Giardia Cyst Wall Protein 1 Is a Lectin That Binds to Curled Fibrils of the GalNAc Homopolymer

The infectious and diagnostic stage of Giardia lamblia (also known as G. intestinalis or G. duodenalis) is the cyst. The Giardia cyst wall contains fibrils of a unique β-1,3-linked N-acetylgalactosamine (GalNAc) homopolymer and at least three cyst wall proteins (CWPs) composed of Leu-rich repeats (CWPLRR) and a C-terminal conserved Cys-rich region (CWPCRR). Our goals were to dissect the structure of the cyst wall and determine how it is disrupted during excystation. The intact Giardia cyst wall is thin (~400 nm), easily fractured by sonication, and impermeable to small molecules. Curled fibrils of the GalNAc homopolymer are restricted to a narrow plane and are coated with linear arrays of oval-shaped protein complex. In contrast, cyst walls of Giardia treated with hot alkali to deproteinate fibrils of the GalNAc homopolymer are thick (~1.2 µm), resistant to sonication, and permeable. The deproteinated GalNAc homopolymer, which forms a loose lattice of curled fibrils, is bound by native CWP1 and CWP2, as well as by maltose-binding protein (MBP)-fusions containing the full-length CWP1 or CWP1LRR. In contrast, neither MBP alone nor MBP fused to CWP1CRR bind to the GalNAc homopolymer. Recombinant CWP1 binds to the GalNAc homopolymer within secretory vesicles of Giardia encysting in vitro. Fibrils of the GalNAc homopolymer are exposed during excystation or by treatment of heat-killed cysts with chymotrypsin, while deproteinated fibrils of the GalNAc homopolymer are degraded by extracts of Giardia cysts but not trophozoites. These results show the Leu-rich repeat domain of CWP1 is a lectin that binds to curled fibrils of the GalNAc homopolymer. During excystation, host and Giardia proteases appear to degrade bound CWPs, exposing fibrils of the GalNAc homopolymer that are digested by a stage-specific glycohydrolase. Author SummaryWhile the walls of plants and fungi contain numerous sugar homopolymers (cellulose, chitin, and β-1,3-glucans) and dozens of proteins, the cyst wall of Giardia is relatively simple. The Giardia wall contains a unique homopolymer of β-1,3-linked N-acetylgalactosamine (GalNAc) and at least three cyst wall proteins (CWPs), each of which is composed of Leu-rich repeats and a C-terminal Cys-rich region. The three major discoveries here are: 1) Fibrils of the GalNAc homopolymer are curled and form a lattice that is compressed into a narrow plane by bound protein in intact cyst walls. 2) Leu-rich repeats of CWP1 form a novel lectin domain that is specific for fibrils of the GalNAc homopolymer, which can be isolated by methods used to deproteinate fungal walls. 3) A cyst-specific glycohydrolase is able to degrade deproteinated fibrils of the GalNAc homopolymer. We incorporate these findings into a new curled fiber and lectin model of the intact Giardia cyst wall and a protease and glycohydrolase model of excystation.National Institutes of Health (AI048082, AI44070, GM31318, RR1088

Glycolipids of the mouse peritoneal macrophage. Alterations in amount and surface exposure of specific glycolipid species occur in response to inflammation and tumoricidal activation

We have characterized the major glycolipid constituents of the mouse peritoneal macrophage, and have demonstrated that alterations in the amount and in the accessibility of specific glycolipid species to galactose oxidase/NaB3H4 labeling, an indicator of glycolipid surface exposure, occur in response to inflammation and as a consequence of activation to a tumoricidal state. The key findings are: (a) Asialo GM1, a major neutral glycolipid constituent of all macrophage populations examined, is accessible to galactose oxidase/NaB3H4 labeling on the surface of TG-elicited and BCG-activated macrophages but not on resident macrophages; (b) GM1 is the predominant ganglioside constituent of the mouse macrophage. Resident macrophages contain two distinct GM1 species, as determined by cholera toxin binding, while TG-elicited and BCG-activated macrophages contain an additional GM1 species. Differences in the relative amounts of these GM1 species, as well as in their accessibility to galactose oxidase/NaB3H4 labeling, exist among the macrophage populations. These observations suggest that both a chemical and spatial reorganization of surface glycolipids occurs in response to inflammation and tumoricidal activation

