Pyroptotic cell corpses are crowned with F-actin-rich filopodia that engage CLEC9A signaling in incoming dendritic cells.

While apoptosis dismantles the cell to enforce immunological silence, pyroptotic cell death provokes inflammation. Little is known of the structural architecture of cells undergoing pyroptosis, and whether pyroptotic corpses are immunogenic. Here we report that inflammasomes trigger the Gasdermin-D- and calcium-dependent eruption of filopodia from the plasma membrane minutes before pyroptotic cell rupture, to crown the resultant corpse with filopodia.

p97/VCP targets vacuoles for parasite restriction in interferon-stimulated human cells.

(Tg) is a ubiquitous parasitic pathogen, infecting about one-third of the global population. Tg is controlled in immunocompetent people by mechanisms that are not fully understood. Tg infection drives the production of the inflammatory cytokine interferon gamma (IFNγ), which upregulates intracellular anti-pathogen defense pathways.

PIM1 controls GBP1 activity to limit self-damage and to guard against pathogen infection.

Disruption of cellular activities by pathogen virulence factors can trigger innate immune responses. Interferon-γ (IFN-γ)-inducible antimicrobial factors, such as the guanylate binding proteins (GBPs), promote cell-intrinsic defense by attacking intracellular pathogens and by inducing programmed cell death. Working in human macrophages, we discovered that GBP1 expression in the absence of IFN-γ killed the cells and induced Golgi fragmentation.

Lorlatinib and compound mutations in ALK+ large-cell neuroendocrine lung carcinoma: a case report.

Large-cell neuroendocrine lung carcinoma (LCNEC) is a high-grade neoplasm with median survival of 1 year and limited therapeutic options. Here, we report the unusual case of a 47-yr-old female smoker with stage IV LCNEC featuring - variant 2 (E20:A20), wild-type , and low tumor mutational burden of 3.91 mut/Mb.

Toxoplasma-proximal and distal control by GBPs in human macrophages.

Human guanylate binding proteins (GBPs) are key players of interferon-gamma (IFNγ)-induced cell intrinsic defense mechanisms targeting intracellular pathogens. In this study, we combine the well-established Toxoplasmagondii infection model with three in vitro macrophage culture systems to delineate the contribution of individual GBP family members to control this apicomplexan parasite. Use of high-throughput imaging assays and genome engineering allowed us to define a role for GBP1, 2 and 5 in parasite infection control.

Comprehensive Dissection of Treatment Patterns and Outcome for Patients With Metastatic Large-Cell Neuroendocrine Lung Carcinoma.

Background: Large-cell neuroendocrine lung carcinoma (LCNEC) is a rare pulmonary neoplasm with poor prognosis and limited therapeutic options.

Methods: We retrospectively analyzed all patients with metastatic LCNEC in the records of a large German academic center since 2010.

Results: 191 patients were identified with a predominance of male (68%) smokers (92%) and a median age of 65 years.

HRMAn 2.0: Next-generation artificial intelligence-driven analysis for broad host-pathogen interactions.

To study the dynamics of infection processes, it is common to manually enumerate imaging-based infection assays. However, manual counting of events from imaging data is biased, error-prone and a laborious task. We recently presented HRMAn (Host Response to Microbe Analysis), an automated image analysis program using state-of-the-art machine learning and artificial intelligence algorithms to analyse pathogen growth and host defence behaviour.

The Gb3-enriched CD59/flotillin plasma membrane domain regulates host cell invasion by Pseudomonas aeruginosa.

The opportunistic pathogen Pseudomonas aeruginosa has gained precedence over the years due to its ability to develop resistance to existing antibiotics, thereby necessitating alternative strategies to understand and combat the bacterium. Our previous work identified the interaction between the bacterial lectin LecA and its host cell glycosphingolipid receptor globotriaosylceramide (Gb3) as a crucial step for the engulfment of P. aeruginosa via the lipid zipper mechanism.

Renal Calyceal Rupture following Ureteral Injury after Total Laparoscopic Hysterectomy.

Ureteral injury (UI) complicates 0.1%-2.5% of total laparoscopic hysterectomies (TLHs).

Human GBP1 Differentially Targets Salmonella and Toxoplasma to License Recognition of Microbial Ligands and Caspase-Mediated Death.

Interferon-inducible guanylate-binding proteins (GBPs) promote cell-intrinsic defense through host cell death. GBPs target pathogens and pathogen-containing vacuoles and promote membrane disruption for release of microbial molecules that activate inflammasomes. GBP1 mediates pyroptosis or atypical apoptosis of Salmonella Typhimurium (STm)- or Toxoplasma gondii (Tg)- infected human macrophages, respectively.

