Autonomous motivation and support flourishes for individuals higher in collaborative personality factors: Agreeableness, assisted autonomy striving, and secure attachment.

INTRODUCTION: Individuals who strive autonomously for their goals, and who perceive autonomy supportive environments are more successful during goal pursuit. What dispositional factors predict autonomy flourishing during goal pursuit? METHODS: Four longitudinal studies were conducted over an 8-month academic year, and university students (Ntotal  = 1,544) completed surveys on motivation, support, and personality. Structural equation models were created using Mplus software to test whether collaborative personality factors were related to growth in autonomous motivation and autonomy support. RESULTS: All three distinct collaborative personality factors, trait Agreeableness, assisted autonomy striving, and secure parental attachment, were related to increases in autonomous motivation over the academic year. Conscientiousness, assisted autonomy, and secure attachment were related to increases in perceived autonomy support. A higher order latent collaborative traits factor, composed of Agreeableness, assisted autonomy, and secure attachment was found to be related to increased autonomous motivation and support over the academic year and resulted in increased goal progress. CONCLUSION: These results suggest that individuals higher in collaborative personality factors experience growth in personal autonomy during goal pursuit. Future research is needed to determine how to promote collaboration in goal pursuit to further help individuals successfully strive for their goals.

MALDI Mass Spectrometry Imaging of N-Linked Glycans in Cancer Tissues.

Glycosylated proteins account for a majority of the posttranslation modifications of cell surface, secreted, and circulating proteins. Within the tumor microenvironment, the presence of immune cells, extracellular matrix proteins, cell surface receptors, and interactions between stroma and tumor cells are all processes mediated by glycan binding and recognition reactions. Changes in glycosylation during tumorigenesis are well documented to occur and affect all of these associated adhesion and regulatory functions. A MALDI imaging mass spectrometry (MALDI-IMS) workflow for profiling N-linked glycan distributions in fresh/frozen tissues and formalin-fixed paraffin-embedded tissues has recently been developed. The key to the approach is the application of a molecular coating of peptide-N-glycosidase to tissues, an enzyme that cleaves asparagine-linked glycans from their protein carrier. The released N-linked glycans can then be analyzed by MALDI-IMS directly on tissue. Generally 40 or more individual glycan structures are routinely detected, and when combined with histopathology localizations, tumor-specific glycans are readily grouped relative to nontumor regions and other structural features. This technique is a recent development and new approach in glycobiology and mass spectrometry imaging research methodology; thus, potential uses such as tumor-specific glycan biomarker panels and other applications are discussed.

Species discovery and diversity in Lobocriconema (Criconematidae: Nematoda) and related plant-parasitic nematodes from North American ecoregions.

There are many nematode species that, following formal description, are seldom mentioned again in the scientific literature. Lobocriconema thornei and L. incrassatum are two such species, described from North American forests, respectively 37 and 49 years ago. In the course of a 3-year nematode biodiversity survey of North American ecoregions, specimens resembling Lobocriconema species appeared in soil samples from both grassland and forested sites. Using a combination of molecular and morphological analyses, together with a set of species delimitation approaches, we have expanded the known range of these species, added to the species descriptions, and discovered a related group of species that form a monophyletic group with the two described species. In this study, 148 specimens potentially belonging to the genus Lobocriconema were isolated from soil, individually measured, digitally imaged, and DNA barcoded using a 721 bp region of cytochrome oxidase subunit 1 (COI). One-third of the specimens were also analyzed using amplified DNA from the 3' region of the small subunit ribosomal RNA gene (18SrDNA) and the adjacent first internal transcribed spacer (ITS1). Eighteen mitochondrial haplotype groups, falling into four major clades, were identified by well-supported nodes in Bayesian and maximum likelihood trees and recognized as distinct lineages by species delimitation metrics. Discriminant function analysis of a set of morphological characters indicated that the major clades in the dataset possessed a strong morphological signal that decreased in comparisons of haplotype groups within clades. Evidence of biogeographic and phylogeographic patterns was apparent in the dataset. COI haplotype diversity was high in the southern Appalachian Mountains and Gulf Coast states and lessened in northern temperate forests. Lobocriconema distribution suggests the existence of phylogeographic patterns associated with recolonization of formerly glaciated regions by eastern deciduous forest, but definitive glacial refugia for this group of plant parasitic nematodes have yet to be identified. Unlike agricultural pest species of plant-parasitic nematodes, there is little evidence of long-distance dispersal in Lobocriconema as revealed by haplotype distribution. Most haplotype groups were characterized by low levels of intragroup genetic variation and large genetic distances between haplotype groups. The localization of nematode haplotypes together with their characteristic plant communities could provide insight into the historical formation of these belowground biotic communities.

