Dynamics of the blood plasma proteome during hyperacute HIV-1 infection.

The complex dynamics of protein expression in plasma during hyperacute HIV-1 infection and its relation to acute retroviral syndrome, viral control, and disease progression are largely unknown. Here, we quantify 1293 blood plasma proteins from 157 longitudinally linked plasma samples collected before, during, and after hyperacute HIV-1 infection of 54 participants from four sub-Saharan African countries. Six distinct longitudinal expression profiles are identified, of which four demonstrate a consistent decrease in protein levels following HIV-1 infection.

Interpreting biologically informed neural networks for enhanced proteomic biomarker discovery and pathway analysis.

The incorporation of machine learning methods into proteomics workflows improves the identification of disease-relevant biomarkers and biological pathways. However, machine learning models, such as deep neural networks, typically suffer from lack of interpretability. Here, we present a deep learning approach to combine biological pathway analysis and biomarker identification to increase the interpretability of proteomics experiments.

A pharmacoproteomic landscape of organotypic intervention responses in Gram-negative sepsis.

Sepsis is the major cause of mortality across intensive care units globally, yet details of accompanying pathological molecular events remain unclear. This knowledge gap has resulted in ineffective biomarker development and suboptimal treatment regimens to prevent and manage organ dysfunction/damage. Here, we used pharmacoproteomics to score time-dependent treatment impact in a murine Escherichia coli sepsis model after administering beta-lactam antibiotic meropenem (Mem) and/or the immunomodulatory glucocorticoid methylprednisolone (Gcc).

Generalized precursor prediction boosts identification rates and accuracy in mass spectrometry based proteomics.

Data independent acquisition mass spectrometry (DIA-MS) has recently emerged as an important method for the identification of blood-based biomarkers. However, the large search space required to identify novel biomarkers from the plasma proteome can introduce a high rate of false positives that compromise the accuracy of false discovery rates (FDR) using existing validation methods. We developed a generalized precursor scoring (GPS) method trained on 2.

Proteome Profiling of Recombinant DNase Therapy in Reducing NETs and Aiding Recovery in COVID-19 Patients.

Severe coronavirus disease 2019 (COVID-19) can result in pneumonia and acute respiratory failure. Accumulation of mucus in the airways is a hallmark of the disease and can result in hypoxemia. Here, we show that quantitative proteome analysis of the sputum from severe patients with COVID-19 reveal high levels of neutrophil extracellular trap (NET) components, which was confirmed by microscopy.

Evaluation of the Forsvall biopsy needle in an model of transrectal prostate biopsy - a novel needle design with the objective to reduce the risk of post-biopsy infection.

Background: Transrectal prostate biopsy (TRbx) transfers colonic bacteria into prostatic tissue, potentially causing infectious complications, including sepsis. Our objective was to determine whether biopsy needle shape, surface properties and sampling mechanism affect the number of bacteria transferred through the colon wall, and evaluate a novel needle with improved properties.

Methods: The standard Tru-Cut biopsy needle used today was evaluated for mechanisms of bacterial transfer in a pilot study.

Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis.

Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae, and treatment options. Here, we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis.

Automated Image-Based Quantification of Neutrophil Extracellular Traps Using NETQUANT.

Neutrophil extracellular traps (NETs) are web-like antimicrobial structures consisting of DNA and granule derived antimicrobial proteins. Immunofluorescence microscopy and image-based quantification methods remain important tools to quantitate neutrophil extracellular trap formation. However, there are key limitations to the immunofluorescence-based methods that are currently available for quantifying NETs.

Fever of Unknown Origin in a Renal Transplant Recipient: Lactate Dehydrogenase as an Important Clue to Diagnosis.

Histoplasmosis is a rare disease in nonendemic areas. We report a case of a 23-year-old male patient who presented with fever of unknown origin, cytopenias, organomegaly, and allograft dysfunction 4 months after renal transplant with father as donor. Bone marrow examination showed intracellular budding yeast cells, which was confirmed as histoplasmosis by culture of bone marrow biopsy sample.

Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis.

Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins.

NETQUANT: Automated Quantification of Neutrophil Extracellular Traps.

Neutrophil extracellular traps (NETs) that are extensive webs of DNA covered with antimicrobial proteins into the extracellular environment during infection or inflammation as a part of their defense arsenal. Image acquisition of fluorescently labeled NETs and subsequent image-based quantification is frequently used to analyze NET formation (NETosis) in response to various stimuli. However, there are important limitations in the present methods for quantification.

Saliva-Induced Clotting Captures Streptococci: Novel Roles for Coagulation and Fibrinolysis in Host Defense and Immune Evasion.

Streptococcal pharyngitis is among the most common bacterial infections, but the molecular mechanisms involved remain poorly understood. Here we investigate the interactions among three major players in streptococcal pharyngitis: streptococci, plasma, and saliva. We find that saliva activates the plasma coagulation system through both the extrinsic and the intrinsic pathways, entrapping the bacteria in fibrin clots.

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 novel mechanism for NETosis provides antimicrobial defense at the oral mucosa.

Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils.

The epidermal growth factor receptor is a regulator of epidermal complement component expression and complement activation.

The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin wounds in vivo and in cultured keratinocytes after exposure to supernatant from stimulated mononuclear cells.

FAF and SufA: proteins of Finegoldia magna that modulate the antibacterial activity of histones.

Many bacterial pathogens have developed methods to overcome the defences of the host innate immune system. One such defence is the release of antimicrobial peptides (AMPs). Histones have been found to function as AMPs, in addition to their main biological function of packaging and organising DNA into nucleosomes.

Azurophil granule proteins constitute the major mycobactericidal proteins in human neutrophils and enhance the killing of mycobacteria in macrophages.

Pathogenic mycobacteria reside in, and are in turn controlled by, macrophages. However, emerging data suggest that neutrophils also play a critical role in innate immunity to tuberculosis, presumably by their different antibacterial granule proteins. In this study, we purified neutrophil azurophil and specific granules and systematically analyzed the antimycobacterial activity of some purified azurophil and specific granule proteins against M.