The road to Wisconsin

In this article Lynne Sears Williams of Calgary describes her family''s decision to leave for the US, where her husband, Dr. Jim Williams, will pursue his career in family medicine. The decision was not made easily, she writes, but eventually a love for Canada was outweighed by her husband''s desire to practise medicine without the financial and other constraints facing physicians in Canada.     

Stem cell tensions mount

The US has been a major battle-ground amongst legislators coming to grips with the issue of embryonic stem cell research but the issue is reaching new heights in Italy. Nigel Williams reports.     

Uncertainties cloud stem cell developments

Scientific promise in the therapeutic potential of early embryonic stem cell research to treat presently intractable diseases is still meeting ethical, regulatory and patent challenges. Nigel Williams reports on recent moves in Europe and the US.     

LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome

Williams Syndrome is a developmental disorder that is characterized by cardiovascular problems, particular facial features and several typical behavioral and neurological abnormalities. In Williams Syndrome patients, a heterozygous deletion is present of a region on chromosome 7q11.23 (the Williams Syndrome critical region), which spans approximately 20 genes. Two of these genes encode proteins that regulate dynamic aspects of the cytoskeleton of the cell, either via the actin filament system (LIM kinase 1, or LIMK1), or through the microtubule network (cytoplasmic linker protein of 115 kDa, or CLIP-115). The recent findings that knockout mice lacking LIMK1 or CLIP-115 have distinct neurological and behavioural phenotypes, indicates that cytoskeletal defects might play a role in the development of neurological symptoms in Williams Syndrome patients. In this review, we discuss the properties of LIMK and CLIP family proteins, their function in the regulation of the actin and microtubule cytoskeletal systems, respectively, and the relationship with neurodevelopmental aspects of Williams Syndrome.     

中国纹蓟马科一新记录属——扇蓟马属记述

Rhipidothrips brunneus Williams of the family Aeolothripidae (Thysanoptera: Terebrantia) is recorded from China for the first time, representing the first record of the genus Rhipidothrips Uzel and the fourth genus of this family in China. A key is provided for the four genera known in China, with comments on each genus.     

Selection of a core set of RILs from Forrest × Williams 82 to develop a framework map in soybean

Soybean BAC-based physical maps provide a useful platform for gene and QTL map-based cloning, EST mapping, marker development, genome sequencing, and comparative genomic research. Soybean physical maps for “Forrest” and “Williams 82” representing the southern and northern US soybean germplasm base, respectively, have been constructed with different fingerprinting methods. These physical maps are complementary for coverage of gaps on the 20 soybean linkage groups. More than 5,000 genetic markers have been anchored onto the Williams 82 physical map, but only a limited number of markers have been anchored to the Forrest physical map. A mapping population of Forrest × Williams 82 made up of 1,025 F₈ recombinant inbred lines (RILs) was used to construct a reference genetic map. A framework map with almost 1,000 genetic markers was constructed using a core set of these RILs. The core set of the population was evaluated with the theoretical population using equality, symmetry and representativeness tests. A high-resolution genetic map will allow integration and utilization of the physical maps to target QTL regions of interest, and to place a larger number of markers into a map in a more efficient way using a core set of RILs.     

A cluster of dispensable genes within the human cytomegalovirus genome short component: IRS1, US1 through US5, and the US6 family.

By insertional mutagenesis, human cytomegalovirus recombinants deleted of each of the US6 glycoprotein family genes were isolated. A recombinant lacking IRS1, US1 through US5, and most of the US6 family was also isolated. The growth kinetics of these mutants were similar to that of the wild type. A dispensable cluster of genes was identified.     

Like one of the family: race,ethnicity, and the paradox of US national identity

The tensions between individual rights promised to US citizens and group discrimination targeted against African Americans and similar racial/ethnic groups constitute one enduring paradox of US society. This essay examines this paradox by exploring how a gendered family rhetoric contributes to understandings of race and US national identity. Using African American women's experiences as a touchstone for analysis, the article suggests that African American women's treatment as second-class citizens reflects a belief that they are 'like one of the family', that is, legally part of the US nation-state, but simultaneously subordinated within it. To investigate these relationships, the article examines 1) how intersecting social hierarchies of race and ethnicity foster racialized understandings of US national identity; 2) how the gendered rhetoric of the American family ideal naturalizes and normalizes social hierarchies; and 3) how gendered family rhetoric fosters racialized constructions of US national identity as a large national family.     

