Defining, collecting, and sharing perishable disaster data.

Researchers across disciplines have long sought to collect 'perishable data' in the context of disasters. Yet, this data type is neither consistently defined nor discussed in specific detail in the literature. To address this gap, this paper defines perishable data and provides guidance on ways to improve both how it is collected and shared. Here, perishable data is conceptualised as highly transient data that may degrade in quality, be irrevocably altered, or be permanently lost if not gathered soon after it is generated. Perishable data may include ephemeral information that must be collected to characterise pre-existing hazardous conditions, near-miss events, actual disasters, and longer-term recovery processes. This data may need to be gathered at multiple points in time across varying geographic scales to accurately characterise exposure, susceptibility to harm, or coping capacity. The paper considers ethical and logistical challenges and discusses opportunities to advance equitable perishable data collection and dissemination.

Incorporating Mental Health Research into Disaster Risk Reduction: An Online Training Module for the Hazards and Disaster Workforce.

There is an expansive and growing body of literature that examines the mental health consequences of disasters and large-scale emergencies. There is a need, however, for more explicit incorporation of mental health research into disaster risk reduction practices. Training and education programs can serve as a bridge to connect academic mental health research and the work of disaster risk reduction practitioners. This article describes the development and evaluation of one such intervention, the CONVERGE Disaster Mental Health Training Module, which provides users from diverse academic and professional backgrounds with foundational knowledge on disaster mental health risk factors, mental health outcomes, and psychosocial well-being research. Moreover, the module helps bridge the gap between research and practice by describing methods used to study disaster mental health, showcasing examples of evidence-based programs and tools, and providing recommendations for future research. Since its initial release on 8 October 2019, 317 trainees from 12 countries have completed the Disaster Mental Health Training Module. All trainees completed a pre- and post-training questionnaire regarding their disaster mental health knowledge, skills, and attitudes. Wilcoxon Signed Rank tests demonstrated a significant increase in all three measures after completion of the training module. Students, emerging researchers or practitioners, and trainees with a high school/GED education level experienced the greatest benefit from the module, with Kruskal-Wallis results indicating significant differences in changes in knowledge and skills across the groups. This evaluation research highlights the effectiveness of the Disaster Mental Health Training Module in increasing knowledge, skills, and attitudes among trainees. This article concludes with a discussion of how this training can support workforce development and ultimately contribute to broader disaster risk reduction efforts.

Mortality From Forces of Nature Among Older Adults by Race/Ethnicity and Gender.

Older adults are especially vulnerable to disasters due to high rates of chronic illness, disability, and social isolation. Limited research examines how gender, race/ethnicity, and forces of nature-defined here as different types of natural hazards, such as storms and earthquakes-intersect to shape older adults' disaster-related mortality risk. We compare mortality rates among older adults (60+ years) in the United States across gender, race/ethnicity, and hazard type using the Centers for Disease Control and Prevention's Wonder database. Our results demonstrate that older adult males have higher mortality rates than females. American Indian/Alaska Native (AI/AN) males have the highest mortality and are particularly impacted by excessive cold. Mortality is also high among Black males, especially due to cataclysmic storms. To address disparities, messaging and programs targeting the dangers of excessive cold should be emphasized for AI/AN older adult males, whereas efforts to reduce harm from cataclysmic storms should target Black older adult males.

Community Advantage and Individual Self-Efficacy Promote Disaster Preparedness: A Multilevel Model among Persons with Disabilities.

Disaster preparedness initiatives are increasingly focused on building community resilience. Preparedness research has correspondingly shifted its attention to community-level attributes that can support a community's capacity to respond to and recover from disasters. While research at the community level is integral to building resilience, it may not address the specific barriers and motivators to getting individuals prepared. In particular, people with disabilities are vulnerable to disasters, yet research suggests that they are less likely to engage in preparedness behaviors. Limited research has examined what factors influence their ability to prepare, with no studies examining both the individual and community characteristics that impact these behaviors. Multilevel modeling thus offers a novel contribution that can assess both levels of influence. Using Los Angeles County community survey data from the Public Health Response to Emergent Threats Survey and the Healthy Places Index, we examined how social cognitive and community factors influence the relationship between disability and preparedness. Results from hierarchical linear regression models found that participants with poor health and who possessed activity limitations engaged in fewer preparedness behaviors. Self-efficacy significantly mediated the relationship between self-rated health and disaster preparedness. Living in a community with greater advantages, particularly with more advantaged social and housing attributes, reduced the negative association between poor self-rated health and preparedness. This study highlights the importance of both individual and community factors in influencing people with disabilities to prepare. Policy and programming should therefore be two-fold, both targeting self-efficacy as a proximal influence on preparedness behaviors and also addressing upstream factors related to community advantage that can create opportunities to support behavioral change while bolstering overall community resilience.

