew up with and, consequently, knowledge of these species is passing from cultural memory. We suggest that engaging older members of the community and linking the preservation of LEK to biodiversity conservation may help generate support for conservation.     

A critical evaluation of host ranges of parasitoids of the subtribe Diabroticina (Coleoptera: Chrysomelidae: Galerucinae: Luperini) using field and laboratory host records

The subtribe Diabroticina is a large group of New World Chrysomelidae that includes corn rootworms, cucumber beetles and other pests. Recent introductions of Diabrotica virgifera virgifera LeConte into Europe, and the development of resistances to current management practices of rootworms in the USA have increased interest in new sustainable options for managing those pests. The only parasitoids that have been shown to consistently target and develop inside the beetle adults are Centistes gasseni Shaw, Centistes diabroticae Gahan (both Hym.: Braconidae), and Celatoria diabroticae Shimer, Celatoria compressa (Wulp), Celatoria bosqi Blanchard, and Celatoria setosa Coquillett (all Diptera: Tachinidae). This review improves our understanding of the realised and potential host range of these known parasitoids by rectifying erroneous references in light of new host records and from laboratory host range tests. Based on this critical review, all tachinid and braconid species studied are considered to be specific at least to the level of subtribe, i.e. Diabroticina. Celatoria setosa, Celatoria diabroticae and C. bosqi, have a narrow realized and potential host range; the former is restricted to the genus Acalymma and the last two to the fucata and virgifera groups of the genus Diabrotica. The braconids Centistes gasseni and C. diabroticae are also specific. The realized host range of C. gasseni includes species in the Diabrotica fucata and virgifera groups; while its potential host range also includes Acalymma species. The realized and potential host range of Centistes diabroticae includes Acalymma species as well as species in the fucata and virgifera groups of Diabrotica. Celatoria compressa has the broadest realised range compared to the other species studied, since it was obtained from species in several genera of Diabroticina; and its potential host range may also include Old World Aulacophora species.