Ezrin drives adaptation of monocytes to the inflamed lung microenvironment.

Ezrin, an actin-binding protein, orchestrates the organization of the cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. Its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to investigate the contribution of ezrin to monocyte recruitment and adaptation to the lung extracellular matrix (ECM) in response to lipopolysaccharide (LPS).

Utility of Film Array Meningoencephalitis Panel in Children With Acute Encephalitis Syndrome: A Single Centre Experience from South India.

Objective: To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES).

Methods: A retrospective audit was conducted between January 2017 to July 2022. We included children aged < 18 years with a diagnosis of AES for whom a CSF analysis study including FAME panel testing performed within 48 hours of admission was available.

Targeted checkpoint control of B cells undergoing positive selection in germinal centers by follicular regulatory T cells.

Follicular regulatory T cells (Tfr) can play opposite roles in the regulation of germinal center (GC) responses. Depending on the studies, Tfr suppress or support GC and B cell affinity maturation. However, which factors determine positive vs.

Molecular characterization of typing and subtyping of Staphylococcal cassette chromosome SCC types I to V in methicillin-resistant from clinical isolates from COVID-19 patients.

Background And Objectives: Methicillin resistance is acquired by the bacterium due to gene which codes for penicillin-binding protein (PBP2a) having low affinity for β-lactam antibiotics. gene is located on a mobile genetic element called staphylococcal cassette chromosome (SCC). SCC genomic island comprises two site-specific recombinase genes namely and [cassette chromosome recombinase] accountable for mobility.

Molecular Characterization of Carbapenem-Resistant with Special Reference to Carbapenemases: A Systematic Review.

Carbapenemases are β-lactamase enzymes that hydrolyze a variety of β-lactams including carbapenem and belong to different Ambler classes (A, B, D). These enzymes can be encoded by plasmid or chromosomal-mediated genes. The major issues associated with carbapenemases-producing organisms are compromising the activity and increasing the resistance to carbapenems which are the last resort antibiotics used in treating serious infections.

Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy.

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma. However, widespread use is deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies.

Ezrin Promotes Antigen Receptor Diversity during B Cell Development by Supporting Ig H Chain Variable Gene Recombination.

Genome-level rearrangements of Ig genes during B cell development are critical for generation of a diverse repertoire of BCRs that bind to a multitude of foreign Ags and some self Ags. Bone marrow B cell development involves a variety of cell-cell interactions, cell migration, and receptor signaling that likely benefit from the activity of membrane-cytoskeletal reorganizing proteins. However, the specific contribution of such proteins toward BCR repertoire diversification is poorly understood.

Tyrosine phosphorylation of NLRP3 by the Src family kinase Lyn suppresses the activity of the NLRP3 inflammasome.

In response to microbes and other danger signals, the NLRP3 inflammasome in immune cells triggers the activation of the protease caspase-1, which mediates the maturation of the inflammatory cytokine IL-1β. Here, we investigated how the NLRP3 inflammasome is regulated. We found that its activation in primary mouse macrophages induced the Src family kinase Lyn to phosphorylate NLRP3 at Tyr, which correlated with a subsequent increase in its ubiquitination that facilitated its proteasome-mediated degradation.

Molecular Characterization Identifies Upstream Presence of IS to Carbapenemase Genes in Carbapenem-Resistant .

 Evaluating the expression pattern of oxacillinases (OXA) carbapenemases is essential to understand the prevalence and spread of carbapenem resistance .  The aim of the study is to evaluate the presence of OXA carbapenemase genes and IS upstream to these genes in carbapenem-resistant clinical isolates.   isolated from clinical samples were phenotypically identified and antibiotics sensitivity was performed.

Cutting Edge: Myosin 18A Is a Novel Checkpoint Regulator in B Cell Differentiation and Antibody-Mediated Immunity.

We investigated the function of the newly discovered myosin family protein myosin 18A (Myo18A) in Ab-mediated immunity by generating B cell-conditional Myo18A-deficient mice. Myo18A deficiency led to expansion of bone marrow progenitor B cells and mature B cells in secondary lymphoid organs. Myo18A-deficient mice displayed serum IgM hyperglobulinemia and increased splenic IgM-secreting cells, with older mice switching to IgG1 hyperglobulinemia and autoantibody development.

Pharmacologic Inhibition of Ezrin-Radixin-Moesin Phosphorylation is a Novel Therapeutic Strategy in Rhabdomyosarcoma.

Intermediate and high-risk rhabdomyosarcoma (RMS) patients have poor prognosis with available treatment options, highlighting a clear unmet need for identification of novel therapeutic strategies. Ezrin-radixin-moesin (ERM) family members are membrane-cytoskeleton linker proteins with well-defined roles in tumor metastasis, growth, and survival. ERM protein activity is regulated by dynamic changes in the phosphorylation at a conserved threonine residue in their C-terminal actin-binding domain.

Cutting Edge: Deletion of Ezrin in B Cells of Lyn-Deficient Mice Downregulates Lupus Pathology.

Genetic deletion of the Src family tyrosine kinase Lyn in mice recapitulates human systemic lupus erythematosus, characterized by hyperactive BCR signaling, splenomegaly, autoantibody generation, and glomerulonephritis. However, the molecular regulators of autoimmunity in Lyn-deficient mice and in human lupus remain poorly characterized. In this study, we report that conditional deletion of the membrane-cytoskeleton linker protein ezrin in B cells of Lyn-deficient mice (double knockout [DKO] mice) ameliorates B cell activation and lupus pathogenesis.

CD6 Receptor Regulates Intestinal Ischemia/Reperfusion-induced Injury by Modulating Natural IgM-producing B1a Cell Self-renewal.

Intestinal ischemia/reperfusion (I/R) injury is a relatively common pathological condition that can lead to multi-organ failure and mortality. Regulatory mechanism for this disease is poorly understood, although it is established that circulating pathogenic natural IgM, which is primarily produced by B1a cells outside of the peritoneal cavity, are integrally involved. CD6 was originally identified as a marker for T cells and was later found to be present on some subsets of B cells in humans; however, whether CD6 plays any role in intestinal I/R-induced injury and, if so, the underlying mechanisms, remain unknown.

Inhibitors of retrograde trafficking active against ricin and Shiga toxins also protect cells from several viruses, Leishmania and Chlamydiales.

Medical countermeasures to treat biothreat agent infections require broad-spectrum therapeutics that do not induce agent resistance. A cell-based high-throughput screen (HTS) against ricin toxin combined with hit optimization allowed selection of a family of compounds that meet these requirements. The hit compound Retro-2 and its derivatives have been demonstrated to be safe in vivo in mice even at high doses.

Sepsis 2016 Agra, India. Agra, India. 5-6 February 2016.

P1 D-Dimer in adult patients with presumed sepsis and their clinical outcomes Surinder Kumar Sharma, Anurag Rohatgi, Mansi Bajaj P2 Diagnosis of infection utilizing Acellix CD64 Charles L. Sprung, Ricardo Calderon Morales, Harvey Kasdan, Allon Reiter, Tobias Volker, Julien Meissonnier P3 High levels of phenylcarboxylic acids reflect the severity in ICU patients and affect phagocytic activity of neutrophils Natalia Beloborodova, Viktor Moroz, Aleksandra Bedova, Yulia Sarshor, Artem Osipov, Katerina Chernevskaya P4 The role of bacterial phenolic metabolites in mitochondrial dysfunction Nadezhda Fedotcheva, Ekaterina Chernevskaya, Natalia Beloborodova P5 The early diagnosis of severe sepsis and judgment of rapid transport to critical care center: better prognostic factor Hisashi Imahase, Kosuke C Yamada, Yuichiro Sakamoto, Miho Ohta, Ryota Sakurai, Mayuko Yahata, Mitsuru Umeka, Toru Miike, Hiroyuki Koami, Futoshi Nagashima, Takashi Iwamura, Satoshi Inoue P6 Translational neuromodulation of the immune system Zhifeng Li, Dennis Grech, Patrick Morcillo, Alex Bekker, Luis Ulloa P7 Pathway-level meta-analysis reveals transcriptional signature of septic shock Samanwoy Mukhopadhyay, Abhay D Pandey, Samsiddhi Bhattacharjee, Saroj K Mohapatra P8 Antibiotic dosing in septic patients on the critical care unit - a literature review Julie K Wilson P9 Pandemic of clone O25: H4-ST131 producing CTX-M-15 extended spectrum- β- lactamase- as serious cause of multidrug resistance extraintestinal pathogenic infections in India Savita Jadhav, Rabindra Nath Misra, Nageswari Gandham, Kalpana Angadi, Chanda Vywahare, Neetu Gupta, Deepali Desai P10 Detection and characterization of meningitis using a DDA-based mass spectrometry approach Anahita Bakochi, Tirthankar Mohanty, Adam Linder, Johan Malmström P11 Diagnostic usefulness of lipid profile and procalcitonin in sepsis and trauma patients Dimple Anand, Seema Bhargava, Lalit Mohan Srivastava, Sumit Ray P12 Heparin – a novel therapeutic in sepsis? Jane Fisher, Peter Bentzer, Adam Linder P13 Hypothalamic impairment is associated with vasopressin deficiency during sepsis Luis Henrique Angenendt da Costa, Nilton Nascimentos dos Santos Júnior Carlos Henrique Rocha Catalão, Maria José Alves da Rocha P14 Presepsin (soluble CD14 subtype) is a dependable prognostic marker in critical septic patients Alfredo Focà, Cinzia Peronace, Giovanni Matera, Aida Giancotti, Giorgio Settimo Barreca, Angela Quirino, Maria Teresa Loria, Pio Settembre, Maria Carla Liberto, Bruno Amantea P15 Safety and efficacy of gelatin-containing solutions versus crystalloids and albumin - a systematic review with quantitative and qualitative summaries Christiane Hartog, Christiane Hartog, Claudia Moeller, Carolin Fleischmann, Daniel Thomas-Rueddel, Vlasislav Vlasakov, Bram Rochwerg, Philip Theurer, Konrad Reinhart P16 Immunomodulatory properties of peripheral blood mesenchymal stem cells following endotoxin stimulation in an equine model Anna E. Smith, Sandra D.