A Program for Local Health Departments to Adapt and Implement Evidence-Based Emergency Preparedness Programs.

The goal of this project was to enhance the capacity of local health departments to translate and implement evidence-based programs in emergency preparedness by using the Getting To Outcomes approach. Our evaluation determined that local health department staff reported improved capacities. A "Getting To Outcomes Guide for Community Emergency Preparedness" guidebook was produced and is available online.

Facilitating Partnerships With Community- and Faith-Based Organizations for Disaster Preparedness and Response: Results of a National Survey of Public Health Departments.

OBJECTIVE: We identify characteristics of local health departments, which enhance collaborations with community- and faith-based organizations (CFBOs) for emergency preparedness and response. METHODS: Online survey data were collected from a sample of 273 disaster preparedness coordinators working at local health departments across the United States between August and December 2011. RESULTS: Using multiple linear regression models, we found that perceptions of CFBO trust were associated with more successful partnership planning (ß=0.63; P=0.02) and capacity building (ß=0.61; P=0.01). Employee layoffs in the past 3 years (ß=0.41; P=0.001) and urban location (ß=0.41; P=0.005) were positively associated with higher ratings of resource sharing between health agencies and CFBOs. Having 1-3 full-time employees increased the ratings of success in communication and outreach activities compared with health departments having less than 1 full-time employee (ß=0.33; P=0.05). Positive attitudes toward CFBOs also enhanced communication and outreach (ß=0.16; P=0.03). CONCLUSIONS: Staff-capacity factors are important for quick dissemination of information and resources needed to address emerging threats. Building the trust of CFBOs can help address large-scale disasters by improving the success of more involved activities that integrate the CFBO into emergency plans and operations of the health department and that better align with federal-funding performance measures. (Disaster Med Public Health Preparedness. 2018;12:57-66).

Who Participates in the Great ShakeOut? Why Audience Segmentation Is the Future of Disaster Preparedness Campaigns.

Background: In 2008, the Southern California Earthquake Center in collaboration with the U.S. Geological Survey Earthquake Hazards Program launched the first annual Great ShakeOut, the largest earthquake preparedness drill in the history of the United States. Materials and Methods: We collected online survey data from 2052 campaign registrants to assess how people participated, whether audience segments shared behavioral patterns, and whether these segments were associated with five social cognitive factors targeted by the ShakeOut campaign. Results: Participants clustered into four behavioral patterns. The Minimal cluster had low participation in all activities (range: 0-39% participation). The Basic Drill cluster only participated in the drop, cover and hold drill (100% participation). The Community-Oriented cluster, involved in the drill (100%) and other interpersonal activities including attending disaster planning meetings (74%), was positively associated with interpersonal communication (ß = 0.169), self-efficacy (ß = 0.118), outcome efficacy (ß = 0.110), and knowledge about disaster preparedness (ß = 0.151). The Interactive and Games cluster, which participated in the drill (79%) and two online earthquake preparedness games (53% and 75%), was positively associated with all five social cognitive factors studied. Conclusions: Our results support audience segmentation approaches to engaging the public, which address the strengths and weaknesses of different segments. Offering games may help "gamers" gain competencies required to prepare for disasters. Targeting the highly active Community-Oriented cluster for leadership roles could help build community resilience by encouraging others to become more involved in disaster planning. We propose that the days of single, national education campaigns without local variation should end.

The LacI-Family Transcription Factor, RbsR, Is a Pleiotropic Regulator of Motility, Virulence, Siderophore and Antibiotic Production, Gas Vesicle Morphogenesis and Flotation in Serratia.

