Rare Manifestation of a Rare Disease, Acute Liver Failure in Adult Onset Still’s Disease: Dramatic Response to Methylprednisolone Pulse Therapy—A Case Report and Review

Adult onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. It is characterized by daily fevers, arthralgias or arthritis, typical skin rash, and leukocytosis. Hepatic involvement is frequently observed in the course of AOSD with mildly elevated transaminases and/or hepatomegaly. Fulminant hepatic failure, occasionally requiring urgent liver transplantation, is a rare manifestation of AOSD. Here, we present a case of 22-year-old woman with no significant medical history who initially came with fever, arthralgias, myalgias, generalized weakness, and sore throat. Laboratory data showed mildly elevated transaminases and markedly elevated ferritin levels. She was diagnosed with AOSD based on Yamaguchi diagnostic criteria and was started on prednisone. Three months later, while she was on tapering dose of steroid, she presented with fever, abdominal pain, jaundice, and markedly elevated transaminases. Extensive workup excluded all potential causes of liver failure. She was diagnosed with AOSD associated acute liver failure (ALF). Intravenous (IV) methylprednisolone pulse therapy was started, with dramatic improvement in liver function. Our case demonstrated that ALF can present as a complication of AOSD and IV mega dose pulse methylprednisolone therapy can be employed as a first-line treatment in AOSD associated ALF with favorable outcome

Trafficking activity of myosin XXI is required in assembly of Leishmania flagellum

Actin-based myosin motors have a pivotal role in intracellular trafficking in eukaryotic cells. The parasitic protozoan organism Leishmania expresses a novel class of myosin, myosin XXI (Myo21), which is preferentially localized at the proximal region of the flagellum. However, its function in this organism remains largely unknown. Here, we show that Myo21 interacts with actin, and its expression is dependent of the growth stage. We further reveal that depletion of Myo21 levels results in impairment of the flagellar assembly and intracellular trafficking. These defects are, however, reversed by episomal complementation. Additionally, it is shown that deletion of the Myo21 gene leads to generation of ploidy, suggesting an essential role of Myo21 in survival of Leishmania cells. Together, these results indicate that actin-dependent trafficking activity of Myo21 is essentially required during assembly of the Leishmania flagellum

IoT MUD enforcement in the edge cloud using programmable switch

Targeted data breaches and cybersecurity attacks involving IoT devices are becoming ever more concerning. To combat these threats and risks, the IETF standardized Manufacturer Usage Description (MUD), which allows IoT device vendors to specify the intended communication patterns (MUD profile) of an IoT device. MUD profile enables validation of the actual communication pattern of an IoT device with the intended behavior at run-time. However, the MUD specification was primarily intended for enforcement at the Local Area Network (LAN) of the IoT device, thus fragmenting the solution across multiple heterogeneous networks. MUD enforcement at higher levels in the network hierarchy (e.g., private edge for enterprise networks) eases security policy management and reduces processing overheads on the existing security infrastructure. To realize MUD enforcement at the edge, there are mainly two challenges: (1) How to identify an IoT device at the edge so that enforcing device-specific MUD profile on the IoT traffic is possible. (2) How to scale MUD enforcement to a large network of IoT devices. In this paper, we present our approach to address these challenges and validate IoT device communication at the edge. In order to scale MUD enforcement to a large IoT network, we leverage multi-stage pipeline architecture and stateful ALUs of P4 programmable switch and process IoT traffic in the dataplane. © 2022 ACM

Friction stir welding of SS 316 LN and Nitronic 50 jacket sections for application in superconducting fusion magnet systems

Article explores the possibility of using friction stir welding (FSW) to join jacket web sections of two nitrogen-containing stainless steels for housing internally cooled superconducting cables which are utilized to generate magnetic fields in tokamak type fusion reactor systems. It has been shown that the FSW fabricated SS 316 LN jackets possessed the required strength and magnetic properties critical to this application

Transcriptional landscape of the human and fly genomes: Nonlinear and multifunctional modular model of transcriptomes

