13 research outputs found
CULTIVATING MEANINGFUL REALTIONSHIPS TO INCREASE FUNDRAISING EFFORTS FOR NONPROFIT ORGANIZATIONS
The donor cultivation process is vital to a gift officer by creating meaningful relationship built on trust and dynamic conversations. Cultivating philanthropic funds for nonprofit organization is essential in advancing a mission and accomplishing the vision. To successfully solicit donor dollars, gift officers must focus on the art of developing and retaining personal relationships. A gift officer is the hands and feet to a nonprofit organization who leads people to understand, motivate, and agree to support a better quality of life for those most in need. The utilization of properly cultivated relationships and uniquely crafted engagements provides the precise development for successful fundraising. The utilization of the donor cultivation process is changing the culture of philanthropy and provides a platform for gift officers to utilize to achieve goals. The future success of nonprofit organizations of mission advancement is dependent on the ability of a gift officers’ strategic engagement with the community’s people. Gift officers promote philanthropy by following donor centered principles and practicing organizational values.
Key Words: Major gift officer (MGOs), Philanthropy, Fiduciary, Cultivation, Donor relations, Organizational culture, Strategic Communicatio
Adolescents, Adults and Rewards: Comparing Motivational Neurocircuitry Recruitment Using fMRI
Background: Adolescent risk-taking, including behaviors resulting in injury or death, has been attributed in part to maturational differences in mesolimbic incentive-motivational neurocircuitry, including ostensible oversensitivity of the nucleus accumbens (NAcc) to rewards. Methodology/Principal Findings: To test whether adolescents showed increased NAcc activation by cues for rewards, or by delivery of rewards, we scanned 24 adolescents (age 12–17) and 24 adults age (22–42) with functional magnetic resonance imaging while they performed a monetary incentive delay (MID) task. The MID task was configured to temporally disentangle potential reward or potential loss anticipation-related brain signal from reward or loss notification-related signal. Subjects saw cues signaling opportunities to win or avoid losing .50, or $5 for responding quickly to a subsequent target. Subjects then viewed feedback of their trial success after a variable interval from cue presentation of between 6 to17 s. Adolescents showed reduced NAcc recruitment by reward-predictive cues compared to adult controls in a linear contrast with non-incentive cues, and in a volume-of-interest analysis of signal change in the NAcc. In contrast, adolescents showed little difference in striatal and frontocortical responsiveness to reward deliveries compared to adults. Conclusions/Significance: In light of divergent developmental difference findings between neuroimaging incentive paradigms (as well as at different stages within the same task), these data suggest that maturational differences i
Role of X11 and ubiquilin as In Vivo Regulators of the Amyloid Precursor Protein in Drosophila
The Amyloid Precursor Protein (APP) undergoes sequential proteolytic cleavages through the action of β- and γ-secretase, which result in the generation of toxic β-amyloid (Aβ) peptides and a C-terminal fragment consisting of the intracellular domain of APP (AICD). Mutations leading to increased APP levels or alterations in APP cleavage cause familial Alzheimer's disease (AD). Thus, identification of factors that regulate APP steady state levels and/or APP cleavage by γ-secretase is likely to provide insight into AD pathogenesis. Here, using transgenic flies that act as reporters for endogenous γ-secretase activity and/or APP levels (GAMAREP), and for the APP intracellular domain (AICDREP), we identified mutations in X11L and ubiquilin (ubqn) as genetic modifiers of APP. Human homologs of both X11L (X11/Mint) and Ubqn (UBQLN1) have been implicated in AD pathogenesis. In contrast to previous reports, we show that overexpression of X11L or human X11 does not alter γ-secretase cleavage of APP or Notch, another γ-secretase substrate. Instead, expression of either X11L or human X11 regulates APP at the level of the AICD, and this activity requires the phosphotyrosine binding (PTB) domain of X11. In contrast, Ubqn regulates the levels of APP: loss of ubqn function leads to a decrease in the steady state levels of APP, while increased ubqn expression results in an increase in APP levels. Ubqn physically binds to APP, an interaction that depends on its ubiquitin-associated (UBA) domain, suggesting that direct physical interactions may underlie Ubqn-dependent regulation of APP. Together, our studies identify X11L and Ubqn as in vivo regulators of APP. Since increased expression of X11 attenuates Aβ production and/or secretion in APP transgenic mice, but does not act on γ-secretase directly, X11 may represent an attractive therapeutic target for AD
Genetic variants and their interactions in disease risk prediction – machine learning and network perspectives
Altered developmental trajectories for impulsivity and sensation seeking among adolescent substance users
A number of studies have associated impulsivity and sensation seeking with level of substance use and risk for developing a substance use disorder. These relationships may be particularly apparent during adolescence, when developmental changes in impulsivity and sensation seeking occur at the same time as increased opportunities for substance use. To examine this, the current study measured impulsivity and sensation seeking from pre-adolescence to mid-adolescence in a sample of youth, the majority of whom were identified as being at risk for developing a substance use disorder based on their family history of substance use disorders. Youth were separated into those who did (n = 117) and did not (n = 269) initiate substance use by mid-adolescence. Results showed that substance users were more impulsive and more sensation seeking during pre-adolescence, prior to any significant substance use, and that greater sensation seeking in pre-adolescence was related to heavier substance use by mid-adolescence. In addition, developmental trajectories for substance-using youth showed a greater increase in sensation seeking but a more modest decrease in impulsivity from pre-adolescence to mid-adolescence. Taken together, these results indicate that increased impulsivity and sensation seeking is apparent in adolescent substance users as early as pre-adolescence, that the difference between substance users and non-users becomes larger across early adolescence as their developmental trajectories diverge, and that greater sensation seeking in pre-adolescence may predict increased substance use by mid-adolescence
Occupational exposure to trichloroethylene is associated with a decline in lymphocyte subsets and soluble CD27 and CD30 markers
Occupational cohort and case–control studies suggest that trichloroethylene (TCE) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings are not consistent. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. We carried out a cross-sectional molecular epidemiology study of 80 healthy workers that used TCE and 96 comparable unexposed controls in Guangdong, China. Personal exposure measurements were taken over a three-week period before blood collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration Permissible Exposure Limit (100 p.p.m. 8 h time-weighted average), with a mean (SD) of 22.2 (36.0) p.p.m. The total lymphocyte count and each of the major lymphocyte subsets including CD4+ T cells, CD8+ T cells, natural killer (NK) cells and B cells were significantly decreased among the TCE-exposed workers compared with controls (P < 0.05), with evidence of a dose-dependent decline. Further, there was a striking 61% decline in sCD27 plasma level and a 34% decline in sCD30 plasma level among TCE-exposed workers compared with controls. This is the first report that TCE exposure under the current Occupational Safety and Health Administration workplace standard is associated with a decline in all major lymphocyte subsets and sCD27 and sCD30, which play an important role in regulating cellular activity in subsets of T, B and NK cells and are associated with lymphocyte activation. Given that altered immunity is an established risk factor for NHL, these results add to the biologic plausibility that TCE is a possible lymphomagen
Mapping the human genetic architecture of COVID-19
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease