Hypoalphalipoproteinemias

Upon infection or immunization, all jawed vertebrate species generate proteins called antibodies that bind and neutralize pathogens. Strong and long-lasting antibody responses in warm-blooded species such as mammals are produced in secondary lymphoid microstructures (SLMs) among which germinal centers (GCs) are the centerpiece. Despite the apparent absence of GCs or similar SLMs in cold-blooded vertebrates (e.g., fish), these species can mount significant antibody responses that can persist for several months. Thus, for decades, the outstanding question has remained as to how and where antibody responses are generated in species that lack GCs or analogous SLM structures. Upon infection or immunization, all jawed vertebrate species generate proteins called antibodies that bind and neutralize pathogens. Strong and long-lasting antibody responses in warm-blooded species such as mammals are produced in secondary lymphoid microstructures (SLMs) among which germinal centers (GCs) are the centerpiece. Despite the apparent absence of GCs or similar SLMs in cold-blooded vertebrates (e.g., fish), these species can mount significant antibody responses that can persist for several months. Thus, for decades, the outstanding question has remained as to how and where antibody responses are generated in species that lack GCs or analogous SLM structures. A new study featured on the cover of the journal Science Immunology, reconsiders the understanding of immune responses in cold-blooded species. Investigators at the University of Pennsylvania's School of Veterinary Medicine (Penn Vet) have discovered, contrary to earlier belief, that induction of antibody responses in bony fish occurs in primordially organized SLMs that play roles similar to those of GCs from warm-blooded animals. More specifically, the study identifies the formation in the spleen of large aggregates of highly proliferating B cells (the cells producing antibodies) and T cells (the cells helping B cells to produce antibodies) upon infection or immunization of fish. The newly induced B and T cell zones are formed nearby melanomacrophage centers (MMCs), which are tissue areas containing groups of dark-colored melanomacrophages where antigen is retained upon infection. These newly discovered MMC-associated lymphoid aggregates (M-LAs), contain numerous antigen-specific B cells, thus highlighting their key role in the immune response. Moreover, similar to what ensues in GCs, B cell clonal expansion and somatic hypermutation processes occur within M-LAs. "Our findings challenge the former dogma that fish do not contain specific lymphoid microenvironments where immune responses are generated while revealing a previously unknown type of SLM in jawed vertebrates" said J. Oriol Sunyer, corresponding author of the study, and professor of Immunology at Penn Vet. "This discovery has far-reaching implications for our understanding of the immune system's evolution and its potential applications in various fields, from fish vaccinology to human medicine." The research presents a new perspective on how immune responses can be induced in vertebrates, thus offering new opportunities to understand primordially conserved principles through which M-LAs and GCs function. "For instance, fish M-LAs are highly polyclonal structures, thus resembling newly identified mammalian GCs that operate in polyclonal settings," said Sunyer. "Therefore, the study of fish M-LAs is likely to shed light on the mechanisms by which both polyclonal GCs and M-LAs are formed." From an applied perspective, these findings are critical for the generation of more effective knowledge-based vaccines for fish. Disease and health management problems are one of the major hurdles for the developing aquaculture industry in the US and worldwide. While vaccines delivered to fish have contributed enormously to the near eradication of several fish diseases, many vaccines for a number of old and emerging fish pathogens are inefficient due to our lack of knowledge on how immune responses are generated in these species. "Now that we know where and how antibody responses are induced in fish, the study of M-LAs will identify correlates of immune activation and protection that will pave the road for the screening and development of more efficacious and safer vaccines and adjuvants for the aquaculture industry," added Sunyer. For more details on this study, please refer to the full paper, titled "Cold-blooded vertebrates evolved organized germinal center like structures," published in the December 2023 issue of Science Immunology and the Focus commentary dedicated to the paper in that issue. This work was funded by the National Institutes of Health (2R01GM085207-09), the U.S. Department of Agriculture (USDA-NIFA 2021-06961, USDA-NIFA 2020-06446), National Natural Science Foundation of China (31802337), and the Japan Society for the Promotion of Science (KAKENHI 20KK0144, KAKENHI 21H02288, KAKENHI 20K22594, Oversees Research Fellowship).