Image-Based Quantitation of Host Cell-Toxoplasma gondii Interplay Using HRMAn: A Host Response to Microbe Analysis Pipeline.

Research on Toxoplasma gondii and its interplay with the host is often performed using fluorescence microscopy-based imaging experiments combined with manual quantification of acquired images. We present here an accurate and unbiased quantification method for host-pathogen interactions. We describe how to plan experiments and prepare, stain and image infected specimens and analyze them with the program HRMAn (Host Response to Microbe Analysis).

C57BL/6 and 129 inbred mouse strains differ in Gbp2 and Gbp2b expression in response to inflammatory stimuli .

: Infections cause the production of inflammatory cytokines such as Interferon gamma (IFNγ). IFNγ in turn prompts the upregulation of a range of host defence proteins including members of the family of guanylate binding proteins (Gbps). In humans and mice alike, GBPs restrict the intracellular replication of invasive microbes and promote inflammation.

Human GBP1 is a microbe-specific gatekeeper of macrophage apoptosis and pyroptosis.

The guanylate binding protein (GBP) family of interferon-inducible GTPases promotes antimicrobial immunity and cell death. During bacterial infection, multiple mouse Gbps, human GBP2, and GBP5 support the activation of caspase-1-containing inflammasome complexes or caspase-4 which trigger pyroptosis. Whether GBPs regulate other forms of cell death is not known.

Defining host-pathogen interactions employing an artificial intelligence workflow.

Unlabelled: For image-based infection biology, accurate unbiased quantification of host-pathogen interactions is essential, yet often performed manually or using limited enumeration employing simple image analysis algorithms based on image segmentation. Host protein recruitment to pathogens is often refractory to accurate automated assessment due to its heterogeneous nature. An intuitive intelligent image analysis program to assess host protein recruitment within general cellular pathogen defense is lacking.

Legal briefing: home birth and midwifery.

This issue's "Legal Briefing" column covers recent legal developments involving home birth and midwifery in the United States. Specifically, we focus on new legislative, regulatory, and judicial acts that impact women's' access to direct entry (non-nurse) midwives. We categorize these legal developments into the following 12 categories.

Novel small-molecule inhibitors of hepatitis C virus entry block viral spread and promote viral clearance in cell culture.

Combinations of direct-acting anti-virals offer the potential to improve the efficacy, tolerability and duration of the current treatment regimen for hepatitis C virus (HCV) infection. Viral entry represents a distinct therapeutic target that has been validated clinically for a number of pathogenic viruses. To discover novel inhibitors of HCV entry, we conducted a high throughput screen of a proprietary small-molecule compound library using HCV pseudoviral particle (HCVpp) technology.

Onset and maintenance of angiogenesis in biomaterials: in vivo assessment by dynamic contrast-enhanced MRI.

Objective: To describe dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a practical tool for longitudinal assessment of angiogenesis in biomaterials.

Background: There is a lack of suitable methods for in vivo evaluation of the integration of biomaterials in a clinical setting. In oncology, DCE-MRI is used for the longitudinal monitoring of altered tumor angiogenesis during therapy.

Detection of pulmonary nodules with move-during-scan magnetic resonance imaging using a free-breathing turbo inversion recovery magnitude sequence.

Purpose: Detection of pulmonary metastases is still a challenging task for magnetic resonance imaging (MRI). It was the aim of this study to evaluate the potential of a free-breathing move-during-scan turbo inversion recovery magnitude sequence for the detection of pulmonary nodules.

Materials And Methods: The sensitivities and positive-predictive values of 2 radiologists to detect pulmonary nodules in 41 move-during-scan MRI examinations of 38 patients with different malignancies were calculated and subgroup analyses according to lesion size and localization were performed.

Purified, proteolytically mature HIV type 1 SOSIP gp140 envelope trimers.

HIV type 1 (HIV-1) envelope is a noncovalent trimer of gp120-gp41 heterodimers, and its lability has hindered structural studies. SOSIP gp140 is a soluble, proteolytically mature form of the HIV-1 envelope wherein gp120-gp41 interactions are stabilized via a disulfide bond and gp41 contains an additional trimer-stabilizing point mutation. We describe the isolation of a substantially pure preparation of SOSIP gp140 trimers derived from KNH1144, a subtype A isolate.

A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120.

The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex.

[Left flank tumor of fluctuating size in a 5-week-old boy: perirenal urinoma caused by urethral valves].

Background: Flank swelling and pseudotumors of the kidney are unusual manifestations of obstructive uropathies in small children. Our case illustrates typical problems and briefly reviews management options.

Case Report: A 5-week-old boy presented with a large, palpable urinoma due to posterior urethral valves.