A Review of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) and Enamel Remineralization.

White-spot lesions are the earliest macroscopic evidence of enamel caries. In such a situation, the enamel surface layer stays intact during subsurface demineralization, but without treatment the subsurface loss will continue, and eventually the surface layer will collapse and lead to a cavity formation. By introducing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) at this stage the lesion can be reversed.

Cutting Edge: Ezrin Regulates Inflammation by Limiting B Cell IL-10 Production.

IL-10 produced by B cells is important for controlling inflammation, thus underscoring the need to identify mechanisms regulating its production. In this study, we demonstrate that conditional deletion of ezrin in B cells increases IL-10 production induced by TLR4 ligation. The MyD88-independent Toll/IL-1R domain-containing adapter inducing IFN-β-IFN regulatory factor 3 pathway is required for Ezrin-deficient B cells to produce higher IL-10 upon LPS stimulation.

Isolation and identification of Acinetobacter species with special reference to antibiotic resistance.

Background: Acinetobacter is clinically important pathogen with widespread resistance to various antibiotics. We assessed the incidence of Acinetobacter infection at a tertiary care hospital, analyze their resistance pattern and identify the production of extended spectrum β-lactamases (ESBLs) and metallo β-lactamases (MBLs).

Materials And Methods: The study was conducted in tertiary care hospital, India over a period of 2 years.

The ezrin-radixin-moesin family of proteins in the regulation of B-cell immune response.

Dynamic reorganization of the cortical cytoskeleton is essential for numerous cellular processes, including B- and T-cell activation and migration. The ezrin-radixin-moesin (ERM) family of proteins plays structural and regulatory roles in the rearrangement of plasma membrane flexibility and protrusions through its members' reversible interaction with cortical actin filaments and the plasma membrane. Recent studies demonstrated that ERM proteins not only are involved in cytoskeletal organization but also offer a platform for the transmission of signals in response to a variety of extracellular stimuli through their ability to cross-link transmembrane receptors with downstream signaling components.

(S)-N-Methyldihydroquinazolinones are the Active Enantiomers of Retro-2 Derived Compounds against Toxins.

This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of a new compound, named Retro-2.1, active against toxins by inhibiting intracellular trafficking via the retrograde route. The absolute configuration of the bioactive enantiomer has been assigned from X-ray diffraction to the (S)-enantiomer.

Primary splenic tubercular abscess in an immunocompromised patient-rapid diagnosis by line probe assay.

Diagnosing extra-pulmonary tuberculosis is a challenge that can confound even the most practiced clinicians as clinical manifestations are vague, non-specific and typical chest radiograph findings may not be evident till late in the disease. Conventional methods for mycobacteriological culture and drug susceptibility testing are slow and cumbersome. Novel technologies for rapid detection of Mycobacterium tuberculosis and its anti-TB drug resistance have therefore become a priority hence with the development of molecular line probe assays are most advanced.

Intraoperative Crede maneuver for tape adjustment during transobturator sling placement: does it improve continence?

Objective: This study evaluated the efficacy of intraoperative extrinsic manual compression on the bladder, or Crede maneuver (CM) for tape adjustment during transobturator tape (TOT) sling procedure versus the traditional method where tension-free tape is adjusted the same for all patients.

Methods: All patients undergoing TOT sling procedure for stress urinary incontinence (SUI) between May 2008 and June 2011 by the first author were assessed. Tape adjustment was either performed in a traditional manner, leaving a tonsil clamp-size space between the sling and posterior urethra, or by using CM after filling the bladder to 300 ml capacity.

Re-defining ERM function in lymphocyte activation and migration.

Lymphocyte activation and migration involve large-scale actin cytoskeletal remodeling. The Ezrin-Radixin-Moesin (ERM) family proteins reversibly link the plasma membrane and cortical actin meshwork and mediate the dynamic nature of the membrane-cytoskeletal interface to facilitate remodeling. The reversibility of this linkage is controlled by the conformation of ERM proteins and depends on the phosphorylation of a conserved threonine residue in the actin-binding domain.