COI haplotype groups in Mesocriconema (Nematoda: Criconematidae) and their morphospecies associations.

Without applying an a priori bias for species boundaries, specimen identities in the plant-parasitic nematode genus Mesocriconema were evaluated by examining mitochondrial COI nucleotide sequences, morphology, and biogeography. A total of 242 specimens that morphologically conformed to the genus were individually photographed, measured, and amplified by a PCR primer set to preserve the linkage between specimen morphology and a specific DNA barcode sequence. Specimens were extracted from soil samples representing 45 locations across 23 ecoregions in North America. Dendrograms constructed by neighbor-joining, maximum likelihood, and Bayesian Inference using a 721-bp COI barcode were used to group COI haplotypes. Each tree-building approach resulted in 24 major haplotype groups within the dataset. The distinctiveness of these groups was evaluated by node support, genetic distance, absence of intermediates, and several measures of distinctiveness included in software used for the exploration of species boundaries. Five of the 24 COI haplotype groups corresponded to morphologically characterized, Linnaean species. Morphospecies conforming to M. discus, Discocriconemella inarata, M. rusticum, M. onoense, and M. kirjanovae were represented by groups composed of multiple closely related or identical COI haplotypes. In other cases, morphospecies names could be equally applied to multiple haplotype groups that were genetically distant from each other. Identification based on morphology alone resulted in M. curvatum and M. ornatum species designations applied to seven and three groups, respectively. Morphological characters typically used for species level identification were demonstrably variable within haplotype groups, suggesting caution in assigning species names based on published compendia that solely consider morphological characters. Morphospecies classified as M. xenoplax formed a monophyletic group composed of seven genetically distinct COI subgroups. The species Discocriconemella inarata is transferred to Mesocriconema inaratum based on its phylogenetic position on the COI tree as well as previous phylogenetic analyses using 18S, ITS1, and cytochrome b nucleotide sequences. This study indicates that some of the species considered cosmopolitan in their distribution are actually multispecies polyphyletic groupings and an accurate assessment of Mesocriconema species distributions will benefit from molecular determination of haplotype relationships. The groups revealed by COI analysis should provide a useful framework for the evaluation of additional Mesocriconema species and will improve the reliability of designating taxonomic units in studies of nematode biodiversity. 

First Report of the Root-Knot Nematode Meloidogyne enterolobii Parasitizing Watermelon from Veracruz, Mexico.

