xnd-1 regulates the global recombination landscape in Caenorhabditis elegans

Meiotic crossover (CO) recombination establishes physical linkages between homologous chromosomes that are required for their proper segregation into developing gametes, and promotes genetic diversity by shuffling genetic material between parental chromosomes. COs require the formation of double strand breaks (DSBs) to create the substrate for strand exchange. DSBs occur in small intervals called hotspots and significant variation in hotspot usage exists between and among individuals. This variation is thought to reflect differences in sequence identity and chromatin structure, DNA topology and/ or chromosome domain organization. Chromosomes show different frequencies of nondisjunction (NDJ), reflecting inherent differences in meiotic crossover control, yet the underlying basis of these differences remains elusive. Here we show that a novel chromatin factor, X non-disjunction factor 1 (xnd-1), is responsible for the global distribution of COs in C. elegans. xnd-1 is also required for formation of double-strand breaks (DSBs) on the X, but surprisingly XND-1 protein is autosomally enriched. We show that xnd-1 functions independently of genes required for X chromosome-specific gene silencing, revealing a novel pathway that distinguishes the X from autosomes in the germ line, and further show that xnd-1 exerts its effects on COs, at least in part, by modulating levels of H2A lysine 5 acetylation.     

Prediction of central nervous system embryonal tumour outcome based on gene expression.

Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.     

Seven components of judgmental forecasting skill: Implications for research and the improvement of forecasts

A decomposition of the Brier skill score shows that the performance of judgmental forecasts depends on seven components: environmental predictability, fidelity of the information system, match between environment and forecaster, reliability of information acquisition, reliability of information processing, conditional bias, and unconditional bias. These components provide a framework for research on the forecasting process. Selected literature addressing each component is reviewed, and implications for improving judgmental forecasting are discussed.     

Feeding behavior and performance of a rabbitbrush leaf-beetle ( Trirhabda lewisii ) feeding on Chrysothamnus nauseosus regrwoth after fire

Fire often positively affects the growth and nutrient content of plants regrowing after a burn. These changes have been associated with preferential feeding by herbivores in burned areas. In this study in southeastern Wyoming, Chrysothamnus nauseosus Pursh (rubber rabbitbrush) regrowing after a fire produced new shoots with a distinct growth form. Shoots were longer than those on unburned control sites and had longer leaves with longer internodes between leaves. We conducted feeding trials to detect whether C. nauseosus shoots regrowing after fire were nutritionally superior to shoots from unburned plants for the specialist leaf beetle, Trirhabda lewisii Crotch (Coleoptera: Chrysomelidae). We also measured C:N ratios and nitrogen and water contents of leaves from burned and unburned plants. Trirhabda lewisii adults preferred shoots from burned plants when given a choice. The beetles ate similar amounts of burned and unburned plants when fed only a single type. Females that were fed either burned or unburned plants did not differ in number of eggs laid. Chemical analyses revealed no significant differences in nitrogen or water content of leaves from burned versus unburned plants. Carbon-to-nitrogen ratio of burned plants was marginally lower compared with unburned plants. In contrast to previous studies, which suggest that herbivore attraction to burned areas leads to enhanced performance, our study shows that performance is not necessarily enhanced after fire.     

Evaluating plant invasions from both habitat and species perspectives

We present an approach to quantitatively assess nonnative plant invasions at landscape scales from both habitat and species perspectives. Our case study included 34 nonnative species found in 142 plots (0.1 ha) in 14 vegetation types within the Grand Staircase-Escalante National Monument, Utah. A plot invasion index, based on nonnative species richness and cover, showed that only 16 of 142 plots were heavily invaded. A species invasive index, based on frequency, cover, and number of vegetation types invaded, showed that only 7 of 34 plant species were highly invasive. Multiple regressions using habitat characteristics (moisture index, elevation, soil P, native species richness, maximum crust development class, bare ground, and rock) explained 60% of variation in nonnative species richness and 46% of variation in nonnative species cover. Three mesic habitats (aspen, wet meadow, and perennial riparian types) were particularly invaded (31 of 34 nonnative species studied were found in these types). Species-specific logistic regression models for the 7 most invasive species correctly predicted occurrence 89% of the time on average (from 80% for Bromus tectorum , a habitat generalist, to 93% for Tamarix spp., a habitat specialist). Even with such a modest sampling intensity (<0.1% of the landscape), this multiscale sampling scheme was effective at evaluating habitat vulnerability to invasion and the occurrence of the 7 most invasive nonnative species. This approach could be applied in other natural areas to develop strategies to document invasive species and invaded habitats.     

Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17

Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival.