Toxicity of baited spinosad formulations to Ceratitis capitata: from the laboratory to the application

GF‐120, a fruit fly bait designed to attract and kill adult fruit flies, was tested in the laboratory and outdoors to determine effects of pre‐treatment diet and bait aging on mortality of Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). Two spinosad‐based compounds, GF‐120 and Tracer^® Ultra, had generated two distinctive dose–mortality responds, with LC⁸⁰, LC⁹⁰, and LC⁹⁹ values of 2.4, 2.8, and 4.1 p.p.m., and 255, 479, and 1 143 p.p.m., respectively. The residues of GF‐120 drops, after feeding to the flies, generated 14.3% mortality. The droplet size of the baited spray plays an important role. The toxicity of large drops lasted more than that of small droplets. In the field, exposure to the sun further deteriorates the compound, which lost 50% of its toxicity within 6 days. Disappearance of the compound in the field, due to consumption by various insects, also played a role as 50% of the GF‐120 drops disappeared within 7 days. As mortality was directly related to the amount of insecticide eaten, the effect of GF‐120 depended on the feeding status of the flies: well‐fed flies were almost unaffected compared with starved ones.     

HIV Malaria Co-Infection Is Associated with Atypical Memory B Cell Expansion and a Reduced Antibody Response to a Broad Array of Plasmodium falciparum Antigens in Rwandan Adults

HIV infected individuals in malaria endemic areas experience more frequent and severe malaria episodes compared to non HIV infected. This clinical observation has been linked to a deficiency in antibody responses to Plasmodium falciparum antigens; however, prior studies have only focused on the antibody response to <0.5% of P. falciparum proteins. To obtain a broader and less-biased view of the effect of HIV on antibody responses to malaria we compared antibody profiles of HIV positive (HIV+) and negative (HIV-) Rwandan adults with symptomatic malaria using a microarray containing 824 P. falciparum proteins. We also investigated the cellular basis of the antibody response in the two groups by analyzing B and T cell subsets by flow cytometry. Although HIV malaria co-infected individuals generated antibodies to a large number of P. falciparum antigens, including potential vaccine candidates, the breadth and magnitude of their response was reduced compared to HIV- individuals. HIV malaria co-infection was also associated with a higher percentage of atypical memory B cells (MBC) (CD19+CD10-CD21-CD27-) compared to malaria infection alone. Among HIV+ individuals the CD4⁺ T cell count and HIV viral load only partially explained variability in the breadth of P. falciparum-specific antibody responses. Taken together, these data indicate that HIV malaria co-infection is associated with an expansion of atypical MBCs and a diminished antibody response to a diverse array of P. falciparum antigens, thus offering mechanistic insight into the higher risk of malaria in HIV+ individuals.     

Genetic diversity in Puerto Rico and its implications for the peopling of the Island and the West Indies

Puerto Rico and the surrounding islands rest on the eastern fringe of the Caribbean's Greater Antilles, located less than 100 miles northwest of the Lesser Antilles. Puerto Ricans are genetic descendants of pre‐Columbian peoples, as well as peoples of European and African descent through 500 years of migration to the island. To infer these patterns of pre‐Columbian and historic peopling of the Caribbean, we characterized genetic diversity in 326 individuals from the southeastern region of Puerto Rico and the island municipality of Vieques. We sequenced the mitochondrial DNA (mtDNA) control region of all of the samples and the complete mitogenomes of 12 of them to infer their putative place of origin. In addition, we genotyped 121 male samples for 25 Y‐chromosome single nucleotide polymorphism and 17 STR loci. Approximately 60% of the participants had indigenous mtDNA haplotypes (mostly from haplogroups A2 and C1), while 25% had African and 15% European haplotypes. Three A2 sublineages were unique to the Greater Antilles, one of which was similar to Mesoamerican types, while C1b haplogroups showed links to South America, suggesting that people reached the island from the two distinct continental source areas. However, none of the male participants had indigenous Y‐chromosomes, with 85% of them instead being European/Mediterranean and 15% sub‐Saharan African in origin. West Eurasian Y‐chromosome short tandem repeat haplotypes were quite diverse and showed similarities to those observed in southern Europe, North Africa and the Middle East. These results attest to the distinct, yet equally complex, pasts for the male and female ancestors of modern day Puerto Ricans. Am J Phys Anthropol 155:352–368, 2014. © 2014 Wiley Periodicals, Inc.     

