When environmental change is rapid or unpredictable, phenotypic plasticity can facilitate adaptation to new or stressful environments to promote population persistence long enough for adaptive evolution to occur. However, the underlying genetic mechanisms that contribute to plasticity and its role in adaptive evolution are generally unknown. Two main opposing hypotheses dominate-genetic compensation and genetic assimilation.
View Article and Find Full Text PDFThe early appearance of broadly neutralizing antibodies (bNAbs) in serum is associated with spontaneous hepatitis C virus (HCV) clearance, but to date, the majority of bNAbs have been isolated from chronically infected donors. Most of these bNAbs use the V1-69 gene segment and target the envelope glycoprotein E2 front layer. Here, we performed longitudinal B cell receptor (BCR) repertoire analysis on an elite neutralizer who spontaneously cleared multiple HCV infections.
View Article and Find Full Text PDFIndividuals who clear primary hepatitis C virus (HCV) infections clear subsequent reinfections more than 80% of the time, but the mechanisms are poorly defined. Here, we used HCV variants and plasma from individuals with repeated clearance to characterize longitudinal changes in envelope glycoprotein E2 sequences, function, and neutralizing antibody (NAb) resistance. Clearance of infection was associated with early selection of viruses with NAb resistance substitutions that also reduced E2 binding to CD81, the primary HCV receptor.
View Article and Find Full Text PDFDysfunctional immune activation accumulates during chronic viral infection and contributes to disease pathogenesis. In HIV-1, immune activation is exacerbated by concurrent infection with hepatitis C virus (HCV), accelerating depletion of CD4 T cells. HIV-1 suppression with antiretroviral therapy (ART) generally reconstitutes CD4 T cell counts, while also reducing the proportion that is activated.
View Article and Find Full Text PDFThis article traces the evolution of the concept of the leading edge in Kohut's work. The leading edge is defined as the growth-promoting dimension of the transference. The authors argue that although Kohut did not ever use the term explicitly in his writings-Marian Tolpin (2002), one of Kohut's gifted pupils, introduced the concept into the psychoanalytic literature in the form of the forward edge-the idea of the leading edge was already present in nascent form in Kohut's earliest papers and became ever more central as his psychology of the self evolved and the concept of the selfobject transference took center stage.
View Article and Find Full Text PDFAn in vitro model of intestinal epithelium with an immune component was bioengineered to mimic immunologic responses seen in inflammatory bowel disease. While intestinal immune phenomena can be modeled in transwells and 2D culture systems, 3D tissue models improve physiological relevance by providing a 3D substrate which enable migration of macrophages towards the epithelium. An intestinal epithelial layer comprised of non-transformed human colon organoid cells and a subepithelial layer laden with monocyte-derived macrophages was bioengineered to mimic native intestinal mucosa cell organization using spongy biomaterial scaffolds.
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