Isolation of the ALG6 locus of Saccharomyces cerevisiae required for glucosylation in the N-linked glycosylation pathway

N-Linked protein glycosylation in most eukaryotic cells initiates with the transfer of the oligosaccharide Glc3Man9GlcNAc2 from the lipid carrier dolichyl pyrophosphate to selected asparagine residues. In the yeast Saccharomyces cerevisiae, alg mutations which affect the assembly of the lipid-linked oligosaccharide at the membrane of the endoplasmic reticulum result in the accumulation of lipid-linked oligosaccharide intermediates and a hypoglycosylation of proteins. Exploiting the synthetic growth defect of alg mutations in combination with mutations affecting oligosaccharyl transferase activity (Stagljar et al., 1994), we have isolated the ALG6 locus. alg6 mutants accumulate lipid-linked Man9GlcNAc2, suggesting that this locus encodes an endoplasmic glucosyltransferase. Alg6p has sequence similarity to Alg8p, a protein required for glucosylation of Glc1Man9GlcNAc

The Ursinus Weekly, October 7, 1963

Customs program: Class of 1967 well underway • Sororities begin Fall rushing Wed. • Harpsichordist Temple Painter to be featured in first Forum Wednesday • Dr. Foster on sabbatical • Choral groups begin rehearsals • Y retreat set for Oct. 11 & 12 • Sue Harmon in Mr. Roberts • More than 980 enrolled this Fall • Honors rating to 23 freshmen • UC student named president of SNEA • Students ready to teach; Banquet set for tonight • Editorial: Word of welcome • Danforth graduate fellowships available • Dateline: Stockholm, Sweden • Letters to the editor • Three faculty members receive distinguished teaching award • Record enrollment in Evening School • National Security Agency test • From behind my dink • Oral cultural vaccine given • Class \u2763 ranks top in education • Summer research, study for faculty • Susquehanna mauls Bears in opener, 32-0 • Ursinus host to foreign teams • Williamson named most valuable in MAC Southern div. • Vernon Morgan ends track careerhttps://digitalcommons.ursinus.edu/weekly/1252/thumbnail.jp

Psychological and physiological correlates of sleep in HIV infection

Insomnia, a common problem associated with HIV disease, is most likely caused by a multitude of factors. This study investigated the correlations between a selected group of physiological and psychological factors and sleep quality in an HIV-infected population. A convenience sample of 79 ethnically diverse HIVpositive adults, ages 24 to 63, completed a number of questionnaires and released their laboratory records for CD4+ cell count and viral load information. Variables significantly related to sleep quality were HIV-related symptoms, total pain, fatigue, depression, state anxiety, and the number of adults in the household. Findings support the need for health care providers to consider factors that contribute to impaired sleep when developing effective care for HIV-infected individuals with sleep disturbance

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

The Ursinus Weekly, February 17, 1964

Preparations in final stage for Four Freshmen concert • Asian students: APO will begin to collect books for foundation • Evolution and world federalism to be topic of Dr. Charles Price • Art exhibit set for weekend • Summer job opportunities • Three sororities begin Spring rush • Traditional Lorelei turnabout held; Dance king crowned, Whitians presented • Freshman pre-med views Christian concept of unity • Women to receive colors Thursday • English Club to hear Harvard poet • Editorial: A bit of discretion, please; Ursinus big time; Apology • Sub-species new theory of race evolution • Review of books • Letters to the editor • After one week the acting Dean: Dr. Vorrath speaks • Lincoln University students featured at Kaffee Klatsch: A well-attended affair • Greek gleanings • Impending crisis in our American railroads: Part two • Grapplers decision Hopkins after bowing at E-town • UC cagers success at PMC, bunglers at Swarthmore • WC drops Ursinus cagettes, 50-31 • Women trounce opponents in season openerhttps://digitalcommons.ursinus.edu/weekly/1264/thumbnail.jp