The world's largest dam removal and restoration project currently underway on the Klamath River in Oregon and California will aid salmon populations that have been devastated by disease and other factors. However, it will not fully alleviate challenges faced by the species, a team of researchers conclude. The world's largest dam removal and restoration project currently underway on the Klamath River in Oregon and California will aid salmon populations that have been devastated by disease and other factors. However, it will not fully alleviate challenges faced by the species, a team of researchers conclude in a just-published paper. "The dam removals will likely go a long way towards restoring balance in the river," said Sascha Hallett, a fish parasitologist at Oregon State University who has studied the river for two decades. "Certainly under certain circumstances there are going to be disease outbreaks, like with people and pathogens. But we envision that they are not going to be as large and not going to be as frequent as we have observed in the past." Michael Belchik, a fisheries biologist with the Yurok Tribe in California and co-author of the paper, said he thinks there will be noticeable gains for fish shortly after the dams are removed. "I think you are going to see fish accessing new habitat right away, and that is going to be a cause for celebration," said Belchik, who has worked for the Tribe since 1995. In the paper, published in Frontiers in Ecology and Evolution, Hallett and a team of researchers from Oregon State, Tribes in Oregon and California, and state and federal agencies outlined their predictions for salmon disease risk in the Klamath River following the removal of four hydroelectric dams. They also provide post-dam removal research and monitoring recommendations and insights to aid habitat restoration efforts. One of the four dams was removed earlier this year, and the other three are slated to be taken down in early 2024. Removal of the dams will result in restoration of habitat originally altered more than 100 years ago with construction of the first dam. The Klamath River runs more than 250 miles from Oregon's high desert interior through the Cascade Mountains before entering the Pacific Ocean in northern California. It has broad ecological, cultural, recreational and economic relevance. The river was once the third largest salmon-producing river on the West Coast. Those salmon served as the foundation of life and culture for Tribes living along the river. Construction of the dams in the early-to-mid-20th century blocked access for salmon and other fish species to hundreds of miles of habitat and created barriers that led to increases in pathogens deadly to the fish. This dynamic received widespread attention in 2002 when there was a die-off of tens of thousands of chinook salmon in the Klamath River. Shortly after this event, Jerri Bartholomew, an Oregon State microbiologist who works with Hallett, started studying the Klamath River salmon. Salmon health is impacted by many factors, including stream-flow levels, water temperature and pathogens. Barthlomew and her colleagues focus on the pathogens. They have spent the past 20 years unraveling how a parasite known as Ceratonova shasta works in conjunction with an aquatic worm host, Manayunkia occidentalis, which is smaller than an eyelash, to create conditions in the Klamath River that are deadly to salmon. In the paper, researchers say that increased habitat availability and longer fish migration routes created by dam removals will increase duration of pathogen exposure. However, restoration of the river's natural flow will decrease fish disease risk by essentially flushing out the pathogens and unclogging a pathogen hot spot that has formed below the Iron Gate Dam, about five miles south of the California-Oregon border just east of Interstate 5. The dam is slated for removal in early 2024. "There's no question in my mind just the removal of these four dams will go a long way to knocking back that current infection zone by shifting things in terms of time and space where the hosts and parasites overlap," said Julie Alexander, an aquatic ecologist who works with Hallett and Barthlomew. She also cautioned that restoration efforts that will occur after dam removal need to be conducted thoughtfully. "You don't want to go and restore a section of river to encourage salmon to spawn somewhere we know there are worms because then you are going to create a hot spot," Alexander said. In addition to co-authors from the Yurok Tribe, authors of the paper include scientists at the Hoopa, Klamath and Karuk Tribes, Oregon Department of Fish and Wildlife, U.S. Fish and Wildlife Service and the National Oceanic and Atmospheric Administration. The ongoing research by Oregon State and its partners has been supported by the U.S. Bureau of Reclamation. That includes a $4.5 million award earlier this year. "Without this funding and without these groups contributing different pieces of the datasets, we would not have been poised at this time to capture that and be able to make predictions," Hallett said. "Those two things are really important going forward to be able to inform short-term and long-term management actions as well as being able to inform 'Was this major environmental change event successful?'"

Scientists using natural tracers off Queensland’s coast have discovered the source of previously unquantified nitrogen and phosphorus having a profound environmental impact on the Great Barrier Reef. Groundwater discharge accounted for approximately one-third of new nitrogen and two-thirds of phosphorus inputs, indicating that nearly twice the amount of nitrogen enters the Reef from groundwater compared to river waters. Scientists using natural tracers off Queensland's coast have discovered the source of previously unquantified nitrogen and phosphorus having a profound environmental impact on the Great Barrier Reef. The findings, published today in Environmental Science and Technology, indicate current efforts to preserve and restore the health of the Reef may require a new perspective. Southern Cross University's Dr Douglas Tait leads the ground-breaking study, 'Submarine groundwater discharge exceeds river inputs as a source of nutrients to the Great Barrier Reef'. Submarine groundwater discharge is any water released to the ocean below the waterline from various sources, including underground aquifers and the seafloor. The research team, which also includes CSIRO, AIMS and Gothenburg University (Sweden), collected data from offshore transects, rivers and coastal bores in an area from south of Rockhampton to north of Cairns. The use of radium isotopes allowed the scientists to track how much nutrient is transported from the land and shelf sediments via invisible groundwater flows. Southern Cross Professor Damien Maher said the team's work showed that groundwater discharge was 10-15 times greater than river inputs, something previously unaccounted for. "Groundwater discharge accounted for approximately one-third of new nitrogen and two-thirds of phosphorus inputs, indicating that nearly twice the amount of nitrogen enters the Reef from groundwater compared to river waters," Professor Maher said. Professor Maher added that the lion's share of efforts to mitigate the impact of nutrients on the Reef were focused on outflow from river systems. Lead author Dr Douglas Tait said: "Nutrients are essential to support the incredible biodiversity of the Great Barrier Reef." "However, an excess of nutrients can lead to detrimental issues such as harmful algal blooms, crown-of-thorns starfish outbreaks, and fish diseases, which have been on the rise in the Reef over the past few decades. "Our study underscores the need for a strategic shift in management approaches aimed at safeguarding the Great Barrier Reef from the effects of excess nutrients." Dr Tait said unlike river outflow, nutrients in groundwater could be stored for decades underground before being discharged into coastal waters, meaning research and strategies to protect the Reef needed to be long-term. "This study sheds new light on the complex nutrient dynamics within the Great Barrier Reef," Dr Tait said. "Our understanding and ability to manage the sources of nutrients is pivotal in preserving the Reef for generations to come." The project was supported with funding from the Australian Research Council, the Herman Slade Foundation and the Great Barrier Reef Foundation.