Neural substrates of semantic memory.

Semantic memory is described as the storage of knowledge, concepts, and information that is common and relatively consistent across individuals (e.g., memory of what is a cup). These memories are stored in multiple sensorimotor modalities and cognitive systems throughout the brain (e.g., how a cup is held and manipulated, the texture of a cup's surface, its shape, its function, that is related to beverages such as coffee, and so on). Our ability to engage in purposeful interactions with our environment is dependent on the ability to understand the meaning and significance of the objects and actions around us that are stored in semantic memory. Theories of the neural basis of the semantic memory of objects have produced sophisticated models that have incorporated to varying degrees the results of cognitive and neural investigations. The models are grouped into those that are (1) cognitive models, where the neural data are used to reveal dissociations in semantic memory after a brain lesion occurs; (2) models that incorporate both cognitive and neuroanatomical information; and (3) models that use cognitive, neuroanatomic, and neurophysiological data. This review highlights the advances and issues that have emerged from these models and points to future directions that provide opportunities to extend these models. The models of object memory generally describe how category and/or feature representations encode for object memory, and the semantic operations engaged in object processing. The incorporation of data derived from multiple modalities of investigation can lead to detailed neural specifications of semantic memory organization. The addition of neurophysiological data can potentially provide further elaboration of models to include semantic neural mechanisms. Future directions should incorporate available and newly developed techniques to better inform the neural underpinning of semantic memory models.     

CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric,pancreatic, and esophageal carcinomas

CD97 expression is related closely to the dedifferentiation and tumor stage in thyroid carcinomas. We systematically examined the role of CD97 and its closest relative, EMR2, in normal and malignant gastric, esophageal, and pancreatic tissue. The normal tissues were EMR2-, whereas CD97 was expressed slightly in the parietal cells of gastric mucosa and in exocrine pancreatic cells. Interestingly, intralobular and interlobular pancreatic ducts were CD97+. All tumors were EMR2-. CD97 was expressed by 44 of 50 gastric, 14 of 18 pancreatic, and 10 of 13 esophageal carcinomas. Of the 44 gastric cancers, 27 showed disseminated or scattered tumor cells at the invasion front with stronger CD97 expression than tumor cells located in solid tumor formations. There was no correlation between CD97 levels in the tumors or soluble CD97 in the serum samples and the clinicopathologic features of the patients. Taken together, significant numbers of gastric, esophageal, and pancreatic carcinomas are CD97+, whereas its homolog, EMR2, does not have any role in such tumors.     

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.     

Preferences for self-care or professional advice for minor illness: a discrete choice experiment

AIM: To determine the relative importance of factors that influence decision making in the management of minor illness, and how people trade between these factors. DESIGN OF STUDY: Discrete choice experiment.Setting:Scottish electoral roll. METHOD: Six hundred and fifty-two responders of a previous national survey were invited to complete a discrete choice experiment questionnaire. This was used to measure relative preferences for managing symptoms of minor illness often associated with analgesic use. Three attributes were identified as important to participants: type of management, availability, and cost of managing symptoms. Trade-offs between these attributes were examined. RESULTS: A 57% response rate was achieved (51% valid response rate). People preferred to manage symptoms by self-care and were willing to pay almost pounds 23 to do so. Community pharmacy was the preferred source of advice. Responders preferred less waiting time and paying less money when managing symptoms, and were willing to trade between factors. A less preferred type of management became more attractive when waiting times and cost were reduced. CONCLUSION: Findings suggest that self-care is the preferred method of managing symptoms of minor illness. When developing services to support self-care, policy makers should invest in services that reduce waiting times and incur least cost to users.     

A rapid method of genomic array analysis of scaffold/matrix attachment regions (S/MARs) identifies a 2.5-Mb region of enhanced scaffold/matrix attachment at a human neocentromere

Human neocentromeres are fully functional centromeres that arise at previously noncentromeric regions of the genome. We have tested a rapid procedure of genomic array analysis of chromosome scaffold/matrix attachment regions (S/MARs), involving the isolation of S/MAR DNA and hybridization of this DNA to a genomic BAC/PAC array. Using this procedure, we have defined a 2.5-Mb domain of S/MAR-enriched chromatin that fully encompasses a previously mapped centromere protein-A (CENP-A)-associated domain at a human neocentromere. We have independently verified this procedure using a previously established fluorescence in situ hybridization method on salt-treated metaphase chromosomes. In silico sequence analysis of the S/MAR-enriched and surrounding regions has revealed no outstanding sequence-related predisposition. This study defines the S/MAR-enriched domain of a higher eukaryotic centromere and provides a method that has broad application for the mapping of S/MAR attachment sites over large genomic regions or throughout a genome.     

