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Researchers on a deep-sea expedition have found PCB in sediment samples from the more than 8,000-meter-deep Atacama Trench in the Pacific Ocean. PCB has been banned in most countries since the 1970s, but that doesn't mean it no longer exists. Now, deep-sea researchers report that they have found PCB at the bottom of the Atacama Trench in the Pacific Ocean. During their expedition to the deep-sea trench, the research team retrieved sediment cores and analyzed them for PCB occurrences at five different locations in the trench. All the samples of surface sediment analyzed contained PCB. The study, led by Professor Anna Sobek from the Department of Environmental Science at Stockholm University and Professor Ronnie N. Glud, director of the Danish Center for Hadal Research at the University of Southern Denmark, has been published in the scientific journal Nature Communications. PCB is short for Poly-Chlorinated Biphenyls, which covers 209 different substances. They were introduced in the 1930s and have been used primarily in building materials and technical components, but are now banned in most countries and classified as a highly persistent environmental toxin. PCB can be carcinogenic and cause reproductive harm. Although the world's production of PCBs dropped significantly in the 1970s, the substances still pose an environmental threat. In 2018 researchers reported, for example, that half of the world's killer whale populations were weakened by PCB. Another study has found that scavenging amphipods in the deep sea contained large amounts of PCBs. "It is thought-provoking that we find traces of human activity at the bottom of a deep-sea trench; a place that most people probably perceive as distant and isolated from our society," says Professor Ronnie N. Glud, who has participated in more than 10 expeditions to deep-sea trenches around the world. These expeditions have helped to dispel the myth that deep-sea trenches are unaffected by what happens on the surface and have provided insight into the surprisingly rich, active, and varied life at the greatest depths of the ocean. The studies have also shown that deep-sea trenches accumulate large amounts of organic material, contributing to the oceans' ability to absorb carbon released into the atmosphere through fossil fuel burning. However, not only organic material accumulates in deep-sea trenches, which are also called hadal trenches. For example, the Danish Center for Hadal Research reported in 2021 that mercury also accumulates in the trenches' sediments, and in 2022, a similar announcement was made about black carbon, which is particles that are mainly formed by the combustion of fossil fuels. The concentration of PCBs in samples from the Atacama Trench is not alarmingly high, according to Ronnie N. Glud. He points out that much higher concentrations have been found in places like the Baltic Sea, North Sea, and Tokyo Bay. Concentrations 300-1500 times higher have been measured in the Baltic Sea. "These are places with a lot of human activity, so one would expect that. The Atacama samples do not show very high concentrations but considering that they were retrieved from the bottom of a deep-sea trench, they are relatively high. A priori no one would expect to find pollutants in such a place," says Ronnie N. Glud. PCBs are hydrophobic, meaning they are not very soluble in water. Instead, they bind to organic material that sinks to the bottom. "The Atacama trench is located in an area with relatively high production of plankton in surface waters. When the plankton dies, it sinks to the bottom of the ocean," explains Anna Sobek. In addition, large amounts of material are transported down the steep slopes and deposit in the deepest areas. Some of the organic material that reaches the bottom of the Atacama trench is eventually decomposed by microorganisms, and as a result, PCBs accumulate in sediment. PCBs are persistent compounds that are slowly redeposited over time, which is why increasing concentrations can be found in inaccessible areas such as the hadal trenches, even though they were largely banned worldwide in the 1970s. "Unlike coastal areas where PCB concentrations are typically higher in deeper sediment layers deposited 50 years ago, PCB concentrations in hadal sediments are highest in the upper sediment layers, indicating that PCBs have only recently reached the deeper trenches and that concentrations have not yet peaked: We may see higher concentrations in a few years," says Ronnie N. Glud. The deep-sea trenches are home to many different microorganisms and animals that have adapted to the extreme living conditions. Perhaps they are also home to organisms that can metabolize the pollutants that are deposited there. That is one of the focus points of Danish Center for Hadal Research and for this research, the center holds a solid stock of frozen sediment samples collected from expeditions to different deep-sea trenches in 2021 and 2022. "We are interested in finding out if PCBs are also present in other deep-sea trenches or if they are unique to the Atacama trench. We also want to investigate the bacteria that live down there and learn more about their function," says Ronnie N. Glud. The deep-sea trenches are located in the hadal zone of the ocean, which lies at depths of 6-11 km. There are about 27 deep-sea trenches, also called hadal trenches, named after the Greek god Hades, who ruled the underworld.

