Abstract
Environmental changes primarily caused by humans are putting our biosphere under growing pressure. The most optimistic predictions indicate that this will continue for decades, potentially ...much longer. Managing global ecology through these challenges requires knowledge of what species are present and how their populations are changing. Yet for vast areas of the ocean, the abundance of most species is simply unknown and not monitored. The failure to monitor means conclusions about their global ecological status cannot be robust (Bindoff, N.L., Cheung, W.W.L., Kairo, J.G., Arístegui, J., Guinder, V.A., Hallberg, R. et al. (2019) Changing ocean, marine ecosystems, and dependent communities. In Pörtner, H.-O., Roberts, D.C., Masson-Delmotte, V., Zhai, P., Tignor, M., Poloczanska, E., Mintenbeck, K., Alegría, A. et al. (eds), IPCC Special Report on the Ocean and Cryosphere in a Changing Climate. https://www.ipcc.ch/srocc/chapter/chapter-5/). Yet, this ignorance delays and limits any response. These changes are, however, disrupting the commercial and indigenous harvest of essential food resources as well as many other ecosystem services important to human well-being. While the global community has made significant progress on designing a monitoring program, there remain significant gaps, hurdles and other challenges to be overcome. Here, we consider some of these challenges and provide specific recommendations regarding potential next steps toward a minimum global monitoring program for plankton.
The Western Australian rock lobster fishery has been both a highly productive and sustainable fishery. However, a recent dramatic and unexplained decline in post-larval recruitment threatens this ...sustainability. Our lack of knowledge of key processes in lobster larval ecology, such as their position in the food web, limits our ability to determine what underpins this decline. The present study uses a high-throughput amplicon sequencing approach on DNA obtained from the hepatopancreas of larvae to discover significant prey items. Two short regions of the 18S rRNA gene were amplified under the presence of lobster specific PNA to prevent lobster amplification and to improve prey amplification. In the resulting sequences either little prey was recovered, indicating that the larval gut was empty, or there was a high number of reads originating from multiple zooplankton taxa. The most abundant reads included colonial Radiolaria, Thaliacea, Actinopterygii, Hydrozoa and Sagittoidea, which supports the hypothesis that the larvae feed on multiple groups of mostly transparent gelatinous zooplankton. This hypothesis has prevailed as it has been tentatively inferred from the physiology of larvae, captive feeding trials and co-occurrence in situ. However, these prey have not been observed in the larval gut as traditional microscopic techniques cannot discern between transparent and gelatinous prey items in the gut. High-throughput amplicon sequencing of gut DNA has enabled us to classify these otherwise undetectable prey. The dominance of the colonial radiolarians among the gut contents is intriguing in that this group has been historically difficult to quantify in the water column, which may explain why they have not been connected to larval diet previously. Our results indicate that a PCR based technique is a very successful approach to identify the most abundant taxa in the natural diet of lobster larvae.
Extensive changes in DNA methylation have been observed in schizophrenia (SC) and bipolar disorder (BP), and may contribute to the pathogenesis of these disorders. Here, we performed genome-scale DNA ...methylation profiling using methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) on two brain regions (including frontal cortex and anterior cingulate) in 5 SC, 7 BP and 6 normal subjects. Comparing with normal controls, we identified substantial differentially methylated regions (DMRs) in these two brain regions of SC and BP. To our surprise, different brain regions show completely distinct distributions of DMRs across the genomes. In frontal cortex of both SC and BP subjects, we observed widespread hypomethylation as compared to normal controls, preferentially targeting the terminal ends of the chromosomes. In contrast, in anterior cingulate, both SC and BP subjects displayed extensive gain of methylation. Notably, in these two brain regions of SC and BP, only a few DMRs overlapped with promoters, whereas a greater proportion occurs in introns and intergenic regions. Functional enrichment analysis indicated that important psychiatric disorder-related biological processes such as neuron development, differentiation and projection may be altered by epigenetic changes located in the intronic regions. Transcriptome analysis revealed consistent dysfunctional processes with those determined by DMRs. Furthermore, DMRs in the same brain regions from SC and BP could successfully distinguish BP and/or SC from normal controls while differentially expressed genes could not. Overall, our results support a major role for brain-region-dependent aberrant DNA methylation in the pathogenesis of these two disorders.
