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

Major Contribution of Somatostatin-Expressing Interneurons and Cannabinoid Receptors to Increased GABA Synaptic Activity in the Striatum of Huntington’s Disease Mice

Huntington’s disease (HD) is a heritable neurological disorder that affects cognitive and motor performance in patients carrying the mutated huntingtin (HTT) gene. In mouse models of HD, previous reports showed a significant increase in spontaneous GABAA receptor-mediated synaptic activity in striatal spiny projection neurons (SPNs). In this study, using optogenetics and slice electrophysiology, we examined the contribution of γ-aminobutyric acid (GABA)-ergic parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons to the increase in GABA neurotransmission using the Q175 (heterozygote) mouse model of HD. Patch clamp recordings in voltage-clamp mode were performed on SPNs from brain slices of presymptomatic (2 months) and symptomatic (8 and 12 months) Q175 mice and wildtype (WT) littermates. While inhibitory postsynaptic currents (IPSCs) evoked in SPNs following optical activation of PV- and SOM-expressing interneurons differed in amplitude, no genotype-dependent differences were observed at all ages from both interneuron types; however, responses evoked by either type were found to have faster kinetics in symptomatic mice. Since SOM-expressing interneurons are constitutively active in striatal brain slices, we then examined the effects of acutely silencing these neurons in symptomatic mice with enhanced Natronomonas pharaonis halorhodopsin (eNpHR). Optically silencing SOM-expressing interneurons resulted in a greater decrease in the frequency of spontaneous IPSCs (sIPSCs) in a subset of SPNs from Q175 mice compared to WTs, suggesting that SOM-expressing interneurons are the main contributors to the overall increased GABA synaptic activity in HD SPNs. Additionally, the effects of activating GABAB and cannabinoid (CB1) receptors were investigated to determine whether these receptors were involved in modulating interneuron-specific GABA synaptic transmission and if this modulation differed in HD mice. When selectively activating PV- and SOM-expressing interneurons in the presence of the CB1 receptor agonist WIN-55,212, the magnitudes of the evoked IPSCs in SPNs decreased for both interneuron types although this change was less prominent in symptomatic Q175 SPNs during SOM-expressing interneuron activation. Overall, these findings show that dysfunction of SOM-expressing interneurons contributes to the increased GABA synaptic activity found in HD mouse models and that dysregulation of the endocannabinoid system may contribute to this effect

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 $0,$.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

The role of testosterone in bib size determination in the male house sparrow Passer domesticus, is age dependent

Secondary sexual signals are thought to indicate individual quality. In order to understand the evolutionary pressures that give rise to such traits it is important to understand the physiological mechanisms underlying their production. The black bib of the house sparrow Passer domesticus is known to function as a badge of social status in males. Past studies have found that the size of the bib in older males is determined, at least partly, by the androgen testosterone. The immunocompetence handicap hypothesis suggests that testosterone has a key role in maintaining honest signalling &ndash; it is both involved in the development or expression of sexual signals and is immunosuppressive. In this paper we test experimentally two hypo theses relating to bib size development, whether 1) testosterone is only immunosuppressive in conditions where the natural feedback loop from the testes has been removed, and 2) testosterone is, in addition to influencing the bib size of older males, responsible for the size of the bib in juvenile sparrows. In the first experiment we found that exogenous testosterone administered to intact males during the winter (when LH and FSH levels are very low and were not artificially increased by castration) caused significant immunosuppression, albeit in interaction with the stress hormone corticosterone. Second, we found that exogenous testosterone administration in castrated fledgling male house sparrows had no effect on subsequent post-juvenile moult bib size relative to controls. Our results suggest that in some circumstances testosterone can be immunosuppressive, but that its role in bib size determination is age-dependent.<br /

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