Aging and related diseases are associated with alterations in oxidative status and low-grade inflammation, as well as a decreased endoplasmic reticulum (ER) unfolded protein response (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress. Researchers analyzed these proteins in peripheral blood mononuclear cells of elderly subjects and used computer simulation to predict the key proteins associated with these biomolecules underlying physiological adaptations to exercise. They collected blood samples about five to six days before and after the training period and analyzed various oxidative stress biomarkers in peripheral blood mononuclear cells. The study takes research one step further in helping to elucidate the benefits of exercise in this population. Aging involves a balance between oxidants and antioxidants, low-grade inflammation and a protein response that occurs at the cellular level, which is responsible for many health disorders. Exercise has been shown to regulate the inflammatory response, balance oxidants such as free radicals that build up in the cells and damage DNA; and ameliorate the process by which cells protect themselves against these stressors. Furthermore, resistance training in older adults is recommended to help maintain muscle, flexibility and balance. Aging and related diseases are associated with alterations in oxidative status and low-grade inflammation, as well as a decreased endoplasmic reticulum (ER) unfolded protein response (UPR). UPR is a functional mechanism by which cells attempt to protect themselves against ER stress, resulting from the accumulation of the unfolded/misfolded proteins. One group of proteins associated with the aging process is the mitochondrial heat shock protein 60 (HSP60), which has been demonstrated to play a protective role in the ability for cells to remain active and healthy. Currently, there is limited research investigating the effects of resistance training in older adults on the expression of HSP60 and Klotho, a gene involved in the aging process in mammals. A new study by researchers at Florida Atlantic University, in collaboration with the University of León in Spain, examined whether an eight-week resistance training program would modulate the oxidative status, the UPR activation and key inflammatory pathways as well as their relationships with HSP60 and Klotho proteins. For the study, researchers analyzed these proteins in peripheral blood mononuclear cells of elderly subjects. In addition, they utilized computer simulation to predict the key proteins associated with these biomolecules underlying physiological adaptations to exercise. They collected blood samples approximately five to six days before and after the training period and just before training intervention in young subjects who were included for basal assessments. Researchers also analyzed various oxidative stress biomarkers in peripheral blood mononuclear cells. Results of the study, published in the journal Antioxidants, demonstrated that the levels of the inflammatory proteins (pIRAK1, TLR4, and TRAF6), as well as different markers of the redox balance (catalase, GSH, LP, NRF2, PC, ROS, SOD1, and SOD2) remained unchanged with training. Importantly, untrained elderly subjects showed a significant reduction in pIRE1/IRE1 ratio when compared to trained elderly subjects. Such a finding was further confirmed by a gene ontology analysis, showing that endoplasmic reticulum stress is a key mechanism modulated by IRE1. Additionally, analysis did not show the training effect on the expression of HSP60 and Klotho or their relationships with other outcome variables. Although elderly male and female subjects were included in the training program, researchers did not find any sex effects in the study. These findings might partially support the modulatory effect of resistance training on the endoplasmic reticulum in the elderly. "Regular physical activity is suggested to be an effective intervention in improving age-related diseases such as osteoporosis, sarcopenia or muscle loss and dynapenia or loss of muscle strength, cardiovascular diseases, and type 2 diabetes," said Chun-Jung "Phil" Huang, Ph.D., co-author and a professor in the Department of Exercise Science and Health Promotion within FAU's Charles E. Schmidt College of Science. "Although the beneficial effects of regular physical exercise to alleviate inflammation and oxidative stress are well-established, the processes of these physiological adaptations with regard to protein folding or UPR remains to be explored. That is why we used a systems biology approach for our study." The resistance training protocol for the study consisted of 16 sessions over eight weeks (two sessions per week), with a minimum of 48 hours between sessions. The participants started with a 10-minute warm-up on a cycle ergometer. Subsequently, eight different resistance exercises (leg press, ankle extension, bench press, leg extension, bicep curl, pec deck, high pulley traction, and dumbbell lateral lift) were performed using the exercise device. For each exercise, participants performed three sets of 12-8-12 repetitions. There was a two-to-three-minute rest between each repetition and a three-minute rest between each exercise. "We know how very important physical activity is for older adults and our study takes research one step further in helping to elucidate the benefits of exercise in this population," said Huang. Study co-authors are senior author Brisamar Estébanez, Ph.D.; Marta Rivera-Viloria; and José A. de Paz, M.D., all with the University of León; José E. Vargas, Ph.D., Universidad Federal do Paraná, Curtiba; and Nishant P. Visavadiay, Ph.D.; and Andy V. Kahmoui, Ph.D., both with FAU's Department of Exercise Science and Health Promotion.

