5-An Archaeological Survey of Kalamazoo County, Michigan: 1979 Multiple Transect Survey in the Middle Kalamazoo River Valley

CONTENTS Prehistoric Site Survey in the Kalamazoo Basin The 1979 Project Area Previous Archaeological Research in the Project Area Previously Known Sites in Transect A Previously Known Sites in Transect B Site Survey Methodology Research Design Field Procedures Curation of Cultural Materials Description of Sites Recorded and Catalog of Surface Collections Sites in Transect A Sites in Transect B Interpretations and Conclusions Comments on Management of Cultural Resources Catalog of Artifactual Material Recovered During Survey References Cited Series of Maps Showing the Locations of Sites not Included on Maps in the Text Kalamazoo Basin Archaeological Project: Allegan County Survey, 1976-1978 General Soils Map: Kalamazoo-Black-Macatawa- Paw Paw Rivers Basin Kalamazoo Basin Survey: Kalamazoo County Kalamazoo Basin Survey; 1979: Transect A Kalamazoo Basin Survey, 1979: Transect B Kalamazoo Basin Survey, 1979: Previously Known Sites in Transect A Kalamazoo Basin Survey, 1979: Previously Known Sites in Transect B Kalamazoo Basin Survey, 1979: Sampling Strata in Transect A Kalamazoo Basin Survey, 1979: Sampling Strata in Transect B Kalamazoo Basin Survey, 1979: Quarter- Sections Surveyed in Transect A Kalamazoo Basin Survey, 1979: New Archaeological Sites in Transect A Kalamazoo Basin Survey, 1979: Quarter- Sections Surveyed in Transect B Kalamazoo Basin Survey, 1979: New Archaeological Sites in Transect B Survey Coverage of Transect A by Stratum and Random Sampling Unit (1/4 Section or 64.75 ha) Survey Coverage of Transect B by Stratum and Random Sampling Unit (1/4 Section or 64.75 ha) Site Density per Km2 (Calculated by Dividing the Number of Sites by the Actual Km2 Surveyed) for Transects A and B by Sampling Stratum Occupational Intensity Values Calculated for Sampling Strata in Transects A and B Plate 1: Schmidtke Collection (KBS-79-Al3) Plate 2: Campbell Collection (KBS-79-B5) Plate 3: Campbell Collection (KBS-79-B5) Plate 4: Campbell Collection (KBS-79-B5) Plate 5: Campbell Collection (KBS-79-BS) Plate 6: Campbell Collection (KBS-79-B5) Plate 7: Campbell Collection (KBS-79-B5) Plate 8: Campbell Collection (KBS-79-B5) Plate 9: Campbell Collection (KBS-79-B5

2-An Archaeological Survey of Allegan County, Michigan: 1977 Transect Survey in the Lower Kalamazoo River Valley

Western Michigan University has sponsored archaeological field work in the Kalamazoo River Valley for the last 10 years. For the most part this research has been carried out by the Department of Anthropology\u27s archaeological field school, which has been located in the lower valley during all or portions of 6 field seasons: 1968, 1969, 1973, 1976, 1977 and 1978. Prior to 1976, the Department\u27s field program was directed by Elizabeth Baldwin Garland; and since that time by Garland and William Cremin. With the inception of the Kalamazoo Basin Archaeological Project in 1976, the research objectives of our program in this universe have necessitated that we initiate systematic site survey as a means of acquiring data which could be used to delineate and explain prehistoric land use patterns. To collect these data, the first in a series of cross-valley transect surveys was conducted in the Hacklander site environs as part of the 1976 field school (Figure 1). On this occasion the survey was supported entirely out of the field school budget. Since then our survey program has been funded by National Register grants obtained through the Michigan History Division, Michigan Department of State

Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells

The functional properties of circulating CD8+ T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8+ T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8+ T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8+ T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4+ T cell–associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8+ T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV

Galectin-9 Controls CD40 Signaling through a Tim-3 Independent Mechanism and Redirects the Cytokine Profile of Pathogenic T Cells in Autoimmunity

