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Pandemic and endemic strains of Vibrio cholerae arise from toxigenic conversion by the CTXφ bacteriophage, a process by which CTXφ infects nontoxigenic strains of V. cholerae. CTXφ encodes the cholera toxin, an enterotoxin responsible for the watery diarrhea associated with cholera infections. Despite the critical role of CTXφ during infections, signals that affect CTXφ-driven toxigenic conversion or expression of the CTXφ-encoded cholera toxin remain poorly characterized, particularly in the context of the gut mucosa. Here, we identify mucin polymers as potent regulators of CTXφ-driven pathogenicity in V. cholerae. Our results indicate that mucin-associated O-glycans block toxigenic conversion by CTXφ and suppress the expression of CTXφ-related virulence factors, including the toxin co-regulated pilus and cholera toxin, by interfering with the TcpP/ToxR/ToxT virulence pathway. By synthesizing individual mucin glycan structures de novo, we identify the Core 2 motif as the critical structure governing this virulence attenuation. Overall, our results highlight a novel mechanism by which mucins and their associated O-glycan structures affect CTXφ-mediated evolution and pathogenicity of V. cholerae, underscoring the potential regulatory power housed within mucus.

Conditional expression of short hairpin RNAs (shRNAs) with binary genetic systems is an indispensable tool for studying gene function. Addressing mechanisms underlying cell-cell communication in vivo benefits from simultaneous use of two independent gene expression systems. To complement the abundance of existing Gal4/UAS-based resources in Drosophila, we and others have developed LexA/LexAop-based genetic tools. Here, we describe experimental and pedagogical advances that promote the efficient conversion of Drosophila Gal4 lines to LexA lines, and the generation of LexAop-shRNA lines to suppress gene function. We developed a CRISPR/Cas9-based knock-in system to replace Gal4 coding sequences with LexA, and a LexAop-based shRNA expression vector to achieve shRNA-mediated gene silencing. We demonstrate the use of these approaches to achieve targeted genetic loss-of-function in multiple tissues. We also detail our development of secondary school curricula that enable students to create transgenic flies, thereby magnifying the production of well-characterized LexA/LexAop lines for the scientific community. The genetic tools and teaching methods presented here provide LexA/LexAop resources that complement existing resources to study intercellular communication coordinating metazoan physiology and development.

Crop Science The parasitic weed Striga infests a large proportion of cereal crops in Africa and parts of Asia, which has a devastating effect on farming, particularly in subsistence communities. An obligate parasite, Striga requires a chemical signal from the host plant to germinate, offering an avenue for genetic improvement of host crops. Gobena et al. studied the difference between sorghum strains associated with high and low Striga germination levels and mapped a mutation associated with low Striga germination ( LGS1 ) to a previously uncharacterized sulfotransferase gene. Deletion of this gene does not result in reduced levels of root chemical signaling, but rather in a change in the composition of chemicals exuded from the root. Identification of this gene could allow marker-assisted breeding to generate sorghum varieties with reduced Striga infestation. Proc. Natl. Acad. Sci. U.S.A. 114 , 4471 (2017).

Cancer Diagnosis of specific types of cancer is vital for decisions regarding treatment and monitoring plans. However, acquiring sufficient tissue from a tumor biopsy to perform a histological examination and diagnosis can be difficult because of limited tumor accessibility or ambiguous tissue samples. Methods that allow minimally invasive biopsies are required to improve patient care. Hao et al. identified DNA methylation profiles associated with four common cancers that can be used to identify tumors from smaller tissue samples with accuracy comparable to that of current diagnostic methods. These methylation markers can also be used to identify the tissue of origin of metastasized cancers, which can be critical for treatment, and as predictors of prognosis and survival to improve standards of diagnosis. Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1703577114 (2017).

Evolutionary Biology![Figure][1] Parasitoid wasps have evolved venoms for host control. PHOTO: HUTTON/TOM STACK ASSOC/ALAMY STOCK PHOTO Parasitoid wasps use venom to immobilize their hosts and manipulate them into providing a suitable environment for the growth of wasp larvae. In response to changes in host ranges and availability, venom genes need to evolve rapidly to maintain efficacy. Martinson et al. studied the sequence and expression of venom genes in closely related wasp species to determine how they evolve. The authors found that many of these genes do not evolve through duplication and neofunctionalization, as expected, but rather are the result of co-opting single-copy genes of different functions. Similarly to genes that have lost venom function, these new venom genes are not a consequence of alterations in the gene sequence itself, but instead have modified cis-regulated expression patterns. Curr. Biol. 10.1016/j.cub.2017.05.032 (2017). [1]: pending:yes

Plant Biology The switch between seed dormancy and germination in Arabidopsis thaliana is regulated by the balance between the hormones abscisic acid (ABA) and gibberellin (GA). Low temperatures are known to cause an increase in GA synthesis and receptor abundance, thereby increasing the probability of germination. Topham et al. studied the integration of temperature signals and determined that the embryo radicle is enriched for factors involved in hormone signaling, synthesis, and degradation. A clear spatial pattern emerged whereby ABA and GA pathway components were broadly separated into different cell types. This spatial separation and control over transport of hormones between cells facilitates processing of fluctuating temperature inputs and increases their propensity to break seed dormancy, compared with signals from continuous cold exposure. This is hypothesized to ensure accurate timing of seedling establishment through recognition of environmental temperature oscillations. Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1704745114 (2017).

