Cooperation and Coordination in Plant Disease Management.

Scaling of management efforts beyond the boundaries of individual farms may require that individuals act collectively. Such approaches have been suggested several times in plant pathology contexts but rarely have been implemented, in part because the institutional structures that enable successful collective action are poorly understood. In this research, we conducted in-depth interviews with hop producers in Oregon and Washington State to identify their motivations for and barriers to collective action regarding communication of disease levels, coordination of management practices, and sharing of best management practices and other data for powdery mildew (caused by Podosphaera macularis). Growers were generally open to and engaged in communication with neighbors and others on disease status in their hop yards and some evidence of higher levels of information sharing on management practices was found. However, growers who had developed extensive knowledge and databases were reluctant to share information viewed as proprietary. Relationships, trust, and reciprocity were facilitating factors for communication and information sharing, whereas lack of these factors and social norms of independence and pride in portions of the grower community were identified as impediments. Given the heterogeneity of trust, lack of confidence in reciprocity, and weak shared norms, communication of disease risk and coordinated management may be most successful if directed at a smaller scale as a series of neighborhood-based partnerships of growers and their immediate neighbors. Developing a disease reporting system and coordinated disease management efforts with more producers and at larger spatial extents would require formalized structures and rules that would provide assurance that there is consistency in disease data collection and reporting, reciprocation, and sanctions for those who use the information for marketing purposes against other growers. Given the analyses presented here, we believe there is potential for collective action in disease management but with limitations on the scope and nature of the actions.

Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Despite the prevalence of HCC, there is no effective, systemic treatment. The transcription factor LSF is a promising protein target for chemotherapy; it is highly expressed in HCC patient samples and cell lines, and promotes oncogenesis in rodent xenograft models of HCC. Here, we identify small molecules that effectively inhibit LSF cellular activity. The lead compound, factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity both in vitro, as determined by electrophoretic mobility shift assays, and in cells, as determined by ChIP. Consistent with such inhibition, FQI1 eliminates transcriptional stimulation of LSF-dependent reporter constructs. FQI1 also exhibits antiproliferative activity in multiple cell lines. In LSF-overexpressing cells, including HCC cells, cell death is rapidly induced; however, primary or immortalized hepatocytes are unaffected by treatment with FQI1. The highly concordant structure-activity relationship of a panel of 23 quinolinones strongly suggests that the growth inhibitory activity is due to a single biological target or family. Coupled with the striking agreement between the concentrations required for antiproliferative activity (GI(50)s) and for inhibition of LSF transactivation (IC(50)s), we conclude that LSF is the specific biological target of FQIs. Based on these in vitro results, we tested the efficacy of FQI1 in inhibiting HCC tumor growth in a mouse xenograft model. As a single agent, tumor growth was dramatically inhibited with no observable general tissue cytotoxicity. These findings support the further development of LSF inhibitors for cancer chemotherapy.

Concepts of Sustainability, Motivations for Pest Management Approaches, and Implications for Communicating Change.

Impact and relevance are valued by both plant pathologists and the supporters of research and extension. Impact has been characterized as the "So what?" of research results, and in applied research in agriculture typically involves some change in human behavior. This might involve, for instance, avoidance of broad spectrum pesticides, use of economic thresholds, or adoption of a new cultural practice in disease management. Changes in human behavior often are slow and difficult, even when the potential benefits of change seem clear. Research and extension personnel working with farmers have discussed for decades the apparent slow pace of adoption of integrated pest management (IPM) and other less-pesticide-intensive management practices. The reasons why change is slow are numerous, but one aspect that warrants consideration is how changes in farm practices are communicated to farmers. Effectively communicating changes in pest management practices at the farm level requires a system of research and extension management that differs from that to which most biological scientists are accustomed. What is the motivation for farmers to deviate from historical practices? How persuasive are concepts of environmental sustainability, integrated pest management, risk management, and economic gain in communicating the needs for change? In addressing these questions, it is useful to understand some of the basic determinants of farmers' decision processes and motivations to adopt practices. This article discusses these issues.

Diabetes Management in Detention Facilities: A Statement of the American Diabetes Association.

