Cysteine residues in a yeast viral A/B toxin crucially control host cell killing via pH-triggered disulfide rearrangements.

K28 is a viral A/B protein toxin that intoxicates yeast and fungal cells by endocytosis and retrograde transport to the endoplasmic reticulum (ER). Although toxin translocation into the cytosol occurs on the oxidized α/ß heterodimer, the precise mechanism of how the toxin crosses the ER membrane is unknown. Here we identify pH-triggered, toxin-intrinsic thiol rearrangements that crucially control toxin conformation and host cell killing. In the natural habitat and low-pH environment of toxin-secreting killer yeasts, K28 is structurally stable and biologically active as a disulfide-bonded heterodimer, whereas it forms inactive disulfide-bonded oligomers at neutral pH that are caused by activation and thiol deprotonation of ß-subunit cysteines. Because such pH increase reflects the pH gradient during compartmental transport within target cells, potential K28 oligomerization in the ER lumen is prevented by protein disulfide isomerase. In addition, we show that pH-triggered thiol rearrangements in K28 can cause the release of cytotoxic α monomers, suggesting a toxin-intrinsic mechanism of disulfide bond reduction and α/ß heterodimer dissociation in the cytosol.

Growth and resilience of pioneering nonprofit human service organizations: a cross-case analysis of organizational histories.

Knowledge of organizational history is important for recognizing patterns in effective management and understanding how organizations respond to internal and external challenges. This cross-case analysis of 12 histories of pioneering nonprofit human service organizations contributes an important longitudinal perspective on organizational history, complementing the cross-sectional case studies that dominate the existing research on nonprofit organizations. The literature on organizational growth, including lifecycle models and growth management, is reviewed, along with the literature on organizational resilience. Based on analysis of the 12 organizational histories, a conceptual model is presented that synthesizes key factors in the areas of leadership, internal operations, and external relations that influence organizational growth and resilience to enable nonprofit organizations to survive and thrive over time. Both cross-sectional and longitudinal examples from the organizational histories illustrate the conceptual map. The paper concludes with a discussion of directions for future research on nonprofit organizational history.

BANANAS: providing child care services to a multi-ethnic community.

BANANAS, Inc. is a nonprofit organization that has provided child care resource and referral services for over 35 years. BANANAS emerged as a grassroots effort initiated by a group of female volunteers who sought to build a network of women with children who needed childcare. As the organization developed, its leaders recognized and responded to additional needs, including resource and information sharing, workshops and classes, and political advocacy. Beginning as a collective, BANANAS has grown into a multifaceted service delivery and advocacy nonprofit operating with an annual budget of $12 million. This history of the agency reflects the development of a unique community-based effort, its challenges and rewards, and the multiple successes that this pioneering nonprofit has experienced.

The Unity Council at 40: a pioneering community development and service organization (1967-2007).

The Spanish Speaking Unity Council (Unity Council) is a community development nonprofit organization that was established in 1964, during the civil rights movement, by a group of community members who wanted to ensure the political representation of the Latino community. Over its 45-year history, the Unity Council has grown into a $12 million community development organization that delivers a range of programming, including social services and employment training as well as facilitating the development and support of local businesses, low-income housing, and neighborhood improvement activities. The history of the agency presents the multiple challenges and rewards associated with development in an underserved community and an example of the important role that leadership plays in the growth of a nonprofit.

Girls Incorporated of Alameda County at 50: a voice for girls (1958-2008).

Girls Incorporated of Alameda County is nonprofit human service organization that has delivered education, counseling, and advocacy services to girls aged 6 to 18 for 50 years. The organization began as a small, local girls club and has grown into a large multi-faceted service delivery organization attached to a national governing body. The history of Girls Incorporated of Alameda County introduces struggles in relation to external and internal factors that altered the way that the agency financed and managed and exemplifies the important role of nonprofit leadership. The organization's many accomplishments have also presented multiple challenges, particularly related to the changing roles of women in American society.

Larkin Street Youth Services: helping kids get off the street for good (1982-2007).

