Precise coordination between nutrient transporters ensures fertility in the malaria mosquito Anopheles gambiae.

Females from many mosquito species feed on blood to acquire nutrients for egg development. The oogenetic cycle has been characterized in the arboviral vector Aedes aegypti, where after a bloodmeal, the lipid transporter lipophorin (Lp) shuttles lipids from the midgut and fat body to the ovaries, and a yolk precursor protein, vitellogenin (Vg), is deposited into the oocyte by receptor-mediated endocytosis. Our understanding of how the roles of these two nutrient transporters are mutually coordinated is however limited in this and other mosquito species. Here, we demonstrate that in the malaria mosquito Anopheles gambiae, Lp and Vg are reciprocally regulated in a timely manner to optimize egg development and ensure fertility. Defective lipid transport via Lp knockdown triggers abortive ovarian follicle development, leading to misregulation of Vg and aberrant yolk granules. Conversely, depletion of Vg causes an upregulation of Lp in the fat body in a manner that appears to be at least partially dependent on target of rapamycin (TOR) signaling, resulting in excess lipid accumulation in the developing follicles. Embryos deposited by Vg-depleted mothers are completely inviable, and are arrested early during development, likely due to severely reduced amino acid levels and protein synthesis. Our findings demonstrate that the mutual regulation of these two nutrient transporters is essential to safeguard fertility by ensuring correct nutrient balance in the developing oocyte, and validate Vg and Lp as two potential candidates for mosquito control.

Interplay between nutrient transporters ensures fertility in the malaria mosquito Anopheles gambiae.

Females from many mosquito species feed on blood to acquire nutrients for egg development. The oogenetic cycle has been characterized in the arboviral vector Aedes aegypti, where after a bloodmeal, the lipid transporter lipophorin (Lp) shuttles lipids from the midgut and fat body to the ovaries, and a yolk precursor protein, vitellogenin (Vg), is deposited into the oocyte by receptor-mediated endocytosis. Our understanding of how the roles of these two nutrient transporters are mutually coordinated is however limited in this and other mosquito species. Here, we demonstrate that in the malaria mosquito Anopheles gambiae, Lp and Vg are reciprocally regulated in a timely manner to optimize egg development and ensure fertility. Defective lipid transport via Lp silencing triggers abortive ovarian follicle development, leading to misregulation of Vg and aberrant yolk granules. Conversely, depletion of Vg causes an upregulation of Lp in the fat body in a manner that appears to be at least partially dependent on target of rapamycin (TOR) signaling, resulting in excess lipid accumulation in the developing follicles. Embryos deposited by Vg-depleted mothers are completely infertile, and are arrested early during development, likely due to severely reduced amino acid levels and protein synthesis. Our findings demonstrate that the mutual regulation of these two nutrient transporters is essential to safeguard fertility by ensuring correct nutrient balance in the developing oocyte, and validate Vg and Lp as two potential candidates for mosquito control.

Adenovirus Remodeling of the Host Proteome and Host Factors Associated with Viral Genomes.

Viral infections are associated with extensive remodeling of the cellular proteome. Viruses encode gene products that manipulate host proteins to redirect cellular processes or subvert antiviral immune responses. Adenovirus (AdV) encodes proteins from the early E4 region which are necessary for productive infection. Some cellular antiviral proteins are known to be targeted by AdV E4 gene products, resulting in their degradation or mislocalization. However, the full repertoire of host proteome changes induced by viral E4 proteins has not been defined. To identify cellular proteins and processes manipulated by viral products, we developed a global, unbiased proteomics approach to analyze changes to the host proteome during infection with adenovirus serotype 5 (Ad5) virus. We used whole-cell proteomics to measure total protein abundances in the proteome during Ad5 infection. Since host antiviral proteins can antagonize viral infection by associating with viral genomes and inhibiting essential viral processes, we used Isolation of Proteins on Nascent DNA (iPOND) proteomics to identify proteins associated with viral genomes during infection with wild-type Ad5 or an E4 mutant virus. By integrating these proteomics data sets, we identified cellular factors that are degraded in an E4-dependent manner or are associated with the viral genome in the absence of E4 proteins. We further show that some identified proteins exert inhibitory effects on Ad5 infection. Our systems-level analysis reveals cellular processes that are manipulated during Ad5 infection and points to host factors counteracted by early viral proteins as they remodel the host proteome to promote efficient infection. IMPORTANCE Viral infections induce myriad changes to the host cell proteome. As viruses harness cellular processes and counteract host defenses, they impact abundance, post-translational modifications, interactions, or localization of cellular proteins. Elucidating the dynamic changes to the cellular proteome during viral replication is integral to understanding how virus-host interactions influence the outcome of infection. Adenovirus encodes early gene products from the E4 genomic region that are known to alter host response pathways and promote replication, but the full extent of proteome modifications they mediate is not known. We used an integrated proteomics approach to quantitate protein abundance and protein associations with viral DNA during virus infection. Systems-level analysis identifies cellular proteins and processes impacted in an E4-dependent manner, suggesting ways that adenovirus counteracts potentially inhibitory host defenses. This study provides a global view of adenovirus-mediated proteome remodeling, which can serve as a model to investigate virus-host interactions of DNA viruses.

