Hashimoto's encephalopathy: a case report with neuropsychological testing.

We report a case of Hashimoto's encephalopathy with detailed neuropsychological testing before, during and after steroid treatment, allowing a more precise characterization of the deficits and their response to treatment. It highlights that behavioral and psychotic symptoms remit before cognitive deficits and suggests that the latter may be more appropriate for guiding the duration of steroid treatment.

Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties.

Emergence of bacterial resistance is a major issue for all classes of antibiotics; therefore, the identification of new classes is critically needed. Recently we reported the discovery of platensimycin by screening natural product extracts using a target-based whole-cell strategy with antisense silencing technology in concert with cell free biochemical validations. Continued screening efforts led to the discovery of platencin, a novel natural product that is chemically and biologically related but different from platensimycin.

Fertilization in mouse does not require terminal galactose or N-acetylglucosamine on the zona pellucida glycans.

Fertilization in mammals requires sperm to bind to the zona pellucida (ZP) that surrounds the egg. Galactose (Gal) or N-acetylglucosamine (GlcNAc) residues on the glycans of ZP protein 3 (ZP3) have been implicated as mouse sperm receptors. However, Mgat1(-/-) eggs with modified N-glycans lacking terminal Gal and GlcNAc residues are fertilized.

Molecular cloning and characterization of the Caenorhabditis elegans alpha1,3-fucosyltransferase family.

The genome of Caenorhabditis elegans encodes five genes with homology to known alpha1,3 fucosyltransferases (alpha1,3FTs), but their expression and functions are poorly understood. Here we report the molecular cloning and characterization of these C. elegans alpha1,3FTs (CEFT-1 through -5).

Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface.

Galectin-8 has two different carbohydrate recognition domains (CRDs), the N-terminal Gal-8N and the C-terminal Gal-8C linked by a peptide, and has various effects on cell adhesion and signaling. To understand the mechanism for these effects further, we compared the binding activities of galectin-8 in solution with its binding and activation of cells. We used glycan array analysis to broaden the specificity profile of the two galectin-8 CRDs, as well as intact galectin-8s (short and long linker), confirming the unique preference for sulfated and sialylated glycans of Gal-8N.

A plea for more research on access to sexual health services.

Access to sexual health services, by those at highest risk of sexually transmitted infections (STI) is critical to effective STI control. Access to services is determined by the systems that clinics use to prioritize clients. However, despite there being thousands of sexual health services world wide, only three published studies in the last 25 years have specifically assessed changes in the process of access to STI clinics in which a control period was used.

Middle ear injury through the external auditory canal: a review of 44 cases.

We performed a retrospective review of 44 patients with middle ear injury incurred through the external auditory canal. Twenty-two of the 44 patients had presented to our center within 1 month of their injury (early group), and 22 presented later (delayed group); the mean interval from the time of the trauma to presentation was 6 days in the early group and 7 years in the delayed group. The causes of injury were penetrating trauma (70% of cases), thermal insults (20%), and explosive and nonexplosive blasts (9%).

Pseudomonas aeruginosa mucoid strain 8830 binds glycans containing the sialyl-Lewis x epitope.

Pseudomonas aeruginosa infection of patients with cystic fibrosis (CF) is a leading cause of their morbidity and mortality. Pathogenesis is initiated in part by molecular interactions of P. aeruginosa with carbohydrate residues in airway mucins that accumulate in the lungs of patients with this disease.

Genetic diversity of Plasmodium vivax Pvcsp and Pvmsp1 in Guyana, South America.

Approximately 55% of malaria infections in the Guyana Amazon region are attributed to Plasmodium falciparum while the other 45% are attributed to non-falciparum, mostly Plasmodium vivax. However, little is known about the P. vivax strain types circulating in the region.

Specificity of DC-SIGN for mannose- and fucose-containing glycans.

The dendritic cell specific C-type lectin dendritic cell specific ICAM-3 grabbing non-integrin (DC-SIGN) binds to "self" glycan ligands found on human cells and to "foreign" glycans of bacterial or parasitic pathogens. Here, we investigated the binding properties of DC-SIGN to a large array of potential ligands in a glycan array format. Our data indicate that DC-SIGN binds with K(d)<2muM to a neoglycoconjugate in which Galbeta1-4(Fucalpha1-3)GlcNAc (Le(x)) trisaccharides are expressed multivalently.

Selectin ligands promote ultrasound contrast agent adhesion under shear flow.

Contrast-enhanced ultrasound imaging has shown promise in the field of molecular imaging. This technique relies upon the adhesion of ultrasound contrast agent (UCA) to targeted molecular markers of disease. This is accomplished by coating the surface of the contrast agent with a ligand that specifically binds to the intended molecular marker.

Human galectin-1, -2, and -4 induce surface exposure of phosphatidylserine in activated human neutrophils but not in activated T cells.

Cellular turnover is associated with exposure of surface phosphatidylserine (PS) in apoptotic cells, leading to their phagocytic recognition and removal. But recent studies indicate that surface PS exposure is not always associated with apoptosis. Here we show that several members of the human galectin family of glycan binding proteins (galectins-1, -2, and -4) induce PS exposure in a carbohydrate-dependent fashion in activated, but not resting, human neutrophils and in several leukocyte cell lines.

Characterization of a sialic acid- and P-selectin glycoprotein ligand-1-independent adhesin activity in the granulocytotropic bacterium Anaplasma phagocytophilum.