Larkin Street Youth Services is a pioneering nonprofit organization that was established in 1981 to serve the growing urban homeless and runaway youth population. What began as a neighborhood effort has evolved into a $12 million organization over the course of its 25-year history. Larkin Street Youth Services delivers a continuum of services to homeless youth including counseling, housing, education, employment, and HIV services. The agency has received significant local and national attention for the success of its targeted program model and continuum of care services. The history of Larkin Street Youth Services provides an example of the important role of internal operations in an agency's ability to re-invent itself and respond to a larger community need.

Asian Community Mental Health Services at 35: a pioneering ethnic organization (1973-2008).

Asian Community Mental Health Services is a nonprofit organization that delivers mental health services to primarily Asian and Pacific Islander communities. From its early beginnings and over its 35-year history, the agency has had to overcome numerous challenges, including gaining legitimacy as a culturally specific nonprofit, combating stigma surrounding mental health issues within the Asian Pacific Islander community, building resources to fund service delivery, and developing an educated and culturally sensitive workforce. The history of the organization highlights the multiple challenges and rewards of developing a culturally specific nonprofit in an urban area as well as the important role that internal operations play in relation to nonprofit expansion and growth.

CompassPoint Nonprofit Services: strengthening the capacities of nonprofits (1971-2008).

CompassPoint Nonprofit Services is a nonprofit organization that delivers cutting-edge research and support services to the nonprofit community. Over its 30-year history, CompassPoint has transitioned from a small management support agency into a nationally-recognized leader in nonprofit capacity building and nonprofit management research. Through its strong internal operations and external connections, the agency has been able to stay current on the multiple challenges facing the local and national nonprofit community. CompassPoint has been a valuable resource for the nonprofit sector as it has struggled to retain its identity over the past 30 years, in relation to political and economic changes that have altered the functioning of the sector as a whole.

Black Adoption Placement and Research Center at 25: placing African-American children in permanent homes (1983-2008).

The Black Adoption Research and Placement Center is a nonprofit organization delivering culturally specific adoption and foster care services. The organization developed as a response to concerns in the African-American community about the high numbers of African-American children entering and not exiting the public foster care system. The organization has undergone significant transformations over its 25-year history in relation to social, political, and economic changes that have altered the ways that the agency finances and delivers services. The history of Black Adoption Research and Placement Center presents an organization that has weathered many challenges because of its strong leadership, its committed governing body, its external relationships, and its internal operations.

Shelter Network: serving homeless families and individuals (1987-2007).

Shelter Network is a nonprofit organization that delivers a range of services that meet the needs of homeless families and individuals in order to help them achieve stable housing and self-sufficiency. The agency began as a grassroots community effort to respond to the growing problem of homelessness and its relationship with its external community continues to play an important role in its financing, growth, and development. Over its 20-year history, Shelter Network has overcome multiple challenges related to leadership, finance, and community support and has grown from a grassroots agency into an organization with a budget of $7 million.

Jewish Family and Children's Services: a pioneering human service organization (1850-2008).

Jewish Family and Children's Services of San Francisco, the Peninsula, Marin, and Sonoma Counties is a pioneering nonprofit human service organization that has delivered services for 157 years. Over the course of its history, the organization has transformed itself from an all-volunteer agency delivering aid to immigrant families during the Gold Rush era to a $30 million nonprofit human service organization offering a full-range of services to adults, children, and families. The history of Jewish Family and Children's Services sheds light on the importance of strong leadership, strategic planning, external relationships, and strong donor support.

The Bayview Hunters Point Foundation for Community Improvement: a pioneering multi-ethnic human service organization (1971-2008).

The Bayview Hunters Point Foundation for Community Improvement is a nonprofit organization established in 1971 to defend the legal rights of African-Americans living in its community. Over the years, the agency diversified its services to include mental health and substance abuse treatment, violence prevention, youth programming, and HIV services. The organization has overcome multiple challenges during its 37-year history in relation to social, political, and economic changes that have influenced the way the organization has financed and delivered its services. The history of the organization presents a collaborative approach to community problem-solving and exemplifies the important role that external relationships play in relationship to nonprofit growth and survival.