Retrotransposition of endogenous retroviruses (ERVs) poses a substantial threat to genome stability. Transcriptional silencing of a subset of these parasitic elements in early mouse embryonic and ...germ cell development is dependent upon the lysine methyltransferase SETDB1, which deposits H3K9 trimethylation (H3K9me3) and the co-repressor KAP1, which binds SETDB1 when SUMOylated. Here we identified the transcription co-factor hnRNP K as a novel binding partner of the SETDB1/KAP1 complex in mouse embryonic stem cells (mESCs) and show that hnRNP K is required for ERV silencing. RNAi-mediated knockdown of hnRNP K led to depletion of H3K9me3 at ERVs, concomitant with de-repression of proviral reporter constructs and specific ERV subfamilies, as well as a cohort of germline-specific genes directly targeted by SETDB1. While hnRNP K recruitment to ERVs is dependent upon KAP1, SETDB1 binding at these elements requires hnRNP K. Furthermore, an intact SUMO conjugation pathway is necessary for SETDB1 recruitment to proviral chromatin and depletion of hnRNP K resulted in reduced SUMOylation at ERVs. Taken together, these findings reveal a novel regulatory hierarchy governing SETDB1 recruitment and in turn, transcriptional silencing in mESCs.
Cellular senescence is a programmed stress response in which cells secrete immunogenic factors that promote senescent cell removal by the immune system or immune surveillance.Different types of ...senescence occur in pancreatic islet β-cells and senescent β-cells accumulate during aging and diabetes but whether these cells are subject to immune surveillance is unknown.We hypothesize that the subpopulation of stressed senescent β-cells is under immune surveillance to limit their accumulation during aging.Available evidence supports the existence of mechanisms for islet-resident immune surveillance of stressed senescent β-cells involving macrophages and the likelihood of impairment of these mechanisms in diabetes.Elucidation of the mechanisms of islet immune surveillance holds promise for improved therapeutic targeting of senescent β-cells in diabetes.
Cellular senescence is a programmed state of cell cycle arrest that involves a complex immunogenic secretome, eliciting immune surveillance and senescent cell clearance. Recent work has shown that a subpopulation of pancreatic β-cells becomes senescent in the context of diabetes; however, it is not known whether these cells are normally subject to immune surveillance. In this opinion article, we advance the hypothesis that immune surveillance of β-cells undergoing a senescence stress response normally limits their accumulation during aging and that the breakdown of these mechanisms is a driver of senescent β-cell accumulation in diabetes. Elucidation and therapeutic activation of immune surveillance mechanisms in the pancreas holds promise for the improvement of approaches to target stressed senescent β-cells in the treatment of diabetes.
Cellular senescence is a programmed state of cell cycle arrest that involves a complex immunogenic secretome, eliciting immune surveillance and senescent cell clearance. Recent work has shown that a subpopulation of pancreatic β-cells becomes senescent in the context of diabetes; however, it is not known whether these cells are normally subject to immune surveillance. In this opinion article, we advance the hypothesis that immune surveillance of β-cells undergoing a senescence stress response normally limits their accumulation during aging and that the breakdown of these mechanisms is a driver of senescent β-cell accumulation in diabetes. Elucidation and therapeutic activation of immune surveillance mechanisms in the pancreas holds promise for the improvement of approaches to target stressed senescent β-cells in the treatment of diabetes.
Species' ranges are shifting globally in response to climate warming, with substantial variability among taxa, even within regions. Relationships between range dynamics and intrinsic species traits ...may be particularly apparent in the ocean, where temperature more directly shapes species' distributions. Here, we test for a role of species traits and climate velocity in driving range extensions in the ocean‐warming hotspot of southeast Australia. Climate velocity explained some variation in range shifts, however, including species traits more than doubled the variation explained. Swimming ability, omnivory and latitudinal range size all had positive relationships with range extension rate, supporting hypotheses that increased dispersal capacity and ecological generalism promote extensions. We find independent support for the hypothesis that species with narrow latitudinal ranges are limited by factors other than climate. Our findings suggest that small‐ranging species are in double jeopardy, with limited ability to escape warming and greater intrinsic vulnerability to stochastic disturbances.