In early April 2012, a sampling of watermelon crop Citrullus lanatus (Thunb.) Matsum & Nakai, 1916 cv. Sunsugar took place as part of the National System of Epidemiological Phytosanitary Surveillance (SINAVEF-MEX). This sampling was conducted at Riachuelos locality, Tecolutla, Veracruz, located at the geographic coordinates: 20.42008° N and 96.9627° W, within 50 meters of the Gulf of Mexico. Plants showed yellowing, stunting, and high levels of infection expressed by extensive galling on the roots. These symptoms were reproduced in the greenhouse on watermelon cv. Sunsugar. Egg masses were extracted to obtain juveniles (J2). Female necks and perineal patterns were mounted as well as males and J2 to take measurements of selected morphometric characters. To determine the nematode identity based on a morphological species concept, the following characters were considered. Females: stylet length, DGO and perineal pattern; males: stylet length; J2: body, stylet, tail, and hyaline tail terminus length. The morphometric analysis showed that those values corresponded to the original description of the root-knot nematode Meloidogyne enterolobii Yang & Eisenback, 1983 (=M. mayaguensis Rammah & Hirschmann, 1988) (1,2,3,4). For confirmation of this finding, a molecular diagnosis was performed using markers located in rDNA and mtDNA by PCR amplification and DNA sequencing. The rDNA region analyzed was the expansion segments D2-D3 of the 28S gene (primers D2A and D3B). This produced an amplified product of 780 bp. With regard to mtDNA, an amplification of the marker located between the genes COII/16S (primers C2F3 and 1108) resulted in a fragment of 705 bp that is specific for M. enterolobii (1). Sequences of the amplified products were compared with sequences from GenBank (NCBI). The sequences of both markers exhibited 99 and 100% identity with sequences corresponding to M. enterolobii isolates from Florida, Puerto Rico, and China. Maximum likelihood phylogenetic trees of rDNA and mtDNA sequences demonstrated that the Mexican isolate of M. enterolobii grouped among other isolates exclusive of other Meloidogyne species. The detection of this nematode in Veracruz, Mexico, expands the previously known worldwide distribution. It represents a serious threat due to the high level of aggressiveness shown in watermelon, which was so severe that growers had to change to a different crop. To our knowledge, this is the first report of the root-knot nematode M. enterolobii infecting watermelon cv. Sunsugar in Veracruz, Mexico. References: (1) J. Brito et al. J. Nematol. 36:232, 2004. (2) G. Karssen et al. ZooKeys 181:67, 2012. (3) A. Rammah and H. Hirshmann. J. Nematol. 20:58, 1988. (4) B. Yang and J. Eisenback. J. Nematol. 15:381, 1983.

Shelf life of case-ready beef steaks (Semitendinosus muscle) stored in oxygen-depleted master bag system with oxygen scavengers and CO2/N2 modified atmosphere packaging.

This study aims to evaluate the stability of beef from Semitendinosus muscle packaged in oxygen permeable wrapped-tray units and stored in a master bag system, with and without oxygen scavengers. Changes in the atmosphere composition, microbiological indexes, myoglobin forms and color parameters were monitored during the storage in master bag, blooming and display life. The presence of scavengers reduced rapidly the oxygen concentration and maintained it at values not detectable instrumentally. Within few days of storage in master bags, the resolution of the transient discoloration was completed and the meat quality was maintained over the anoxic storage. After the removal from master bags meat bloomed completely reaching OxyMb level and Chroma values higher than those on fresh meat at t(0). During 48 h of display life at 4 °C, quality attributes had a decay slower than samples stored traditionally in air. Without scavengers the oxygen caused the irreversible discoloration within 7 days, due to the formation of metmyoglobin on the surface.

DNA barcoding distinguishes pest species of the black fly genus Cnephia (Diptera: Simuliidae).

Accurate species identification is essential for cost-effective pest control strategies. We tested the utility of COI barcodes for identifying members of the black fly genus Cnephia Enderlein (Diptera: Simuliidae). Our efforts focus on four Nearctic Cnephia species-Cnephia dacotensis (Dyar & Shannon), Cnephia eremities Shewell, Cnephia ornithophilia (Davies, Peterson & Wood), and Cnephia pecuarum (Riley)--the latter two being current or potential targets of biological control programs. We also analyzed one Palearctic species, Cnephia pallipes (Fries). Although Cnephia adults can be identified anatomically to species, control programs target the larval stage, which is difficult or impossible to distinguish morphologically. By using neighbor-joining, maximum parsimony, and Bayesian methods, we found that COI barcodes successfully identified three Nearctic Cnephia species, but not C. pecuarum. The Palearctic C. pallipes was also successfully identified. Despite nonmonophyly of C. pecuarum, we show that data from COI barcoding, in combination with geographical and ecological information, can be used to distinguish all four Nearctic species. Finally, we discussed 1) possible reasons for paraphyly in C. pecuarum, 2) topological concordance to previously reported chromosomal dendrograms, and 3) evolution of diverse feeding strategies within the genus Cnephia.