Deletion of the Human Cytomegalovirus US17 Gene Increases the Ratio of Genomes per Infectious Unit and Alters Regulation of Immune and Endoplasmic Reticulum Stress Response Genes at Early and Late Times after Infection

Human cytomegalovirus (HCMV) employs numerous strategies to combat, subvert, or co-opt host immunity. One evolutionary strategy for this involves capture of a host gene and then its successive duplication and divergence, forming a family of genes, many of which have immunomodulatory activities. The HCMV US12 family consists of 10 tandemly arranged sequence-related genes in the unique short (US) region of the HCMV genome (US12 to US21). Each gene encodes a protein possessing seven predicted transmembrane domains, patches of sequence similarity with cellular G-protein-coupled receptors, and the Bax inhibitor 1 family of antiapoptotic proteins. We show that one member, US17, plays an important role during virion maturation. Microarray analysis of cells infected with a recombinant HCMV isolate with a US17 deletion (the ΔUS17 mutant virus) revealed blunted host innate and interferon responses at early times after infection (12 h postinfection [hpi]), a pattern opposite that previously seen in the absence of the immunomodulatory tegument protein pp65 (pUL83). Although the ΔUS17 mutant virus produced numbers of infectious particles in fibroblasts equal to the numbers produced by the parental virus, it produced >3-fold more genome-containing noninfectious viral particles and delivered increased amounts of pp65 to newly infected cells. These results suggest that US17 has evolved to control virion composition, to elicit an appropriately balanced host immune response. At later time points (96 hpi), ΔUS17 mutant-infected cells displayed aberrant expression of several host endoplasmic reticulum stress response genes and chaperones, some of which are important for the final stages of virion assembly and egress. Our results suggest that US17 modulates host pathways to enable production of virions that elicit an appropriately balanced host immune response.     

Priming of Social Distance? Failure to Replicate Effects on Social and Food Judgments

Williams and Bargh (2008) reported an experiment in which participants were simply asked to plot a single pair of points on a piece of graph paper, with the coordinates provided by the experimenter specifying a pair of points that lay at one of three different distances (close, intermediate, or far, relative to the range available on the graph paper). The participants who had graphed a more distant pair reported themselves as being significantly less close to members of their own family than did those who had plotted a more closely-situated pair. In another experiment, people's estimates of the caloric content of different foods were reportedly altered by the same type of spatial distance priming. Direct replications of both results were attempted, with precautions to ensure that the experimenter did not know what condition the participant was assigned to. The results showed no hint of the priming effects reported by Williams and Bargh (2008).     

Two Novel Human Cytomegalovirus NK Cell Evasion Functions Target MICA for Lysosomal Degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family.     

Replacement mutagenesis of the human cytomegalovirus genome: US10 and US11 gene products are nonessential.

The US6 gene family, located within the unique short region (US) of the human cytomegalovirus (HCMV) genome, contains six open reading frames (US6 through US11) which may encode glycoproteins, such as gcII (D. Gretch, B. Kari, R. Gehrz, and M. Stinski, J. Virol. 62:1956-1962, 1988). By homologous recombination, several different recombinant HCMV were created which contain a marker gene, beta-glucuronidase, inserted within this gene family. It was demonstrated that beta-glucuronidase has utility as a marker gene for the identification of recombinants in this herpesvirus system, without the occurrence of deletions in other regions of the viral genome. DNA and RNA blot analyses attested to the fidelity of the recombination. Immunoprecipitation experiments using monospecific polyclonal antisera indicated that the US10 and/or US11 gene products were not expressed in the recombinants, as predicted. These results, along with single-cycle growth analyses, indicated that the US10 and US11 gene products are nonessential for virus replication and growth in tissue culture. HCMV recombinants expressing beta-glucuronidase seemed to be genetically stable.     

The US16 gene of human cytomegalovirus is required for efficient viral infection of endothelial and epithelial cells