Synaptosomal Associated Protein-25 kilodaltons (SNAP-25) is an integral member of the SNARE complex. This complex is essential for calcium-triggered synaptic vesicular fusion and release of ...neurotransmitters into the synaptic cleft. In addition to neurotransmission, SNAP-25 is associated with insulin release, the regulation of intracellular calcium, and neuroplasticity. Because of SNAP-25's varied and crucial biological roles, the consequences of changes in this protein can be seen in both the central nervous system and the periphery. In this review, we will look at the published literature from human genetic, postmortem, and animal studies involving SNAP-25. The accumulated data indicate that SNAP-25 may be linked with some symptoms associated with a variety of psychiatric disorders. These disorders include bipolar disorder, schizophrenia, major depressive disorder, attention deficit hyperactivity disorder, autism, alcohol use disorder, and dementia. There are also data suggesting SNAP-25 may be involved with non-psychiatric seizures and metabolic disorders. We believe investigation of SNAP-25 is important for understanding both normal behavior and some aspects of the pathophysiology of behavior seen with psychiatric disorders. The wealth of information from both animal and human studies on SNAP-25 offers an excellent opportunity to use a bi-directional research approach. Hypotheses generated from genetically manipulated mice can be directly tested in human postmortem tissue, and, conversely, human genetic and postmortem findings can improve and validate animal models for psychiatric disorders.
•SNAP-25 is important for regulated exocytosis.•SNAP-25 may be involved with ADHD and schizophrenia.•Altered SNAP-25 expression animals have face validity to aspects of mental illness.
Colchicine is a widely available, inexpensive drug with a range of antiinflammatory properties that may make it suitable for the secondary prevention of atherosclerosis. This review examines how past ...and contemporary approaches to antiinflammatory therapy for atherosclerosis have led to a better understanding of the nature of the disease and sets out the reasons why colchicine has the potential to become a cornerstone therapy in its management.
We performed a literature search using PubMed, the Cochrane library, and clinical trial registries to identify completed and ongoing clinical studies on colchicine in coronary artery disease, and a PubMed search to identify publications on the mechanism of action of colchicine relevant to atherosclerosis.
A large body of data confirms that inflammation plays a pivotal role in atherosclerosis. The translation of this extensive knowledge into improved clinical outcomes has until recently been elusive. Findings from statin trials support the possibility that targeting inflammation may be beneficial, but this evidence has been inconclusive. Direct inhibition of atherosclerotic inflammation is being explored in current clinical trials. Targeted inhibition of interleukin 1β with canakinumab provided the proof of principle that limiting inflammation can improve outcomes in atherosclerotic vascular disease, but long-term treatment with a monoclonal antibody is unlikely to have widespread uptake. Other approaches using agents with a wider set of targets are being explored. Findings from observational studies suggest that methotrexate may reduce cardiovascular risk in patients with rheumatoid arthritis, but CIRT (Cardiovascular Inflammation Reduction Trial) demonstrated that methotrexate provided no cardiovascular benefit in patients with atherosclerotic vascular disease. Recent demonstration that cholesterol crystals trigger the NLRP3 (nucleotide oligomerization domain–, leucine-rich repeat–, and pyrin domain–containing protein 3) inflammasome and the release of inflammatory cytokines that also drive uric acid crystal–induced inflammation indicates that the multiple actions of colchicine that make it effective in gout may be relevant to preventing inflammation and limiting inflammatory injury in atherosclerosis. The ongoing LoDoCo2 (Low Dose Colchicine2) and COLCOT (Colchicine Cardiovascular Outcomes Trial) trials and several other planned large-scale rigorous trials will determine the long-term tolerability and efficacy of low-dose colchicine for secondary prevention in patients with coronary disease.
Colchicine holds promise as an important, accessible drug that could be successfully repurposed for the secondary prevention of atherosclerotic cardiovascular disease should its tolerability and cardiovascular benefits be confirmed in ongoing clinical trials.
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