This statement provides guidance for diabetes care in detention facilities. It focuses on areas where the processes for delivery of care to people with diabetes in detention facilities may differ from those in the community, and key points are made at the end of each section. Areas of emphasis, which inform multiple aspects discussed in this statement, include 1) timely identification or diagnosis of diabetes treatment needs and continuity of care (at reception/intake, during transfers, and upon discharge), 2) nutrition and physical activity, 3) timely access to diabetes management tools (insulin, blood glucose monitoring, tracking data, current diabetes management technologies, etc.), and 4) treatment of the whole person with diabetes (self-management education, mental health support, monitoring and addressing long-term complications, specialty care, etc.).

Extent and nature of child maltreatment-related fatalities: implications for policy and practice.

This article reviews significant research findings regarding child maltreatment fatalities over the last thirty years. Notably, the article focuses on several important subsets of children who die from maltreatment, including young children, children reported to child protective services, and children who live in families with poor parental attachment, mental illness, substance abuse, and domestic violence. The article then sets forth three proposals for broadening the United States' approach to child protection and reducing child maltreatment fatalities.

Care of Young Children With Diabetes in the Childcare and Community Setting: A Statement of the American Diabetes Association.

Diabetes management in children extends from the home to other settings where children spend a significant portion of their waking hours. For young children (generally, aged <5 years) with diabetes, this includes childcare centers. Given their age and developmental stage, young children require a carefully thought-out, proactive diabetes care plan for the childcare setting, developed jointly by the health care provider and parents/guardians, and implemented by childcare staff. In the U.S., federal laws and some state laws protect the rights of children with diabetes in childcare and other settings to ensure they receive appropriate assistance with the diabetes management and care. This American Diabetes Association (ADA) Statement addresses the legal rights of children in the childcare setting, outlines the current best practices for diabetes care, and provides resources and responsibilities for parents/guardians, childcare providers, and health care providers. The ADA intends for these tools and information to support the health and well-being of young children with diabetes and offer helpful guidance to those caring for them.

Falling for the Ones That Were Abusive: Cycles of Violence in Low-Income Women's Intimate Relationships.

This study examines low-income women's cycles of lifelong violence victimization. A qualitative analysis of in-depth interviews with 24 low-income women living in Eastern Washington State illustrates the complexity of abusive interpersonal relationships, and the decision-making processes that abused women utilize to escape violence. The data illustrate patterns of a discursive process of normalization, wherein early experiences of violence socialized women to treat abuse as a normal and expected component of adult intimate unions. The normalization of abuse also set the stage for later abuse within intimate relationships to be downplayed. The participants' narratives demonstrate victims' efforts to interrupt cycles of violence by identifying protection of children and partners' other problematic behaviors as motivators in terminating their relationships. Abuse itself, however, is rarely stated as a main reason for victims to leave their abusers. The study's findings also highlight the importance of utilizing alternative sampling strategies, as the sample of domestic violence victims was not recruited via victim support services, but rather for a study of economic strain. The patterns elucidate the multiple ways in which abuse goes unrecognized and unreported within marginalized communities. These findings also provide insight for those within the victim advocacy network and researchers of domestic violence by showcasing the experiences of victims who are often excluded from studies of domestic violence. To those who work actively in the field, this study serves as a call to action to widen sampling strategies and examine abuse in ways that better fit victims' understandings and experiences of intimate partner and domestic violence.

Drug delivery-mediated control of RNA immunostimulation.

RNA interference (RNAi) has generated significant interest as a strategy to suppress viral infection, but in some cases antiviral activity of unmodified short-interfering RNA (siRNA) has been attributed to activation of innate immune responses. We hypothesized that immunostimulation by unmodified siRNA could mediate both RNAi as well as innate immune stimulation depending on the mode of drug delivery. We investigated the potential of immunostimulatory RNAs (isRNAs) to suppress influenza A virus in vivo in the mouse lung. Lipidoid 98N12-5(1) formulated with unmodified siRNA targeting the influenza nucleoprotein gene exhibited antiviral activity. Formulations were optimized to increase antiviral activity, but the antiviral activity of lipidoid-delivered siRNA did not depend on sequence homology to the influenza genome as siRNA directed against unrelated targets also suppressed influenza replication in vivo. This activity was primarily attributed to enhancement of innate immune stimulation by lipidoid-mediated delivery, which indicates increased toll-like receptor (TLR) activation by siRNA. Certain chemical modifications to the siRNA backbone, which block TLR7/8 activation but retain in vitro RNAi activity, prevented siRNA-mediated antiviral activity despite enhanced lipidoid-mediated delivery. Here, we demonstrate that innate immune activation caused by unmodified siRNA can have therapeutically relevant effects, and that these non-RNAi effects can be controlled through chemical modifications and drug delivery.