The Ursinus Weekly, March 9, 1964

Junior Prom and Agency concert highlight coming weekend • Curtain Club chooses cast; Meridy Murphy will direct Remarkable Mr. Pennypacker • Kaffee Klatsch topic politics • Sig Nu and ZX win Songfest • Photo contest • Wedgwood, controversial historian, author, here Wednesday evening • Campus Chest plans underway • Red Cross seeking qualified swimmers • 1,100 applications filed at UC for Fall admissions • Jean Hunter, Howard Smith elected Ruby co-editors • March placement schedule posted • Ursinus to raise tuition rate $200 effective Sept. 1 • Review: Mr. Lincoln on civil rights • Navy OCS team will visit campus next week • Letters to the editor • Fall of man topic of Bible Study • Genevieve Blatt: Our role in politics • Dateline: Stockholm • Greek gleanings • Modern tri-mesters used in 1880 here • Girls BB falls to ES, 46-36; JV team continues unbeaten • West Chester wins intercollegiates • Mermaids lose in two close meets • Wrestling: Win last match • Hofmann receives sportswriter\u27s award • MAC tournamenthttps://digitalcommons.ursinus.edu/weekly/1267/thumbnail.jp

Cardiovascular and cortisol reactions to acute psychological stress and cognitive ability in the Dutch Famine Birth Cohort Study

Objective: Recently, in analyses of data from a large community sample, negative cross-sectional and prospective associations between cardiac stress reactivity and obesity were observed. The present study re-examined the association between cardiovascular reactivity and adiposity in the Dutch Famine Birth Cohort, with the additional aim of examining the association between cortisol reactivity and adiposity. Methods: Blood pressure, heart rate, and salivary cortisol were measured at rest and in response to standard laboratory stress tasks in 725 adults. Height, weight, waist and hip circumference, and skin fold thickness were measured. Four to seven years later 460 participants reported current height and weight. Obesity was defined as a BMI > 30kg/m2. Results: Cross-sectional analyses revealed negative associations between all measures of adiposity and heart rate reactivity; those with a greater BMI (ß = -0.39 bpm), waist-hip ratio (ß = -0.15 bpm), and triceps and subscapular skin fold thicknesses (ß = -1.0 bpm and -1.8 bpm), or categorized as obese (-3.9 bpm) displayed smaller cardiac reactions to acute stress (all p <.001). With the exception of waist-hip ratio, the same negative associations emerged for cortisol reactivity (all p ≤ .01). In prospective analyses, low cardiac reactivity was associated with an increased likelihood of becoming or remaining obese in the subsequent 4-7 years (OR 1.03, p = .01). All associations withstood adjustment for a range of possible confounders. Conclusions: The present analyses provide additional support for the hypothesis that it is low not high cardiac and cortisol stress reactivity that is related to adiposity

The Ursinus Weekly, November 11, 1963

Carol Heber, Homecoming queen; Emmert receives Walker trophy • Catherine Drinker Bowen to be guest speaker at Forum • WSGA meeting set for Sunday • Past UC speaker in protest against Mme. Nhu before fall of regime • Volunteers for St. Gabriels to meet Tuesday • Alumni contribute $220,000 to Centennial Fund • Student rumor clarified • 17 men go Greek in Fall rushing • AAUW discusses community college • Professor chief editor of new publication • Ursinus gets portrait of Henry T. Spangler • Folksing begins weekend • MSGA sponsors bus to next game • Editorial: Women, it\u27s now or never; Kaffee Klatsch; Complaint for complaint\u27s sake? • Have you read: Travels with Charley • Swedish student studying here • Art class tours Philly museum • Letters to the editor • Excellent concert heard by students • Colgan views Cuba as potential source of war • Republicans view election returns • Thai student to speak at Kaffee Klatsch Friday • Ursinus Band: Review & outlook • Greek gleanings • Senior women reply to WSGA questionnaire with emphatic views • Jobs open for political interns • Parsons speaks on Daniel Claus • Outing Club on spelunking trip • Alpha Phi Omega plans open meeting • Bears trounce Fords 32 to 8 as Emmert stars in Homecoming tilt • Player of the week interview: Ron Emmert • UC puts three on college team • Soccer team beats La Salle, alumni • JV and 3rd teams take Immaculatahttps://digitalcommons.ursinus.edu/weekly/1257/thumbnail.jp