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How the COVID-19 pandemic propelled an intermediary to take on running a pooled philanthropic fund, and seven lessons for first-time, pooled-fund managers.

In February 2012, the New Jersey Sea Grant Consortium (NJSGC) held the first series of Coastal Issues Caucuses to gain feedback on coastal community issues. The meetings were held in Asbury Park, Toms River, and Wildwood and were attended by a variety of municipal, county, and state officials representing a number of coastal regions throughout New Jersey. The caucuses proved to be an excellent way to bring together different community stakeholders to start a discussion on coastal related challenges and to promote thoughtful consideration of some of the potential solutions available to these communities. Some of the resultant ideas and comments will be used in the development of the future programs and activities of NJSGC’s Coastal Communities Agent. Although participants from each region had issues specific to their own context, in general participants felt that stormwater management; fertilizer training and education; beach maintenance and dune management; offshore energy development; and tourism and coastal heritage were the most important issues relevant to our mission. The Coastal Communities Agent and other extension staff will pursue some of the project ideas that came from the meetings and hope to conduct similar caucuses in the future to promote continuing dialogue between the organization and its coastal constituents. In addition, the information listed here will be used to finalize items in the Coastal Communities Agent’s work plan for 2013.

Research into the disequilibrium of microglial phenotypes has become an area of intense focus in neurodegenerative disease as a potential mechanism that contributes to chronic neuroinflammation and neuronal loss in Parkinson's disease (PD). There is growing evidence that neuroinflammation accompanies and may promote progression of alpha-synuclein (Asyn)-induced nigral dopaminergic (DA) degeneration. From a therapeutic perspective, development of immunomodulatory strategies that dampen overproduction of pro-inflammatory cytokines from chronically activated immune cells and induce a pro-phagocytic phenotype is expected to promote Asyn removal and protect vulnerable neurons. Cannabinoid receptor-2 (CB2) is highly expressed on activated microglia and peripheral immune cells, is upregulated in the substantia nigra of individuals with PD and in mouse models of nigral degeneration. Furthermore, modulation of CB2 protects against rotenone-induced nigral degeneration; however, CB2 has not been pharmacologically and selectively targeted in an Asyn model of PD. Here, we report that 7 weeks of peripheral administration of CB2 inverse agonist SMM-189 reduced phosphorylated (pSer129) alpha-synuclein in the substantia nigra compared to vehicle treatment. Additionally, SMM-189 delayed Asyn-induced immune cell infiltration into the brain as determined by flow cytometry, increased CD68 protein expression, and elevated wound-healing-immune-mediator gene expression. Additionally, peripheral immune cells increased wound-healing non-classical monocytes and decreased pro-inflammatory classical monocytes. In vitro analysis of RAW264.7 macrophages treated with lipopolysaccharide (LPS) and SMM-189 revealed increased phagocytosis as measured by the uptake of fluorescence of pHrodo E. coli bioparticles. Together, results suggest that targeting CB2 with SMM-189 skews immune cell function toward a phagocytic phenotype and reduces toxic aggregated species of Asyn. Our novel findings demonstrate that CB2 may be a target to modulate inflammatory and immune responses in proteinopathies., Competing Interests: Competing interests. The authors declare that they have no competing interests. FPM is cofounder of Neuralina Therapeutics, nVector, and CavGene Therapeutics. Not related to this paper.

Social controllability, defined as the ability to exert influence when interacting with others, is crucial for optimal decision-making. Inability to do so might contribute to maladaptive behaviors such as drug use, which often takes place in social settings. Here, we examined nicotine-dependent humans using fMRI, as they made choices that could influence the proposals from simulated partners. Computational modeling revealed that smokers under-estimated the influence of their actions and self-reported a reduced sense of control, compared to non-smokers. These findings were replicated in a large independent sample of participants recruited online. Neurally, smokers showed reduced tracking of forward projected choice values in the ventromedial prefrontal cortex, and impaired computation of social prediction errors in the midbrain. These results demonstrate that smokers were less accurate in estimating their personal influence when the social environment calls for control, providing a neurocomputational account for the social cognitive deficits in this population.