The human cytomegalovirus (HCMV) US12 gene family comprises a set of 10 contiguous genes (US12 to US21), each encoding a predicted seven-transmembrane protein and whose specific functions have yet to be ascertained. While inactivation of individual US12 family members in laboratory strains of HCMV has not been found to affect viral replication in fibroblasts, inactivation of US16 was reported to increase replication in microvascular endothelial cells. Here, we investigate the properties of US16 further by ascertaining the expression pattern of its product. A recombinant HCMV encoding a tagged version of the US16 protein expressed a 33-kDa polypeptide that accumulated with late kinetics in the cytoplasmic virion assembly compartment. To elucidate the function(s) of pUS16, we generated US16-deficient mutants in the TR clinical strain of HCMV. According to previous studies, inactivation of US16 had no effect on viral replication in fibroblasts. In contrast, the US16-deficient viruses exhibited a major growth defect in both microvascular endothelial cells and retinal pigment epithelial cells. The expression of representative IE, E, and L viral proteins was impaired in endothelial cells infected with a US16 mutant virus, suggesting a defect in the replication cycle that occurs prior to IE gene expression. This defect must be due to an inefficient entry and/or postentry event, since pp65 and viral DNA did not move to the nucleus in US16 mutant-infected cells. Taken together, these data indicate that the US16 gene encodes a novel virus tropism factor that regulates, in a cell-specific manner, a pre-immediate-early phase of the HCMV replication cycle.     

Complete genome sequence of the aquatic bacterium Runella slithyformis type strain (LSU 4(T))

Runella slithyformis Larkin and Williams 1978 is the type species of the genus Runella, which belongs to the Cytophagaceae, a family that was only recently classified to the order Cytophagales in the class Cytophagia. The species is of interest because it is able to grow at temperatures as low as 4°C. This is the first completed genome sequence of a member of the genus Runella and the sixth sequence from the family Cytophagaceae. The 6,919,729 bp long genome consists of a 6.6 Mbp circular genome and five circular plasmids of 38.8 to 107.0 kbp length, harboring a total of 5,974 protein-coding and 51 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.     

A cross-cultural study of physician treatment decisions in relation to demented nursing home patients who develop pneumonia

This qualitative interview study in The Netherlands and North Carolina (US) found that physician treatment decisions are influenced by contextual differences in physician training and healthcare delivery in the US and The Netherlands. Dutch physicians treating nursing home residents with dementia and pneumonia assumed active, primary responsibility for treatment decisions while US physicians were more passive and deferential to family preferences, even in cases where they considered the families' wishes inappropriate. Dutch physicians knew their patients well and made treatment decisions based on what they perceived was in the best interest of the patient while US physicians reported limited knowledge of their nursing home patients due to a lack of contact time. Efforts to improve care for patients with poor quality of life who lack decision-making capacity must consider the context of societal values, physician training, and the processes by which physicians negotiate patient and family preferences.     

The composition and origins of genomic variation among individuals of the soybean reference cultivar Williams 82

Soybean (Glycine max) is a self-pollinating species that has relatively low nucleotide polymorphism rates compared with other crop species. Despite the low rate of nucleotide polymorphisms, a wide range of heritable phenotypic variation exists. There is even evidence for heritable phenotypic variation among individuals within some cultivars. Williams 82, the soybean cultivar used to produce the reference genome sequence, was derived from backcrossing a Phytophthora root rot resistance locus from the donor parent Kingwa into the recurrent parent Williams. To explore the genetic basis of intracultivar variation, we investigated the nucleotide, structural, and gene content variation of different Williams 82 individuals. Williams 82 individuals exhibited variation in the number and size of introgressed Kingwa loci. In these regions of genomic heterogeneity, the reference Williams 82 genome sequence consists of a mosaic of Williams and Kingwa haplotypes. Genomic structural variation between Williams and Kingwa was maintained between the Williams 82 individuals within the regions of heterogeneity. Additionally, the regions of heterogeneity exhibited gene content differences between Williams 82 individuals. These findings show that genetic heterogeneity in Williams 82 primarily originated from the differential segregation of polymorphic chromosomal regions following the backcross and single-seed descent generations of the breeding process. We conclude that soybean haplotypes can possess a high rate of structural and gene content variation, and the impact of intracultivar genetic heterogeneity may be significant. This detailed characterization will be useful for interpreting soybean genomic data sets and highlights important considerations for research communities that are developing or utilizing a reference genome sequence.     

Comparative attraction of four different fiberglass traps to various age and sex classes of stable fly (Diptera: Muscidae) adults

An Alsynite cylinder trap and three different Williams cross-configuration traps with three adhesives were compared to determine their relative attraction to stable fly, Stomoxys calcitrans (L.), adults. Williams traps coated with Olson Sticky Stuff performed as well as Williams traps coated with Tack Trap, thus allowing fly samples collected with either adhesive to be compared. The cylinder trap captured fewer total flies, but more flies per cm2 than any of the Williams traps. Sex ratio of flies captured on the cylinder trap was 50:50, while the three Williams traps captured predominantly males. The cylinder trap captured a larger percentage of nulliparous, unmated females than did the other traps tested.