Impact of CUX2 on the female mouse liver transcriptome: activation of female-biased genes and repression of male-biased genes.

The growth hormone-regulated transcription factors STAT5 and BCL6 coordinately regulate sex differences in mouse liver, primarily through effects in male liver, where male-biased genes are upregulated and many female-biased genes are actively repressed. Here we investigated whether CUX2, a highly female-specific liver transcription factor, contributes to an analogous regulatory network in female liver. Adenoviral overexpression of CUX2 in male liver induced 36% of female-biased genes and repressed 35% of male-biased genes. In female liver, CUX2 small interfering RNA (siRNA) preferentially induced genes repressed by adenovirus expressing CUX2 (adeno-CUX2) in male liver, and it preferentially repressed genes induced by adeno-CUX2 in male liver. CUX2 binding in female liver chromatin was enriched at sites of male-biased DNase hypersensitivity and at genomic regions showing male-enriched STAT5 binding. CUX2 binding was also enriched near genes repressed by adeno-CUX2 in male liver or induced by CUX2 siRNA in female liver but not at genes induced by adeno-CUX2, indicating that CUX2 binding is preferentially associated with gene repression. Nevertheless, direct CUX2 binding was seen at several highly female-specific genes that were positively regulated by CUX2, including A1bg, Cyp2b9, Cyp3a44, Tox, and Trim24. CUX2 expression and chromatin binding were high in immature male liver, where repression of adult male-biased genes and expression of adult female-biased genes are common, suggesting that the downregulation of CUX2 in male liver at puberty contributes to the developmental changes establishing adult patterns of sex-specific gene expression.

A rapid two-step method for isolation of functional primary mouse hepatocytes: cell characterization and asialoglycoprotein receptor based assay development.

Primary mouse hepatocytes are an important tool in the biomedical research field for the assessment of hepatocyte function. Several methods for hepatocyte isolation have been published; however, many of these methods require extensive handling and can therefore compromise the viability and function of the isolated cells. Since one advantage of utilizing freshly isolated cells is to maintain an environment in which the cells are more comparable to their in vivo state, it is important to have robust methods that produce cells with high viability, good purity and that function in a similar manner to that in their in vivo state. Here we describe a modified two-step method for the rapid isolation and characterization of mouse primary hepatocytes that results in high yields of viable cells. The asialoglycoprotein receptor (ASGPR), which is one of the most abundant cell surface receptors on hepatocytes, was used to monitor the function of the isolated hepatocytes by demonstrating specific binding of its ligand using a newly developed flow cytometry based ligand-receptor binding assay. Also, an in vitro screening method for siRNA drug candidates was successfully developed utilizing freshly isolated hepatocytes with minimum culture time.

Dual-energy X-ray absorptiometry-based body volume measurement for 4-compartment body composition.

BACKGROUND: Total body volume (TBV), with the exclusion of internal air voids, is necessary to quantify body composition in Lohman's 4-compartment (4C) model. OBJECTIVE: This investigation sought to derive a novel, TBV measure with the use of only dual-energy X-ray absorptiometry (DXA) attenuation values for use in Lohman's 4C body composition model. DESIGN: Pixel-specific masses and volumes were calculated from low- and high-energy attenuation values with the use of first principle conversions of mass attenuation coefficients. Pixel masses and volumes were summed to derive body mass and total body volume. As proof of concept, 11 participants were recruited to have 4C measures taken: DXA, air-displacement plethysmography (ADP), and total body water (TBW). TBV measures with the use of only DXA (DXA-volume) and ADP-volume measures were compared for each participant. To see how body composition estimates were affected by these 2 methods, we used Lohman's 4C model to quantify percentage fat measures for each participant and compared them with conventional DXA measures. RESULTS: DXA-volume and ADP-volume measures were highly correlated (R(2) = 0.99) and showed no statistically significant bias. Percentage fat by DXA volume was highly correlated with ADP-volume percentage fat measures and DXA software-reported percentage fat measures (R(2) = 0.96 and R(2) = 0.98, respectively) but were slightly biased. CONCLUSIONS: A novel method to calculate TBV with the use of a clinical DXA system was developed, compared against ADP as proof of principle, and used in Lohman's 4C body composition model. The DXA-volume approach eliminates many of the inherent inaccuracies associated with displacement measures for volume and, if validated in larger groups of participants, would simplify the acquisition of 4C body composition to a single DXA scan and TBW measure.