Clinical outcomes at 9-10 years of age in children born with cystic fibrosis transmembrane conductance regulator related metabolic syndrome.

Background And Objectives: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR).

Methods: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020.

Impaired lung function following e-cigarette or vaping product use associated lung injury in the first cohort of hospitalized adolescents.

Background: Beginning June 2019, Children's Wisconsin was the first hospital to identify a cohort of adolescent patients hospitalized with symptoms likely associated with e-cigarette use. Our report adds to the growing literature describing the radiographic, gross and cytopathologic bronchoscopic findings, and short-term lung function outcomes in this cohort of adolescents with e-cigarette or vaping product use associated lung injury (EVALI).

Methods: We present 15 adolescents hospitalized from June to September, 2019 with confirmed EVALI.

Experimental and natural vertical transmission of West Nile virus by California Culex (Diptera: Culicidae) mosquitoes.

Culex (Diptera: Culicidae) mosquitoes, the primary summer vectors of West Nile virus (family Flaviviridae, genus Flavivirus, WNV), also may serve as overwintering reservoir hosts. Detection of WN viral RNA from larvae hatched from eggs deposited by infected females during late summer and fall may provide evidence for the vertical passage of WNV to overwintering cohorts. To determine whether vertical transmission to the overwintering generation occurs in populations of Culex mosquitoes throughout California, larvae from naturally infected females were tested by family for WN viral RNA by real-time quantitative reverse transcription-polymerase chain reaction during August through October 2011.

Detection of persistent west nile virus RNA in experimentally and naturally infected avian hosts.

To determine whether West Nile virus (WNV) persistent infection in avian hosts may potentially serve as an overwintering mechanism, House Sparrows and House Finches, experimentally and naturally infected with several strains of WNV, and two naturally infected Western Scrub-Jays were held in mosquito-proof outdoor aviaries from 2007-March 2008. Overall, 94% (n = 36) of House Sparrows, 100% (n = 14) of House Finches and 2 Western Scrub-Jays remained WNV antibody positive. When combined by species, 37% of the House Sparrows, 50% of the House Finches, and 2 Western Scrub-Jays were WNV RNA positive at necropsy, up to 36 weeks post-infection.

Isolation of bitter acids from hops (Humulus lupulus L.) using countercurrent chromatography.

Commercially available hops (Humulus lupulus L.) bitter acid extracts contain a mixture of three major congeners (co-, n-, and ad-) in addition to cis/trans diastereomers for each congener. Individual isomerized α-acids were obtained by the consecutive application of two separate countercurrent chromatography methods.

N-methylation of the amide bond by methyltransferase asm10 in ansamitocin biosynthesis.

Ansamitocins are potent antitumor agents produced by Actinosynnema pretiosum. As deduced from their structures, an N-methylation on the amide bond is required among the various modifications. The protein encoded by asm10 belongs to the SAM-dependent methyltransferase family.

Efficacy of three vaccines in protecting Western Scrub-Jays (Aphelocoma californica) from experimental infection with West Nile virus: implications for vaccination of Island Scrub-Jays (Aphelocoma insularis).

The devastating effect of West Nile virus (WNV) on the avifauna of North America has led zoo managers and conservationists to attempt to protect vulnerable species through vaccination. The Island Scrub-Jay (Aphelocoma insularis) is one such species, being a corvid with a highly restricted insular range. Herein, we used congeneric Western Scrub-Jays (Aphelocoma californica) to test the efficacy of three WNV vaccines in protecting jays from an experimental challenge with WNV: (1) the Fort Dodge West Nile-Innovator(®) DNA equine vaccine, (2) an experimental DNA plasmid vaccine, pCBWN, and (3) the Merial Recombitek(®) equine vaccine.

Effects of warm winter temperature on the abundance and gonotrophic activity of Culex (Diptera: Culicidae) in California.

Culex tarsalis Coquillett, Cx. quinquefasciatus Say, and Cx. pipiens L.

Repeated West Nile virus epidemic transmission in Kern County, California, 2004-2007.

West Nile virus (WNV) has remained epidemic in Kern County, CA, since its introduction in 2004 through 2007 when the human case annual incidence increased from 6-8 to 17 per 100,000, respectively. The 2007 increase in human infection was associated with contradicting surveillance indicators, including severe drought, warm spring but cool summer temperature anomalies, decreased rural and urban mosquito abundance but increased early season infection in urban Culex quinquefasciatus Say, moderate avian "herd immunity," and declines in the catch of competent (western scrub-jay and house finch) and noncompetent (California quail and mourning dove) avian species. The decline in these noncompetent avian hosts may have increased contact with competent avian hosts and perhaps humans.

West Nile Virus Activity in Kern County and the Factors Leading to the 2007 Outbreak.

West Nile virus (WNV) reappeared in Kern County in late-May 2007, amplified rapidly and was detected concurrently by all surveillance methods. Enzootic activity during 2007 had some similarities to that of the previous three years, with 77 seropositive sentinel chickens in 9 flocks, 207 positive mosquito pools, 124 dead birds that tested positive, and 168 seropositive wild birds. WNV disease in equines remained infrequent, with only 4 cases reported.

DIFFERENTIAL IMPACT OF WEST NILE VIRUS ON CALIFORNIA BIRDS.

The strain of West Nile virus (WNV) currently epidemic in North America contains a genetic mutation elevating its virulence in birds, especially species in the family Corvidae. Although dead American Crows (Corvus brachyrhynchos) have been the hallmark of the epidemic, the overall impact of WNV on North America's avifauna remains poorly understood and has not been addressed thoroughly in California. Here, we evaluate variation by species in the effect of WNV on California birds from 2004 to 2007 by using (1) seroprevalence in free-ranging birds, (2) percentage of carcasses of each species reported by the public that tested positive for WNV, (3) mortality determined from experimental infections, and (4) population declines detected by trend analysis of Breeding Bird Survey (BBS) data.

Delinquent mortgages, neglected swimming pools, and West Nile virus, California.

Adjustable rate mortgages and the downturn in the California housing market caused a 300% increase in notices of delinquency in Bakersfield, Kern County. This led to large numbers of neglected swimming pools, which were associated with a 276% increase in the number of human West Nile virus cases during the summer of 2007.

Structural genomics of pathogenic protozoa: an overview.

The Structural Genomics of Pathogenic Protozoa (SGPP) Consortium aimed to determine crystal structures of proteins from trypanosomatid and malaria parasites in a high throughput manner. The pipeline of target selection, protein production, crystallization, and structure determination, is sketched. Special emphasis is given to a number of technology developments including domain prediction, the use of "co-crystallants," and capillary crystallization.

Safety, efficacy and anti-inflammatory activity of rho iso-alpha-acids from hops.

A defined mixture of rho iso-alpha-acids (RIAA), a modified hop extract, was evaluated for anti-inflammatory efficacy and safety. RIAA inhibited LPS-stimulated PGE(2) formation with >200-fold selectivity of COX-2 (IC(50)=1.3 microg/ml) over COX-1 (IC(50)>289 microg/ml).

Clinical safety and efficacy of NG440: a novel combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid for inflammatory conditions.

In this report, we examine the clinical safety and efficacy of NG440, a phytochemical-based antiinflammatory formula consisting of a combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid. In a previous study, we demonstrated that NG440 significantly decreased pain by 50% in patients with osteoarthritis. Consistent with these data, results from a multicentre trial indicate that NG440 reduced pain scores in patients with joint discomfort, as measured by VAS (visual analog scale) methodology.

On the biosynthetic origin of methoxymalonyl-acyl carrier protein, the substrate for incorporation of "glycolate" units into ansamitocin and soraphen A.

Feeding experiments with isotope-labeled precursors rule out hydroxypyruvate and TCA cycle intermediates as the metabolic source of methoxymalonyl-ACP, the substrate for incorporation of "glycolate" units into ansamitocin P-3, soraphen A, and other antibiotics. They point to 1,3-bisphosphoglycerate as the source of the methoxymalonyl moiety and show that its C-1 gives rise to the thioester carbonyl group (and hence C-1 of the "glycolate" unit), and its C-3 becomes the free carboxyl group of methoxymalonyl-ACP, which is lost in the subsequent Claisen condensation on the type I modular polyketide synthases (PKS). d-[1,2-(13)C(2)]Glycerate is also incorporated specifically into the "glycolate" units of soraphen A, but not of ansamitocin P-3, suggesting differences in the ability of the producing organisms to activate glycerate.

