SAP-controlled T-B cell interactions underlie germinal centre formation

Generation of long-term antibody-mediated immunity depends on the germinal centre reaction, which requires cooperation between antigen-specific T and B lymphocytes. In human X-linked lymphoproliferative disease and its gene-targeted mouse model, loss-of-function mutations in signalling lymphocyte activation molecule-associated protein (SAP, encoded by SH2D1a) cause a profound defect in germinal centre formation by an as yet unknown mechanism. Here, using two-photon intravital imaging, we show that SAP deficiency selectively impairs the ability of CD4(+) T cells to stably interact with cognate B cells but not antigen-presenting dendritic cells. This selective defect results in a failure of antigen-specific B cells to receive adequate levels of contact-dependent T-cell help to expand normally, despite Sap(-/-) T cells exhibiting the known characteristics of otherwise competent helper T cells. Furthermore, the lack of stable interactions with B cells renders Sap(-/-) T cells unable to be efficiently recruited to and retained in a nascent germinal centre to sustain the germinal centre reaction. These results offer an explanation for the germinal centre defect due to SAP deficiency and provide new insights into the bi-directional communication between cognate T and B cells in vivo.     

Chromosome instability and deregulated proliferation: an unavoidable duo

The concept that aneuploidy is a characteristic of malignant cells has long been known; however, the idea that aneuploidy is an active contributor to tumorigenesis, as opposed to being an associated phenotype, is more recent in its evolution. At the same time, we are seeing the emergence of novel roles for tumor suppressor genes and oncogenes in genome stability. These include the adenomatous polyposis coli gene (APC), p53, the retinoblastoma susceptibility gene (RB1), and Ras. Originally, many of these genes were thought to be tumor suppressive or oncogenic solely because of their role in proliferative control. Because of the frequency with which they are disrupted in cancer, chromosome instability caused by their dysfunction may be more central to tumorigenesis than previously thought. Therefore, this review will highlight how the proper function of cell cycle regulatory genes contributes to the maintenance of genome stability, and how their mutation in cancer obligatorily connects proliferation and chromosome instability.     

Astrocytes in multiple sclerosis: A product of their environment

It has long been thought that astrocytes, like other glial cells, simply provide a support mechanism for neuronal function in the healthy and inflamed central nervous system (CNS). However, recent evidence suggests that astrocytes play an active and dual role in CNS inflammatory diseases such as multiple sclerosis (MS). Astrocytes not only have the ability to enhance immune responses and inhibit myelin repair, but they can also be protective and limit CNS inflammation while supporting oligodendrocyte and axonal regeneration. The particular impact of these cells on the pathogenesis and repair of an inflammatory demyelinating process is dependent upon a number of factors, including the stage of the disease, the type and microenvironment of the lesion, and the interactions with other cell types and factors that influence their activation. In this review, we summarize recent data supporting the idea that astrocytes play a complex role in the regulation of CNS autoimmunity.     

Western diamondback rattlesnake in southern Nevada: a correction and comments

Reports of the occurrence of Crotalus atrox Baird & Girard from Nevada are reviewed. There is no evidence to support the occurrence of this species in Nevada.     

Phlox longifolia Nutt. (Polemoniaceae) complex of North America

Over 1,000 herbarium specimens including 24 type specimens were examined in an attempt to achieve a clearer understanding of the Phlox longifolia complex. Four variables were measured for each specimen and the data were statistically analyzed by discriminant analysis. Using a previously published system of classification for the complex, approximately 73 percent of the measured variation among the specimens was accounted for by that system. The clustering patterns produced in this first analysis indicated that a more conservative approach would be advisable. The formulation and subsequent application of a modified system produced a grouping of specimens that accounted for 95 percent of the measured variation for the four morphological characters considered. From four species and seven subspecies previously recognized, one species with five varieties is proposed. The typification of Phlox longifolia Nutt. and other related taxa is resolved.        

Evaluation of road track surveys for cougars ( Felis concolor )

Road track surveys were a poor index of cougar density in southern Utah. The weak relationship we found between track finding frequency and cougar density undoubtedly resulted in part from the fact that available roads do not sample properly from the nonuniformly distributed cougar population. However, the significantly positive relationship ( r 2 = .73) we found between track-finding frequency and number of cougar home ranges crossing the survey road suggested the technique may be of use in monitoring cougar populations where road abundance and location allow the population to be sampled properly. The amount of variance in track-finding frequency unexplained by number of home ranges overlapping survey roads indicates the index may be useful in demonstrating only relatively large changes in cougar population size.     

Physical characteristics of Blue Grouse winter use-trees and roost sites

Physical characteristics of winter use-trees and roost sites of Blue Grouse ( Dendragapus obscurus ) were studied in northeastern Utah. Blue Grouse selectively roosted in the largest Douglas-fir ( Pseudotsuga menziesii ) trees during the day and subalpine fir ( Abies lasiocarpa ) trees at night. Diurnal and nocturnal roosts were typically adjacent to tree trunks in the lower two-thirds of trees. Nocturnal roosts provided greater canopy and denser shelter than diurnal roosts. Roost site selection was consistent with occupation of favorable microhabitat, particularly at night, and foraging strategy during the day. Timber management strategies should perpetuate large trees within Douglas-fir-subalpine fir habitat in areas occupied by wintering Blue Grouse.     

Role for DNA methylation in the control of cell type specific maspin expression

The major histocompatibility complex (MHC) is a source of unique individual odors that influence individual recognition, mating preferences, nesting behavior and selective block of pregnancy in animals. Such phenomena have been difficult to study in humans, because the human leukocyte antigen (HLA, human MHC) loci are the most polymorphic loci in the human genome, with the potential to generate millions of unique combinations of genotypes. In addition, high variability in background odors, encoded by the rest of the genome and influenced by cultural practices, contribute to a low signal-to-noise ratio that could mask HLA-based olfactory cues. Here we show that women can detect differences of one HLA allele among male odor donors with different MHC genotypes. Notably, the mechanism for a woman's ability to discriminate and choose odors is based on HLA alleles inherited from her father but not her mother. The parents' HLA alleles that she does not inherit show no relationship with odor choice, despite exposure to these HLA-encoded odors throughout her life. Our data indicate that paternally inherited HLA-associated odors influence odor preference and may serve as social cues.