IL-13Rα2-Targeted Therapy Escapees: Biologic and Therapeutic Implications

Glioblastoma multiforme (GBM) overexpresses interleukin 13 receptor α2 (IL-13Rα2), a tumor-restricted receptor that is not present in normal brain. We and others have created targeted therapies that specifically eradicate tumors expressing this promising tumor-restricted biomarker. As these therapies head toward clinical implementation, it is critical to explore mechanisms of potential resistance. We therefore used a potent IL-13Rα2-targeted bacterial cytotoxin to select for naturally occurring "escapee" cells from three different IL-13Rα2-expressing GBM cell lines. We found that these side populations of escapee cells had significantly decreased IL-13Rα2 expression. We examined clinically relevant biologic characteristics of escapee cell lines compared to their parental cell lines and found that they had similar proliferation rates and equal sensitivity to temozolomide and radiation, the standard therapies given to GBM patients. In contrast, our escapee cell lines were less likely to form colonies in culture and migrated more slowly in wound healing assays. Furthermore, we found that escapee cells formed significantly less neurospheres in vitro, suggesting that IL-13Rα2-targeted therapy preferentially targeted the "stem-like" cell population and possibly indicating decreased tumorigenicity in vivo. We therefore tested escapee cells for in vivo tumorigenicity and found that they were significantly less tumorigenic in both subcutaneous and intracranial mouse models compared to matching parental cells. These data, for the first time, establish and characterize the clinically relevant biologic properties of IL-13Rα2-targeted therapy escapees and suggest that these cells may have less malignant characteristics than parental tumors.     

1-substituted cyclopropenes: Effective Blocking Agents for Ethylene Action in Plants

A series of 1-alkane substituted cyclopropenes has been prepared and tested as ethylene antagonists using banana fruits as an assay system. 1-Methyl-, 1-ethyl-, 1-propyl-, 1-butyl-, 1-pentyl-, 1-hexyl-, 1-heptyl-, 1-octyl-, 1-nonyl-, and 1-decylcyclopropene were all very active compounds. 1-Methylcyclopropene protected bananas from ethylene with a minimum concentration of 0.7 nl.l^–1 after a 24 h exposure. As the carbon chain length was extended the minimum requirement increased some, but starting with 1-butylcyclopropene, the minimum concentration requirement declined and many cyclopropenes were required in lower concentrations than 1-methylcyclopropene. The time of protection at ambient temperature (22–23 °C) was 12 d for 1-methyl-, 1-ethyl-, 1-propyl-, and 1-butylcyclopropene. 1-Pentylcyclopropene protected bananas for 14 d, 1-hexylcyclopropene for 20 d, 1-heptylcyclopropene for 21 d, 1-octylcyclopropene for 25 d, 1-nonylcyclopropene for 35 d, and 1-decylcyclopropene for 36 d.     

Oxidative stress in diseases of the human cornea

Intense exposure to light, robust metabolic activity, and high oxygen tension render the human eye particularly vulnerable to oxidative damage and the list of ophthalmological disorders implicating reactive oxygen and nitrogen species is rapidly expanding. Here, we review the roles of oxidative stress in the etiopathogeneses and pathophysiology of diseases of the human cornea including pterygium, keratoconus, trauma and chemical injury, and a host of inflammatory, metabolic, degenerative, and iatrogenic conditions. Data from animal and tissue culture experimentation germane to these conditions are also adduced.     

The CCAAT binding factor can mediate interactions between CONSTANS-like proteins and DNA

CONSTANS-Like (COL) proteins are plant-specific nuclear regulators of gene expression but do not contain a known DNA-binding motif. We tested whether a common DNA-binding protein can deliver these proteins to specific cis-acting elements. We screened for proteins that interact with two members of a subgroup of COL proteins. These COL proteins were Tomato COL1 (TCOL1), which does not seem to be involved in the control of flowering time, and the Arabidopsis thaliana CONSTANS (AtCO) protein which mediates photoperiodic induction of flowering. We show that the C-terminal plant-specific CCT (CO, CO-like, TIMING OF CAB EXPRESSION 1) domain of both proteins binds the trimeric CCAAT binding factor (CBF) via its HAP5/NF-YC component. Chromatin immunoprecipitation demonstrated that TCOL is recruited to the CCAAT motifs of the yeast CYC1 and HEM1 promoters by HAP5. In Arabidopsis, each of the three CBF components is encoded by several different genes that are highly transcribed. Under warm long days, high levels of expression of a tomato HAP5 (THAP5a) gene can reduce the flowering time of Arabidopsis. A mutation in the CCT domain of TCOL1 disrupts the interaction with THAP5 and the analogous mutation in AtCO impairs its function and delays flowering. CBFs are therefore likely to recruit COL proteins to their DNA target motifs in planta.     

