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The modifiable areal unit problem (MAUP) is a cause of statistical and visual bias when aggregating data according to spatial units, particularly when spatial units may be changed arbitrarily. The MAUP is a concern in vector-borne disease research when entomological metrics gathered from point-level sampling data are related to epidemiological data aggregated to administrative units like counties or ZIP Codes. Here, we assess the statistical impact of the MAUP when calculating correlations between randomly aggregated cases of anaplasmosis in New York State during 2017 and a geostatistical layer of an entomological risk index for Anaplasma phagocytophilumin blacklegged ticks (Ixodes scapularisSay, Acari: Ixodidae) collected during the fall of 2017. Correlations were also calculated using various administrative boundaries for comparison. We also demonstrate the impact of the MAUP on data visualization using choropleth maps and offer pycnophylactic interpolation as an alternative. Polygon simulations indicate that increasing the number of polygons decreases correlation coefficients and their variability. Correlation coefficients calculated using ZIP Code tabulation area and Census tract polygons were beyond 4 standard deviations from the mean of the simulated correlation coefficients. These results indicate that using smaller polygons may not best incorporate the geographical context of the tick-borne disease system, despite the tendency of researchers to strive for more granular spatial data and associations.

Blacklegged ticks (Ixodes scapularisSay, Acari: Ixodidae) were collected from 432 locations across New York State (NYS) during the summer and autumn of 2015–2020 to determine the prevalence and geographic distribution of Borrelia miyamotoi(Spirochaetales: Spirochaetaceae) and coinfections with other tick-borne pathogens. A total of 48,386 I. scapulariswere individually analyzed using a multiplex real-time polymerase chain reaction assay to simultaneously detect the presence of Bo. miyamotoi, Borrelia burgdorferi(Spirochaetales: Spirochaetaceae), Anaplasma phagocytophilum(Rickettsiales: Anaplasmataceae), and Babesia microti(Piroplasmida: Babesiidae). Overall prevalence of Bo. miyamotoiin host-seeking nymphs and adults varied geographically and temporally at the regional level. The rate of polymicrobial infection in Bo. miyamotoi-infected ticks varied by developmental stage, with certain co-infections occurring more frequently than expected by chance. Entomological risk of exposure to Bo. miyamotoi-infected nymphal and adult ticks (entomological risk index [ERI]) across NYS regions in relation to human cases of Bo. miyamotoidisease identified during the study period demonstrated spatial and temporal variation. The relationship between select environmental factors and Bo. miyamotoiERI was explored using generalized linear mixed effects models, resulting in different factors significantly impacting ERI for nymphs and adult ticks. These results can inform estimates of Bo. miyamotoidisease risk and further our understanding of Bo. miyamotoiecological dynamics in regions where this pathogen is known to occur.

The γchain of human fibrinogen is heterogeneous in length at the C-terminus due to differential RNA processing of the 7 chain-gene primary transcript. We have produced two specific monoclonal antibodies (MoAbs) against the γ-chain epitopes generated by this alternative processing event: anti-γ57.5408-416(L2B), which reacts with γ57.5 and γ55 chains, and anti γ50, (H9B7), which reacts preferentially with γ50 chains. Using these MoAbs we have studied the expression of γ-chain polypeptides by immunofluorescence microscopy in the tissues of fibrinogen biosynthesis and have determined that γ57.5 polypeptide is expressed in hepatocytes but is absent or present in significantly reduced amounts in megakaryocytes. Therefore the γ50 chain is found in plasma, platelet, and megakaryocyte fibrinogens, but the γ57.5 chain is found only in plasma fibrinogen. The C-terminal amino acid sequence of γ55 includes the L2B epitope 57.5408-416Using MoAb L2B we have determined that γ55, which is a post-translationally modified γ57.5 chain, is found only in plasma fibrinogen and is absent or present in markedly reduced amounts in platelet or megakaryocte fibrinogen. In addition, the conformation of the L2B epitope is preserved in γ55, as determined by Western blot analysis. The hepatocyte-specific expression of the γ57.5-chain polypeptide and the post-translational modification to γ55 result in a compart-mentalization of γ-chain polypeptide expression. This is suggestive of different mechanisms regulating human fibrinogen 7-chain gene expression in hepatocytes vmegakaryocytes that may operate in a tissue-specific manner at the level of 3'RNA processing events. © 1989 by Grune & Stratton. Inc.

Cellular fibronectin (Fn) bearing an alternatively spliced extra type III structural repeat (ED1) is normally present at low concentrations in blood plasma. The source of this material remains uncertain. In this study, primary cultures of human umbilical vein endothelial cells (HUVEC) labeled with 35S-methionine were observed to synthesize Fn monomers both with and without this segment. Monomers isolated from cell lysates with antibodies to the ED1 sequence comigrated in nonreduced sodium dodecyl sulfate polyacrylamide gel electrophoresis with the slower (designated M1). but not the faster (designated M2), of two major monomeric populations that were recognized by antibodies raised to plasma-derived Fn. The differences between M1 and M2 were not due to glycosylation, since they were also observed between species of Fn monomer purified from cells grown in the presence of tunicamycin. M1 and M2 were both observed to incorporate with a similar rate into dimeric Fn, indicating that Fn monomers with and without the ED1 site can dimerize with similar efficiency. Analysis of reduced samples of Fn isolated from cells with anti-ED1 antibodies indicated the presence of both M1-M1 and M1-M2 dimers. In addition to being incorporated into extracellular matrix, ED1 + Fn was observed to be secreted in soluble form into the medium, potentially reflecting intravascular release of this protein by endothelial cells in vivo.

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.

ABSTRACTThe vascular endothelial cell (EC) is a primary target of infection with Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever. Changes in gene transcription elicited by intracellular infection, including EC expression of the coagulation pathway initiator known as tissue factor (TF), may contribute to the vascular pathology observed during disease. Nuclear run-on analysis of uninfected and infected, cultured human endothelial cells revealed that the rate of TF mRNA transcription is enhanced more than twofold at 3 h following infection, thus coinciding with increased steady-state levels of TF mRNA. TF mRNA remained relatively unstable during infection, with a half-life of 1.6 h. The eukaryotic protein synthesis inhibitor cycloheximide did not block R. rickettsii-induced increase in TF mRNA levels and actually resulted in its superinduction, thus revealing that de novo synthesis of host cell protein was not prerequisite to this transcriptional response. Involvement of the transcription factor NF-κB in R. rickettsii-induced TF expression was demonstrated by using two unrelated inhibitors of NF-κB activation. The antioxidant pyrrolidinedithiocarbamate and the proteasome inhibitorN-tosyl-l-phenylalanine chloromethyl ketone blocked expression of TF mRNA and activity during infection. This study demonstrates that R. rickettsiiinfection results in transcriptional activation of the TF gene and that this response involves activation of the transcription factor NF-κB.