Gas vesicles (GVs) are proteinaceous, gas-filled organelles used by some bacteria to enable upward movement into favorable air/liquid interfaces in aquatic environments. Serratia sp. ATCC39006 (S39006) was the first enterobacterium discovered to produce GVs naturally. The regulation of GV assembly in this host is complex and part of a wider regulatory network affecting various phenotypes, including antibiotic biosynthesis. To identify new regulators of GVs, a comprehensive mutant library containing 71,000 insertion mutants was generated by random transposon mutagenesis and 311 putative GV-defective mutants identified. Three of these mutants were found to have a transposon inserted in a LacI family transcription regulator gene (rbsR) of the putative ribose operon. Each of these rbsR mutants was GV-defective; no GVs were visible by phase contrast microscopy (PCM) or transmission electron microscopy (TEM). GV deficiency was caused by the reduction of gvpA1 and gvrA transcription (the first genes of the two contiguous operons in the GV gene locus). Our results also showed that a mutation in rbsR was highly pleiotropic; the production of two secondary metabolites (carbapenem and prodigiosin antibiotics) was abolished. Interestingly, the intrinsic resistance to the carbapenem antibiotic was not affected by the rbsR mutation. In addition, the production of a siderophore, cellulase and plant virulence was reduced in the mutant, whereas it exhibited increased swimming and swarming motility. The RbsR protein was predicted to bind to regions upstream of at least 18 genes in S39006 including rbsD (the first gene of the ribose operon) and gvrA. Electrophoretic mobility shift assays (EMSA) confirmed that RbsR bound to DNA sequences upstream of rbsD, but not gvrA. The results of this study indicate that RbsR is a global regulator that affects the modulation of GV biogenesis, but also with complex pleiotropic physiological impacts in S39006.

Understanding where and why Senegalese adolescents and young adults access health information: A mixed methods study examining contextual and personal influences on health information seeking.

BACKGROUND: Adolescent and young adult years are critical to the development of behaviors that influence health across the life course. To reveal which health communication channels should be used to effectively reach and influence younger populations in Senegal, we used a mixed methods approach to identify and interpret the multifaceted influences surrounding where and why this population accesses health information. METHODS: We conducted 16 focus group discussions among adolescents and young adults in Senegal in September 2012. We then collected survey data from a larger, more diverse sample of Senegalese youth in October-November 2014. RESULTS: Our results demonstrate that information sources vary by health topic, differential access, age, and other demographics. While there is a greater perception of credibility and usefulness in information received from health professionals, stigma remains a barrier for obtaining information about HIV/AIDS from health centers. Older youth are also less likely to seek health information from adults, which may be influenced by preferred use of information technologies, especially for information about taboo health topics. CONCLUSIONS: Our findings support multi-pronged, targeted approaches to health communication efforts. We recommend that doctors continue to provide actionable information about preventing or treating specific diseases, whereas teachers should educate youth about general health topics and health promotion behaviors. The results suggest that traditional mass media, such as radio and television, are the best communication channels for information about HIV and sexual/reproductive health, especially for older adolescents and young adults.

Who Participates in Building Disaster Resilient Communities: A Cluster-Analytic Approach.

CONTEXT: The Los Angeles County Community Disaster Resilience project is a community-based program to improve disaster resilience. We collected baseline measures of resilience-related attitudes and practices among targeted communities prior to the implementation of the intervention. OBJECTIVES: This study identified community disaster resilience behavior patterns and assessed their associations with sociodemographic and social cognitive characteristics. DESIGN: Telephone surveys during summer 2013. SETTING: Sixteen communities in Los Angeles County (2 per service planning area). PARTICIPANTS: The address-based sample of adults (≥18) was selected to be representative of 2010 census tracts in each of the communitiesMAIN OUTCOME MEASURES:: We examined relationships between sociodemographic characteristics, social cognitive factors, and participation in community disaster resilience activities. RESULTS: Three clusters of community resilience behavior patterns emerged. Cluster distribution significantly differed across several sociodemographic and social cognitive factors. Participants who were African American, Hispanic, had higher education, income, self-efficacy, trust in the public health department, civic engagement, and social capital were significantly associated with being in the cluster most active in resilience-building activities. CONCLUSIONS: The results confirm that there are distinct community resilience behavior patterns. These patterns vary according to population characteristics, which supports audience segmentation approaches and developing a range of emergency preparedness programs targeted to the strengths and weaknesses of the different audience segments.

Human papillomavirus (HPV) awareness and vaccine receptivity among Senegalese adolescents.

OBJECTIVE: To examine HPV vaccine awareness and receptivity among adolescents and young adults in Senegal. METHODS: Participants from six high schools and five community centres across five regions of Senegal (n = 2286) completed a self-administered questionnaire in October and November 2014. The study assessed HPV awareness and receptivity towards receiving the HPV vaccine. Multivariable logistic regression explored statistically significant relationships between the predictor variables and both outcomes. RESULTS: Twenty-seven percent had heard of HPV. Among those who had heard of HPV (n = 616), only 28% indicated willingness to vaccinate. Multivariable analysis showed that respondents from rural areas had 63% higher odds (95% CI: 1.24, 2.12) of having heard of HPV than those in urban areas. Respondents with fathers who had completed higher education had 41% higher odds (95% CI: 1.04, 1.92) of being aware of HPV (P < 0.05); however, every level of father's education (as compared to no education at all) was negatively associated with willingness to vaccinate. Respondents who had previously spoken to a healthcare professional about the HPV vaccine had 80% higher odds (95% CI: 1.16, 2.81) of willingness to vaccinate than those who did not speak to a provider about the vaccine. CONCLUSIONS: Healthcare providers and parents are important stakeholders in disseminating HPV vaccine information. Given the overall low levels of awareness, there is a great opportunity for public health communication efforts to craft health messaging and information in a way to maximise receptivity, outlining benefits and providing information on the minimal risks associated with the vaccine.

Measuring Outcomes in a Community Resilience Program: A New Metric for Evaluating Results at the Household Level.

Community resilience programs require metrics for evaluation but none exist for measuring outcomes at the household and neighborhood level. OBJECTIVES: We develop and describe a new index, the LACCDR index of community resilience, to examine how resilience varied across communities at baseline, prior to implementation of the Los Angeles County Community Disaster Resilience Project (LACCDR). METHODS: We surveyed 4700 adult residents in the sixteen LACCDR communities in English, Spanish and Korean. Each of the survey domains were selected a priori as outcome indicators aligned to the theoretical levers of community resilience. Survey questions were drawn and adapted from published studies and national surveys. RESULTS: Factor analysis demonstrated five separate factors composed from 18 items and explaining 46.7% of the variance. The factors were characterized as community engagement, emergency supplies, communication with neighbors, civic engagement, and collective efficacy. Baseline results for the 16 communities are provided. CONCLUSIONS: We conclude that the LACCDR community resilience index can be used to measure resilience program outcomes at the neighborhood and household levels.

Transformation of chlorpyrifos and chlorpyrifos-methyl in prairie pothole pore waters.

Non-point source pesticide pollution is a concern for wetlands in the prairie pothole region (PPR). Recent studies have demonstrated that reduced sulfur species (e.g., bisulfide and polysulfides) in PPR wetland pore waters directly undergo reactions with chloroacetanilide and dinitroaniline compounds. In this paper, the abiotic transformation of two organophosphate compounds, chlorpyrifos and chlorpyrifos-methyl, was studied in PPR wetland pore waters. Chlorpyrifos-methyl reacted significantly faster (up to 4 times) in pore water with reduced sulfur species relative to hydrolysis. No rate enhancement was observed in the transformation of chlorpyrifos in pore water with reduced sulfur species. The lack of reactivity was most likely caused by steric hindrance from the ethyl groups and partitioning to dissolved organic matter (DOM), thereby shielding chlorpyrifos from nucleophilic attack. Significant decreases in reaction rates were observed for chlorpyrifos in pore water with high concentrations of DOM. Rate enhancement due to other reactive species (e.g., organo-sulfur compounds) in pore water was minor for both compounds relative to the influence of bisulfide and DOM.

Metaproteomics reveals functional shifts in microbial and human proteins during a preterm infant gut colonization case.

Microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. To this end, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data. More specifically, the function of the microbial community initially involved biomass growth, protein production, and lipid metabolism, and then switched to more complex metabolic functions, such as carbohydrate metabolism, once the community stabilized and matured. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Likewise, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. This study provides the first snapshot of coordinated human and microbial protein expression in a preterm infant's gut during early development.

Moving away from the reference genome: evaluating a peptide sequencing tagging approach for single amino acid polymorphism identifications in the genus Populus.