Tropical nematode diversity: vertical stratification of nematode communities in a Costa Rican humid lowland rainforest.

Comparisons of nematode communities among ecosystems have indicated that, unlike many organisms, nematode communities have less diversity in the tropics than in temperate ecosystems. There are, however, few studies of tropical nematode diversity on which to base conclusions of global patterns of diversity. This study reports an attempt to estimate nematode diversity in the lowland tropical rainforest of La Selva Biological Research Station in Costa Rica. We suggest one reason that previous estimates of tropical nematode diversity were low is because habitats above the mineral soil are seldom sampled. As much as 62% of the overall genetic diversity, measured by an 18S ribosomal barcode, existed in litter and understorey habitats and not in soil. A maximum-likelihood tree of barcodes from 360 individual nematodes indicated most major terrestrial nematode lineages were represented in the samples. Estimated 'species' richness ranged from 464 to 502 within the four 40 x 40 m plots. Directed sampling of insects and their associated nematodes produced a second set of barcodes that were not recovered by habitat sampling, yet may constitute a major class of tropical nematode diversity. While the generation of novel nematode barcodes proved relatively easy, their identity remains obscure due to deficiencies in existing taxonomic databases. Specimens of Criconematina, a monophyletic group of soil-dwelling plant-parasitic nematodes were examined in detail to assess the steps necessary for associating barcodes with nominal species. Our results highlight the difficulties associated with studying poorly understood organisms in an understudied ecosystem using a destructive (i.e. barcode) sampling method.

Sentinel nematodes of land-use change and restoration in tallgrass prairie.

Changes in land use and the associated changes in land cover are recognized as the most important component of human-induced global change. Much attention has been focused on deforestation, but grasslands are among the most endangered ecosystems on Earth. The North American tallgrass prairie is a dramatic example, exhibiting a greater than 95% decline in historical area. Renewed interest in prairie conservation and restoration has highlighted the need for ecological indicators of disturbance and recovery in native systems, including the belowground component. The tallgrass prairie differs from the agricultural systems that have replaced it in having greater diversity and heterogeneity of resources, less physical soil disturbance (although other disturbances, such as fire and grazing, are prominent), and greater nitrogen limitation. Understanding the responses of nematode taxa to these characteristic differences is crucial to the development and improvement of community indices, but while knowledge of disturbance responses by individual taxa is accumulating, the level of necessary taxonomic resolution remains in question. Although nematode communities generally are better described for temperate grasslands than for other natural ecosystems, identification of sentinel taxa is further confounded by high levels of diversity, and both spatial and temporal heterogeneity.

Hand dominance and performance in a laparoscopic skills curriculum.

BACKGROUND: This study evaluated the influence of hand dominance on skill acquisition during a basic laparoscopic skills curriculum. METHODS: A total of 27 surgical residents (5 postgraduate year 3 [PGY-3] and 22 PGY-2 residents) participated in a 4-week laparoscopic skills curriculum. The residents were pre- and posttested on six laparoscopic tasks during weeks 1 and 4. During weeks 2 and 3, the residents attended a proctored practice session. The results were compared using analysis of variance (ANOVA), (with significance determined by a p value less than 0.05. RESULTS: The posttest scores were significantly higher than the pretest scores. On the pretest, lefthand-dominant (LHD) surgeons (n = 4) performed significantly better than righthand-dominant (RHD) surgeons (n = 23). In the analysis of individual task pretest scores, LHD surgeons performed significantly better on pattern cutting and vessel loop application. Posttest analysis of overall performance did not show significant differences between the RHD and LHD surgeons. CONCLUSIONS: Participation in a laparoscopic skills curriculum improved overall performance. The LHD surgeons demonstrated better initial performance, but posttest comparison showed no difference between the two groups.

Incorporating Molecular Identification of Meloidogyne spp. into a Large-scale Regional Nematode Survey.