While it has long been understood that CD40 plays a critical role in the etiology of autoimmunity, glycobiology is emerging as an important contributor. CD40 signaling is also gaining further interest in transplantation and cancer therapies. Work on CD40 signaling has focused on signaling outcomes and blocking of its ligand, CD154, while little is known about the actual receptor itself and its control. We demonstrated that CD40 is in fact several receptors occurring as constellations of differentially glycosylated forms of the protein that can sometimes form hybrid receptors with other proteins. An enticing area of autoimmunity is differential glycosylation of immune molecules leading to altered signaling. Galectins interact with carbohydrates on proteins to effect such signaling alterations. Studying autoimmune prone NOD and non-autoimmune BALB/c mice, here we reveal that in-vivo CD40 signals alter the glycosylation status of non-autoimmune derived CD4 T cells to resemble that of autoimmune derived CD4 T cells. Galectin-9 interacts with CD40 and, at higher concentrations, prevents CD40 induced proliferative responses of CD4loCD40+ effector T cells and induces cell death through a Tim-3 independent mechanism. Interestingly, galectin-9, at lower concentrations, alters the surface expression of CD3, CD4, and TCR, regulating access to those molecules and thereby redirects the inflammatory cytokine phenotype and CD3 induced proliferation of autoimmune CD4loCD40+ T cells. Understanding the dynamics of the CD40 receptor(s) and the impact of glycosylation status in immunity will gain insight into how to maintain useful CD40 signals while shutting down detrimental ones

HIV-1 envelope, integrins and co-receptor use in mucosal transmission of HIV

It is well established that HIV-1 infection typically involves an interaction between the viral envelope protein gp120/41 and the CD4 molecule followed by a second interaction with a chemokine receptor, usually CCR5 or CXCR4. In the early stages of an HIV-1 infection CCR5 using viruses (R5 viruses) predominate. In some viral subtypes there is a propensity to switch to CXCR4 usage (X4 viruses). The receptor switch occurs in ~ 40% of the infected individuals and is associated with faster disease progression. This holds for subtypes B and D, but occurs less frequently in subtypes A and C. There are several hypotheses to explain the preferential transmission of R5 viruses and the mechanisms that lead to switching of co-receptor usage; however, there is no definitive explanation for either. One important consideration regarding transmission is that signaling by R5 gp120 may facilitate transmission of R5 viruses by inducing a permissive environment for HIV replication. In the case of sexual transmission, infection by HIV requires the virus to breach the mucosal barrier to gain access to the immune cell targets that it infects; however, the immediate events that follow HIV exposure at genital mucosal sites are not well understood. Upon transmission, the HIV quasispecies that is replicating in an infected donor contracts through a “genetic bottleneck”, and often infection results from a single infectious event. Many details surrounding this initial infection remain unresolved. In mucosal tissues, CD4+ T cells express high levels of CCR5, and a subset of these CD4+/CCR5high cells express the integrin α4β7, the gut homing receptor. CD4+/CCR5high/ α4β7high T cells are highly susceptible to infection by HIV-1 and are ideal targets for an efficient productive infection at the point of transmission. In this context we have demonstrated that the HIV-1 envelope protein gp120 binds to α4β7 on CD4+ T cells. On CD4+/CCR5high/ α4β7high T cells, α4β7 is closely associated with CD4 and CCR5. Furthermore, α4β7 is ~3 times the size of CD4 on the cell surface, that makes it a prominent receptor for an efficient virus capture. gp120-α4β7 interactions mediate the activation of the adhesion-associated integrin LFA-1. LFA-1 facilitates the formation of virological synapses and cell-to-cell spread of HIV-1. gp120 binding to α4β7 is mediated by a tripeptide located in the V1/V2 domain of gp120. Of note, the V1/V2 domain of gp120 has been linked to variations in transmission fitness among viral isolates raising the intriguing possibility that gp120-α4β7 interactions may be linked to transmission fitness. Although many details remain unresolved, we hypothesize that gp120-α4β7 interactions play an important role in the very early events following sexual transmission of HIV and may have important implication in the design of vaccine strategies for the prevention of acquisition of HIV infectio

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials