EVIDENCE for the PARTICIPATION of the SSP-3 ANTIGEN in the INVASION of NONPHAGOCYTIC MAMMALIAN-CELLS BY TRYPANOSOMA-CRUZI

Trypomastigotes of Trypanosoma cruzi have to invade mammalian cells in order to multiply. They bear on their plasma membrane a sialic acid-containing epitope (Ssp-3) defined by a series of monoclonal antibodies (mAbs). Previous investigations have shown that Fab fragments of these mAbs inhibit the attachment of trypomastigotes to 3T3 fibroblasts. To further define the role of Ssp-3 in invasion, here we use, as targets for infection, L cells and CHO cells stably transfected with cDNA coding for the mouse Fc receptors genes. When the trypomastigotes are incubated with small, nonagglutinating amounts of antibodies to Ssp-3, their attachment to the transfected cells is greatly enhanced, without a parallel increase in invasion. the enhancement in attachment is Fc mediated, since it is abolished by treatment of the transfected cells with mAbs to Fc receptors. in contrast, both attachment to, and invasion of, the transfected cells are increased if the parasites are incubated with polyclonal or monoclonal antibodies against T. cruzi surface membrane antigens other than Ssp-3. If, however, antibodies to Ssp-3 are added to the incubation mixtures containing any of the other anti-T. cruzi antibodies, the enhancement of invasion (but not of attachment) is reversed. These results suggest that Ssp-3-bearing molecules participate in the process of parasite internalization.NYU MED CTR,DEPT PATHOL,550 1ST AVE,NEW YORK,NY 10016NYU MED CTR,KAPLAN CANC CTR,NEW YORK,NY 10016SLOAN KETTERING MEM CANC CTR,DEWITT WALLACE LAB,NEW YORK,NY 10021ESCOLA PAULISTA MED SCH,DISCIPLINA BIOL CELULAR,BR-04023 São Paulo,BRAZILESCOLA PAULISTA MED SCH,DISCIPLINA BIOL CELULAR,BR-04023 São Paulo,BRAZILWeb of Scienc

A Combination of Two Human Monoclonal Antibodies Limits Fetal Damage by Zika Virus in Macaques

Human infection by Zika virus (ZIKV) during pregnancy can lead to vertical transmission and fetal aberrations, including microcephaly. Prophylactic administration of antibodies can diminish or prevent ZIKV infection in animal models, but whether passive immunization can protect nonhuman primates and their fetuses during pregnancy has not been determined. Z004 and Z021 are neutralizing monoclonal antibodies to domain III of the envelope (EDIII) of ZIKV. Together the two antibodies protect nonpregnant macaques against infection even after Fc modifications to prevent antibody-dependent enhancement in vitro (ADE) and extend their half-lives. Here we report on prophylactic co-administration of the Fc-modified antibodies to pregnant rhesus macaques challenged 3 times with ZIKV during first and second trimester. The two antibodies did not entirely eliminate maternal viremia but limited vertical transmission protecting the fetus from neurologic damage. Thus, maternal passive immunization with two antibodies to EDIII can shield primate fetuses from the harmful effects of ZIKV

Characterization of the ligand binding site of the bovine IgA Fc receptor (bFcαR)

Recently, we identified a bovine IgA Fc receptor (bFcαR), which shows high homology to the human myeloid FcαR, CD89. IgA binding has previously been shown to depend on several specific residues located in the B-C and F-G loops of the membrane-distal extracellular domain 1 of CD89. To compare the ligand binding properties of these two FcαRs, we have mapped the IgA binding site of bFcαR. We show that, in common with CD89, Tyr-35 in the B-C loop is essential for IgA binding. However, in contrast to earlier observations on CD89, mutation of residues in the F-G loop did not significantly inhibit IgA binding.</p

Peer Collaborative Networks in Undergraduate Computing Classrooms

Peers are an invaluable resource for students at undergraduate universities. Many factors can impact how students form connections, some of which are tied to the students’ identities. While social networks have been studied in the context of universities, little research has been done specifically about peer collaboration and even less in the context of computer science classes. Our research aims to gain an understanding of how peer networks form in computing classes and the effect of being involved in one on students’ academic performances. We collected survey data (n = 139) about students’ peer collaborative behaviors in computer science classes. Several patterns were observed. Students were more likely to collaborate with students with their same demographic identity, including gender and ethnicity. A student’s demographic identity had no predictive quality on their participation in a peer network. Students who participated in a peer network had a higher grade performance in the class compared to students who did not

Twitch Trivia Battle Royale: Interactive Entertainment Engineering Game

As the world of digital media evolves, so too does the way producers and consumers of entertainment content interact with each other. Live streaming is one such evolution. In this format, one person broadcasts their camera and/or their computer screen to a large audience of viewers in real time. People tuning in can communicate with other viewers and the streamer using the chat feature built-in to the streaming platform. A new type of entertainment has recently entered the marketplace: interactive entertainment. Concerts are being held virtually in games like Fortnite (Epic Games 2021). TV Shows on Netflix are beginning to experiment with choice-based narrative options akin to a “Choose Your Own Adventure” game. Live streaming has also embraced this new direction of engaging content. In the past decade, the chat feature has been utilized as more than just a communication tool. In 2014, a programmer utilized the Twitch API to convert chat messages into game commands, starting the first iteration of “Twitch Plays Pokemon” (Helixpedia 2022). The goal for my project was to create a trivia game targeted specifically for Twitch streamers to play with their viewers. Rather than have viewers collectively control one character, each viewer has an individual entity they are in charge of, using basic chat commands to move in the game. While the core gameplay is simple, moving one’s character to the correct location corresponding to the answer of a trivia question, the competitive element of this game distinguishes it from other Twitch chat controlled experiences

Carcinoembryonic Antigen Gene Family

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2

Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR γ-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cγ (PLCγ). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5′-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR γ-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation

A mouse model for HIV-1 entry

Passive transfer of neutralizing antibodies against HIV-1 can prevent infection in macaques and seems to delay HIV-1 rebound in humans. Anti-HIV antibodies are therefore of great interest for vaccine design. However, the basis for their in vivo activity has been difficult to evaluate systematically because of a paucity of small animal models for HIV infection. Here we report a genetically humanized mouse model that incorporates a luciferase reporter for rapid quantitation of HIV entry. An antibody’s ability to block viral entry in this in vivo model is a function of its bioavailability, direct neutralizing activity, and effector functions

The antiinflammatory activity of IgG: the intravenous IgG paradox

How high doses of intravenous IgG (IVIG) suppress autoimmune diseases remains unresolved. We have recently shown that the antiinflammatory activity of IVIG can be attributed to a minor species of IgGs that is modified with terminal sialic acids on their Fc-linked glycans. Here we propose that these Fc-sialylated IgGs engage a unique receptor on macrophages that, in turn, leads to the upregulation of an inhibitory Fcγ receptor (FcγR), thereby protecting against autoantibody-mediated pathology