Oral presentation describes a unique APC nanobody library and its potential as a source for novel treatments to diseases including trauma, hemophilia, ischemia and sepsis. SAN FRANCISCO, Dec. 11, 2022 /PRNewswire/ -- Coagulant Therapeutics Corporation, a privately held company focused on the design, development and commercialization of therapeutics targeted to the coagulation cascade and its adjacencies, announced data from pre-clinical studies on a novel llama-derived antibody (nanobody) library directed to the APC exosite. An oral presentation titled "Selective Modulation of Activated Protein C Activities by an Exosite-Specific Nanobody Library" will be presented at the American Society of Hematology Annual Meeting in New Orleans, Louisiana, December 10-13, 2022. "This nanobody library not only offers potential treatments for acute bleeding conditions, such as trauma and hemorrhagic stroke, it also provides the opportunity to identify possible treatments in indications beyond acute bleeding where APC plays an important role, such as hemophilia and sepsis ," said Terry Hermiston, Ph.D., founder and CEO of Coagulant Therapeutics. Dr. Hermiston pointed out that the different mechanisms of action between the APC-targeting molecules and the companies lead molecule, CT-001, an engineered highly potent, fast clearing FVIIa molecule, suggest that these molecules may actually complement one another in the clinic. "We are excited to explore their potential as additive or synergistic agents in the treatment of acute bleeds." The data, presented by Derek Sim, Ph.D., Chief Scientific Officer for Coagulant Therapeutics, described novel llama-derived nanobodies to the exosite of Activated Protein C (APC) that affected anticoagulation, histone cleavage and receptor mediated cleavage activities of APC. The characterization resulted in 13 novel activity profiles that can be employed to regulate specific APC functions for therapeutic purposes. "APC differs from the parent molecule protein C (PC) by the absence of 12 amino acids. Our hope was to use the unique properties of nanobodies to generate antibodies that selectively inhibit some of the APC associated functions" reported Dr. Sim "and we are very pleased to report the number and surprising diversity of APC-specific nanobodies, exemplified by LP 11, whose activity profile of hemostasis and cytoprotection promotion make it an appealing candidate for the treatment of Hemophilia and Trauma, respectively." In addition to the oral presentation on the APC library, Coagulant presented a poster on their lead molecule, CT-001. Abstract Title: CT-001, a Rapid Clearing Factor VIIa, Provides Pro-Hemostatic Activity to Reduce Blood Loss in Coagulopathic Conditions Induced by Activated Protein C Abstract Number: 2458 Session Name: 321. Coagulation and Fibrinolysis: Basic and Translational: Poster II Session Date: Sunday, December 11, 2022 Presentation Time: 6:00-8:00 PM CST/7:00-9:00 PM EST Presenter: Dr. Derek Sim Summary: These data, presented by Derek Sim, Ph.D., the Chief Scientific Officer of Coagulant Therapeutics, suggest that a FVIIa molecule engineered to be both safer and more active than recombinant FVIIa (rFVIIa) can be an effective treatment for acute bleeding, including bleeding with Coagulopathy, broadly defined as a derangement of hemostasis resulting in impaired clot formation. CT-001 is being developed as a new treatment for severe postpartum hemorrhage, a growing problem and a significant factor in maternal morbidity and mortality not only in the US but globally. These studies support its potential broader use in coagulopathic settings such as trauma. About CT-001 CT-001 is an engineered version of FVIIa that is designed to address the limitations of the recombinant FVIIa (rFVIIa), approved for use in Hemophilia A and B patients with inhibitors, congenital FVII deficiency, and Glanzmann's thrombasthenia with refractoriness to platelet transfusions but not approved in the US for use in the acute bleeding settings such as trauma, traumatic brain injury, intracranial hemorrhage or severe postpartum hemorrhage. To improve safety, and to address the unwanted clotting risk with rFVIIa, CT-001 was engineered for rapid clearance from the blood. This feature reduces the time in which an individual is exposed to pro-coagulant activity, which reduces the risk of thromboembolic events. To improve efficacy, while compensating for the rapid removal of CT-001 from the blood, the molecule has also been engineered to target the site of bleeding more efficiently and effectively than rFVIIa, with resultant increase in activity. CT-001 was originally developed by Dr. Hermiston while he served as Vice President of Biologics at Bayer AG and subsequently acquired by the Company. CT-001 is currently under investigation for treatment of severe postpartum hemorrhage. About APC Antibody Program APC is a pleiotropic enzyme that has been identified as a target in the treatment of a variety of disease indications including Trauma, Hemophilia, Ischemia and Sepsis. Coagulant Therapeutics Corporation has initiated a research program into the identification of APC-directed therapeutic antibodies, leveraging the unique features of llama antibodies (nanobodies) to derive novel nanobodies to the exosite of the protein. The nanobody library has an array of different antibodies to differing epitopes and, importantly, generated a lead which is being studied for treatment of trauma and hemophilia, respectively. As these nanobodies have a different target and mechanism of action to CT-001, it is anticipated that these can be independent treatments with the potential for additive or synergistic effects to CT-001 in the acute bleeding setting. About Coagulant Therapeutics Corporation Coagulant Therapeutics is a privately held company focused on the design, development and commercialization of therapeutics targeted to the coagulation cascade and its adjacencies. The Company's lead product candidate, CT-001, is a next-generation Factor VIIa designed for enhanced efficacy and safety in the setting of acute bleeding. Coagulant is also developing additional therapeutics targeted to APC for the treatment of acute bleeding and other coagulation cascade-related diseases. Founded in 2019, the company is based in Berkeley, California. Media Contact: Eliza Schleifstein 917-763-8106 [email protected] SOURCE Coagulant Therapeutics Corporation