Anaplasma phagocytophilum, the aetiologic agent of human granulocytic anaplasmosis, is an obligate intracellular bacterium that colonizes neutrophils and neutrophil precursors. The granulocytotropic bacterium uses multiple adhesins that cooperatively bind to the N-terminal region of P-selectin glycoprotein ligand-1 (PSGL-1) and to sialyl Lewis x (sLe(x)) expressed on myeloid cell surfaces. Recognition of sLe(x) occurs through interactions with alpha2,3-sialic acid and alpha1,3-fucose.

Role of the carbohydrate recognition domains of mouse galectin-4 in oligosaccharide binding and epitope recognition and expression of galectin-4 and galectin-6 in mouse cells and tissues.

Galectin-4 and its homologue galectin-6 are members of the tandem-repeat subfamily of monomer divalent galectins. Expression of mouse galectin-4 and galectin-6 by RT-PCR using primers designed to distinguish both galectin transcripts indicates that both are expressed in the small intestine, colon, liver, kidney, spleen and heart and P19X1 cells while only galectin-4 is expressed in BW-5147 and 3T3 cell lines. In situ hybridization confirmed the presence of galectin-4/-6 transcripts in the liver and small intestine.

Lectin from the Manila clam Ruditapes philippinarum is induced upon infection with the protozoan parasite Perkinsus olseni.

Glycan-binding proteins (lectins) are widely expressed in many invertebrates, although the biosynthesis and functions of the lectins are not well understood. Here we report that Manila clam (Ruditapes philippinarum) synthesizes a lectin termed Manila clam lectin (MCL) upon infection with the protozoan parasite Perkinsus olseni. MCL is synthesized in hemocytes as a approximately 74-kDa precursor and secreted into hemolymph where it is converted to 30- and 34-kDa polypeptides.

Identification of core 1 O-glycan T-synthase from Caenorhabditis elegans.

The common O-glycan core structure in animal glycoproteins is the core 1 disaccharide Galbeta1-3GalNAcalpha1-Ser/Thr, which is generated by the addition of Gal to GalNAcalpha1-Ser/Thr by core 1 UDP-alpha-galactose (UDP-Gal):GalNAcalpha1-Ser/Thr beta1,3-galactosyltransferase (core 1 beta3-Gal-T or T-synthase, EC2.4.1.

Platensimycin is a selective FabF inhibitor with potent antibiotic properties.

Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis.

Very long term studies of the seeding of beta-amyloidosis in primates.

Cerebral beta-amyloidosis was found in 16/18 marmosets aged <10 yrs and 8/9 marmosets aged >10 yrs, injected intracerebrally with human or marmoset brain homogenate containing beta-amyloid 1-8 years previously. It was found in only 2/12 marmosets aged <10 yrs and 1/15 marmosets aged >10 yrs, injected with synthetic Abeta-peptides, CSF, or brain tissue which did not contain beta-amyloid. Cerebral beta-amyloidosis was found in 0/11 uninjected marmosets aged <10 yrs and in 5/29 uninjected marmosets aged >10 yrs.

The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection.

A potent and selective anthrax LF inhibitor 40, (2R)-2-[(4-fluoro-3-methylphenyl)sulfonylamino]-N-hydroxy-2-(tetrahydro-2H-pyran-4-yl)acetamide, was identified through SAR study of a high throughput screen lead. It has an IC50 of 54 nM in the enzyme assay and an IC50 of 210 nM in the macrophage cytotoxicity assay. Compound 40 is also effective in vivo in several animal model studies.

Development of a high-capacity homogeneous fluorescent assay for the measurement of leukotriene B4.

Current immunoassays for the measurement of leukotriene B(4) (LTB(4)) typically utilize an enzyme-linked immunosorbent assay (ELISA) format that requires multiple incubations and washing steps and often expensive immunoassay kits. We have developed a bead-based, mix and read, indirect fluorescence-linked immunosorbent assay utilizing fluorometric microvolume assay technology (FMAT). The assay employs a monoclonal anti-LTB(4) antibody-coated onto goat antimouse antibody coupled polystyrene beads and an AlexaFluor-647-coupled LTB(4) ligand.

Versatile fluorescent derivatization of glycans for glycomic analysis.

The new field of functional glycomics encompasses information about both glycan structure and recognition by carbohydrate-binding proteins (CBPs) and is now being explored through glycan array technology. Glycan array construction, however, is limited by the complexity of efficiently generating derivatives of free, reducing glycans with primary amines for conjugation. Here we describe a straightforward method to derivatize glycans with 2,6-diaminopyridine (DAP) to generate fluorescently labeled glycans (glycan-DAP conjugates or GDAPs) that contain a primary amine for further conjugation.

Protein glycosylation: chaperone mutation in Tn syndrome.

Tn syndrome is a rare autoimmune disease in which subpopulations of blood cells in all lineages carry an incompletely glycosylated membrane glycoprotein, known as the Tn antigen. This truncated antigen has the sugar N-acetylgalactosamine alpha-linked to either a serine or threonine amino-acid residue, whereas the correct T antigen has an additional terminal galactose; the defect may be due to a malfunction of the glycosylating enzyme T-synthase. Here we show that Tn syndrome is associated with a somatic mutation in Cosmc, a gene on the X chromosome that encodes a molecular 'chaperone' that is required for the proper folding and hence full activity of T-synthase.

Glycans modulate immune responses in helminth infections and allergy.

Infections of humans and animals by parasitic helminths share key features with atopic diseases, such as allergic asthma. Both diseases lead to the induction of high levels of Th2- type cytokines associated with abundant IgE production and eosinophilia. This immunological association has raised strong interest in the nature of the molecules that promote Th2 and regulatory T cell responses, and the molecular mechanism.