DNA fingerprinting of sister blastomeres from human IVF embryos

BACKGROUND: Previously published single cell DNA fingerprinting systems have been plagued by high rates of allele drop-out (ADO) and preferential amplification (PA) preventing clinical application in preimplantation genetic diagnosis. METHODS: Tetranucleotide microsatellite markers with high heterozygosity, known allelic size ranges and minimal PCR stutter artefacts were selected for chromosomes X, 13, 18 and 21 and optimized in a multiplex fluorescent (FL)-PCR format. FL-PCR products were analysed using the ABI Prism 377 DNA sequenator and Genescan software. Validation of the DNA fingerprinting system was performed on single diploid (n = 50) and aneuploid (n = 25) buccal cells and embryonic blastomeres (n = 21). RESULTS: The optimized pentaplex PCR DNA fingerprinting system displayed a high proportion of successful amplifications (>91%) and low ADO and PA (<6%) when assessed on 50 human buccal cells. DNA fingerprints of single cells from a subject with Down's syndrome detected the expected tri-allelic pattern for the chromosome 21 marker, confirming trisomy 21. In a blind study on 21 single blastomeres, all embryos were identifiable by their unique DNA fingerprints and shared parental alleles. CONCLUSIONS: A highly specific multiplex FL-PCR based on the amplification of five highly polymorphic microsatellite markers was developed for single cells. This finding paves the way for the development of a more complex PCR DNA fingerprinting system to assess aneuploidy and single gene mutations in IVF embryos from couples at genetic risk.     

B cells regulate autoimmunity by provision of IL-10

To assess the importance of B cell control of T cell differentiation, we analyzed the course of the T helper type 1 (T(H)1)-driven disease experimental autoimmune encephalomyelitis in mice with an altered B cell compartment. We found that recovery was dependent on the presence of autoantigen-reactive B cells. B cells from recovered mice produced interleukin 10 (IL-10) in response to autoantigen. With a bone marrow chimeric system, we generated mice in which IL-10 deficiency was restricted to B cells but not T cells. In the absence of IL-10 production by B cells, the pro-inflammatory type 1 immune response persisted and mice did not recover. These data show that B cell-derived IL-10 plays a key role in controlling autoimmunity.     

Digoxin assay: results of 10 years of intralaboratory controls

Serum digoxin measurement is often performed in medical laboratories. A professional association specialized in quality control, based in Lyon, has been organizing punctual controls of medication measurement for the past ten years. The results are analysed in term of intra and inter-technique precision, difference between methods and specificity in regard to endogenous or exogenous interfering substances. Methods have changed with a quasi disappearance of the methods used ten years ago (FPIA, EMIT) and introduction of new technologies on recent immunoanalysis automates. The results observed with the different instruments are similar. Reproductibility has not changed over ten years. Some difficulties remain in the measurement of low concentrations of digoxin. Many substances interfere in digoxin measurement : digoxigenine (inactive metabolite), endogenous digoxin-like immunoreactive factors, spironolacton, antidigoxin antibodies used for treatment of digitalic intoxications. These interferences depend on the method which is used, but it is essential to know them in order to interpret the results correctly.     

Inhibition of prostaglandin synthesis reduces cyclic AMP levels and inhibits chondrogenesis in cultured chick limb mesenchyme

The present study investigated effects of inhibiting the synthesis of prostaglandins (PGs) on cyclic AMP concentrations and chondrogenesis in cultured chick limb mesenchyme. Indomethacin produced concentration-dependent inhibition of both PGE₂ synthesis and chondrogenesis over a concentration range of 50--200 M. Half maximal inhibition of PGE₂ was achieved with 50 M concentrations of the drug which also produced visibly reduced amounts of cartilage matrix in cell cultures as evaluated by Alcian green staining on day 6 of culture. The inhibitory effects of indomethacin on chondrogenesis were largely reversed by addition of 1 mM dibutyryl cAMP, indicating that cells could still respond to cyclic AMP stimulation. Endogenous levels of cyclic AMP, which increased by 6 fold during the six days of culture in control cells, did not increase significantly from dissociated cells at the time of plating (day 0) in indomethacin-treated cultures. The results indicate that inhibition of the prechondrogenic rise in PGE₂ concentrations in limb mesenchyme prevents the increase in cyclic AMP levels which occur during this same period resulting in inhibition of chondrogenesis. The data provide further support for the hypothesis that PGE₂, through its effects on the adenylate cyclase-cAMP system, plays an important role in the differentiation of cartilage.