A regional nematode survey of potato fields was conducted in the central United States during 2002 and 2003. The survey encompassed seven states and included a morphological and molecular examination of nematodes of regulatory concern from 1,929 soil samples. No regulated pest species were recovered during this survey. Meloidogyne juveniles extracted from soil were identified by mitochondrial and 18S ribosomal molecular markers. Eighty-two DNA sequences representing the two marker regions for Meloidogyne species were submitted to GenBank to facilitate evaluation of marker variability. Sufficient 18S variation was observed among some Meloidogyne species to aid in identification; however, nucleotide sequence from this highly conserved region of 18S did not discriminate among M. arenaria, M. incognita, and M. javanica. The mitochondrial gene region provided greater species discrimination and revealed intraspecific variation among many isolates. One nucleotide substitution found in a subset of M. hapla isolates from west Texas and New Mexico affected a DraI restriction site used in the PCR/RFLP diagnostic protocol. None of the mitochondrial sequence variants observed in this study compromised the PCR/RFLP identification protocol for M. chitwoodi. Additional sequence analysis is recommended for validation and evaluation of genetic markers used in diagnostic decisions.

Molecular differentiation of two sibling species of the black fly Simulium vittatum (Diptera: Simuliidae) based on random amplified polymorphic DNA.

Larvae of the black fly morphospecies Simulium vittatum from Colorado, Montana, Nebraska, and New Hampshire were cytologically identified as either the IS-7 or the IIIL-1 cytospecies. DNA was PCR amplified from cytotyped larvae using eight 10-mer primers, labeled with 33P, and run on polyacrylamide gels. The entire data set of 96 amplicons produced incomplete separation of the two cytospecies when subjected to neighbor-joining and maximum parsimony analyses. However, when analyzed within geographical regions, separate species status was supported. Bootstrap support for distinctness of the two cytospecies was best in Colorado where they were collected in true sympatry. The IS-7 cytospecies was more polymorphic in the western states, where it differed most from IIIL-1, which was most variable in the eastern states. The frequencies of the 17 most common amplicons in the two cytospecies were inversely correlated. A model of speciation derived from the molecular evidence suggests that IS-7 evolved in the west and spread eastward, whereas IIIL-1 later originated in the east and spread westward.

Morphological and Molecular Characterization of Meloidogyne mayaguensis Isolates from Florida.

The discovery of Meloidogyne mayaguensis is confirmed in Florida; this is the first report for the continental United States. Meloidogyne mayaguensis is a virulent species that can reproduce on host cultivars bred for nematode resistance. The perineal patterns of M. mayaguensis isolates from Florida show morphological variability and often are similar to M. incognita. Useful morphological characters for the separation of M. mayaguensis from M. incognita from Florida are the male stylet length values (smaller for M. mayaguensis than M. incognita) and J2 tail length values (greater for M. mayaguensis than M. incognita). Meloidogyne mayaguensis values for these characters overlap with those of M. arenaria and M. javanica from Florida. Enzyme analyses of Florida M. mayaguensis isolates show two major bands (VS1-S1 phenotype) of esterase activity, and one strong malate dehydrogenase band (Rm 1.4) plus two additional weak bands that migrated close together. Their detection requires larger amounts of homogenates from several females. Amplification of two separate regions of mitochondrial DNA resulted in products of a unique size. PCR primers embedded in the COII and 16S genes produced a product size of 705 bp, and amplification of the 63-bp repeat region resulted in a single product of 322 bp. Nucleotide sequence comparison of these mitochondrial products together with sequence from 18S rDNA and ITS1 from the nuclear genome were nearly identical with the corresponding regions from a M. mayaguensis isolate from Mayaguez, Puerto Rico, the type locality of the species. Meloidogyne mayaguensis reproduced on cotton, pepper, tobacco, and watermelon but not on peanut. Preliminary results indicate the M. mayaguensis isolates from Florida can reproduce on tomato containing the Mi gene. Molecular techniques for the identification of M. mayaguensis will be particularly useful in cases of M. mayaguensis populations mixed with M. arenaria, M. incognita, and M. javanica, which are the most economically important root-knot nematode species in Florida, and especially when low (<25) numbers of specimens of these species are recovered from the soil.

Yeast TOR signaling: a mechanism for metabolic regulation.

