One of the strongest drivers in evolution is the struggle to survive a host-pathogen battle. This pressure selects for diversity among the factors directly involved in this battle, including virulence factors deployed by pathogens, their corresponding host targets, and host immune factors. A logical outcome of this diversification is that over time, the sequence of many immune factors will not be evolutionarily conserved across a broad range of species. Thus, while universal sequence conservation is often hailed as the hallmark of the importance of a particular gene, the immune system does not necessarily play by these rules when defending against co-evolving pathogens. This loss of sequence conservation is in contrast to many signaling pathways in development and basic cell biology that are not targeted by pathogens. In addition to diversification, another consequence of host-pathogen battles can be an amplification in gene number, thus leading to large gene families that have sequence relatively specific to a particular strain, species, or clade. Here we highlight this general theme across a variety of pathogen virulence factors and host immune factors. We summarize the wide range and number across species of these expanded, lineage-specific host-pathogen factors including ubiquitin ligases, nucleotide-binding leucine-rich repeat receptors, GTPases, and proteins without obvious biochemical function but that nonetheless play key roles in immunity.
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http://dx.doi.org/10.1111/febs.15627 | DOI Listing |
Neurology
February 2025
Department of Neurology and Center of Clinical Neuroscience, First Medical Faculty, General University Hospital and Charles University, Prague, Czech Republic.
Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).
Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.
JCO Glob Oncol
January 2025
Genitourinary Medical Oncology Service, Instituto do Câncer do Estado de São Paulo (ICESP), University of São Paulo, São Paulo, Brazil.
Purpose: Prior noncontemporary studies showed that oral cyclophosphamide is an active treatment of metastatic castration-resistant prostate cancer (mCRPC). However, cyclophosphamide is currently underutilized in routine clinical practice given the lack of survival benefit and the emergence of more effective treatments.
Methods: We retrospectively reviewed our institutional database to identify patients with mCRPC treated with cyclophosphamide.
JCO Glob Oncol
January 2025
Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia.
Purpose: Pancreatic cancer is one of the deadliest cancers in the world. In Armenia, it is 12th by incidence. The aim of this study is to evaluate treatment and outcomes of pancreatic cancer in Armenia during the past 12 years.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI) in 3 groups (n = 7 each): i) no mAb; ii) 4-mAb combination; and iii) 2-mAb combination.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Biological Sciences, College of Liberal Arts and Sciences, Wayne State University, Detroit, MI 48202.
The mammalian Hippo kinases, MST1 and MST2, regulate organ development and suppress tumor formation by balancing cell proliferation and death. In macrophages, inflammasomes detect molecular patterns from invading pathogens or damaged host cells and trigger programmed cell death. In addition to lytic pyroptosis, the signatures associated with apoptosis are induced by inflammasome activation, but how the inflammasomes coordinate different cell death processes remains unclear.
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