Listeria monocytogenes exploits efferocytosis to promote cell-to-cell spread

Efferocytosis, the process by which dying/dead cells are removed by phagocytosis, plays an important role in development, tissue homeostasis and innate immunity1. Efferocytosis is mediated, in part, by receptors that bind to exofacial phosphatidylserine (PS) on cells or cellular debris after loss of plasma membrane asymmetry. Here we show that a bacterial pathogen, Listeria monocytogenes (Lm), can exploit efferocytosis to promote cell-to-cell spread during infection. These bacteria can escape the phagosome in host cells using the pore-forming toxin Listeriolysin O (LLO) and two phospholipases C2. Expression of the cell surface protein ActA allows Lm to activate host actin regulatory factors and undergo actin-based motility in the cytosol, eventually leading to formation of actin-rich protrusions at the cell surface. We show that protrusion formation is associated with plasma membrane damage due to LLO’s pore-forming activity. LLO also promotes the release of bacteria-containing protrusions from the host cell, generating membrane-derived vesicles with exofacial PS. The PS-binding receptor TIM-4 contributes to efficient cell-to-cell spread by Lm in macrophages in vitro and growth of these bacteria is impaired in TIM-4−/− mice. Thus, Lm promotes its dissemination in a host by exploiting efferocytosis. Our study suggests that PS-targeted therapeutics may be useful in the fight against infections by Lm and other bacteria that utilize similar strategies of cell-to-cell spread during infection

IXPE Mission System Concept and Development Status

The Goal of the Imaging X-Ray Polarimetry Explorer (IXPE) Mi SMEX), is to expand understanding of high-energy astrophysical processes and sources, in support of NASAs first science objective in Astrophysics: Discover how the universe works. IXPE, an international collaboration, will conduct X-ray imaging polarimetry for multiple categories of cosmic X-ray sources such as neutron stars, stellar-mass black holes, supernova remnants and active galactic nuclei. The Observatory uses a single science operational mode capturing the X-ray data from the targets. The IXPE Observatory consists of spacecraft and payload modules built up in parallel to form the Observatory during system integration and test. The payload includes three X-ray telescopes each consisting of a polarization-sensitive, gas pixel X-ray detector, paired with its corresponding grazing incidence mirror module assembly (MMA). A deployable boom provides the correct separation (focal length) between the detector units (DU) and MMAs. These payload elements are supported by the IXPE spacecraft which is derived from the BCP-small spacecraft architecture. This paper summarizes the IXPE mission science objectives, updates the Observatory implementation concept including the payload and spacecraft ts and summarizes the mission status since last years conference

Positive Semidefinite Zero Forcing

The positive semidefinite zero forcing number Z+(G) of a graph G was introduced in [4]. We establish a variety of properties of Z+(G): Any vertex of G can be in a minimum positive semidefinite zero forcing set (this is not true for standard zero forcing). The graph parameters tw(G) (tree-width), Z+(G), and Z(G) (standard zero forcing number) all satisfy the Graph Complement Conjecture (see [3]). Graphs having extreme values of the positive semidefinite zero forcing number are characterized. The effect of various graph operations on positive semidefinite zero forcing number and connections with other graph parameters are studied

Imaging X-Ray Polarimeter Explorer Systems Engineering Approach and Implementation

The Imaging X-ray Polarimetry Explorer (IXPE) is a NASA Small Explorer x-ray astrophysics mission being implemented by a geographically dispersed team. Each IXPE partner provides unique capabilities and experience which are utilized to design, build and launch the IXPE observator. A rigorous and iterative systems engineering approach is essential to ensuring the successful realization of reliable and cost effective IXPE mission system. The IXPE collaboration and observatory complexity provide both unique challenges and advantages for project systems engineering. The project uses established and tailored systems engineering (SE) methods and teaming approaches to achieve the IXPE mission goals. The IXPE systems engineering team spans all partner organizations. Currently, the project is in system integration and test working through structural environmental testing–vibration testing is just starting. Systems work is now focused on requirements management and maturity assessments, requirements verification and validation via sell-off packages (SOP) and interface control document (ICD) verification while supporting environmental test planning and execution. IXPE verification, validation and characterization (V&V) starts at the component/unit level and rolls up to appropriate higher levels where V&V compliance is assured by collaborative development by the cross-organizational V&V Team. This paper provides a technical summary of the IXPE concept of operations and mission-system (payload, spacecraft, observatory, ground system, launch vehicle), overviews the IXPE systems engineering approach (communications, project reviews, requirements analysis and management, baseline design and design trade studies, interfaces definition and documentation, resource management), describes the verification, validation and characterization activities (requirements validation, models and simulations validation, systems integration and test (I&T), system validation), discusses risk and opportunities philosophy and implementation, outlines COVID 19 accommodations, itemizes some key challenges and lessons-learned followed by the path to launch and conclusions

Long COVID clinical severity types based on symptoms and functional disability: A longitudinal evaluation

Background: Long COVID (LC) is a multisystem clinical syndrome with functional disability and compromised overall health. Information on LC clinical severity types is emerging in cross-sectional studies. This study explored the pattern and consistency of long COVID (LC) clinical severity types over time in a prospective sample. Methods: Participants with LC completed the condition-specific outcome measure C19-YRSm (Yorkshire Rehabilitation Scale modified version) at two assessment time points. A cluster analysis for clinical severity types was undertaken at both time points using the k-means partition method. Results: The study included cross-sectional data for 759 patients with a mean age of 46.8 years (SD = 12.7), 69.4% females, and a duration of symptoms of 360 days (IQR 217 to 703 days). The cluster analysis at first assessment revealed three distinct clinical severity type clusters: mild (n = 96), moderate (n = 422), and severe (n = 241). Longitudinal data on 356 patients revealed that the pattern of three clinical severity types remained consistent over time between the two assessments, with 51% of patients switching clinical severity types between the assessments. Conclusions: This study is the first of its kind to demonstrate that the pattern of three clinical severity types is consistent over time, with patients also switching between severity types, indicating the fluctuating nature of LC

Religious Identification, Switching, and Apostasy Among Protestants and Catholics in Northern Ireland:Individual and Cohort Dynamics Between Two Censuses 2001–2011

Religious identification has historically been salient in Northern Ireland as an ethnic‐national identity marker. Thirteen years after the Good Friday Agreement that marked the start of the peace process in the country, the question arises whether religious affiliation in Northern Ireland has become less of an ethnonational identity marker and more of a personal choice. This article analyzes religious switching and apostasy between 2001 and 2011, using data from the Northern Ireland Longitudinal Study, a representative sample of approximately 28 percent of the population, linked to the 2001 and 2011 censuses. We found that the vast majority retained their self‐reported religious affiliation, a tiny minority switched between Protestantism and Catholicism, and a significant minority, particularly among the young, switched to “none/not stated” or between Protestant denominations. Religious switching is associated with young age, higher education, and also socioeconomic deprivation. Experiences of social frustration appear to drive many to leave their faith