Role of California (Callipepla californica) and Gambel's (Callipepla gambelii) quail in the ecology of mosquito-borne encephalitis viruses in California, USA.

Gambel's and California quail were infected repeatedly whenever western equine encephalomyelitis virus (WEEV), St. Louis encephalitis virus (SLEV), and (WNV) West Nile virus were active during summer in California. The timing of virus appearance and quail infection coincided well with the appearance of chicks in nature, leading us to hypothesize that large coveys containing these non-immune birds could be important in focal virus amplification in rural settings.

Role of corvids in epidemiology of west Nile virus in southern California.

The invasion of different southern California landscapes by West Nile virus (WNV) and its subsequent amplification to epidemic levels during 2004 enabled us to study the impact of differing corvid populations in three biomes: the hot Colorado desert with few corvids (Coachella Valley), the southern San Joaquin Valley (Kern County) with large western scrub-jay but small American crow populations, and the cool maritime coast (Los Angeles) with a large clustered American crow population. Similar surveillance programs in all three areas monitored infection rates in mosquitoes, seroconversion rates in sentinel chickens, seroprevalence in wild birds, numbers of dead birds reported by the public, and the occurrence of human cases. Infection rates in Culex tarsalis Coquillett and sentinel chicken seroconversion rates were statistically similar among all three areas, indicating that highly competent mosquito hosts were capable of maintaining enzootic WNV transmission among less competent and widely distributed avian hosts, most likely house sparrows and house finches.

The post-polyketide synthase modification steps in the biosynthesis of the antitumor agent ansamitocin by Actinosynnema pretiosum.

The functions of six genes in the ansamitocin biosynthetic gene cluster of Actinosynnema pretiosum have been investigated by gene inactivation and chemical analysis of the mutants. They encode a halogenase (asm12), a carbamoyltransferase (asm21), a 20-O-methyltransferase (asm7), a 3-O-acyltransferase (asm19), an epoxidase (asm11), and an N-methyltransferase (asm10), respectively, and are responsible for the six post-PKS modification steps in ansamitocin formation. Several of the enzymes have relaxed substrate specificities, resulting in multiple parallel pathways in a metabolic grid, albeit with a preferred sequence of reactions as listed above.

Particle growth by acid-catalyzed heterogeneous reactions of organic carbonyls on preexisting aerosols.

Aerosol growth by the heterogeneous reactions of different aliphatic and alpha,beta-unsaturated carbonyls in the presence/absence of acidified seed aerosols was studied in a 2 m long flow reactor (2.5 cm i.d.

Identification of asm19 as an acyltransferase attaching the biologically essential ester side chain of ansamitocins using N-desmethyl-4,5-desepoxymaytansinol, not maytansinol, as its substrate.

The potent antitumor activity of the ansamitocins, polyketides isolated from Actinosynnema pretiosum, is absolutely dependent on a short acyl group esterified to the C-3 oxygen of the macrolactam ring. Asm19, a gene in the ansamitocin biosynthetic gene cluster with homology to macrolide O-acyltransferase genes, is thought to encode the enzyme catalyzing this esterification. A mutant carrying an inactivated asm19 no longer produced ansamitocins but accumulated N-desmethyl-4,5-desepoxymaytansinol, rather than maytansinol, indicating that the acylation is not the terminal step of the biosynthetic sequence.

Identification of a set of genes involved in the formation of the substrate for the incorporation of the unusual "glycolate" chain extension unit in ansamitocin biosynthesis.

The unusual "glycolate" extender unit at C-9/C-10 of ansamitocin is not derived from 2-hydroxymalonyl-CoA or 2-methoxymalonyl-CoA, as demonstrated by feeding experiments with the corresponding 1-13C-labeled N-acetylcysteamine thioesters but is formed from an acyl carrier protein (ACP)-bound substrate, possibly 2-methoxymalonyl-ACP, elaborated by enzymes encoded by a subcluster of five genes, asm12-17, from the ansamitocin bisosynthetic gene cluster.