Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides.

Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world's most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2',3',4',3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2',3',4'-Trihydroxychalcone (IC50 = 4.2 µM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15-45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.

Protective effect of CCR5 delta 32 heterozygosity is restricted by SDF-1 genotype in children with HIV-1 infection.

OBJECTIVE: To determine the influences on pediatric AIDS of a heterozygous 32 base pair deletion in the CC-chemokine receptor 5 gene (CCR5 wt/Delta 32) and a common polymorphism in the 3' untranslated region of stromal cell-derived factor-1 beta gene transcript (SDF1-3'A). DESIGN: The rate of HIV-1 disease progression and viral burden were compared according to the CCR5 and SDF-1 genotypes in 127 (58 Caucasians, 60 African-Americans and nine Hispanics) perinatally HIV-1-infected children. RESULTS: Regardless of ethnic background, the CCR5 wt/Delta 32 genotype was associated with a delayed onset of AIDS-defining infectious complications during the first 5 years of infection [relative hazard (RH) = 0.22; 95% confidence interval (CI), 0.012--1.02; P = 0.053]. Similarly, CCR5 wt/Delta 32 conferred an early protection against severe immune suppression and HIV-1 encephalopathy, but only in those without SDF1-3'A (RH = 0; 95% CI, 0--0.70; P = 0.020, and RH = 0; 95% CI, 0--0.71; P = 0.021, respectively). When examined before 5 years of age (n = 81), the children with CCR5 wt/Delta 32 had significantly lower levels of cell-associated HIV-1 DNA than wild-type homozygotes (P = 0.016, adjusted by race), while SDF1-3'A carriers had relatively higher levels (P = 0.047, adjusted by race). Although the disease-retarding effect of CCR5 wt/Delta 32 subsequently disappeared, time to death was still significantly delayed in the CCR5 Delta 32 heterozygotes without SDF1-3'A (RH = 0; 95% CI, 0--0.53; P = 0.008). CONCLUSION: In pediatric AIDS, the protective effect of CCR5 wt/Delta 32 is more pronounced in early years of infection and appears to be abrogated by the SDF1-3'A genotype.

Status of infection surveillance and control programs in the United States, 1992-1996. Association for Professionals in Infection Control and Epidemiology, Inc.

BACKGROUND: Nosocomial infections have been recognized as a source of morbidity and mortality throughout the world for several decades. In the United States, an estimated 2.1 million nosocomial infections occur annually in acute care hospitals alone. Infection surveillance and control programs (ISCPs) play a vital role in addressing this problem, but no national studies have described the status and composition of these programs since the 1970s. METHODS: In January 1997, a voluntary survey was sent by mail to members of the Association for Professionals in Infection Control and Epidemiology, Inc. Only one response per facility was requested. The survey asked for information for the years 1992 to 1996 (study period), and questions pertained to characteristics of the health care facility in which the respondent worked, characteristics of the ISCP and its personnel, and the overall level of administration support for infection control activities. RESULTS: Completed questionnaires were received from personnel at 187 health care facilities located in 40 states and the District of Columbia. The majority (76.5%) of responding facilities were nongovernment owned, and 57.2% were classified as general acute care facilities. The number of licensed beds at these facilities remained stable throughout the study period, but all other measures of facility size and activity (eg, number of patient days and number of nurses) decreased by as much as 28.9%. In 1992, ISCPs were most likely to be organizationally located in the Nursing Department, but by 1996, many had been transferred to departments of Medical Records, Quality Assurance, or Risk Management. Throughout the course of the study period, the number of facilities performing surveillance for health care-associated infections in outpatient settings increased by 44.0%, from 100 to 144. In 1996, only 47.6% of facilities had a hospital epidemiologist (HE), and HEs devoted a median of 15% or less of their time to infection control activities. For the most part, HEs were trained in infectious diseases, and few had certification in infection control. Infection control professionals (ICPs) were much more common than were HEs (ICPs were reported at 97.9% of respondents' facilities in 1996), and they spent the majority (80% in 1996) of their time on infection control activities. During the course of the study period, increasing numbers of facilities had ICPs who had certification in infection control. Furthermore, most respondents did not report a change over time in the level of administration support for infection control activities. CONCLUSIONS: Health care delivery has changed dramatically during the past 20 years. This study presents an updated description of ISCPs in the United States. Our results illustrate several changing parameters, such as departmental shifts and increased outpatient surveillance, that reflect adjustments in health care priorities during the study period. As the transformation of the health care system continues, continued evaluation of the status of ISCPs on a national level will be necessary. Diligent monitoring, proactive measures, and collaboration between infection control organizations and government agencies will be vital for the prevention and control of health care-associated infections in the future.

Phenotypic expressions of CCR5-delta32/delta32 homozygosity.

OBJECTIVE: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-delta32/delta32 homozygous genotype has phenotypic expressions other than those related to HIV-1. DESIGN: Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-delta32/delta32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-delta32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. RESULTS: Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-delta32/delta32 study subjects. Based on blood pressure measurement and treatment history, CCR5-delta32/delta32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were approximately 20% higher in CCR5-delta32/delta32 study subjects than in CCR5-+/+ study subjects (p < .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-delta32/delta32 homozygotes (p < .05), but serum HCV levels did not differ by CCR5-delta32 genotype. CCR5-delta32/delta32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. CONCLUSIONS: CCR5-delta32/delta32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-delta32/delta32 homozygosity does not provide broad protection against viral infections.

Protection from the sun: a survey of area beachgoers.

There is a link between skin cancer and sunlight. A study of area beachgoers reveals gaps in public awareness about the hazards of ultraviolet light. Beachgoers, including children, are ideal target groups for educational programs on ultraviolet protection.