The genetic diversity across natural populations of the model organism, Populus, is extensive, containing a single nucleotide polymorphism roughly every 200 base pairs. When deviations from the reference genome occur in coding regions, they can impact protein sequences. Rather than relying on a static reference database to profile protein expression, we employed a peptide sequence tagging (PST) approach capable of decoding the plasticity of the Populus proteome. Using shotgun proteomics data from two genotypes of P. trichocarpa, a tag-based approach enabled the detection of 6653 unexpected sequence variants. Through manual validation, our study investigated how the most abundant chemical modification (methionine oxidation) could masquerade as a sequence variant (Ala→Ser) when few site-determining ions existed. In fact, precise localization of an oxidation site for peptides with more than one potential placement was indeterminate for 70% of the MS/MS spectra. We demonstrate that additional fragment ions made available by high energy collisional dissociation enhances the robustness of the peptide sequence tagging approach (81% of oxidation events could be exclusively localized to a methionine). We are confident that augmenting fragmentation processes for a PST approach will further improve the identification of single amino acid polymorphism in Populus and potentially other species as well.

Putting the pieces together: high-performance LC-MS/MS provides network-, pathway-, and protein-level perspectives in Populus.

High-performance mass spectrometry (MS)-based proteomics enabled the construction of a detailed proteome atlas for Populus, a woody perennial plant model organism. Optimization of experimental procedures and implementation of current state-of-the-art instrumentation afforded the most detailed look into the predicted proteome space of Populus, offering varying proteome perspectives: (1) network-wide, (2) pathway-specific, and (3) protein-level viewpoints. Together, enhanced protein retrieval through a detergent-based lysis approach and maximized peptide sampling via the dual-pressure linear ion trap mass spectrometer (LTQ Velos), have resulted in the identification of 63,056 tryptic peptides. The technological advancements, specifically spectral-acquisition and sequencing speed, afforded the deepest look into the Populus proteome, with peptide abundances spanning 6 orders of magnitude and mapping to ∼25% of the predicted proteome space. In total, tryptic peptides mapped to 11,689 protein assignments across four organ-types: mature (fully expanded, leaf plastichronic index (LPI) 10-12) leaf, young (juvenile, LPI 4-6) leaf, root, and stem. To resolve protein ambiguity, identified proteins were grouped by sequence similarity (≥ 90%), thereby reducing the protein assignments into 7538 protein groups. In addition, this large-scale data set features the first systems-wide survey of protein expression across different Populus organs. As a demonstration of the precision and comprehensiveness of the semiquantitative analysis, we were able to contrast two stages of leaf development, mature versus young leaf. Statistical comparison through ANOVA analysis revealed 1432 protein groups that exhibited statistically significant (p ≤ 0.01) differences in protein abundance. Experimental validation of the metabolic circuitry expected in mature leaf (characterized by photosynthesis and carbon fixation) compared with young leaf (characterized by rapid growth and moderate photosynthetic activities) strongly testifies to the credibility of the approach. Instead of quantitatively comparing a few proteins, a systems view of all the changes associated with a given cellular perturbation could be made.

Systematic comparison of label-free, metabolic labeling, and isobaric chemical labeling for quantitative proteomics on LTQ Orbitrap Velos.

A variety of quantitative proteomics methods have been developed, including label-free, metabolic labeling, and isobaric chemical labeling using iTRAQ or TMT. Here, these methods were compared in terms of the depth of proteome coverage, quantification accuracy, precision, and reproducibility using a high-performance hybrid mass spectrometer, LTQ Orbitrap Velos. Our results show that (1) the spectral counting method provides the deepest proteome coverage for identification, but its quantification performance is worse than labeling-based approaches, especially the quantification reproducibility; (2) metabolic labeling and isobaric chemical labeling are capable of accurate, precise, and reproducible quantification and provide deep proteome coverage for quantification; isobaric chemical labeling surpasses metabolic labeling in terms of quantification precision and reproducibility; and (3) iTRAQ and TMT perform similarly in all aspects compared in the current study using a CID-HCD dual scan configuration. On the basis of the unique advantages of each method, we provide guidance for selection of the appropriate method for a quantitative proteomics study.

Discovery and annotation of small proteins using genomics, proteomics, and computational approaches.

