Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and receptors in type 1, type 2 and type 17 inflammation in cross-sectional asthma study.

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) reportedly promotes, or conversely, resolves inflammation in asthma. In this study of TRAIL and cell receptors in sputum, bronchoalveolar lavage and biopsy from subjects in the Severe Asthma Research Program at Wake Forest, the high TRAIL group had significant increases in all leucocytes, and was associated with increased type 1, type 2 and type 17 cytokines, but not type 9 interleukin 9. Two variants at loci in the TRAIL gene were associated with higher sputum levels of TRAIL. Increased TRAIL decoy receptor R3/DcR1 was observed on sputum leucocytes compared with death receptor R1/DR4, suggesting reduced apoptosis and prolonged cellular inflammation.

Population growth rate of dry bulb mite, Aceria tulipae (Acariformes: Eriophyidae), on agriculturally important plants and implications for its taxonomic status.

Dry bulb mite (DBM), Aceria tulipae, is an economically important mite with a worldwide distribution and a broad host range. As a generalist, it is the most important eriophyoid mite attacking bulbous plants such as garlic, onion and tulip. To date, DBM has been recorded on host plants belonging to the families Liliaceae, Amaryllidaceae, Melanthiaceae and Asparagaceae. However, a precise understanding of DBM host range is lacking as it is largely based on casual records of mites on plants, some of which may include accidental hosts. Moreover, the possible existence of cryptic species has not been considered. In this study the hypothesis that DBM may be a complex of distinct genetic lineages or cryptic species was tested by comparing the common barcode sequence marker mtDNA COI of specimens from several populations originating from the Netherlands and Poland. The population growth rate of DBM on seven agriculturally important plant species and on various parts of the garlic plant was also experimentally assessed in the laboratory. The results did not support the first hypothesis, and indicated that DBM populations originating from Poland and the Netherlands shared essentially the same genome. In addition, they indicated that DBM reached the highest population growth rate on leek and also displayed high growth rates on garlic, chive and red onion, whereas white onion and wheat were not colonized by the mites. Answering the question of whether DBM is a single polyphagous species rather than a complex of cryptic lineages is of particular importance since the misidentification of pests may lead to ineffective control strategies. Moreover, improved knowledge of DBM host range is essential for assessing risk to crops.

Small molecule induction of MSH2-dependent cell death suggests a vital role of mismatch repair proteins in cell death.

Avoidance of apoptosis is one of the hallmarks of cancer development and progression. Chemotherapeutic agents aim to initiate an apoptotic response, but often fail due to dysregulation. MSH proteins are capable of recognizing cisplatin damage in DNA and participate in the initiation of cell death. We have exploited this recognition and computationally simulated a MutS homolog (MSH) "death conformation". Screening and docking experiments based on this model determined that the MSH2-dependent cell-death pathway can be induced by a small molecule without DNA damage, reserpine. Reserpine was identified via virtual screening on structures obtained from molecular dynamics as a small molecule that selectively binds a protein "death" conformation. The virtual screening predicts that this small molecule binds in the absence of DNA. Cell biology confirmed that reserpine triggers the MSH2-dependent cell-death pathway. This result supports the hypothesis that the MSH2-dependent pathway is initiated by specific protein conformational changes triggered by binding to either DNA damage or small compound molecules. These findings have multiple implications for drug discovery and cell biology. Computational modeling may be used to identify and eventually design small molecules that selectively activate particular pathways through conformational control. Molecular dynamics simulations can be used to model the biologically relevant conformations and virtual screening can then be used to select for small molecules that bind specific conformations. The ability of a small molecule to induce the cell-death pathway suggests a broader role for MMR proteins in cellular events, such as cell-death pathways, than previously suspected.

Divergent host acceptance behavior suggests host specialization in populations of the polyphagous mite Abacarus hystrix (Acari: Prostigmata: Eriophyidae).

For phytophagous arthropods, host acceptance behavior is a key character responsible for host plant specialization. The grain rust mite, Abacarus hystrix (Nalepa), is an obligately phytophagous, polyphagous eriophyid mite recorded from at least 70 grass species. In this study, the hypothesis that two host populations of this mite (one collected from quackgrass and the other from ryegrass) are highly host-specific was tested using behavioral data. For this purpose, female behavior when exposed to familiar and novel host plants was observed in no-choice cross experiments. Altogether, 13 variables were used to describe mite behavior. Data were subjected to principal component analysis, and host acceptance behavior was subsequently tested with generalized estimating equations (GEE). Distinct variation in female behavior between familiar and novel hosts was observed. Females from neither population accepted novel hosts. This was recorded as significant differences in the occupation of and overall activity on particular plant parts. On their familiar host, females were not active and showed little tendency to move. On novel hosts females were more active and mobile, spending more time walking, running, and climbing on the whole plant surface and showing a tendency to disperse. Other differences in behavior between studied populations were also observed. Thus, the results suggest that mites of these two studied populations (1) differ in their behaviors during plant exploitation and (2) can quickly distinguish between their familiar host and an unfamiliar host used by a conspecific. These findings support the hypothesis of narrow host specialization of ryegrass and quackgrass populations of this highly polyphagous species.