Screening for Victims of Sex Trafficking in the Emergency Department: A Pilot Program.

INTRODUCTION: Estimates suggest that hundreds of thousands of sex trafficking victims live in the United States. Several screening tools for healthcare professionals to identify sex trafficking victims have been proposed, but the effectiveness of these tools in the emergency department (ED) remains unclear. Our primary objective in this study was to evaluate the feasibility of a screening survey to identify adult victims of sex trafficking in the ED. We also compared the sensitivity of emergency physician concern and a screening survey for identifying sex trafficking victims in the ED and determined the most effective question(s) for identifying adult victims of sex trafficking. METHODS: We enrolled a convenience sample of medically stable female ED patients, age 18-40 years. Patients completed a 14-question survey. Physician concern for sex trafficking was documented prior to informing the physician of the survey results. A "yes" answer to any question or physician concern was considered a positive screen, and the patient was offered social work consultation. We defined a "true positive" as a patient admission for or social work documentation of sex trafficking. Demographic and clinical information were collected from the electronic medical record. RESULTS: We enrolled 143 patients, and of those 39 (27%, 95% confidence interval [CI] [20%-35%]) screened positive, including 10 (25%, 95% CI [13%-41%]) ultimately identified as victims of sex trafficking. Sensitivity of the screening survey (100%, 95% CI [74%-100%]) was better than physician concern (40%, 95% CI [12%-74%]) for identifying victims of sex trafficking, difference 60%, 95% CI [30%-90%]. Physician specificity (91%, 95% CI [85%-95%]), however, was slightly better than the screening survey (78%, 95% CI [70%-85%]), difference 13%, 95% CI [4%-21%]. All 10 (100%, 95%CI [74%-100%]) "true positive" cases answered "yes" to the screening question regarding abuse. CONCLUSION: Identifying adult victims of sex trafficking in the ED is feasible. A screening survey appears to have greater sensitivity than physician concern, and a single screening question may be sufficient to identify all adult victims of sex trafficking in the ED.

National Survey of Medical Spanish Curriculum in U.S. Medical Schools.

BACKGROUND: Patients with limited English proficiency (LEP) may be at risk for medical errors and worse health outcomes. Language concordance between patient and provider has been shown to improve health outcomes for Spanish-speaking patients. Nearly 40 % of Hispanics, a growing population in the United States, are categorized as having limited English proficiency. Many medical schools have incorporated a medical Spanish curriculum to prepare students for clinical encounters with LEP patients. OBJECTIVE: To describe the current state of medical Spanish curricula at United States medical schools. METHODS: The Latino Medical Student Association distributed an e-mail survey comprising 39 items to deans from each U.S. medical school from July 2012 through July 2014. This study was IRB-exempt. RESULTS: Eighty-three percent (110/132) of the U.S. medical schools completed the survey. Sixty-six percent (73/110) of these schools reported offering a medical Spanish curriculum. In addition, of schools with no curriculum, 32 % (12/37) planned to incorporate the curriculum within the next two years. Most existing curricula were elective, not eligible for course credit, and taught by faculty or students. Teaching modalities included didactic instruction, role play, and immersion activities. Schools with the curriculum reported that the diverse patient populations in their respective service areas and/or student interest drove course development. Barriers to implementing the curriculum included lack of time in students' schedules, overly heterogeneous student language skill levels, and a lack of financial resources. Few schools reported the use of validated instruments to measure language proficiency after completion of the curriculum. CONCLUSIONS: Growing LEP patient populations and medical student interest have driven the implementation of medical Spanish curricula at U.S. medical schools, and more schools have plans to incorporate this curriculum in the near future. Studies are needed to reveal best practices for developing and evaluating the curriculum.