Small proteins (10-200 amino acids [aa] in length) encoded by short open reading frames (sORF) play important regulatory roles in various biological processes, including tumor progression, stress response, flowering, and hormone signaling. However, ab initio discovery of small proteins has been relatively overlooked. Recent advances in deep transcriptome sequencing make it possible to efficiently identify sORFs at the genome level. In this study, we obtained ~2.6 million expressed sequence tag (EST) reads from Populus deltoides leaf transcriptome and reconstructed full-length transcripts from the EST sequences. We identified an initial set of 12,852 sORFs encoding proteins of 10-200 aa in length. Three computational approaches were then used to enrich for bona fide protein-coding sORFs from the initial sORF set: (1) coding-potential prediction, (2) evolutionary conservation between P. deltoides and other plant species, and (3) gene family clustering within P. deltoides. As a result, a high-confidence sORF candidate set containing 1469 genes was obtained. Analysis of the protein domains, non-protein-coding RNA motifs, sequence length distribution, and protein mass spectrometry data supported this high-confidence sORF set. In the high-confidence sORF candidate set, known protein domains were identified in 1282 genes (higher-confidence sORF candidate set), out of which 611 genes, designated as highest-confidence candidate sORF set, were supported by proteomics data. Of the 611 highest-confidence candidate sORF genes, 56 were new to the current Populus genome annotation. This study not only demonstrates that there are potential sORF candidates to be annotated in sequenced genomes, but also presents an efficient strategy for discovery of sORFs in species with no genome annotation yet available.

Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress.

The StarD4 and StarD5 proteins share approximately 30% identity, and each is a steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain. We previously showed StarD4 expression is sterol-repressed, consistent with regulation by sterol regulatory element-binding proteins (SREBPs), whereas StarD5 is not sterol-regulated. Here we further address the regulation and function of StarD4 and StarD5. Unlike StAR, the START family prototype, StarD4 and StarD5 were not induced by steroidogenic stimuli in Leydig cells. However, StarD4 and StarD5 showed StAR-like activity in a cell culture steroidogenesis assay, indicating cholesterol transfer. In transgenic mice expressing active SREBPs, StarD4 was predominantly activated by SREBP-2 rather than SREBP-1a. The mouse and human StarD4 proximal promoters share approximately 70% identity, including several potential sterol regulatory elements (SREs). Reporters driven by the StarD4 promoter from either species were transfected into NIH-3T3 cells, and reporter activity was highly repressed by sterols. Site-directed mutagenesis of potential SREs identified a conserved functional SRE in the mouse (TCGGTCCAT) and human (TCATTCCAT) promoters. StarD5 was not sterol-repressed via SREBPs nor was it sterol-activated via liver X receptors (LXRs). Even though StarD4 and StarD5 were not LXR targets, their overexpression stimulated LXR reporter activity, suggesting roles in cholesterol metabolism. StarD5 expression increased 3-fold in free cholesterol-loaded macrophages, which activate the endoplasmic reticulum (ER) stress response. When NIH-3T3 cells were treated with agents to induce ER stress, StarD5 expression increased 6-8-fold. Because StarD4 is regulated by sterols via SREBP-2, whereas StarD5 is activated by ER stress, they likely serve distinct functions in cholesterol metabolism.

The cholesterol-regulated StarD4 gene encodes a StAR-related lipid transfer protein with two closely related homologues, StarD5 and StarD6.

Using cDNA microarrays, we identified StarD4 as a gene whose expression decreased more than 2-fold in the livers of mice fed a high-cholesterol diet. StarD4 expression in cultured 3T3 cells was also sterol-regulated, and known sterol regulatory element binding protein (SREBP)-target genes showed coordinate regulation. The closest homologues to StarD4 were two other StAR-related lipid transfer (START) proteins named StarD5 and StarD6. StarD4, StarD5, and StarD6 are 205- to 233-aa proteins consisting almost entirely of START domains. These three constitute a subfamily among START proteins, sharing approximately 30% amino acid identity with one another, approximately 20% identity with the cholesterol-binding START domains of StAR and MLN64, and less than 15% identity with phosphatidylcholine transfer protein (PCTP) and other START domains. StarD4 and StarD5 were expressed in most tissues, with highest levels in liver and kidney, whereas StarD6 was expressed exclusively in the testis. In contrast to StarD4, expression of StarD5 and MLN64 was not sterol-regulated. StarD4, StarD5, and StarD6 may be involved in the intracellular transport of sterols or other lipids.