Substrate specificity profiling of heat-sensitive serine protease from the fungus Onygena corvina.

Proteases catalyze hydrolysis of amide bonds within peptides and proteins, therefore they play crucial functions for organism functioning, but also in industry to facilitate numerous processes. Feather-degrading fungus Onygena corvina (O. corvina) is loaded with numerous proteases that can be utilized for variety of applications.

Fluorescent Activity-Based Probe To Image and Inhibit Factor XIa Activity in Human Plasma.

Anticoagulation therapy is a mainstay of the treatment of thrombotic disorders; however, conventional anticoagulants trade antithrombotic benefits for bleeding risk. Factor (f) XI deficiency, known as hemophilia C, rarely causes spontaneous bleeding, suggesting that fXI plays a limited role in hemostasis. In contrast, individuals with congenital fXI deficiency display a reduced incidence of ischemic stroke and venous thromboembolism, indicating that fXI plays a role in thrombosis.

Selective chemical reagents to investigate the role of caspase 6 in apoptosis in acute leukemia T cells.

Activated effector caspases 3, 6 and 7 are responsible for cleaving a number of target substrates, leading to the ultimate destruction of cells apoptosis. The functions of caspases 3 and 7 in apoptosis execution have been widely studied over the years with multiple chemical probes for both of these enzymes. In contrast, caspase 6 seems to be largely neglected when compared to the heavily studied caspases 3 and 7.

Investigation of osteoclast cathepsin K activity in osteoclastogenesis and bone loss using a set of chemical reagents.

Cathepsin K (CatK) is a lysosomal cysteine protease whose highest expression is found in osteoclasts, which are the cells responsible for bone resorption. Investigations of the functions and physiological relevance of CatK have often relied on antibody-related techniques, which makes studying its activity patterns a challenging task. Hence, we developed a set of chemical tools for the investigation of CatK activity.

Parallel imaging of coagulation pathway proteases activated protein C, thrombin, and factor Xa in human plasma.

Activated protein C (APC), thrombin, and factor (f) Xa are vitamin K-dependent serine proteases that are key factors in blood coagulation. Moreover, they play important roles in inflammation, apoptosis, fibrosis, angiogenesis, and viral infections. Abnormal activity of these coagulation factors has been related to multiple conditions, such as bleeding and thrombosis, Alzheimer's disease, sepsis, multiple sclerosis, and COVID-19.

Extended subsite profiling of the pyroptosis effector protein gasdermin D reveals a region recognized by inflammatory caspase-11.

Pyroptosis is the caspase-dependent inflammatory cell death mechanism that underpins the innate immune response against pathogens and is dysregulated in inflammatory disorders. Pyroptosis occurs via two pathways: the canonical pathway, signaled by caspase-1, and the noncanonical pathway, regulated by mouse caspase-11 and human caspase-4/5. All inflammatory caspases activate the pyroptosis effector protein gasdermin D, but caspase-1 mostly activates the inflammatory cytokine precursors prointerleukin-18 and prointerleukin-1β (pro-IL18/pro-IL1β).

Noninvasive optical detection of granzyme B from natural killer cells with enzyme-activated fluorogenic probes.

Natural killer (NK) cells are key innate immunity effectors that combat viral infections and control several cancer types. For their immune function, human NK cells rely largely on five different cytotoxic proteases, called granzymes (A/B/H/K/M). Granzyme B (GrB) initiates at least three distinct cell death pathways, but key aspects of its function remain unexplored because selective probes that detect its activity are currently lacking.

Detection of Active Granzyme A in NK92 Cells with Fluorescent Activity-Based Probe.

Cytotoxic T-lymphocytes (CTLs) and natural killer cells (NKs) kill compromised cells to defend against tumor and viral infections. Both effector cell types use multiple strategies to induce target cell death including Fas/CD95 activation and the release of perforin and a group of lymphocyte granule serine proteases called granzymes. Granzymes have relatively broad and overlapping substrate specificities and may hydrolyze a wide range of peptidic epitopes; it is therefore challenging to identify their natural and synthetic substrates and to distinguish their localization and functions.

Internally quenched fluorogenic substrates with unnatural amino acids for cathepsin G investigation.

Cathepsin G is one of four members of the neutrophil serine protease family and constitutes an important biological target in various human inflammatory diseases, such as chronic obstructive pulmonary disease, acute respiratory distress syndrome and cystic fibrosis. Many studies have been focused on determining its biological roles, the latest ones concerning its involvement in acute myeloid leukemia, and as such, multiple chemical and biochemical tools were developed to investigate cathepsin G. Nevertheless, most of them lack selectivity or sensitivity and therefore cannot be used in complex systems.

High prevalence of duodenal ulcer in Indochinese immigrants attending an Australian university hospital.

Indochinese migrants to Australia appear to have a high prevalence of duodenal ulcer (DU). To examine this hypothesis a 2 year audit of the prevalence of symptomatic DU among patients attending a general hospital was conducted. The last 6 months of this period included a prospective assessment of ulcer risk factors.

Embolisation in the management of peripancreatic pseudoaneurysm--a case report.

Peripancreatic pseudoaneurysms are an unusual cause of haemorrhage in patients with chronic pancreatitis and pseudocysts. We describe a 28 year old alcoholic male with documented chronic pancreatic pseudocysts, who presented with melaena and a large pulsatile epigastric mass. Ultrasound and digital subtraction angiography revealed a pseudoaneurysm of the gastroduodenal artery.

Biliary ascariasis--a worm in the duct.

Objective: Migration of Ascaris lumbricoides into the biliary tree may cause biliary obstruction, cholangitis or pancreatitis. Although common in endemic areas, none of these complications have previously been reported in Australia. We report here a case of obstruction of the common bile duct by an ascarid.