The novel ethylene antagonist, 3-cyclopropyl-1-enyl-propanoic acid sodium salt (CPAS), increases grain yield in wheat by delaying leaf senescence

Orchid is a major floral crop around the world and Dendrobium hybrids are considered to be one of the most popular orchids. In vitro germination of hybrid seeds is a common practice among orchid growers, however, in many cross pollinations the embryos may not develop to maturity, leading to poor seed germination. The effect of seed maturity and sucrose concentration were investigated via asymbiotic germination of nobile Dendrobium hybrids. Capsules were harvested from two hybrids (Den. Lucky Girl × Den. Second Love ‘Kirameki’ and Den. Lucky Girl × Den. Hamana Lake ‘Kumi’) and one selfing of Den. Second Love ‘Kirameki’ at 2, 3, 4, and 5 months after pollination and immature seeds were taken. Immature seeds from 3- to 5-month old capsules could be successfully germinated on Hyponex based medium. Immature seeds from 4-month old capsules showed greatest germination rate of tested treatments, whereas 3-month old immature seeds showed the least germination. After 6 weeks of in vitro culture, protocorms derived from embryos developed on every concentration of sucrose, but germination was greater at lower concentrations. Greater concentration of sucrose decreased normal-developed protocorms.     

Large-Scale Determination of Sequence,Structure, and Function Relationships in Cytosolic Glutathione Transferases across the Biosphere

The cytosolic glutathione transferase (cytGST) superfamily comprises more than 13,000 nonredundant sequences found throughout the biosphere. Their key roles in metabolism and defense against oxidative damage have led to thousands of studies over several decades. Despite this attention, little is known about the physiological reactions they catalyze and most of the substrates used to assay cytGSTs are synthetic compounds. A deeper understanding of relationships across the superfamily could provide new clues about their functions. To establish a foundation for expanded classification of cytGSTs, we generated similarity-based subgroupings for the entire superfamily. Using the resulting sequence similarity networks, we chose targets that broadly covered unknown functions and report here experimental results confirming GST-like activity for 82 of them, along with 37 new 3D structures determined for 27 targets. These new data, along with experimentally known GST reactions and structures reported in the literature, were painted onto the networks to generate a global view of their sequence-structure-function relationships. The results show how proteins of both known and unknown function relate to each other across the entire superfamily and reveal that the great majority of cytGSTs have not been experimentally characterized or annotated by canonical class. A mapping of taxonomic classes across the superfamily indicates that many taxa are represented in each subgroup and highlights challenges for classification of superfamily sequences into functionally relevant classes. Experimental determination of disulfide bond reductase activity in many diverse subgroups illustrate a theme common for many reaction types. Finally, sequence comparison between an enzyme that catalyzes a reductive dechlorination reaction relevant to bioremediation efforts with some of its closest homologs reveals differences among them likely to be associated with evolution of this unusual reaction. Interactive versions of the networks, associated with functional and other types of information, can be downloaded from the Structure-Function Linkage Database (SFLD; http://sfld.rbvi.ucsf.edu).     

Early Quick Acuity Score Provides More Complete Data on Emergency Department Walkouts

Introduction

Many prior studies have compared the acuity of Emergency Department (ED) patients who have Left Without Being Seen (LWBS) against non-LWBS patients. A weakness in these studies is that patients may walk out prior to the assignment of a triage score, biasing comparisons. We report an operational change whereby acuity was assessed immediately upon patient arrival. We hypothesized more patients would receive acuity scores with EQAS. We also sought to compare LWBS and non-LWBS patient characteristics with reduced bias.

Methods

Setting: urban, academic medical center. Retrospective cohort study, electronic chart review, collecting data on all ED patients presenting between 4/1/2010 and 10/31/2011 (“Traditional Acuity Score” period, TAS) and from 11/1/2011 to 3/31/2012 (“Early Quick Acuity Score” period, EQAS). We recorded disposition (LWBS versus non-LWBS), acuity and demographics. For each subject during the EQAS period, we calculated how many prior ED visits and how many prior walkouts the subject had had during the TAS period.

Results

Acuity was recorded in 92,275 of 94,526 patients (97.6%) for TAS period, and 25,577 of 25,760 patients (99.3%) for EQAS period, a difference of 1.7% (1.5%, 1.8%). LWBS patients had acuity scores recorded in 5,180 of 7,040 cases (73.6%) during TAS period, compared with 897 of 1,010 cases (88.8%) during the EQAS period, a difference of 15.2% (14.8%, 15.7%). LWBS were more likely than non-LWBS to be male, were younger and had lower acuity scores. LWBS averaged 5.3 prior ED visits compared with 2.8 by non-LWBS, a difference of 2.5 (1.5, 3.5). LWBS averaged 1.3 prior ED walkouts compared with 0.2 among non-LWBS, a difference of 1.1 (0.8, 1.3).

Conclusions

EQAS resulted in a higher proportion of patients receiving acuity scores, particularly among LWBS. This offers more complete data when comparing LWBS and non-LWBS patient characteristics. The comparison reinforced findings from prior studies.