Regions of the genome not coding for proteins or not involved in cis-acting regulatory activities are frequently viewed as lacking in functional value. However, a number of recent large-scale studies have revealed significant regulated transcription of unannotated portions of a variety of plant and animal genomes, allowing a new appreciation of the widespread transcription of large portions of the genome. High-resolution mapping of the sites of transcription of the human and fly genomes has provided an alternative picture of the extent and organization of transcription and has offered insights for biological functions of some of the newly identified unannotated transcripts. Considerable portions of the unannotated transcription observed are developmental or cell-type-specific parts of protein-coding transcripts, often serving as novel, alternative 5′ transcriptional start sites. These distal 5′ portions are often situated at significant distances from the annotated gene and alternatively join with or ignore portions of other intervening genes to comprise novel unannotated protein-coding transcripts. These data support an interlaced model of the genome in which many regions serve multifunctional purposes and are highly modular in their utilization. This model illustrates the underappreciated organizational complexity of the genome and one of the functional roles of transcription from unannotated portions of the genome. Copyright 2006, Cold Spring Harbor Laboratory Press © 2006 Cold Spring Harbor Laboratory Press

Evaluating the Cellular Targets of Anti-4-1BB Agonist Antibody during Immunotherapy of a Pre-Established Tumor in Mice

Manipulation of the immune system represents a promising avenue for cancer therapy. Rational advances in immunotherapy of cancer will require an understanding of the precise correlates of protection. Agonistic antibodies against the tumor necrosis factor receptor family member 4-1BB are emerging as a promising tool in cancer therapy, with evidence that these antibodies expand both T cells as well as innate immune cells. Depletion studies have suggested that several cell types can play a role in these immunotherapeutic regimens, but do not reveal which cells must directly receive the 4-1BB signals for effective therapy.We show that re-activated memory T cells are superior to resting memory T cells in control of an 8-day pre-established E.G7 tumor in mice. We find that ex vivo activation of the memory T cells allows the activated effectors to continue to divide and enter the tumor, regardless of antigen-specificity; however, only antigen-specific reactivated memory T cells show any efficacy in tumor control. When agonistic anti-4-1BB antibody is combined with this optimized adoptive T cell therapy, 80% of mice survive and are fully protected from tumor rechallenge. Using 4-1BB-deficient mice and mixed bone marrow chimeras, we find that it is sufficient to have 4-1BB only on the endogenous host alphabeta T cells or only on the transferred T cells for the effects of anti-4-1BB to be realized. Conversely, although multiple immune cell types express 4-1BB and both T cells and APC expand during anti-4-1BB therapy, 4-1BB on cells other than alphabeta T cells is neither necessary nor sufficient for the effect of anti-4-1BB in this adoptive immunotherapy model.This study establishes alphabeta T cells rather than innate immune cells as the critical target in anti-4-1BB therapy of a pre-established tumor. The study also demonstrates that ex vivo activation of memory T cells prior to infusion allows antigen-specific tumor control without the need for reactivation of the memory T cells in the tumor

Actin-interacting and flagellar proteins in Leishmania spp.: Bioinformatics predictions to functional assignments in phagosome formation

Several motile processes are responsible for the movement of proteins into and within the flagellar membrane, but little is known about the process by which specific proteins (either actin-associated or not) are targeted to protozoan flagellar membranes. Actin is a major cytoskeleton protein, while polymerization and depolymerization of parasite actin and actin-interacting proteins (AIPs) during both processes of motility and host cell entry might be key events for successful infection. For a better understanding the eukaryotic flagellar dynamics, we have surveyed genomes, transcriptomes and proteomes of pathogenic Leishmania spp. to identify pertinent genes/proteins and to build in silico models to properly address their putative roles in trypanosomatid virulence. In a search for AIPs involved in flagellar activities, we applied computational biology and proteomic tools to infer from the biological meaning of coronins and Arp2/3, two important elements in phagosome formation after parasite phagocytosis by macrophages. Results presented here provide the first report of Leishmania coronin and Arp2/3 as flagellar proteins that also might be involved in phagosome formation through actin polymerization within the flagellar environment. This is an issue worthy of further in vitro examination that remains now as a direct, positive bioinformatics-derived inference to be presented