Diet Binge-like eating (BE) predominantly affects females and usually manifests in late adolescence. Previous studies have linked eating disorders to early life stress, and it is known that perinatal stress increases susceptibility to a variety of psychiatric disorders. Schroeder et al. have

HIV Survival rates of patients with HIV have improved enormously as a result of antiretroviral therapy, but increased life expectancy is now associated with a high risk of comorbidities. HIV–1-associated chronic obstructive pulmonary disease (COPD) often manifests as emphysema, originating around the airways and extending into lung tissue. Chung et al. have discovered that this is caused by HIV binding to basal cells in the airway and activating a tissue-destructive phenotype through a mitogen-activated protein kinase signaling cascade. HIV binding triggers up-regulation of matrix metalloproteinase 9, which is known to be elevated in COPD patients and may contribute to the degradation of extracellular matrix seen in emphysema sufferers. Cell Rep. 19 , 1091 (2017).

Ocean Ecology Ocean temperatures in the North Atlantic and North Pacific oceans have increased in recent decades, particularly in coastal areas. This has been associated with increased algal blooms and, where these blooms include algal species that produce biotoxins, the potential for increases in cases of paralytic and diarrhetic shellfish poisoning. Gobler et al. used high-resolution records of sea surface temperature from 1982 to 2016 and temperature-dependent growth rates of two toxic algal species to create models of harmful algal blooms. These models were validated in areas of the North Atlantic by observations in other studies of increased bloom frequency and range that matched predicted locations. This information could potentially be used to predict the future spread of harmful algal blooms and the consequent impact on human health. Proc. Natl. Acad. Sci. U.S.A. 114 , 4975 (2017).

Caffeine, a commonly consumed psychoactive substance, can have significant effects on sleep. Caffeine intake among children is increasing, mainly in the form of sodas. However, adolescent caffeine consumers may lack knowledge about the caffeine content in common beverages. If true, this very fact may hamper the assessment of the effects of caffeine consumption on sleep in children if such assessments are a priori dependent on responders being able to reliably distinguish between caffeinated and noncaffeinated beverages. This preliminary study investigated adolescents' caffeine knowledge and intake at a Cleveland-area public middle school.Seventh- and eighth-grade students were surveyed using: (1) the Caffeine Literacy and Sleep Study (CLASS), a 15-question pilot instrument designed to assess caffeine knowledge and intake by type, quantity and timing, as well as sleep habits; and (2) the Cleveland Adolescent Sleepiness Questionnaire (CASQ), a validated survey measuring excessive daytime sleepiness in adolescents. These questionnaires were distributed and collected during a specified class period.Of the 635 seventh- and eighth-grade students who attended school on the day of the study, 555 (87%) participated. Lack of knowledge about caffeine content of particular drinks was noted in seventh and eighth graders of both sexes with nearly 29% unaware that their favorite drinks contain caffeine and more than 50% unable to correctly identify the drinks with the most caffeine. A low percentage of students correctly identified light-colored sodas lacking caffeine: 7-Up (24.1%), Sierra Mist (38.9%), ginger ale (39.8%), Sprite (39.8%), and Fresca (53.7%). The percentages of students correctly identifying caffeinated light-colored beverages were: Arizona Green Tea (43.5%), Mello Yellow (50.9%), and AW cream soda (67.6%). However, Mountain Dew was correctly identified by most (93.5%) as caffeinated.Students were not consistently able to identify caffeine content or lack thereof in some common beverages. The results of this pilot study show that caffeine literacy in adolescents warrants further investigation and educational intervention.

The “Rotten Apple” theory states that deviant police officers are those who psychological testing fails to screen out. This concept is favored by police administrators because it offers a quick and easy solution to police deviant behavior. However, there is a growing body of literature that suggests that it is the stressful occupation that is policing that is the fertile soil from which police deviant behavior springs otherwise known as the “Rotten Barrel” theory. This article shall explore police deviant behavior from the perspective that it is the “Rotten Barrel” that leads to police deviant behavior.

The ability to compensate for previous activities, often in the case of failure or exceptional events, is an important feature of long-running business transactions. In this paper, we present several extensions to existing notions of compensation for business transactions. The extensions are described using a business process modeling language called StAC (Structured Activity Compensation) but are also placed in the context of IBM's BPBeans (Business Process Beans) enterprise technology. The meaning of the compensation mechanisms is made precise, as are issues of compensation scoping in multilevel transactions. The compensation extensions result in flexible and powerful mechanisms for modeling and implementing long-running business transactions.