Understanding how cell growth is regulated in response to environmental signals remains a challenging biological problem. Recent studies indicate the TOR (target of rapamycin) kinase acts within an intracellular regulatory network used by eukaryotic cells to regulate their growth according to nutrient availability. This network affects all aspects of gene expression, including transcription, translation, and protein stability, making TOR an excellent candidate as a global regulator of cellular activity. Here we review our recent studies of two specific transcriptional outputs controlled by TOR in the budding yeast, S. cerevisiae: (1) positive regulation of genes involved in ribosome biogenesis, and (2) negative regulation of genes required for de novo biosynthesis of glutamate and glutamine. These studies have raised the important issue as to how diverse nutritional cues can pass through a common signaling pathway and yet ultimately generate distinct transcriptional responses.

Time does not heal all wounds. Patients report lower satisfaction levels as time goes by.

Tracking patient satisfaction over time is an effective way to learn about patient perceptions and can also help draw attention to service areas that need improvement. This research compared patient satisfaction levels immediately following hospital discharge and then again two years later. Both overall satisfaction and satisfaction with particular attributes tended to decrease over time. These findings raise questions about the long-term stability of satisfaction ratings and have implications for the timing of satisfaction surveys.

The role of complaint management in the service recovery process.

BACKGROUND: Patient satisfaction and retention can be influenced by the development of an effective service recovery program that can identify complaints and remedy failure points in the service system. Patient complaints provide organizations with an opportunity to resolve unsatisfactory situations and to track complaint data for quality improvement purposes. SERVICE RECOVERY: Service recovery is an important and effective customer retention tool. One way an organization can ensure repeat business is by developing a strong customer service program that includes service recovery as an essential component. The concept of service recovery involves the service provider taking responsive action to "recover" lost or dissatisfied customers and convert them into satisfied customers. Service recovery has proven to be cost-effective in other service industries. THE COMPLAINT MANAGEMENT PROCESS: The complaint management process involves six steps that organizations can use to influence effective service recovery: (1) encourage complaints as a quality improvement tool; (2) establish a team of representatives to handle complaints; (3) resolve customer problems quickly and effectively; (4) develop a complaint database; (5) commit to identifying failure points in the service system; and (6) track trends and use information to improve service processes. SUMMARY AND CONCLUSIONS: Customer retention is enhanced when an organization can reclaim disgruntled patients through the development of effective service recovery programs. Health care organizations can become more customer oriented by taking advantage of the information provided by patient complaints, increasing patient satisfaction and retention in the process.

First Report of Columbia Root Knot Nematode (Meloidogyne chitwoodi) in Potato in Texas.

Columbia root-knot nematode, Meloidogyne chitwoodi Golden et al. (1) was identified from potatoes, Solanum tuberosum L., collected from Dallam County, Texas in October 2000. Seed potatoes are the most likely source for this introduction. This nematode is currently found infecting potatoes grown in California, Colorado, Idaho, New Mexico, Nevada, Oregon, Utah, and Washington. Some countries prohibit import of both seed and table stock potatoes originating in states known to harbor M. chitwoodi. Lesions on the potatoes had discrete brown coloration with white central spots in the outer 1 cm of the tuber flesh. Female nematode densities averaged 3 per square centimeter of a potato section beneath the lesions. Nematodes were morphologically identified as M. chitwoodi based on the perineal pattern of mature females and the tail shape of juveniles per Golden et al. (1). Using polymerase chain reaction-RFLP of the rDNA ITS1 region and the mtDNA COII-16S rRNA region (2), individual juveniles were identified as M. chitwoodi based on their restriction fragment patterns. This is the first report of Columbia root-knot nematode infecting potatoes in Texas. The distribution of this nematode in potato fields throughout central United States should be determined. References: (1) A. N. Golden et al. J. Nematol. 12:319, 1980. (2) T. O. Powers and T. S. Harris. J. Nematol. 25:1, 1993.

Identification of Seed Gall Nematodes of Agronomic and Regulatory Concern with PCR-RFLP of ITS1.

