A Meta-Analysis of Seaweed Impacts on Seagrasses: Generalities and Knowledge Gaps

Seagrasses are important habitat-formers and ecosystem engineers that are under threat from bloom-forming seaweeds. These seaweeds have been suggested to outcompete the seagrasses, particularly when facilitated by eutrophication, causing regime shifts where green meadows and clear waters are replaced with unstable sediments, turbid waters, hypoxia, and poor habitat conditions for fishes and invertebrates. Understanding the situations under which seaweeds impact seagrasses on local patch scales can help proactive management and prevent losses at greater scales. Here, we provide a quantitative review of available published manipulative experiments (all conducted at the patch-scale), to test which attributes of seaweeds and seagrasses (e.g., their abundances, sizes, morphology, taxonomy, attachment type, or origin) influence impacts. Weighted and unweighted meta-analyses (Hedges d metric) of 59 experiments showed generally high variability in attribute-impact relationships. Our main significant findings were that (a) abundant seaweeds had stronger negative impacts on seagrasses than sparse seaweeds, (b) unattached and epiphytic seaweeds had stronger impacts than ‘rooted’ seaweeds, and (c) small seagrass species were more susceptible than larger species. Findings (a) and (c) were rather intuitive. It was more surprising that ‘rooted’ seaweeds had comparatively small impacts, particularly given that this category included the infamous invasive Caulerpa species. This result may reflect that seaweed biomass and/or shading and metabolic by-products like anoxia and sulphides could be lower for rooted seaweeds. In conclusion, our results represent simple and robust first-order generalities about seaweed impacts on seagrasses. This review also documented a limited number of primary studies. We therefore identified major knowledge gaps that need to be addressed before general predictive models on seaweed-seagrass interactions can be build, in order to effectively protect seagrass habitats from detrimental competition from seaweeds

Beyond the genetics of HDL:why is HDL cholesterol inversely related to cardiovascular disease?

There is unequivocal evidence that high-density lipoprotein (HDL) cholesterol levels in plasma are inversely associated with the risk of cardiovascular disease (CVD). Studies of families with inherited HDL disorders and genetic association studies in general (and patient) population samples have identified a large number of factors that control HDL cholesterol levels. However, they have not resolved why HDL cholesterol and CVD are inversely related. A growing body of evidence from nongenetic studies shows that HDL in patients at increased risk of CVD has lost its protective properties and that increasing the cholesterol content of HDL does not result in the desired effects. Hopefully, these insights can help improve strategies to successfully intervene in HDL metabolism. It is clear that there is a need to revisit the HDL hypothesis in an unbiased manner. True insights into the molecular mechanisms that regulate plasma HDL cholesterol and triglycerides or control HDL function could provide the handholds that are needed to develop treatment for, e.g., type 2 diabetes and the metabolic syndrome. Especially genome-wide association studies have provided many candidate genes for such studies. In this review we have tried to cover the main molecular studies that have been produced over the past few years. It is clear that we are only at the very start of understanding how the newly identified factors may control HDL metabolism. In addition, the most recent findings underscore the intricate relations between HDL, triglyceride, and glucose metabolism indicating that these parameters need to be studied simultaneously

Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers

Synaptic interactome mining reveals p140Cap as a new hub for PSD proteins involved in psychiatric and neurological disorders

Altered synaptic function has been associated with neurological and psychiatric conditions including intellectual disability, schizophrenia and autism spectrum disorder (ASD). Amongst the recently discovered synaptic proteins is p140Cap, an adaptor that localizes at dendritic spines and regulates their maturation and physiology. We recently showed that p140Cap knockout mice have cognitive deficits, impaired long-term potentiation (LTP) and long-term depression (LTD), and immature, filopodia-like dendritic spines. Only a few p140Cap interacting proteins have been identified in the brain and the molecular complexes and pathways underlying p140Cap synaptic function are largely unknown. Here, we isolated and characterized the p140Cap synaptic interactome by co-immunoprecipitation from crude mouse synaptosomes, followed by mass spectrometry-based proteomics. We identified 351 p140Cap interactors and found that they cluster to sub complexes mostly located in the postsynaptic density (PSD). p140Cap interactors converge on key synaptic processes, including transmission across chemical synapses, actin cytoskeleton remodeling and cell-cell junction organization. Gene co-expression data further support convergent functions: the p140Cap interactors are tightly co-expressed with each other and with p140Cap. Importantly, the p140Cap interactome and its co-expression network show strong enrichment in genes associated with schizophrenia, autism, bipolar disorder, intellectual disability and epilepsy, supporting synaptic dysfunction as a shared biological feature in brain diseases. Overall, our data provide novel insights into the molecular organization of the synapse and indicate that p140Cap acts as a hub for postsynaptic complexes relevant to psychiatric and neurological disorders

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease