Assessment of chemical-crosslink-assisted protein structure modeling in CASP13

With the advance of experimental procedures obtaining chemical crosslinking information is becoming a fast and routine practice. Information on crosslinks can greatly enhance the accuracy of protein structure modeling. Here, we review the current state of the art in modeling protein structures with the assistance of experimentally determined chemical crosslinks within the framework of the 13th meeting of Critical Assessment of Structure Prediction approaches. This largest-to-date blind assessment reveals benefits of using data assistance in difficult to model protein structure prediction cases. However, in a broader context, it also suggests that with the unprecedented advance in accuracy to predict contacts in recent years, experimental crosslinks will be useful only if their specificity and accuracy further improved and they are better integrated into computational workflows.     

Intraspecific evolution of Canary Island Plecotine bats,based on mtDNA sequences

Island differentiation and relationships with congenerics were investigated in the endemic Canary Island bat Plecotus teneriffae, based on approximately 1 kb of mtDNA from the 16S rRNA and cytochrome b genes. P. teneriffae had closer affinities with P. austriacus than with P. auritus. Levels of differentiation between Canary Islands were quite high relative to Pipistrelle-like bats, consistent with philopatric behaviour in the Plecotus genus. Cladogenesis within P. teneriffae appears to have occurred after the emergence of the islands of El Hierro and La Palma during the Pleistocene. An intraspecific network shows that haplotypes from the younger islands of La Palma and El Hierro are connected to the Tenerife haplotype by a similarly large number of mutational steps. This suggests that they were both colonised at a similar time from the much older island of Tenerife. The other Plecotine bat species, Barbastellus barbastellus shows close affinities with B. barbastellus from mainland Spain, with levels of mtDNA divergence being comparable with intraspecific variation within other mammal species.     

Gonadotropins at menopause: the influence of obesity, insulin resistance, and estrogens

Obese, postmenopausal women have lower FSH levels. To determine whether this is due to higher estrogen exposure, we compared feedback gonadotropin sensitivity and its relation to insulin resistance in four groups of obese and lean, postmenopausal women. Group one was treated with 400 mg troglitazone (TG) daily for two weeks; 150 clomiphene citrate (CC) was added daily for the second week. Group two received 150 mg CC daily for a week. Group three received 1000 mg metformin (MET) daily for two weeks, with 120 mg raloxifene (RAL) added during the second week. Group four received 120 mg RAL for a week. Before and after each period, a serum pool was obtained from samples taken every minute during a 10 ml interval. The women recruited for this study were categorized as obese or lean based on BMI >/= 29 or BMI < 29, respectively. Obese, menopausal women had lower FSH (45.5 IU/l) and LH (16.2 IU/l) values than those of lean (64.1 IU/l and 23.0 IU/l), but the obese menopausal women had higher leptin, DHEAS, glucose, insulin, and HOMA-IR levels. Log [FSH] was associated with BMI (r = -0.53, P < 0.000001) and number of pregnancies (r = -0.37, P = 0.0009). TG treatment did not change HOMA-IR or gonadotropin levels, but DHEAS and androstenedione levels decreased significantly. CC alone or together with TG, diminished FSH (-7.9 and -9.2) and LH (-2.5 and -3.6) concentrations, with a greater reduction in lean women. MET reduced glucose and the HOMA-IR index without affecting gonadotropin or steroid levels. Conclusions: obese, menopausal women have lower FSH levels due to greater estrogen exposure, by mechanisms unrelated to insulin resistance.     

Serum-Induced Differentiation of Glioblastoma Neurospheres Leads to Enhanced Migration/Invasion Capacity That Is Associated with Increased MMP9

Glioblastoma (GBM) is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs), have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM.     

Biology of the solitary wasp Trypoxylon (Trypargilum) agamemnon Richards 1934 (Hymenoptera: Crabronidae) in trap‐nests

Buschini, M.L.T. and Fajardo, S. 2009. Biology of the solitary wasp Trypoxylon (Trypargilum) agamemnon Richards 1934 (Hymenoptera: Crabronidae) in trap‐nests. —Acta Zoologica (Stockholm) 91 : 426–432. Some Trypoxylon species build their nests in preexisting tubular cavities like hollow stems and beetle borings in branches. Study of the biology of these insects is relatively easy because the females of these wasps nest with enormous success in trap‐nests. The aim of this study was to investigate the abundance, seasonality and life‐history of Trypoxylon agamemnon. For capture of these insects, trap‐nests were installed in the Parque Municipal das Araucárias in araucaria forest, grassland and swamp, from December, 2001 to December, 2005. Two hundred and ninety seven nests were obtained. They were constructed more often during the summer (from December to April). The nests were built only in araucaria forest and consisted of a linear series of cells, divided by mud partitions, whose number varied from 1 to 7. Normally they have only one vestibular cell. The inner cells had been provisioned, usually with spiders of Anyphaenidae family. Sex‐ratio was strongly female biased. Its main natural enemies included Chrysididae, Ichneumonidae and Tachinidae.     

Merged trees in second-growth, fire-origin forests in Patagonia, Chile: positive spatial association patterns and their ecological implications

?Premise of the Study: Negative density-dependent processes have been thought to be the primary cause of shifting spatial patterns of tree populations through time. The existence of adult tree clusters might challenge this classical prediction. Here, we document the prevalence of merged stems (clustering of mature trees leading to stem fusion) in second-growth forests of Nothofagus pumilio and hypothesize that it is nonrandom but predictable in space. ?Methods: We stem-mapped nine sites in second-growth edge and interior forests of fire origin and in mature forests of N. pumilio (>3500 trees) in central Patagonia, Chile. The spatial structure of stand-level and individual-level features was estimated with spatial analyses (pair-correlation function and nearest-neighbor distances). ?Key Results: Multistemmed trees were merged clusters of separate individuals. Merged trees were predominantly found at the edge of the second-growth forests. We found strong clustering (≤5 m) at forest edge sites and none at interior sites. Nearest-neighbor distance distributions were unimodal for unmerged trees and monotonically decreasing for merged trees; interstem distances were much smaller at the edge sites than at the interior sites. ?Conclusions: The occurrence of merged trees at the forest edge, and the resulting high spatial aggregation of stems, is consistent with the hypothesis that establishment was probably aggregated. The spatial pattern found at the forest edge changes the standard spatial pattern sequence through time in temperate forests, altering traditional forest-stand-dynamics models.