A molecular analysis of eight described species of seed gall nematode, along with six undescribed isolates from different hosts, has revealed a strong association between nucleotide sequence polymorphism and host status. Each anguinid nematode associated with a unique host produced a unique PCR-RFLP pattern for the ITS1 region. Anguina species that had been synonymized in the past, Anguina agrostis, A. funesta, and A. wevelli (Afrina wevelli), were readily discriminated. Two undescribed species from northern New South Wales and southeastern South Australia, reported to be vectors of Rathyaibacter toxicus in the disease called ''floodplain staggers,'' were differentiated by a single restriction enzyme, and both could be separated easily from A. funesta, the vector of R. toxicus in annual ryegrass toxicity. Other species differentiated in this study include A. agropyronifloris, A. graminis, A. microlaenae, A. pacificae, and undescribed species from host species Dactylis glomerata, Agrostis avenacea, Polypogon monospeliensis, Stipa sp., Astrebla pectinata, and Holcus lanatus. Phylogenetic analysis of the ITS1 region suggests that considerable anguinid genetic diversification has accompanied specialization on different host species.

Effectiveness of palivizumab: evaluation of outcomes from the 1998 to 1999 respiratory syncytial virus season. The Palivizumab Outcomes Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) remains a significant cause of morbidity, especially in premature infants and immunocompromised children, resulting in approximately 100 000 hospitalizations annually. A study was performed to evaluate the outcomes of those given palivizumab (Synagis; MedImmune, Inc., Gaithersburg, MD) during the 1998 to 1999 RSV season, its first season in general use. METHODS: A retrospective chart review of 1839 patients from 9 United States sites was conducted, representing all patients given palivizumab at each site. Those evaluated were to have a gestational age of < or =35 weeks, were to be <2 years old at their first injection and were to have received at least one dose of palivizumab (humanized monoclonal antibody against RSV) between September, 1998, and May, 1999. Gestational age, comorbidities, frequency of injections, hospitalizations and length of hospital stays were assessed. RESULTS: The antigen- or culture-positive RSV hospitalization rates for those given prophylaxis were 2.3% (42 of 1839) overall, 16/399 (4.0%) with chronic lung disease of infancy and 26 of 1227 (2.1%) born prematurely without chronic lung disease of infancy. Twenty-six patients had a gestational age of >35 weeks and were included in the analysis. CONCLUSIONS: Only 2.3% of children receiving palivizumab prophylaxis were hospitalized with RSV lower respiratory infection. This compares favorably with the rates observed in the pivotal trial (IMpact-RSV trial in 1996 to 1997), in which prophylaxis reduced hospitalization from 10.6% in the placebo group to 4.8% in those children receiving prophylaxis.

Mechanism of metabolic control. Target of rapamycin signaling links nitrogen quality to the activity of the Rtg1 and Rtg3 transcription factors.

De novo biosynthesis of amino acids uses intermediates provided by the TCA cycle that must be replenished by anaplerotic reactions to maintain the respiratory competency of the cell. Genome-wide expression analyses in Saccharomyces cerevisiae reveal that many of the genes involved in these reactions are repressed in the presence of the preferred nitrogen sources glutamine or glutamate. Expression of these genes in media containing urea or ammonia as a sole nitrogen source requires the heterodimeric bZip transcription factors Rtg1 and Rtg3 and correlates with a redistribution of the Rtg1p/Rtg3 complex from a predominantly cytoplasmic to a predominantly nuclear location. Nuclear import of the complex requires the cytoplasmic protein Rtg2, a previously identified upstream regulator of Rtg1 and Rtg3, whereas export requires the importin-beta-family member Msn5. Remarkably, nuclear accumulation of Rtg1/Rtg3, as well as expression of their target genes, is induced by addition of rapamycin, a specific inhibitor of the target of rapamycin (TOR) kinases. We demonstrate further that Rtg3 is a phosphoprotein and that its phosphorylation state changes after rapamycin treatment. Taken together, these results demonstrate that target of rapamycin signaling regulates specific anaplerotic reactions by coupling nitrogen quality to the activity and subcellular localization of distinct transcription factors.